Long afterwards, look for a recanalized thrombus.

Recanalized thrombus WebPath photo

*Space-age medicine! Viewing the thrombus by angioscopy NEJM 326: 287, 1993. Unstable angina thrombi are likely to be white fibrin-platelet thrombi or organizing thrombi (why?), etc. And the thrombi overlie plaques that are lipid-rich and/or disrupted (no surprise): Am. J. Card. 79: 1106, 1997.

COCAINE: Rough on the heart, and (your lecturer believes) the second most common cause of myocardial infarction and sudden cardiac death in the U.S. Review Med. Clin. N.A. 89: 1323, 2005; South. Med. J. 98: 794, 2005.

The recreational drug (1) produces coronary artery constriction (spasm, or whatever, nobody really understands it NEJM 333: 1267, 1995; Am. J. Card. 79: 492, 1997) and cardiac ischemia and even infarction (Circulation 99: 2737, 1999), especially when combined with cigaret smoking (NEJM 330: 454, 1994), which is bad because both increase the heart's need for oxygen; (2) makes the heart more prone to rhythm disturbances, perhaps by enhancing the effects of endogenous catecholamines; (3) can produce single-fiber necrosis/apoptosis and contraction bands (something to do with ion channels), perhaps leading to myocarditis and/or dilated cardiomyopathy. It is also known to produce (4) a dilated cardiomyopaty (Lancet 369: 1574, 2007).

Future pharmacologists: The drug opens sodium channels, perhaps opens calcium channels, and prevents synaptic re-uptake of catecholamines. Crystal meth probably does the same thing (J. Tox. 41: 981, 2003).

* Hopefully no one was surprised by the results of a huge study that showed that cocaine's effects on the heart are not mediated by its causing precocious atherosclerosis (Am. Heart. J. 150: 921, 2005).

PRINZMETAL'S CORONARY SPASM

MYOCARDIAL BRIDGE and DIVING CORONARY ARTERY, especially involving a portion of the left anterior coronary artery.

See below. Do you believe these rather familiar autopsy findings actually kill people? I don't know. Maybe 7% of folks have myocardial bridges (J. Cardio CT 1: 78, 2007). Insurance studies show that most people with myocardial bridges (i.e., bands of muscle across a coronary artery; picture NEJM 358: 392, 2008) never have trouble. Since the bridge constricts the artery worst during systole, and since the coronaries actually fill during diastole, you wouldn't think so... However, the anecdotal reports are interesting (Clin. Card. 20 1032, 1998). Most recently, the Japanese have an autopsy series of 100 MI deaths; half had myocardial bridges, and this seems to shift the atherosclerosis, making it worst just proximal to the bridge. Turbulence -- makes sense (Circulation 120: 376, 2009).

VASCULITIS

Remember (1) lupus; (2) polyarteritis nodosa; (3) rheumatoid arthritis; (4) Kawasaki's; (5) Takayasu's; (6) mycotic aneurysms (remember what those are? seen in bacterial endocarditis); (7) rarely, exotic infections.

{06569} polyarteritis nodosa of a coronary artery
{06587} aspergillus infection of a coronary artery

Kawasaki disease Article and photos AAFP

Epstein-Barr coronary aneurysm Advanced students Yutaka Tsutsumi MD

EMBOLIZATION (i.e., bacterial endocarditis)

SYPHILIS (classic!)

{03525} syphilis. Nice plasma cells.

DISSECTING HEMATOMA

A "dissecting aneurysm" can slide right up through a coronary ostium and cause occlusion. Or trauma can induce this change in an artery.

{06575} coronary artery dissection

SHOCK and LEFT-SIDED FAILURE, even if mild, in the setting of serious coronary artery stenosis.

A drop in blood pressure from any cause is likely to produce a SUBENDOCARDIAL INFARCT. (By definition, a subendocardial infarct is less than 50% as thick as the wall). This is a watershed infarct of the myocardium farthest from the coronary, but not close enough to the chamber to get its nutrients from the blood in the chamber.) If all three coronaries are stenotic, the infarct is likely to be circumferential.

* A favorite place to find subendocardial infarcts is in the tips of the mitral valve's papillary muscles. Why?

* Amyloid of the coronaries shouldn't cause an infarct, as the lumen is open and the endothelium undamaged.

{03386} coronary artery amyloidosis
{06584} amyloid (special stain)
{17483} amyloid myocardium

CILNICAL PICTURE OF THE "MI" PATIENT

Everyone knows the "typical" uncomplicated heart attack victim. There is chest pain (maybe, perhaps "crushing") radiating to the (left arm? jaw? abdomen? wherever?), perhaps with diaphoresis, perhaps with shortness of breath, perhaps with a feeling of fear, or perhaps with none of these ("silent infarct").

Serum enzymes (troponin, CK, perhaps with an "MB" cardiac isoenzyme band) begin to rise in perhaps 2-4 hours, but may be normal in a day or two. Ask your cardiologist how often to check. Later, look for the famous "LDH1>LDH2" isoenzyme flip.

The EKG changes depend on the location. Remember the subendocardial infarcts are notoriously hard to pinpoint by EKG, and that posterior wall infarcts are easy to miss, too.

You'll learn of the management and treatment of these patients while in the "unit". Remember that education about reducing risk factors is an important part of cardiac rehabilitation.

* Speaking of "cardiac rehabilitation": As a med student, I watched heart-attack survivors participate at great expense in kindergarten-level exercise programs in special hospital areas, supervised by boarded cardiologists. Not surprisingly, this got replaced (under the much-maligned "managed care") by expenditures on prevention (Am. J. Card. 79: 1075, 1997); for the "medically indigent" who need to change their lifestyles, good results are obtained simply by talking and explaining nicely (Am. J. Card. 79: 281, 1997).

PATHOLOGY

0-30 minutes

Wavy fibers at the edges, loss of glycogen from cytoplasm.

1- 2 hours

Mitochondrial calcium, maybe contraction bands, maybe hydropic changes, maybe even a little fatty change.

4-8 hours

Earliest nuclear changes, polys appear; you may see a bit of dark mottling grossly

8-24 hours

First clear gross changes, i.e., pallor; good coagulation necrosis; often good contraction bands; definitely feels soft by 24 hours

24-72 hours

Looks under the microscope, lots of polys, fibers are obviously necrotic; infarct feels soft and looks pale and yellowish (why?)

3- 7 days

Macrophages, granulation tissue starts at rim; grossly you see the red granulation tissue around the infarct

10 days

Nice granulation tissue; macrophage cleanup team may be removing the dead fibers

2-6 weeks

Macrophages continue the cleanup as scar forms; necrotic muscle may persist but is not inflamed

7 weeks

Nice scar.

* Today's standard for autopsy reports: "Acute" means polys, "Healing" means the polys are gone but there are macrophages, "Healed" means the macrophages are gone. "Microscopic" means less than 10% of the left ventricle (sic.), medium is 10% to 30%, large is more than 30% (Am. Heart. J. 144: 957, 2001).

Contraction bands WebPath photo

Early MI WebPath photo

Early MI WebPath photo

Infarct, ~3-4 days WebPath photo

Infarct, 1-2 weeks WebPath photo

Healed subendocardial infarct WebPath photo

Old MI, scar WebPath photo

Myocardial infarct Karyorrhectic neutrophils KU Collection

Myocardial ischemic scar Slide from Andrea McCollum MD Cuyahoga County Coroner's Office

Subendocardial ischemic scar Slide from Andrea McCollum MD Cuyahoga County Coroner's Office

Subendocardial scar Healed watershed infarct KCUMB Team

Subendocardial scar Healed watershed infarct KCUMB Team

Among these, the only items that may be unfamiliar are WAVY FIBERS (they had stopped beating and were roughed-up by the beating of the rest of the heart) and CONTRACTION BANDS ("myofibrillar degeneration"; densely eosinophilic cross-bands that probably result from calcium entering membrane-damaged cells during reperfusion, i.e., REPERFUSION INJURY. Remember that?)

* The AFIP has finally documented what real-world pathologists have known and used for decades: contraction bands let you know that a sudden death is of cardiac ischemic origin (gee whiz, Lancet 347: 1710, 1996)

* Future pathologists also note: Contraction bands can probably result from epinephrine administration and/or electric shocks in CPR.

NOTE: Classically, the coronary arteries have the following distribution, and their occlusion will result in TRANSMURAL (across-the-wall, or at least more than 50%) infarcts in the corresponding distribution

Right: Posterior-inferior wall, posterior 1/3 of septum

Left anterior descending: Anterior wall, anterior 2/3 of septum

Left circumflex: Lateral wall

There's plenty of variability. Especially when there's atherosclerosis, collateral formation may result in the "best" artery supplying most of the heart, with minor occlusions producing "infarction at a distance". Don't worry yet about "which gives you a bundle branch block", etc., etc.

NOTE: Infarcts almost never involve the right ventricle, unless it is extremely hypertrophied (why do you think?) If the infarct EXTENDS as a result of more mayhem in the coronaries, expect a mix of ages.

* Future pathologists: Try the NITROBLUE TETRAZOLIUM technique to demonstrate early myocardial infarcts. Drop a slice of heart in the solution, and viable heart, containing an oxidizing enzyme, will stain brown, and dead heart remain pale. I could never get this to work.

* Future pathologists: Don't mistake livor mortis for a posterior wall MI!

{10103} myocardial infarct, acute
{06639} very early MI (bottom only)
{06428} myocyte degeneration (hydropic change)
{06431} myocyte degeneration (hydropic change)
{06642} contraction bands
{06651} contraction bands
{06645} necrosis and polys
{06630} subendocardial MI
{06654} good necrosis and polys (NOTE: the myocyte are homogenized rather than pyknotic; that still means "dead")
{06443} road-kill, lots of polys, fibers very dead; good contraction bands remain
{06446} nice granulation tissue
{06663} nice granulation tissue
{06666} nice granulation tissue (left)
{06449} nice scar
{06338} nice scar
{06455} nice scar (trichrome)

You will learn how treat myocardial infarction on rotations.
In 2004, the first reports came in from experiments in which stem cells (from bone marrow, not embryos) were injected into the injured myocardium. After recovery, treated patients got about 6% new muscle, with controls getting almost none (Lancet 364: 121 & 141, 2004). The use of marrow stem cells in reperfused tissue has enjoyed further success, with patients seemingly benefitting (NEJM 355: 1210, 2006).

COMPLICATIONS occur in many but not all myocardial infarcts.

RHYTHM DISTURBANCES may begin at any time until the damage to the conduction system is healed. Formerly the great killer of "MI" patients, pharmacologic therapy is now generally successful in managing these.

LEFT-SIDED CONGESTIVE HEART FAILURE results from extensive damage to the heart. Whether or not there's been a known episode of infarction, a person with severe coronary disease can get intractable heart failure on the basis of ischemic scarring.

CARDIOGENIC SHOCK results from necrosis of more than >=40% of a non-athlete's myocardium. This is usually fatal.

RUPTURE (ouch!) of the heart may occur, typically when the damaged heart is most soft (days 3-7 or thereabouts), but day 1 ruptures are not unheard-of.

Ruptured MI Dino Laporte's PathosWeb

Ruptured MI WebPath photo

Ruptured MI WebPath photo

Rupture of the FREE WALL will result in hemopericardium, tamponade, and instant death.

Rupture of the SEPTUM will result in a sudden left-to-right shunt.

Rupture of the PAPILLARY MUSCLE produces severe mitral regurgitation.

{03614} ruptured wall
{07141} hemopericardium
{03617} ruptured septum
{53285} ruptured septum

ANEURYSM FORMATION, MURAL THROMBUS FORMATION, AND EMBOLIZATION are dread, common side-effects of myocardial infarcts. Ventricular aneurysms begin with the paradoxical movement of the necrotic myocardium outward during systole; later the fibrous scar balloons. Large infarcts can produce large aneurysms that continue to balloon out. Having a big aneurysm following a myocardial infarct greatly interferes with pump effectiveness. Embolization from a mural thrombus (with or without an aneurysm) is often devastating.

{06323} myocardial ventricular aneurysm

Old MI WebPath photo

Aneurysm of ventricle WebPath photo

Ventricular aneurysm with thrombus
WebPath photo

* DRESSLER'S PERICARDITIS ("postpericardiotomy syndrome") is pericarditis (sometimes with life-threatening effusion) that supposedly occurs weeks to years after an MI or cardiac surgery.

Although there are no accepted immunologic criteria, Dressler's is supposed to have an autoimmune basis, since anti-heart antibodies supposedly appear in the blood and the response to steroids is good.

Dressler's is rare at best (Heart 80: 98, 1998), and some cardiologists don't believe in it (Angiology 47: 83, 1996).

Distinguish this late-onset illness (if it exists) from the pericarditis that's common during the first week following myocardial infarction just from the necrosis.

CHRONIC ISCHEMIC HEART DISEASE is cardiac muscle insufficiency due to scarring from old infarcts, not necessarily large or known to have occurred. It is a major cause of congestive heart failure. Think of this especially if your patient has nighttime symptoms but the heart is perhaps not enlarged.

SUDDEN CARDIAC DEATH

Definition: Death from cardiac causes in previously-asymptomatic person, within 1 (or 24) hours after onset of symptoms. Most often, the person feels odd, then falls over dead. Either there's a rhythm disturbance (most often, and typically "ventricular fibrillation"), or there's some sudden, severe outflow obstruction. (Of course, the "forme fruste" of sudden cardiac death is a "fainting spell"!)

Every day, around 1000 people in the U.S. get "sudden cardiac death". (Some of these are probably included in the "1 million MI's" statistic; some probably aren't.)

Here's a rule: "Sudden death" means "sudden cardiac death". (Of course that includes pulmonary emboli.) Apart from extreme trauma, severing of a major body vessel, seizure death, anaphylactic shock, super-fast poisons, or a hemorrhage that destroys the brain's medulla, there's probably nothing that can kill a human being in less than an hour that isn't on this list.

Here's another rule: There's almost always at least some warning in the weeks beforehand. See Circulation 114: 1146, 2006.

THE CAUSES OF SUDDEN CARDIAC DEATH

• Coronary artery atherosclerosis: The most common on the list.

NOTE: Usually 75% concentric stenosis of all 3 coronaries, often more severe stenosis

When I was doing a lot of forensic autopsies, this was what I needed to see before I felt comfortable making the call. I like to hektoen (my neologism for cutting them the next day after decalcifying them in formic acid overnight) the coronary arteries; most pathologists don't do this.

If involvement of only one vessel is sufficient, at the textbooks tell you, it happens only in a small minority of these cases. The best study I've seen agrees (Hum. Path. 18: 485, 1987; still good.) Given the problems (not hektoening, which artery's dominant, etc., etc.) I remain unpersuaded that someone with 75% occlusion only at the widowmaker point can drop dead as a result unless something really exciting is going on in their life.

My former teammates Amy Kragel and her colleagues looked hard at the histopathology, and found that about 80% of these folks had a recanalized thrombus -- a surprising but credible finding (Am. Heart J. 127: 1588, 1994.

Being stressed (epinephrine -- no wonder, see Lancet 370: 1089, 2007) and having tobacco on board probably exacerbate the rhythm disturbance, in ischemia due to atherosclerosis or anything else.

* Future whole-person-oriented medical examiners: When somebody drops dead with no pathology except three narrow coronary arteries, ask "Why today rather than yesterday?" You will almost always find out if you ask about the circumstances. For example, I hope no one was surprised that firemen are much more likely to have heart attacks while fighting fires than at any other time (NEJM 356: 1207, 2007 -- a firefighter seems to be almost equally in danger from the fire and from his coronaries).

• Cocaine heart

Vasospasm

Fiber necrosis

Rhythm disturbances

• Coronary malformations

For example, having only one (Pete Maravich had no left main, also J. For. Sci. 35: 981, 1990), or having one come off the pulmonary artery. These birth defects can cause other problems, too.

Ask a forensic pathologist about sudden death due to a "diving coronary artery", i.e., one which enters the myocardium too soon, and "myocardial bridging" (very common in hypertrophic cardiomyopathy and common enough in "normal people"), in which a band of heart muscle overlies a coronary artery (NEJM 339: 1201, 1998; Chest 116: 574, 1999).

• Inflow problems
Extreme straining against a closed glottis while upright (i.e., constipation death)

Atrial myxoma or thrombus obstructing the mitral valve

• Outflow problems

Hypertrophic cardiomyopathy

Aortic valve stenosis from most any cause

NOTE: This is important. The mechanism is acute coronary insufficiency.

(1) The intra-myocardial branches of the coronary arteries fill only during diastole. In aortic valve stenosis, diastole is greatly shortened (why?).

(2) Bernoulli's principle (remember that?) results in blood being sucked out of the coronary arteries by the super-fast jet of blood passing through the narrowed aortic valve.

Cor pulmonale

Pulmonary embolus ("Do you think that should count as sudden cardiac death?"; maybe 50,000 extra "sudden death" cases among previously-healthy people in the U.S. per year)

• Conduction system problems / rhythm woes

Wolff-Parkinson-White, others ("bypass fibers", bundle of Kent; you'll learn about these on rotations; surgery Sci. Am. 269(1): 68, July 1993; gene NEJM 344: 1823, 2001)

Amyloid in the bundle of His (real frequency as cause of death is unknown, may be high)

Anti-Ro/SSA disease of the unborn and babies ("neonatal lupus").

In keeping with the idea that lupus involves defective clearance of apoptotic bodies, one group found that heart cells themselves clear heart cells that undergo apoptosis, and this clearing is inhibited by anti-Ro/SSA and anti-La/SSB: J. Clin. Inv. 116: 2413, 2006.

After surgically-induced trauma

Commotio cordis (myocardial concussion): Piezoelectric effect after a blow to the chest on top of the T-wave. See NEJM 333: 382, 1995. Special hazard for basketball, baseball catchers, hockey goalies, other activities: JAMA 287: 1142, 2002.

Recreational inhalant use (i.e., glue sniffing, etc.) sensitizes the heart to rhythm disturbances. This one's easy to miss, especially if the family or friends have removed the evidence. Finding this at autopsy is hard (Am. J. For. Med. Path. 27: 188, 2006); in fact, it's a famous cause of "negative autopsy" that you'll never solve.

Iron overload (rhythm disturbances)

Myocarditis (even a little patch can cause rhythm problems and even death: "Hank Gathers's disease"); I "buy this" when you see necrotic myocytes along with a (T-)lymphocytic infiltrate ("Dallas criteria")

Hank Gathers

* Endocardial fibroelastosis (Am. J. For. Med. Path. 20: 357, 1999).

Ventricular septal defect involving bundle of His

* Familial syndromes with apoptosis of the sinus node and AV node (Circulation 93: 1424, 1996).

Right ventricular dysplasia (see below)

Channelopathies

The LONG QT INTERVAL DISEASES (NEJM 339: 960, 1998; Circulation 99: 3165, 1999; stratifying risk NEJM 348: 1866, 2003; JAMA 289: 2120, 2003; Nat. Med. 10: 463, 2004; NEJM 358: 169, 2008 -- there are now ten different loci and over a hundred alleles; full-genome search Nat. Genet. 41: 388, 2009). Several different channelopathies including some sodium channel mutations (Circulation 101: 1698, 2000; Circulation 102: 584 & 921, 2000) and a common potassium channel mutation (Circulation 100: 1264, 1999). This is now known to be a common cause of sudden death with no anatomic findings at autopsy; this includes SIDS cases. An episode of torsade de pointes may tip the alert clinician, or the first sign may just be sudden death. Updates Am. J. Med. 110: 50 & 385, 2001; Arch. Path. Lab. Med. 125: 116, 2001; Ann. Int. Med. 137: 981, 2002.
You need to be alert to these; presently the estimate is that they cause about 4000 deaths in the US per year, i.e., around three times as many as die of thyroid cancer.

The unusual EKG is not always expressed, so keep a high index of suspicion. Whenever you suspect long-QT, either on EKG or family history (i.e., unexplained sudden death, including SIDS, or an episode of torsade de pointes) or personal history (torsade, syncope), get consultation; genetic screening for suspected families will be routine probably by 2005. This business is very tricky. You'll learn on rotations what medications are contra-indicated in which syndromes, when to place a defibrillator, and so forth.

You shouldn't need to be reminded to do an EKG on all pre-sports physicals where there's a history of syncopal spells or sudden unexplained death in a family member under age 30.

Swimming seems to trigger sudden death when the mutation is in the potassium channel KCNQ1 (Mayo Clin. Proc. 74: 1088, 1999), while loud noises trigger when the mutation is in the potassium channel KCNH2 / HERG. When the mutation is in the SCN5A channel (same as a Brugada locus but a different allele), death is likely to occur during sleep.

Future pathologists: See Am. J. For. Med. Path. 22: 105, 2001 for "the molecular autopsy" (i.e., gene searches for long QT and so forth; see J. Am. Coll. Card. 43: 1625, 2004) that follows your performing an autopsy on a young person who has died suddenly without a previous EKG or any anatomic or toxicologic explanation for death. You can conact the Sudden Death Genomics Lab at the Mayo Clinic (Mayo Clin. Proc. 80: 596, 2005; in particular they're finding a great deal of long QT J. Am. Coll. Card. 49: 240, 2007). UK position statements on screening family members after sudden, unexpected death of a young person: Heart 94: 502, 2008.

Mayo's now finds that a third of unexplained sudden deaths are due to known channelopathies. Regrettably, Mayo's reports that paraffin-embedded material, which is all that's usually left long after an autopsy, doesn't seem to preserve these genes well. See Am. J. Clin. Path. 129: 391, 2008.

Although some old-time pathologists remain skeptical, your lecturer believes that it will soon be standard practice to check all first- and second-degree relatives of a person (especially someone under age 18) who dies suddenly and has a negative autopsy, or who has near-sudden-death. In a 2005 Dutch study of the families of under-40 sudden death victims, 17 of 43 had a gene (catecholaminergic polymorphic V-tach was most common, followed by long-QT, Brugada, arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy Circulation 112: 207, 2005). Check includes EKG, exercise testing, and echocardiography. In a 2007 series limited to youngsters who died, a hereditary disease was found in 14 of 25 families (Pediatrics 120: 3967, 2007). European pathologists suggest professional standards for medical examiners inclding molecular examination of "negative autopsies" in the young (For. Sci. Int. 156: 138, 2006; I don't predict this will become standard in today's cost-conscious USA medical examiners' offices.)

You also know that prolongation of the QT interval in response to antipsychotic drugs predicts sudden unexpected death from drug-induced rhythm disturbance: Lancet 355: 1048, 2000.

BRUGADA SYNDROME (mutated sodium channel; see below, clinical features Circulation 99: 666, 1999; Lancet 355: 808, 2000).

Sudden ventricular fibrillation with no anatomic findings at autopsy.

Previous EKG's showed:

• "right bundle branch block" (pseudo-)


• elevated ST segments in V1, V2, V3


• maybe late inversions of the T-waves in V1-V3


• normal QT interval



Usually men, more common among people of Asian ancestry, usually die in their sleep at night. Runs in families of course, and worth getting an implanted defibrillator for if you have it (Am. J. Card. 83: 98-D, 1999).

About 3% of Thai and Laotian males have Brugada, and this accounts for the flap about "delayed death from yellow rain in Laotian immigrants" in the 1980's.

The sodium channel mutation (LQT3 / SCN5A, "idiopathic ventricular fibrillation" -- Nature 392: 293, 1998) is the Brugada gene.

* Less deadly, but interesting to scientists: KVLQT1 is a gene for familial atrial fibrillation (Science 299: 251, 2003).

* "Catecholamine-sensitive / catecholaminergic polymorphic V-tach" is a childhood disease in which exercise reproducibly causes the arrhythmias. As I predicted, it's a channelopathy, around half of cases it's in RYR2 (Mayo Clin. Proc. 79: 1367, 2004.

* "Idiopathic ventricular fibrillation", not familial and not caused by stress, surely covers a few entities that have not yet been discovered. Update on this and other causes of sudden cardiac death in structurally normal hearts: J. Am. Coll. Card. 43: 1137, 2004. Don't let this make anyone a cardiac neurotic, but "early polarization", a supposedly-harmless variant seen in maybe 5% of adults, is seen among 31% of people with "idiopathic V-fib" (NEJM 358: 2016, 2008).

* Myotonic dystrophy with abnormal EKG? NEJM 358: 2698, 2008

• "Mitral valve prolapse" (do you believe that one? I don't.)
• Hyperkalemia ("not really sudden death, since you were sick already..."; deaths from intravenous potassium are dreaded hospital mishaps Am. J. For. Med. Path. 24: 128, 2003)
• * Acute eosinophilic myocarditis (Crit. Care Med. 32: 714, 2004), an entity that typically appears superimposed on another cardiomyopathy and is attributed to drugs given to patients awaiting transplantation
• * Cadaveric spasm (see below)

NOTE: Syncope can warn of most of these. How?

NOTE: The other major causes of sudden unexpected death are pulmonary emboli, anaphylaxis, brain hemorrhages, and epileptic seizures ("SUDEP"; "Jett Travolta's disease"; Lancet 353: 888, 1999; Neurology 57: 430, 2001; Neurology 64: 1131, 2005; future medical examiners see Am. J. For. Med. Path. 23: 307, 2002).

OTHER PROBLEMS IN CARDIAC ISCHEMIA

There's no room here to talk about the various rhythm disturbances and kinds of heart block that may result from coronary insufficiency.

Worth remembering: ATRIAL FIBRILLATION is a troublesome rhythm disturbance affecting about 3 million people in the US, seen in coronary disease, mitral valve disease (why?), hyperthyroidism (George Bush Sr.; why?), ectopic (and ablatable) foci in the pulmonary veins (NEJM 339: 659, 1998; now mainstream NEJM 354: 934, 2006), etc. It is especially dangerous because thrombi tend to form in the quivering atria and embolize; this causes 1/3 of strokes in older folks. (* Hereditary a-fib: NEJM 336: 905, 1997). For the hard-cases, the left atrial appendage occlusion device (to prevent embolization) is now fast-tracked for development (NEJM 360: 2601, 2009).

Serious degrees of HEART BLOCK can cause people with coronary disease (or other problems; remember amyloid) to drop over suddenly ("Stokes-Adams attacks", etc.) Get them pacemakers.

Bypass grafts and pacer
WebPath photo


WHILE WE ARE TALKING ABOUT SUDDEN CARDIAC DEATH...

Despite the slight statistical advantage of a one-drink-a-day person over a non-drinker with the same other risk factors (Br. Med. J. 312: 1200, 1996; Br. Med. J. 314: 18, 1997), "your heart" is no reason to drink if you'd prefer not to. Because of the media hype over red wine ("tannins in wine protect the heart, the French paradox"), a couple of groups have looked at the cardioprotective properties of how-much vs. what-kind of alcohol (Br. Med. J. 312: 731 & 736, 1996); it's how much alcohol, not the kind of beverage.

It's now painfully clear that a person's successful return to near-normal living after a heart attack is largely a function of his or her knowledge about the disease. Fatalism turns you into a cardiac neurotic, a bad way to live. Education is the key to success. The implications for a primary-care physician are clear (Br. Med. J. 312: 1191, 1996).

No, it's probably not going to happen because you were having sex, even if you have angina or had a myocardial infarct (JAMA 275: 1405, 1996).

The Cambridge Heart Anti-Oxidant Study finds a good protective effect from vitamin E (Lancet 347: 781, 1996).

HIBERNATING MYOCARDIUM: "Chronic but reversible ischemic dysfunction". The most interesting discovery in "heart pathology" in recent memory (NEJM 339, 173, 1998; update Am. J. Path. 160: 1425, 2002).

When there is longstanding, sublethal ischemia of a portion of the myocardium, the fibers do not beat, but do not die.

This seems to be an adaptation that allows fairly good survival despite poor oxygenation (Am. J. Card. 98: 1574, 2006). Pathologists can spot hibernating cells (at autopsy, of course) by...

• loss of sarcomeres, but not loss of cytoplasmic volume, i.e., the actin and myosin are disrupted;


• more glycogen surrounding the nucleus


• the heterochromatin is distributed uniformly around the nucleus, as in immature cardiac muscle

* You can usually find a few of cells with the same morphology normally in the subendocardium.

If circulation is restored, the fibers reconstitute themselves and begin beating, though it may take several months.

A similar subject is the "myocardial stunning" seen after heart surgery; the cause is apoptosis of cells (Ann. Thor. Surg. 73: 1229, 2002).

Conduction System I From Chile In Spanish

Conduction System II From Chile In Spanish

* There's a lack of good pathology photos of stent mishaps. The bare metal stents perhaps cause more neointimal proliferation. The drug-eluting stents perhaps cause more late stent thrombosis. Stay tuned.

HYPERTENSIVE HEART DISEASE

In systemic hypertension, the left ventricle undergoes hypertrophy and, later, dilatation.

Probably the hypertrophy is mostly the result of pushing against the greatly increased load (more blood, more vascular resistance). Some hypertensives do have abnormally high cardiac outputs, so perhaps in these folks the heart is over-working for its own reasons.

There are rumors that some hypertensives suffer from chronic excess of catecholamines, and perhaps this exacerbates the hypertrophy.

Ultimately, the hypertensive's left ventricle will probably fail. To make the diagnosis, the heart must weigh more than 350 gm, and the left ventricle be more than 1.5 cm thick, with no other reason. You remember the microscopic appearance of the hypertrophied myocardial cell (thick fibers, many-ploid squared "boxcar nuclei"). It helps if the patient has a history of "high blood pressure", but when congestive heart failure supervenes on the salt-overloaded, hyper-constricted vascular system, "the high blood pressure may be cured".

NOTES: I doubt that "hypertrophy" itself causes myocyte injury or heart failure. I think that these result from the underlying hypertension.

NOTE: We talk about the etiologies of systemic hypertension under "Kidney".

NOTE: Somebody may tell you that most congestive heart failure in the elderly is due to coronary atherosclerosis, even in the absence of ischemic scarring, and that the ischemia causes the hypertrophy. This pathologist doesn't follow this logic. If that were true, then probably you could build muscle by holding your breath.

Remember that hypertension is also an important risk factor for atherosclerosis, stroke, and so forth.

COR PULMONALE

A quaint name for a very serious problem. Any right-heart problem resulting from increased pulmonary vascular resistance (usually poor ventilation, less often fibrosis or primary vascular problems).

The cause of the poor ventilation may be anything from emphysema to a kyphoscoliosis. (If the emphysema patient is a "blue bloater" with extra-low oxygen in the alveoli, the vessels will of course constrict even more. However, you'll see plenty of pink puffers with cor pulmonale.)

"Cor pulmonale" would also include right-sided heart extra burden from narrowing of the pulmonary vascular tree (Wegener's, pulmonary plexiform angiopathies, etc.) Whether "cor pulmonale" includes failure due to pulmonary emboli is a question for semantics experts.

You already know how pulmonary ventilation causes increased pulmonary vascular resistance ("causes pulmonary hypertension"). The right ventricle undergoes hypertrophy ("Feel that sternal heave!"), dilates, loses its familiar crescent shape and becomes more rounded, and eventually fails.

The polycythemia that accompanies hypoxia make the blood more viscous and prone to clot. This doesn't make the heart's job easier.

Increased pulmonary vascular resistance is a great impediment to a person's well-being. Often the right ventricle's problems set the real limit on quality of life in lung disease.

NOTE: The strained right ventricle is extremely vulnerable to rhythm disturbances. Patients with emphysema and cor pulmonale typically die very suddenly and unexpectedly as a result of an electrical storm in their strained ventricle. This mechanism probably underlies many (if not most) deaths from pulmonary emboli.

Cor pulmonale Great gross photo KU Collection

CONGENITAL HEART DISEASE: INTRODUCTION

Heart Rotation Problems From Chile In Spanish

Venous malformatins From Chile In Spanish

Arterial malformations From Chile In Spanish

Around 6-8 babies out of every 1000 has some kind of significant cardiac malformation.

Worth remembering:

• Down's kids have more endocardial cushion-area (crux-of-the-heart) defects;
• Turner's women have more patent ductus and preductal coarctation of the aorta;
• Immotile-cilia (Kartagener's, etc.) kids tend to have mirror-image hearts;
• Fetal rubella syndrome produces a plethora of cardiac defects;
• "Fetal alcohol syndrome" kids get VSD's.

Most of the time, nobody really knows why one heart forms normally and the next one doesn't (even folks who study the molecular biology have no breakthroughs: Ped. Clin. NA 53: 989, 2006). If one sibling has a defect, the next sibling has a 5% chance of having some (not necessarily the same) defect.

Around 5% of cardiac defects are attributed to the chromosomal abnormalities, and the others now account for <1% of new cases.

Classic "SIDS" cases (i.e., the child was reported to be asleep) seldom reveal a cardiac malformation, but in the much less common situation in which a child falls dead while awake is often caused by a cardiac anomaly (and remember long QT): J. Ped. 141: 336, 2002.

A "shunt", of course, is abnormal flow of blood from one part of the circulation to another, which aren't supposed to communicate directly. Intracardiac shunts are usually the result of birth defects.

Remember that intra-cardiac shunts that produce turbulence are also prone to get infected (bacterial endocarditis; why?) As with other lesions with abnormal flow, look for JET LESIONS where turbulence leads to endocardial thickening, and sometimes fibrin deposition and even infection.

CONGENITAL HEART DISEASE WITH RIGHT-TO-LEFT SHUNTS ("early cyanosis"; "blue baby", "cyanotic congenital heart disease")

"Cyanosis", you remember, refers to a concentration of >=5 gm/dL of unoxygenated hemoglobin in the arterial blood. Kids who are chronically hypoxic as a result of right-to-left shunts may become polycythemic. If the hematocrit gets about 65% or so, the blood becomes over-viscous and hard to pump. Polycythemic blood also clots more readily (why?)

People with right-to-left shunts develop clubbing of the digits.

The cause of clubbing is probably embolization of megakaryocyte remnants from the bone marrow. In health, many of these settle in the lungs. Where there is a right-to-left shunt through the pulmonary circulation (i.e., congenital heart disease, lung tumor, TB, granulation tissue), megakaryocytes get into the systemic circulation, and because they are large they tend to take the straight-shot to the fingers and toes. Evidence comes from histopathology (i.e., clubbed digits are packed with megakaryocytes), and from the fact that people with patent ductus arteriosus causing Eisenmenger's get clubbing of the toes but not the fingers. See Am. J. Card. 86: 1198, 2000.

You also know that these kids are prone to paradoxical embolization (i.e., a systemic venous embolus goes directly to the systemic arterial circulation), and particularly brain abscesses due to septic emboli.

Not surprisingly, we now know that the small coronary arteries are substantially wider in these patients than in normal folks, with more blood being delivered to the heart muscle. We must think this is an adaptive change, though the mechanism remains unknown (Circulation 114: 196, 2006).

Tetralogy of Fallot (Lancet 374: 1462, 2009).

Sketch it, and it makes sense. In the usual model, these babies have:

1. Overriding aorta (i.e., it straddles the ventricular septum, which is possible only because it has a hole in its top)

2. Pulmonic stenosis (usually, there is both stenosis of the pulmonic valve, which is often two-cusped, and much hypertrophy of the muscle trabeculae surrounding the track out of the right ventricle toward the pulmonary artery). This is the main determinant of severity in individual cases.

3. Ventricular septal defect (of course)

4. Right ventricular hypertrophy (obviously, since it must work so hard to perfuse the lungs through the defective pulmonic valve).

* If there is also an atrial septal defect, it is of course "pentalogy of Fallot". Around a quarter of patients have a right-sided aortic arch.

As you'd expect, these babies have a right-to-left shunt, and are born cyanotic. The lungs are hypoperfused (of course), and therefore won't suffer the ill-effects of hyperperfusion seen in left-to-right shunting.

The narrowed right-ventricular outflow track is the usual site of endocarditis.

"Tet attacks" are cyanotic episodes triggered by anything that briefly triggers increased pulmonary vascular resistance. A minor mystery of medicine is why these patients squat in the knee-chest position to relieve this. One investigator found that squatting changes the aortic wave form (Am. J. Hypertens. 15: 986, 2002); I have wondered if the altered shape of the thoracic cavity is sufficient to push the septum upward and partially close the VSD. Nobody knows.

Most of these people benefit from surgery.

The classic Taussig-Thomas-Blalock shunt, first performed in 1944 with dramatic results, anastamosed the pulmonary and subclavian arteries.

Complete repair, with careful dissection of the pulmonary outflow tract and repair of the ventricular septal defect, was not available until the 1950's; it has become more and more successful. Mild cases of tetralogy may present in adulthood and most of these people do well after operation (Ann. Thorac. Surg. 83: 1790, 2007).

Histologic study of the resected muscle, mostly from the resected crista supraventriculis, often shows tremendous hypertrophy, and usually much interstitial fibrosis and endocardial thickening (J. Thor. Card. Surg. 132: 270, 2006).

{49021} tetralogy of Fallot
{08627} tetralogy of Fallot
{08630} tetralogy of Fallot
{08483} clubbing

Tetralogy WebPath photo

* TAUSSIG-BING: "Kind of the opposite of Tetralogy of Fallot", with the aorta arising from the right ventricle and the pulmonary artery overriding the ventricle ("double outlet right ventricle"), which in Taussig-Bing bears a subpulmonic ventricular septal defect.

TRANSPOSITION OF THE GREAT VESSELS: A family of disorders in which the aorta arises from the anatomic right ventricle, the pulmonary artery from the anatomic left ventricle. Usually the aorta is anterior to the pulmonary artery at their origin.

In UNCORRECTED TRANSPOSITION ("dextro-"), the blood flow is:

right atrium --> right ventricle --> aorta

left atrium --> left ventricle --> pulmonary artery

If the child is to survive for any length of time after birth, an atrial (usually; septum primum) or ventricular septal defect must be present (why?). Surgeons may be able to switch the aorta and pulmonary artery for a cure, or switch the atria (Mustard and Senning operations). There are now many survivors, and many do very well into adulthood (Circulation 114: 2699, 2006).

In CONGENITALLY CORRECTED TRANSPOSITION ("levo-"), the atria are also switched by the malformation, so that the blood flow is:

right atrium --> left ventricle --> pulmonary artery

left atrium --> right ventricle --> aorta

This wouldn't be a problem, except that with this setup, the tricuspid and mitral valves can't really be normal. This may present in adulthood and also benefit from surgery.

{08644} transposition of the great vessels
{08647} transposition of the great vessels
{08650} transposition of the great vessels
{40920} transposition of the great vessels

Transposition of the great vessels
Pittsburgh Pathology Cases

*There are many other variants. In DOUBLE-OUTLET RIGHT VENTRICLE, both pulmonary artery and aorta arise from the right ventricle.

* We are just now beginning to study the brain abnormalities in these children, which seem to result from the poor perfusion during development (NEJM 357: 1928, 2007).

TRUNCUS ARTERIOSUS

The pulmonary artery and aorta are a single vessel, overriding a ventricular septal defect. Their valve typically has four cusps, etc.

Eventually the lungs are damaged by the high-pressure flow into their arteries.

{08656} truncus arteriosus

Truncus
WebPath photo

TRICUSPID ATRESIA

"Atresia", of course, means failure of a normal lumen to develop.

Obviously, survival is only possible if there is an atrial septal defect and some other route to get the blood to the lungs. (Think! How could this happen?)

The prognosis is still guarded. Closure of the ductus during the first few days of life can be a catastrophe (why?)

"Ebstein's anomaly" is a curious lesion with a low-slung valve outlet, large anterior leaflet and functional problems that vary in severity from patient to patient. As you'd expect, there are often major problems filling the right ventricle and/or serious tricuspid regurgitation; often there is an atrial septal defect and/or some other problem involving the left side as well (Mayo Clin. Proc. 80: 361, 2005). Surgery may involve creating a single ventricle, though today the two-ventricle approach is favored by some groups (Ann. Thorac. Surg. 84: 587, 2007). Valvuloplasty: Ann. Thor. Surg. 83: 676, 2007.

HYPOPLASTIC LEFT HEART

Underdevelopment of the aortic and mitral valves, left ventricle, and proximal aorta. The blood returning from the lungs goes through the atrial septal defect.

Severity ranges from mild hypoplasia to atresia of the mitral and aortic valves without any left ventricle at all. Altogether, these are quit common, around 2.3 per 10,000 live births (J. Am. Coll. Card. 39: 1890, 2002).

Untreated, this is lethal shortly after birth, though compatible with normal life as an unborn child while the ductus stays open.

Transplantation is of course an option if a heart is available.

Today's three-stage procedure works like this.

• First, the main pulmonary artery is separated from the right and left pulmonary arteries and joined to the aorta (Norwood procedure). An artificial shunt is placed between the right ventricle and the junction of the right and left pulmonary arteries ("Sano shunt"). The child's heart is now working very, very hard.
• After a few months, two more surgeries are performed. They connected the superior vena cava and inferior vena cava to the pulmonary arterial circulation, so that blood goes directly to the lungs due to systemic venous pressure ("Glenn" and "Fontan" procedures).

Update on surgical treatment: Pediatrics 119: 109, 2007.

* One of the "great ethical debates" of the early 1990's led to the prohibition of the use of anencephalic babies' ("Baby Theresa") hearts to treat hypoplastic left heart syndrome. These used to save lots of lives. Because hearts are now seldom available, about half of these kids ended up dying as a result (NEJM 330: 501, 1994).

*"Baby Fae" was born with a hypoplastic left heart. She was given a baboon's heart by a surgeon interested in "independent scientific thought". Do you remember the press conference in which the surgeon predicted she'd live a normal life? Most people would consider the whole business unethical. I think that reasonable people can disagree about this. Please remember this was the first infant heart transplant, and prepared the way to many lives saved, especially from anencephalic donors before saving lives in this way was made illegal.

{11483} hypoplastic left heart

Vivien Thomas Behind the surgical light Classic photo

There are a host of others forms; one relatively common entity is double-inlet left ventricle with hypoplastic right ventricle. The great arteries may arise normally or anomalously.

* Vivien Thomas, the famous surgical genius who was assistant to and collaborator with Alfred Blalock, was an African-American who because of the racism of his era never obtained formal education beyond high school. While developing operative procedures for tetralogy and other birth defects at Vanderbilt in the 1930's, he had to be classified and paid as a janitor. As recognition of his part in the development of "blue baby surgery", one of the colleges in Johns Hopkins medical school is named for him. His autobiography is "Partners of the Heart." See JAMA 300: 328, 2008.

CONGENITAL HEART DISEASE WITH LEFT-TO-RIGHT SHUNTS ("late cyanosis")

A family of diseases in which much of the left cardiac output returns to the pulmonary system. This eventually causes serious damage to the pulmonary vasculature.

This is bad. The left-to-right shunt will make the heart work harder, and the increased blood flow to the lungs will eventually damage the pulmonary arteries. When pulmonary artery pressure exceeds aortic pressure, the shunt will reverse ("Eisenmenger's syndrome"), cyanosis will occur, and death will follow shortly.

* Pregnancy, with increased blood volume, speeds this up.

Eisenmenger's is a major disaster. Long-term prostacyclin (PGI₂) for these people: Circulation 99: 1858, 1999.

VENTRICULAR SEPTAL DEFECT ("VSD", "Roger's disease" if <=5 mm, etc.): A hole in the ventricular septum. This can be serious.

90% of these are in the membranous septum. Unfortunately, this is near the bundle of His; these patients may develop heart block.

The remaining 10% are in the muscular septum.

The best thing about VSD is that around 50% close spontaneously, either when the muscle hypertrophies or the tricuspid leaflet adheres to the defect. Natural hystory: Arch. Dis. Child. 81: 413, 1999.

When treatment is necessary, some can be closed by percutaneous endovascular procedures with placement of little VSD occluders. Larger defects still require open-chest surgery.

{03281} ventricular septal defect
{03287} ventricular septal defect (sorry about ruler over hole)
{03635} membranous ventricular septal defect
{03638} membranous ventricular septal defect
{08525} ventricular septal defect
{03650} complete atrioventricular septum defect

Ventricular Septal Defects From Chile In Spanish

Eisenmenger's, lung Lung pathology series; follow the arrows Dr. Warnock's Collection

Ventricular septal defect WebPath photo

The most extreme example is "univentricular heart" (Circulation 115: 800, 2007) with no septum at all. (When there is a good atrial septum, it is called "cor triloculare biatrium", Why the name?)

* Surprisingly, some of these these patients can do remarkably well without surgery (Am. J. Card. 77: 542, 1996).

ATRIAL SEPTAL DEFECT: A hole in the atrial septum.

Among these:

90% are OSTIUM SECUNDUM DEFECTS, problems with the foramen ovale ("patent foramen ovale", etc.). Often this is just a probe-patent slit where the flap joins the rest of the muscle. If a flap covers such a defect, it may re-open in the setting of pulmonary hypertension (i.e., pulmonary embolization) and explain paradoxical embolization.

Where there's a real, obvious hole, there will always be some right-to-left shunting whenever central venous pressure exceeds left atrial pressure. Hence the danger of paradoxical embolization.

The famous physical exam sign in atrial septal defect is loss of the physiologic splitting of S₂. Here's why it happens. When you breathe in, the negative pressure in the chest pulls more blood into the right atrium and ventricle. Hence P₂ comes a bit later than A₂. When there's an atrial septal defect, the pressure between the atria is equal, so more blood enters the left ventricle as well, so A₂ is also relatively delayed.

One-fourth of humankind who have a probe-patent foramen ovale (i.e., the autopsy pathologist can slide a probe through the atrium by twisting it around the membrane) when no actual shunt occurred in life. In these people, there's talk of a link to cryptogenic stroke, and of course it's a great danger for scuba divers (South. Med. J. 99: 1367, 2006). There is a current claim that closing this transcutaneously is an effective treatment for migraine; the procedure seems safe enough and perhaps there'll be some hard science soon (Neurology 65: 1415, 2005; Chest 130: 896, 2006; Am. J. Card. 99: 1316, 2007; Nat. Clin. Pract. Cardio 3: 446, 2006).

* Early surgical closure to prevent rhythm problems after the operation: NEJM 348: 839, 1999.

Patent foramen ovale Paradoxical embolus WebPath photo

5% are SINUS VENOSUS DEFECTS, near the superior vena cava. These people are likely to have one or more of the right pulmonary veins that return to the right side of the heart, rather than the left side.

5% are OSTIUM PRIMUM DEFECTS, low on the septum at the cardiac crux. Often these are Down's children, and there's generally some mitral insufficiency, too.

* "Coronary sinus type" is rare. Look for a persistent left superior vena cava.

* LUTEMBACHER'S SYNDROME merely refers to mitral stenosis plus an atrial septal defect. What do you think happens?



Functionally significant atrial septal defects need surgery or transcatheter repair to prevent the same pulmonary problems seen in VSD's, as well as the often-devastating effects of a right-to-left shunt.

{08498} atrial septal defect
{08501} atrial septal defect
{08513} atrial septal defect

Atrial septal defect, small WebPath photo

Atrial septal defect, large WebPath photo

PATENT DUCTUS ARTERIOSUS

The ductus ordinarily closes in the first few days of life. Prostaglandin E apparently keeps it open, and closure can be induced in many cases using prostaglandin antagonists.

If the ductus fails to close, the child's "machinery murmur" needs to be turned off by surgical ligation. If not, the same problems with left-to-right shunting seen with VSD and ASD will occur.

Note that closure can exacerbate certain cardiac birth defects. In pulmonic stenosis, transposition of the great vessels, and hypoplastic right heart syndrome, it's best for the ductus to remain open to supply blood to the lungs. More about this on rotations.

{08566} patent ductus arteriosus
{08569} patent ductus arteriosus

VARIATIONS

"Endocardial cushion defects" / "complete atrioventricular septal defects" / "common AV canal" are a group of defects that involve the formation of the AV valves, the anterior atrial septum, and the posterior part of the ventricular septum.

In the most severe forms, the tricuspid and mitral valves are a single valve. A majority of these patients have trisomy 21. Despite its severity, nowadays surgical repair is often very successful (review Ann. Thor. Surg. 78: 666, 2004).

{08603} AV canal
{08617} AV canal

OBSTRUCTIVE, NON-CYANOTIC CONGENITAL ANOMALIES ("acyanotic")

COARCTATION OF THE AORTA

A fibrous ring around a portion of the aorta, or perhaps another large artery. This is common in Turner's, or may be idiopathic.

If the occlusion is pre-ductal (the rare "infantile type", i.e., proximal to the ductus arteriosus), patents may even have heart failure while in the womb. In this case, the upper half of the body is supplied by the aorta, and the lower half is supplied by the pulmonary artery via a patent ductus arteriosus.

In the post-ductal (common, "adult") type, the stenosis is distal to the ductus arteriosus. Since the lower half of the body is likely to be under-perfused (claudication, etc.), renal hypertension is usual, and collateral arterial circulation will develop (via which arteries? HINT: It notches the ribs!) If the femoral pulses on a hypertensive patient seem late and weak, it's probably coarctation of the aorta.

You want to get most cases of "co-arc" fixed, not the least reason being that the site is prone to become infected. Surgical and catheter-based options are both in widespread use (J. Am. Coll. Card. 43: 1062, 2004; Ann. Thorac. Surg. 80: 1659, 2005; AJR 187: W302, 2006).

Even after repair, hypertension can be a problem, especially when exercising (underperfusion of the kidneys: Am. J. Card. 99: 1284, 2007).

Coarctation WebPath photo

Coarctation WebPath photo

PULMONARY STENOSIS / STRESIA WITH INTACT INTERVENTRICULAR SEPTUM

Not rare. Obviously, the blood must flow to the left side of the heart (usually through an atrial septal defect), and then to the lungs via a patent ductus.

This is a very serious lesion, and prognosis depends largely upon how much of the right side of the heart has formed properly, and whether the coronary circulation might be compromised by decompression of the right ventricle by the shunt that will need to be placed (for example, there's often a fistula between a coronary and the right ventricle). See Ann. Thor. Surg. 84: 574, 2007.

Today, the diagnosis may be made before birth, and a catheter introduced to try to improve the opening. Details Am. J. Card. 99: 699, 2007.

AORTIC VALVE STENOSIS AND ATRESIA

In congenital VALVULAR aortic stenosis, the valve is a fibrous diaphragm.

In congenital SUB-VALVULAR aortic stenosis, there is a thick, fibrous ring below the valve itself.

In congenital SUPRA-VALVULAR aortic stenosis, there's a similar ring just past the valve. * This one's genetic. One mutation is now known to be the elastin gene: Hum. Genet. 106: 577, 2000, Am. J. Card. 83: 1141, 1999, others.

Milder birth defects of the aortic valve are much more common. BICUSPID AORTIC VALVE, seen in around 1% of folks, produces more "congenital heart disease" patients with real problems than any other among the birth defects. It tends to calcify later in life, and become stenotic. The right coronary and left coronary leaflets are the most likely to be fused, while in turn this is the least likely to be troublesome (J. Am. Coll. Card. 44: 1648, 2004). Fusion of the right coronary and non-coronary leaflets is more likely to cause valve dysfunction. Pathologists see J. Thor. Card. Surg. 133: 1226, 2007 for a subclassification based on number and position of raphes and whether there is stenosis; at the very least, report the number of raphes, if any.

UNICUSPID AORTIC VALVE, surprisingly, also works. Tetracuspid valve is a curiosity.

{06779} bicuspid aortic valve
{46205} bicuspid aortic valve
{06818} bicuspid aortic valve, this had both stenosis and insufficiency
{06785} unicommissural aortic valve
{53319} aortic valve with four cusps

Bicuspid aortic valve
WebPath photo

* These was recently a flap over chlamydia as contributing to the calcification of normal aortic valves, just as they've getting blamed for atherosclerosis. I predicted in 1996 that this will prove to be non-related, and that the bugs were just hangers-on. This now seems to be correct (Am. J. Coll. Card. 29: 1054, 1997; Circulation 99: 2733, 1999; Mayo's Atherosclerosis 174: 337, 2004) though some groups still find a relationship (?? immune complexes Eur. Heart J. 24: 198, 2003).

MALPOSITIONS OF THE HEART

An ACARDIUS is a birth defect in which there is no heart. If the pregnancy goes to term, it is always because the child shares circulation with a twin.

{21109} acardius
{21110} acardius

Acardius WebPath Photo

Acardius WebPath Photo

DEXTROCARDIA means the heart's on the right side. In Kartagener's syndrome, the cilia are immotile due to lack of dynein arms, so the organ often end up backwards. In SITUS INVERSUS TOTALIS, with everything backwards, the heart is usually well-formed. If the heart is the only organ that is mal-positioned, it often bears other defects.

ENDOCARDIAL AND VALVULAR DISEASE

The page [Lydgate] opened on was under the head[ing] of Anatomy, and the first passage that drew his eyes was on the valves of the heart. He was not much acquainted with valves of any sort, but he knew that valvae were folding-doors, and through this crevice came a sudden light startling him with his first vivid notion of finely adjusted mechanism in the human frame... The moment of vocation had come, and before he got down from his chair, the world was made new to him... From that hour Lydgate felt the growth of an intellectual passion.

-- George Eliot, "Middlemarch"

Endocardium I From Chile In Spanish

Endocardium II From Chile In Spanish

Acquired Valvular Disease I From Chile In Spanish

Acquired Valvular Disease II From Chile In Spanish

Endocardium Exhibit Virtual Pathology Museum University of Connecticut

Valve Exhibit Virtual Pathology Museum University of Connecticut

Non-Infectious Endocarditis From Chile In Spanish

KNOW YOUR COMMON ETIOLOGIES!

MITRAL STENOSIS (Lancet 374: 1271, 2009)

Old rheumatic fever

We are now seeing occasional older folks with severe calcification of the mitral valve annulus who get some mitral valve stenosis. No one knows what to do about this.

(All other causes are very uncommon -- Libman-Sacks is perhaps "the other cause"; see Am. J. Med. 120: 636, 2007. Fabry's and some of the mucopolysaccharidoses are occasionally causes)

NOTE: Isolated mitral stenosis is pretty well tolerated most of the time.

MITRAL REGURGITATION (Lancet 373: 1382, 2009)

Old rheumatic fever

Bacterial endocarditis

Barlow's syndrome

Other birth defects at the crux

Ruptured papillary muscle (MI)

Ruptured chorda (bacterial endocarditis, Barlow's)

Dilated annulus (left CHF)

Libman-Sacks

Calcified mitral annulus (maybe)

Mucopolysaccharidosis (why? -- Hunter's Ann. Thor. Surg. 80: 1911, 2005).

Degenerative changes of old age (the most common today: NEJM 335: 1417, 1996)

AORTIC VALVE STENOSIS (Lancet 373: 956, 2009)

Old rheumatic fever

Congenital bicuspid valve that calcified

Normal valve that calcified

Birth defects (valvular, sub-valvular)

Libman-Sacks

Alkaptonuria ("somebody poured India Ink all over the aortic valve")

NOTE: Some of the biggest hearts in clinical medicine result from aortic valve stenosis. Obviously, the pulse pressure is narrowed, and systole is prolonged. This can have very bad consequences for myocardial perfusion.

NOTE: As I trust you've figured out, "aortic stenosis" (by custom) refers to stenosis of the valve, not the aorta. If a portion of the aorta is stenotic, it's called "coarctation". If the entire aorta is stenotic, you didn't get born.

AORTIC REGURGITATION (review Circulation 99: 1851, 1999 urges aggressive surgical management)

Old rheumatic fever

Bacterial endocarditis

Syphilis

Dissecting hematoma / steering wheel injury

Marfan's

Libman-Sacks

Fenfluramine (diet pill fiasco): about 9% of those treated got aortic regurgitation on echo, but cardiac symptoms are not much greater than in controls: JAMA 283: 1703, 2000.

The ring dilates:

Rheumatoid arthritis

Ankylosing spondylitis / HLA-B27 family

Syphilis

"Annuloaortic ectasia" (usually older hypertensives)

NOTE: You'll learn about increased pulse pressure, "Corrigan's jumping pulse", pistol-shot sign, etc., etc. on rotations.

TRICUSPID STENOSIS

Old rheumatic fever

Carcinoid heart disease

TRICUSPID REGURGITATION

Old rheumatic fever

Carcinoid heart disease

Bacterial endocarditis (ask about IV drug use!)

Loeffler's

Dilated annulus (right CHF)

Carcinoid heart disease

Libman-Sacks

NOTE: Look for those jumping neck veins!

PULMONIC STENOSIS

Tetralogy of Fallot

Congenital ("funnel")

Carcinoid heart disease

PULMONIC INSUFFICIENCY

Dilated annulus (right CHF). Rare.

Carcinoid heart disease

KNOW YOUR VEGETATIONS!

ACUTE RHEUMATIC FEVER

Small, warty, sterile, on the lines of closure and perhaps chordae

Seldom embolize

BACTERIAL ENDOCARDITIS

Often large, loaded with bacteria

Find them on any deformed intracardiac surface

Very prone to embolize

NON-BACTERIAL THROMBOTIC ("MARANTIC") ENDOCARDITIS

Small, sterile, on the lines of closure

May embolize

LIBMAN-SACKS ENDOCARDITIS -- lupus and antiphospholipid antibody syndrome

Any size, sterile, on either surface of the leaflet / chordae

May embolize

NOTES: (1) You'll learn your murmurs in clinical medicine. "Is this a worrisome systolic murmur?" JAMA 277: 564, 1997. (2) As with any intracardiac lesion involving turbulence, deformed valves are prone to develop bacterial endocarditis. (3) Future pathologists: Again, look for jet lesions on the endocardium if you suspect a valve of having produced abnormal flow.

CALCIFIC AORTIC VALVE STENOSIS (BMJ 336: 550, 2008)

While bicuspid valves are notorious for calcifying later in life, sometimes a normal, tricuspid valve accumulates calcium-rich excrescences in its cusps. We now know that 3-5% of older folks will have at least some aortic valve calcification. Maybe 1 older man in 100 will need to be treated; women are at somewhat lower risk.

The etiology remains obscure, though of course "inflammation, just like in atherosclerosis" is commonly cited. I was not surprised, though, by the complete failure of intensive cholesterol-lowering to affect the disease (NEJM 359: 1343, 2008).

The calcification is an active process; the local cells pump out osteopontin, a bone-laying-down protein (Circulation 92: 2163, 1995).

These can interfere with the valve opening, and can block the coronary ostia. The latter is very serious.

{03560} calcified tricuspid aortic valve
{06461} calcified tricuspid aortic valve

Calcific aortic valve stenosis WebPath photo

MITRAL VALVE PROLAPSE ("Barlow's", "floppy mitral valve", "ballooning mitral valve", etc.)

In this semi-disease that affects around 2-3% of humankind, the mitral valve has an elongated posterior leaflet with some extra ground substance ("myxoid degeneration"). The leaflet looks like a parachute canopy, and billows up into the atrium.

The other valves may show the same thing. The histopathology exhibits weird derangements of all connective-tissue components (Am. Heart J. 129: 1149, 1995).

The typical patient has a slim build (the more "Marfanoid" you are, the most likely you are to have "Barlow's"), a mid-systolic click (the leaflet snapping tight) and ever-so-slight mitral regurgitation. The timing will vary with how full the ventricle gets.

There's differing opinions as to whether Barlow folks should take endocarditis prophylaxis prior to visiting the dentist.

If there's a stroke risk at all, it's small (Mayo Clin. Proc. 69: 632, 1994; NEJM 341: 48, 1999).

Occasionally, they get re-entry type atrial rhythm disturbances (notably "supraventricular tachycardia", in which one's heart "goes off like an alarm clock" at around 190 beats per minute, making adequate filling impossible. This is moderately annoying and happens to your lecturer, who has Barlow's, if he neglects exercise for a while and thereby drops his vagal tone). There are rumors of people suddenly falling over dead with no abnormality except Barlow's. Is it causal? Who knows? It's very, very infrequent.

Occasionally a chorda will rupture, producing serious mitral regurgitation.

The greatest Barlow morbidity is probably that lots of them become "cardiac neurotics". This is really unfortunate. Natural history of Barlow's: NEJM 341: 48, 1999.

{06470} floppy mitral valve
{40363} floppy mitral valve
{03440} floppy aortic valve, from a Barlow's case

Barlow valve WebPath photo

RHEUMATIC FEVER / RHEUMATIC HEART DISEASE By and by, Beth said the needle was "so heavy", and put it down forever. Talking wearied her, faces troubled her, pain claimed her for its own, and her tranquil spirit was sorrowfully perturbed by the ills that vexed her feeble flesh.

Rheumatic fever ("romantic fever", "scarletina / scarlatina", etc., etc.) is a systemic, autoimmune disease triggered by a beta-hemolytic streptococcal throat infection. (The major reason for going after "strep throat" with penicillin is to prevent rheumatic fever; around 3-5% of untreated strep throat turns into rheumatic fever.)

The acute disease declares itself about two weeks after the "strep throat" gets better.

Most patients are kids 5-15 years old. In the developed world, it is mostly the poorer kids. (* HLA-B5 is a risk factor too; most recently, a susceptibility gene close to HLA has been predicted Circulation 89: 138, 1994) but nobody is immune. The disease is endemic in the poor nations (Ann. Int. Med. 120: 177, 1994), and currently in resurgence in the U.S. (the West Pennsylvania outbreak, which features a distinctive streptococcus subtype: J. Ped. 149: 58, 2006).

* Although the history and physical exam have been the usual way of old detecting rheumatic valvular disease, it's now clear that, at least in the poor nations, many patients without obvious physical exam findings (i.e., easy-to-hear mitral stenosis) have the pathology on echocardiography (NEJM 357: 470, 2007).

Update on the acute illness: Lancet 366: 155, 2005.

The classic teaching about the pathogenesis of the disease involves molecular mimicry. The M-protein of the streptococcus, and at least one other antigen now being characterized, are attacked by antibodies which then cross-react with the heart (anti-myosin antibody: J. Inf. Dis. 168: 915, 1993, probably others), brain, skin, and joints.

* This can't be the whole story, of course, since some people have these antibodies without having rheumatic fever. Perhaps the streptococcal hyaluronidase damages the endothelium, or a hapten is involved, or....

The cardiac pathology is a pancarditis (i.e., any layer can be involved, even the pericardium). The characteristic lesion in the myocardium (especially near the vessels) is the ASCHOFF BODY (Aschoff nodule), a mass of fibrinoid surrounded by distinctive ANITSCHKOW CELLS ("caterpillar cells"), bloated, pale-purple-staining macrophages with a curious caterpillar-shaped mass of heterochromatin running the length of the nucleus (in cross-section, this is an "owl eye" instead). You may see big multinucleated forms, with large "eyes" in cross-section (ASCHOFF GIANT CELLS).

There's often a type III immune-injury type systemic vasculitis.

Curiously, textbooks differ about whether the Anitschkow cells are macrophages or altered myocardial cells. Their appearance is very different from macrophages anyplace else, and this observer thinks he sees transitional forms to nearby myocytes. However, they stain uncharacteristically for mature myocytes, but look like they bear immature mesenchymal nuclei (Pathology 31: 98, 1999). Stay tuned.

* Despite the textbooks, Aschoff nodules simply do not look like other granulomas, and I am not aware of any reason to think they should be considered granulomas.

Here are the symptoms and signs of rheumatic fever:

EVIDENCE OF CARDITIS (i.e., pericardial pain, enlarged heart, murmurs, failure)

POLYARTHRITIS

SYDENHAM'S CHOREA (St. Vitus's dance), from involvement of the basal ganglia. This is a big deal right now. Mediated by antibodies that cross-react with neurons (type II immune injury, non-destructive).

* The autoantibody, its target, and the strep protein that evokes it have been identified (Nat. Med. 9: 823 & 914, 2003.

ERYTHEMA MARGINATUM, a snake-like red skin eruption

SUBCUTANEOUS NODULES, little masses of fibrinoid with granulomas around them, over the bony bumps on arms and legs.

FEVER

LAB EVIDENCE OF RECENT STREP INFECTIONS (i.e., a high anti-streptolysin O and/or anti-hyaluronidase and/or anti-DNAse titer, a culture result, or whatever)

Here are the JONES CRITERIA for making the diagnosis. You need one major and two minor, or two majors.

Major: Polyarthritis; carditis; chorea; subcutaneous nodules; erythema marginatum.

Minor: Arthralgia; fever; preceding group A strep infection; preceding bout of rheumatic fever; elevated sed rate; prolonged PR interval on EKG.

The inflamed heart may fail. More often, the endocarditis manifests as VERRUCAE, tiny sterile masses of fibrin and platelets along the lines of closure of the valve leaflets.



Unfortunately, the verrucae are prone to organize, causing deformity of the heart. If the cusps stick together, STENOSIS results. If scar contraction shortens and bends the valve leaflets, INSUFFICIENCY / REGURGITATION results.

The aortic and mitral valves are usually affected; the tricuspid sometimes, the pulmonic rarely.

Rheumatic fever usually ends in recovery after a few weeks, but recurrences are common and likely to be more severe.

Old rheumatic fever is one of the most common causes of cardiac valve disease.

If you suspect the cause of valve disease is rheumatic, look for FUSION OF THE CUSPS, where the verrucae have organized.

One hallmark of old rheumatic mitral valve disease is thickening of the chordae tendineae. Also, check the posterior aspect of the left atrium for the white, geographic fibrous patches called MACCALLUM'S PATCHES; probably these are just the jet lesions from mitral insufficiency.

{11489} old rheumatic fever, mitral valve
{11492} acute rheumatic fever
{49008} acute rheumatic fever, vegetations
{18809} Aschoff nodule
{28587} Aschoff nodule
{28590} Aschoff nodule
{53304} Aschoff nodule
{46305} Aschoff nodule
{46481} Aschoff nodule, great caterpillar chromatin
{06467} old rheumatic fibrosis of mitral valve
{06845} old rheumatic mitral stenosis
{06847} old rheumatic mitral stenosis
{06850} old rheumatic mitral stenosis, large left atrium
{06815} old rheumatic aortic valve disease with insufficiency
{11549} old rheumatic aortic valve disease, good fusion of cusps
{11486} old rheumatic aortic valve stenosis

Rheumatic fever Yutaka Tsutsumi MD

Rheumatic mitral valve Great picture WebPath Case of the Week

Acute rheumatic fever Urbana Atlas of Pathology

Rheumatic fever verrucae Classic drawing Adami & McCrae, 1914

Aschoff nodule WebPath photo

Rheumatic fever Caterpillar cell ("Anitschkow myocyte")

Acute rheumatic fever Verrucae WebPath photo

Old rheumatic fever WebPath photo

Old rheumatic mitral valve WebPath photo

Old Rheumatic Fever Australian Pathology Museum High-tech gross photos

Mitral Stenosis (old rheumatic fever)
CDC
Wikimedia Commons

Rheumatic aortic valve CDC Wikimedia Commons

Old rheumatic mitral valve CDc Wikimedia Commons

INFECTIVE (BACTERIAL) ENDOCARDITIS (Lancet 363: 139, 2004.

Blood flow in the normal heart is laminar. If the flow becomes turbulent (i.e., usually due to congenital or rheumatic deformities), endothelium is likely to be damaged.

If endothelium is damaged, tiny platelet-fibrin clots can form on the valves. This wouldn't be much of a problem, and they'd probably go away, except for that fact that every once in a while, a bacterium can get enwrapped in the clot.

Yes, there's often a bacterium or two in your bloodstream. If you brush your teeth or pass stool, you're going to get a few bacteria into your blood. If you go to the dentist or get catheterized, proctoscoped or cystoscoped, or have colon cancer, you'll get lots more. All of these place you at risk for endocarditis. And if you do IV drugs without using sterile technique, you're begging for trouble.

Once the bacterium has found a place to live under the fibrin cocoon, it is protected from the body's defenses, since the valve leaflets are avascular, and the blood in the chamber is flowing too fast to allow neutrophils to stop here. The surrounding endocardium will probably get damaged, and the vegetation can grow.

Sooner or later, the polys will notice the bacteria and start fighting them, but by this time, they are generally massive. They are going to cause problems.

Naturally, the foul breakdown products of these bacteria are going to make a person systemically sick. Fever, arthritis, the acute phase reaction, anemia of chronic disease, diffuse proliferative glomerulonephritis, evidence of B-cell hyper-activation (rheumatoid factor, cryoglobulins, false-positive syphilis test), clubbing, etc., etc., are prone to supervene.

The vegetations are notoriously crumbly ("friable"; why might this be? Hint: polys), and prone to embolize. Embolic phenomena include SPLINTER HEMORRHAGES of the nails (if they are in the proximal nailbed I'd worry), OSLER'S NODES (sore spots in the finger pulp), JANEWAY LESIONS (on the palms) and ROTH SPOTS (vasculitis where arterial branch-points have caught septic emboli, seen in the eyegrounds). More serious are infarcts (strokes, heart attack, and so forth) and the development of mycotic aneurysms and/or abscesses throughout the body.

Endocarditis is rightly dreaded. Even nowadays, about 1 patient in 6 will die despite everything you can do (JAMA 288: 75, 2002).

* Future pathologists: Enjoy J. Inf. Dis. 193: 1711, 2006 for a technique to see the bacteria in a fatal case, even after treatment, using the patient's own tagged antibodies.

Splinter hemorrhages Supposedly from endocarditis WebPath photo

More credible endocarditis splinter WebPath photo

Pulmonic valve endocarditis producing lung abscesses; great photos Dr. Warnock's Collection

Endocarditis Urbana Atlas of Pathology

MRSA endocarditis Yutaka Tsutsumi MD

Infective Endocarditis Australian Pathology Museum High-tech gross photos

Torulopsis glabrata endocarditis Advanced students Yutaka Tsutsumi MD

Meningococcal endocarditis Yutaka Tsutsumi MD

Bacterial endocarditis Severe valve damage KU Collection

Trichosporon beigelii endocarditis Advanced students Yutaka Tsutsumi MD

Bacterial Endocarditis From Chile In Spanish

Bacterial endocarditis, aortic valve Classic drawing Adami & McCrae, 1914

Bacterial endocarditis
CDC
Wikimedia Commons

* Your instructor almost always has splinter hemorrhages, from piano and typing and his habit of playing with his nail-clippers. ("No one wants to shake hands with a pathologist with fingernails!") These are distal in the nailbed; proximal splinters are more worrisome.

The vegetations (actually, probably the polys) are prone to eat through valve cusps and chordae, causing further damage and even perforation.

ACUTE BACTERIAL ENDOCARDITIS may affect a normal valve, is often caused by virulent staphylococci (less often, beta-hemolytic streptococci, gonococci, proteus, pseudomonas;), and is highly lethal (death in less than 6 weeks). These people may be IV drug abusers or have a severe infection elsewhere (especially if the infection is on the right side; the higher pressures, greater turbulence, and higher oxygen concentrations make the left side more popular with most bacteria). Or they have occult colon cancer. Or they may just be unlucky.

SUBACUTE BACTERIAL ENDOCARDITIS generally affects cardiac surfaces where there's been turbulent blood flow. The usual culprit is viridans α-hemolytic streptococci; enterococci or gram-negatives are common if the person's had a below-the-belt medical procedure. Actually, lots of bacteria, as well as candida and aspergillus (Arch. Path. Lab. Med. 129: 511, 2005), can produce subacute bacterial endocarditis. The HACEK group (Hemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingii) are mouth gram-negatives that are coming to be more recognized as infectious agents -- all are hard to grow in the lab unless you're tipped off this is endocarditis.

The distinction between acute and subacute is kind of artificial, of course.

* Culture-negative endocarditis should make you think of coxiella, bartonella, or Whipple's (J. Inf. Dis. 193: 1711, 2006).

Clinicians spend a great deal of time looking for endocarditis, which is good. It's notoriously subtle in producing symptoms, it is treatable, and it is fatal if untreated. The mainstay of making the diagnosis is the positive blood culture, coupled with findings on daily meticulous physical exam (changing murmurs, petechiae, etc.)

If some Hippocrates has given your patient antibiotics "for that fever", don't expect to grow the bacteria even if the vegetations are massive.

*Q-fever endocarditis: Am. J. Med. 100: 629, 1997. Diagnosis by serology.

{06563} acute bacterial endocarditis
{08458} acute bacterial endocarditis
{38563} bacterial endocarditis
{03293} bacterial endocarditis, aortic valve cusp perforation
{03413} bacterial endocarditis, gross
{06986} bacterial endocarditis
{06989} bacterial endocarditis

Bacterial endocarditis WebPath photo

Bacterial endocarditis WebPath photo

Endocarditis Fistula formation

Bacterial endocarditis WebPath photo

Bacterial endocarditis WebPath photo

NON-BACTERIAL THROMBOTIC ENDOCARDITIS ("marantic endocarditis")

This is a non-bacterial accumulation of fibrin and platelets on the lines of closure of valves. Individual vegetations are seldom more than 5 mm across. Tissue pathology is reviewed in Mayo Clin. Proc. 76: 1204, 2001.

Classically patients have been cancer victims (notably pancreatic cancer), but more recently the syndrome has been appearing in patients with autoimmune disease, notably lupus anticoagulant.

Sometimes these contain a few polys, but usually they don't. (The fact that they are not inflamed lets you distinguish them from acute rheumatic fever.) Sometimes they embolize (for example, Ann. Thor. Surg. 79: 2145, 2005), but usually they don't.

{06326} Non-bacterial thrombotic endocarditis
{06965} Non-bacterial thrombotic endocarditis
{53315} Non-bacterial thrombotic endocarditis
{53317} Non-bacterial thrombotic endocarditis

Aortic valve vegetations Probably marantic thrombi KU Collection

Non-bacterial thrombotic endocarditis WebPath photo

Non-bacterial thrombotic endocarditis WebPath photo

Non-bacterial thrombotic endocarditis WebPath photo

Non-bacterial thrombotic endocarditis WebPath photo

LUPUS ENDOCARDITIS ("Libman-Sacks")

Lupus and/or the antiphospholipid syndrome (Circulation 93: 1579, 1996) can result in small masses of fibrin on various valve surfaces and anywhere else on the endocardium.

It seems reasonable to think that these are foci of type III immune injury. Be this as it may, you might spot a hematoxylin body here.

We know now that lupus patients are living longer and being studied more closely that Libman-Sacks is anything but benign. Valves often end up mutilated (Am. J. Med. 120: 636, 2007) much like rheumatic fever.

{06962} Libman-Sacks endocarditis

Libman-Sacks Endocarditis
Thailand

CALCIFICATION OF THE MITRAL ANNULUS

A common, minor problem seen in many older patients. While various rhythm disturbances and mitral insufficiency are attributed to this lesion, most often it seems harmless.

Calcified mitral valve annulus
WebPath photo


CARCINOID HEART DISEASE (Prog. Card. Dis. 49: 439, 2007)

Carcinoids that release their products into the great veins (i.e., those in the ovary or metastatic in the liver) often produce endocardial fibrosis, generally limited to the right side of the heart (i.e., whatever does it is "detoxified" in the lung). The tricuspid and pulmonic valves may malfunction, with tricuspid regurgitation being the usual finding.

Though much of "carcinoid syndrome" is caused by serotonin and bradykinin, it's still not clear which molecules are responsible. The Fenphen fiasco has focused attention back on serotonin, and the higher the 5-HIAA (serotonin metabolite) secretion in the urine, the worse the heart disease (NEJM 348: 1005, 2003).

{08044} carcinoid heart disease (trust me; look for the white fibrous stuff)
{08047} carcinoid heart disease (pulmonic valve, trust me)

ENDOMYOCARDIAL FIBROELASTOSIS ("endocardial fibroelastosis", etc.)

Some infants in the U.S. develop endocardial fibroelastosis, a tough thickening of the endocardium that ultimately interferes with the heart's ability to contract. The cause remains obscure; there are rumors of a link to mumps.

Especially in central Africa, there's a relatively common, similar lesion centered on the apex. The fibrosis stiffens the entire heart, and eventually leads to mitral and tricuspid insufficiency. In the past, this has been blamed on eating little green bananas ("rich in serotonin, mimicking the carcinoid syndrome"); however I understand these are also a staple in the Caribbean and that the disease isn't a well-recognized problem there as it is in tropical Africa. I have been unable to find anything recent about its likely causes.

The truth is that the disease is greatly under-recognized, with perhaps ten million cases worldwide, making it by far the most common "restrictive" heart disease. Survival is around two years. See NEJM 359: 43, 2008.

{10739} endocardial fibroelastosis

* WHIPPLE'S ENDOCARDITIS is a fibrosing process caused by Tropheryma whipplei which is familiar from the gut. Bacteria fill macrophages which in turn fill and deform the endocardial tissue with resulting scarring. See J. Inf. Dis. 190: 935, 2004.

Q-FEVER endocarditis, caused by the rickettsia, is also well-known (J. Inf. Dis. 187: 1097, 2003.

COMPLICATIONS OF ARTIFICIAL VALVES: common and serious. Nobody makes valves as good as the Good Lord's, but sometimes the originals do need to be replaced. Ask a cardiac surgeon about these problems.

{53323} Bjork-Shiley "toilet seat"/"disk" valve

• PARA-VALVULAR LEAKING. Perhaps a stitch came loose, perhaps from infection (uh-oh....)
• INFECTION: Candida and staph (aureus or epidermidis; update JAMA 297: 1354, 2007).

{03626} infection on prosthetic valves
{07732} prosthetic valve endocarditis
{07723} worn-out prosthetic valve

Pig valve WebPath photo

Toilet seat valve WebPath photo

Birdcage valve WebPath photo

• THROMBOSIS
• EMBOLIZATION
• OVERGROWTH BY TISSUE (endothelium, etc.)

MYOCARDITIS

Myocarditis I From Chile In Spanish

Myocarditis II From Chile In Spanish

Viral myocarditis Great labels Romanian Pathology Atlas

Inflammation of the heart. The heart muscle itself is incredibly resistant to bacterial infections unless they extend from endocarditis. Most myocarditis is probably viral and/or autoimmune.

The only systemic bacterial infection that is likely to produce a neutrophilic myocarditis is meningococcemia, and this seems to be the exception even with this dread micro-organism. The well-known negative inotropic effect in meningococcemia now seems to be mediated by interleukin 6 (Lancet 363: 203, 2004).

Most worthy of note are coxsackie A and coxsackie B virus infections (look for single-fiber necrosis; remember the selenium deficiency in China made people much more vulnerable to this), diphtheria (remember the toxin?), trichinosis (look for eosinophils, even if you see no worms), anthracyclines (adriamycin-doxorubicin; classic work Am. J. Clin. Path. 100: 158, 1993; Ann. Int. Med. 125: 40, 1996) and Chagas' disease (look for the T. cruzi bugs in the heart cells, and/or an "autoimmune" cardiomyopathy that has to date not yielded up its secrets: Am. J. Card. 79: 1135, 1997).

* A horrifying account of coxsackie myocarditis and deaths in a cargo box full of illegal immigrants: Am. J. For. Med. Path. 25: 117, 2004.

Also worth mentioning are the rickettsial diseases: typhus, Rocky Mountain spotted fever, Q-fever.

For research, you'll want to see necrosis of myocaridal fibers plus a lymphocytic infiltrate to make the call of "active myocarditis" ("the Dallas criteria").

* More on the Dallas Criteria: Hum Path. 18: 619, 1987. More recently the World Heart Federation suggests fourteen or more white cells (preferably lymphocytes) per square millimeter of slide, plus necrosis or degenerative changes in muscle fibers.

You may find abscesses in the heart muscle in people dying of sepsis, or with severe diabetes.

Viral myocarditis Yutaka Tsutsumi MD

Myocardial microabscess WebPath photo

Myocardial microabscess WebPath photo

{24946} coxsackie B myocarditis
{03461} myocarditis, microscopic
{15753} Chagas' disease
{26582} Chagas' disease
{53320} toxoplasmosis

Chagas disease Yutaka Tsutsumi MD

Chagas's disease of the heart WebPath Case of the Week

Coxsackie B myocarditis WebPath photo

Chagas cardiomyopathy
CDC
Wikimedia Commons

In most of these forms of myocarditis, look for a lymphocytic infiltrate coupled with various kinds of damage to myocardial fibers.

Loeffler's eosinophilic disease of the heart usually features fibrosis of the endocardium with a lot of eosinophils. It is part of the "hypereosinophilic syndrome", not well-understood but now treatable with the anti-IL-5 antibody mepolizumab (NEJM 358: 1215, 2008).

* Acute eosinophilic myocarditis is a spectacular, deadly illness in which eosinophils massively infiltrate the heart and necrosis occurs (Heart 81: 669, 1999).

Sarcoidosis produces non-caseating granulomas and fibrosis. It's quite common in the illness and probably gets missed a lot (Chest 133: 1426, 2008). Sarcoidosis identified on heart biopsy is ominous (Am. Heart J. 150: 459, 2005).

Hypersensitivity myocarditis is quite common, usually due to medications. You'll see eosinophils in the heart muscle, especially around the vessels.

"Idiopathic giant-cell myocarditis" ("Fiedler's myocarditis") is a thankfully-rare disease, mostly of young men. The giant cells are probably of muscle origin and there are no granulomas. It's likely that Fiedler's is a reaction pattern, at least sometimes caused by autoimmunity, very deadly and with variable responses to immunosuppression. See Mayo Clin. Proc. 74: 1221, 1999. In humans, the eye muscles are prone to be involved also. The animal model involves immunizing with myosin.

{07946} sarcoid heart

Giant cell myocarditis KU Collection

Idiopathic giant cell myocarditis
Pittsburgh Pathology Cases

Also remember: As you reject your heart transplant, it will become inflamed.

* Update on heart transplantation: NEJM 355: 231, 2006.

As you would expect, all lead to a dilated, failing heart in severe cases.

If death is due to heart failure, expect to see widespread apoptosis of heart muscle cells (Am. J. Card. 94: 746, 2004). They will be less prominent if death is due to a rhythm problem.

CARDIOMYOPATHIES: Non-inflammatory, non-ischemic heart muscle disease. (Call the heart transplant team!) Review (still good): Br. Med. J. 315: 1529, 1997.

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY ("arrhythmogenic right ventricular dysplasia"; Uhl's; "parchment right venricle"; (J. For. Sci. 42: 32, 1997; Circulation 94: 983, 1996; Arch. Path. Lab. Med. 129: 1330, 2005; South. Med. J. 101: 309, 2008; Am. Fam. Phys. 73: 1391, 2006; Lancet 373: 1289, 2009; sudden death AMFJP 30: 78, 2009 progressive nature of the lesion with apoptosis Am. J. Path. 152: 479, 1998; sudden death in vigorous good health AJFMP 18: 345, 1997).

"Arrhythmogenic right ventricular dysplasia" ("fibrolipomatosis") Recently-described cause of sudden death, especially in the young, especially the athletic young but seldom actually while exercising. If heralded at all, it's most likely been only by mild rhythm problems.
Several genes are known. Plakophilin-2: Circulation 113: 1641 & 1650, 2006 (common). Cardiac ryanodine receptor 2 / RYR2 / ARVD2 and desmoplakin ARVD8: Circulation 109: 1180, 2004. As we examine relatives of patients, we're discovering folks with primarily left ventricular, or biventricular, involvement (Circulation 115: 1710, 2007). However, because of the heterogeneity of expression, the variety of genes, and the difficulty of analysis, genetic screening isn't going to happen any time soon (JACC 50: 1813, 2007). For now, hope to see the classic "epsilon wave" on EKG.

The pathologist sees a curious mix of fatty ingrowth and fibrosis in the wall of the right ventricle (sometimes the left also or instead). We're working out the pathology and mechanism. The cell pathology is bizarre (Am. J. Med. Sci. 320: 310, 2000). First series of 200 deaths: Circulation 108: 3000, 2003.

Today's diagnostic imaging specialist must be familiar with this entity. You'll follow-up suspicious EKG"s with MRI's, which show both the fat (less important, since it's often mostly fibrosis instead of fat) and the dysfunction (more important). Update Am. Heart. J. 155: 147, 2008.

Arrhythmogenic Right Ventricular Dysplasia Tabib's paper from circulation Dramatic transillumination photo

Arrhythmogenic Right Ventricular Dysplasia Essay and good photos

Arrhythmogenic Right Ventricular Dysplasia Indian Journal Essay and great photos

Arrhythmogenic Right Ventricular Dysplasia JACC Essay and photos

Arrhythmogenic Right Ventricular Dysplasia National Registry Essay and one really good gross photo

Arrhythmogenic Right Ventricular Dysplasia Imaging -- worth a look Radiographics journal

Arrhythmogenic Right Ventricular Dysplasia Wikimedia Shows its importance

DILATED ("flabby heart"; "congestive cardiomyopathy")

{03629} dilated cardiomyopathy vs. normal
{03632} dilated cardiomyopathy
{07769} dilated cardiomyopathy
{11555} dilated cardiomyopathy

Dilated heart Urbana Atlas of Pathology

Dilated cardiomyopathy WebPath photo

Dilated cardiomyopathy WebPath photo

Dilated cardiomyopathy Most myocytes replaced by scar

Dilated Cardiomyopathy
CDC
Wikimedia Commons

There are a host of lesions that cause the heart muscle to lose its strength. There's a list in "Big Robbins"; most cases never get a diagnosis (NEJM 331: 1564, 1994; still probably true). Only 50% of cases of dilated cardiomyopathy even have a diagnosable lesion on microscopy.

In the dilated cardiomyopathies, the heart usually weighs more than "normal", but it is very distended and thus the wall is usually of normal thickness or even unusually thin. (Why?)

ALCOHOLIC'S HEART

Alcohol is rough on most organs, and the liver and brain damage take precedence most of the time to the cardiac toxicity.

Alcohol may or may not have a direct toxic effect on the heart, by itself or through a metabolite.

Lots of alcoholics are deficient in vitamin B₁, and this can produce high-output failure or even weaken the muscle.

In 1966, some folks added cobalt to Quebec beer to make a nicer head of foam. Cobalt poisons pyruvate metabolism and produced a beriberi-like cardiomyopathy. (* The classic pathology: Ann. N.Y.Acad. Sci. 156: 577, 1969).

Selenium deficiency led to an epidemic of dilated cardiomyopathy in China, and occurs in patients in the developed world who suffer from malabsorption (Med. Sci. Law 42: 10, 2002).

PREGNANCY

Around the time of parturition and/or up to six months after, some women get a dilated cardiomyopathy. This "peripartum cardiomyopathy" is very serious: JAMA 283: 1183, 2000 (NIH conference).

Sadly, this is mostly a disease of poor women, especially those who have had several babies close to one another. Perhaps it is the result of a deficiency in some trace nutrient. It remains mysterious: Am. Heart J. 130: 860, 1995; and it's likely to recur: NEJM 344: 1567, 2001.

ACROMEGALY (apoptosis of myocytes for some reason): Circulation 99: 426, 1999.

POLYMYOITIS-DERMATOMYOSITIS can produce a cardiomyopathy, accelerate atherosclerosis, and/or promote widespread small-artery disease, depending on the patient (Rheumatology 45 S4: iv18, 2006.)

"POST-VIRAL", allegedly autoimmune ("Barney Clark's disease"). Lots of people with "end-stage idiopathic dilated cardiomyopathy with lymphocytes" have some lab evidence of autoimmunity against the heart (specifics vary, and will bewilder you), and "a possible history of viral myocarditis". Actually, the link between this entity and viral infection is pretty weak. Many of these people have antibodies against coxsackie viruses, grow enteroviruses or adenoviruses from heart muscle (Circulation 99: 1348, 1999) etc., etc., and nobody has been able to come up with anything more convincing. To nobody's surprise, the lymphocytes turn out to be T-cells, and unlike those in a normal person's heart, most of these seem to be active (Circulation 92: 2876, 1996). * Update on autoimmunity and viruses, and how they may work together, in causing "idiopathic cardiomyopathy": Nat. Med. 9: 1448, 2003. Autoantibodies against the beta-1 adrenergic receptor are also fairly common in idiopathic dilated cardiomyopathy. These seem to induce apoptosis (Circulation 116: 399, 2007). Here's a classification scheme for "idiopathic, probably viral myocarditis": MYOCARDITIS: For now, look for at least patches of lymphocytes near at least a few really necrotic fibers. BORDERLINE MYOCARDITIS: Enough lymphocytes, but you can't really find those necrotic fibers FULMINANT MYOCARDITIS: The left ventricle fails, but is NOT dilated yet. On biopsy, there are lots of white cells, mostly neutrophils. The patient will either recover or die. CHRONIC ACTIVE MYOCARDITIS: Just as in the liver, there are patches of lymphocytes and ongoing fibrosis, over years, progressing to end-staged dilated cardiomyopathy EOSINOPHILIC MYOCARDITIS: The "acute" form mentioned above, or one of the eosinophil-rich diseases like Loeffler's, or CMV in the immunocompromised, or who-knows-what? GIANT-CELL MYOCARDITIS: Fiedler's. The giant cells are of myocyte origin, and there are no granulomas. The prognosis is ominous without treatment.

Barney Clark

GENETIC SYNDROMES: Syndromes worth remembering for general medicine include Friedreich's ataxia and Duchenne's-Becker's muscular dystrophy. Even female carriers of the latter often get a dilated cardiomyopathy (JAMA 275: 1335, 1996).

There are some other syndromes that give only a dilated cardiomyopathy (* one is due to mutant actin: Circulation 99: 1022, 1999; others to mutant troponin T (pathology Circulation 104: 1380, 2001), and beta-myosin heavy chain NEJM 343: 1688, 2000; mutated desmin affects skeletal and cardiac muscle NEJM 342: 770, 2000; phospholamban Science 299: 1410, 2003; troponin I: Lancet 363: 371, 2004 is unusual for being recessive).

"Noncompaction cardiomyopathy" ("spongiform cardiomyopathy"; Circulation 108: 2672, 2003) features very much enlarged trabeculae with blood lakes in the wall or one or both ventricles. Easy to spot on echo (Am. J. Card. 94: 389, 2004), it is is acquired during embryogenesis, either with a known mutation / syndrome or by itself. It can produce a dilated or a restrictive pattern.

Remember sarcoidosis, Chagas, radiation, giant-cell myocarditis, rheumatic fever, ipecac (munchausen's by proxy: Pediatrics 97: 902, 1995).

"Stress cardiomyopathy / myocardial stunning / transient apical ballooning syndrome / broken heart syndrome", after a jolt of epinephrine, has been precipitated even by surprise parties (NEJM 352: 539, 2005) or opiate withdrawal (Mayo Clin. Proc. 81: 825, 2006). The quaint term for this illness, which features ballooning of the ventricle especially at the apex, raised cardiac enzymes, and generally a good outcome, is "takotsubo", Japanese for "octopus trap". There's one report of rupture after a quarrel (literally dying of a broken heart: Mayo Clin Proc. 79: 821, 2004).

Seldom fatal, but worth knowing: In the most severely injured patients, notably those with SEVERE BURNS, there is weakening of the heart; in the animal model, there is widespread apoptosis of cardiac myocytes (J. Trauma 65: 401, 2008).

Seldom fatal, but worth knowing: A common cardiac lesion in patients with chronic renal failure (UREMIC CARDIOMYOPATHY) is fibrosis around individual fibers throughout large areas. This greatly enlarges the left ventricle, but doesn't really interfere so much with function at least during systole. Update Kid. Int. 69: 1839, 2006.

* The old story about the earlobe crease as a marker for precocious atherosclerosis holds up on the Swedish autopsy service: AJFMP 27: 129, 2006.

* Still controversial is whether diabetes itself causes a cardiomyopathy, perhaps by increasing the connective tissue among the myocardial cells. See Heart 92: 296, 2006; J. Am. Coll. Card. 47: 693, 2006).

One of the biggest pieces of recent news in cardiology is the triumph of the left-ventricle assist device (plus a medical regimen) to sustain patients with cardiomyopathy as it heals over time. This now seems to be a life-saver, and will probably be fairly common when you are in residency. See NEJM 355: 1873 & 1922, 2006.



HYPERTROPHIC ("idiopathic septal hypertrophy", "asymmetric septal hypertrophy"; "Les Aspin's disease"; "Reggie Lewis's disease"; "muscle-bound heart"; Hank Gathers supposedly had myocarditis rather than hypertrophic cardiomyopathy NEJM 329: 55, 1993)

{07811} hypertrophic cardiomyopathy {07814} hypertrophic cardiomyopathy {07799} hypertrophic cardiomyopathy {07820} hypertrophic cardiomyopathy, microscopic {11561} hypertrophic cardiomyopathy, microscopic {07823} hypertrophic cardiomyopathy, electron micrograph

Hypertrophic cardiomyopathy WebPath photo

This curious lesion, generally autosomal-dominant, exhibits (1) variable regions of hypertrophy (in contrast to the "concentric hypertrophy" of left ventricular overwork and the "eccentric hypertrophy" of left ventricular overfilling); (2) disarray of cardiac muscle cells by light and electron microscopy; (3) fibrosis around muscle cells; (4) some fibrous narrowings of the small arteries.

This is serious. The outflow tract from the left ventricle toward the aortic valve is likely to be obstructed by the large mass of muscle ("obstructive hypertrophic cardiomyopathy"; "HOCM").

Be careful! If you do aerobic exercise and develop your heart muscle, you're likely to make this particular problem worse. (Here's the case for routine auscultation of the heart in would-be athletes. See J. Fam. Pract. 52: 127, 2003 for the pre-sports physical, author recommends what I've always done and taught.) The septum typically takes its thick shape in the teenaged years. Like other causes of anatomic or functional aortic stenois, patients are troubled with exercise intolerance, angina, syncope, and/or sudden death. Infamously, sudden death can be the first "warning".

Most cases are autosomal-dominant, and a majority are caused by a mutated beta-myosin gene. Mouse with the mutation: Science 271: 663, 1996. Other loci are now known, mutant troponin T is common and especially deadly (histopathology Circulation 104: 1380, 2001), and tropomyosin and myosin binding protein are rare (NEJM 332: 1058, 1995; J. Am. Coll. Card. 29: 635, 1997; NEJM 338: 1249, 1998; Lancet 355: 58, 2000).

* Two genes for a very severe form, lethal early in life, are known (Am. J. Med. Genet. 72: 101, 2003); one is cytochrome oxidase itself and the other is one of its assembly proteins.

Many patients die suddenly in youth. But many others do not die of the disease, or die of it in old age (CHF or rhythm problems: JAMA 281: 650, 1999).

Hypertrophic cardiomyopathy is the most common cause of sudden death in competitive athletes, by a substantial margin (JAMA 276: 199, 1996). Common sense: The pathology at death correlates with the type of death. As you'd expect, the more fibrosis, the greater the risk of failure and late rhythm problems. The more fiber disarray, the greater the risk of sudden death during sports in youth because of rhythm troubles: Am. J. Coll. Card. 88: 275, 2001.

* When in doubt about how to manage this, put the patient on a treadmill. Dropping the blood pressure is a warning of more ominous things to come. The risk for sudden death cannot be predicted simply by measuring the thickness of the wall (Lancet 357: 420, 2001). Gadolinium scan to predict risk: J. Am. Coll. Card. 41: 1561, 2003.

The implantable defibrillator for these people: NEJM 342: 422, 2000.

Today, alcohol ablation of the obstructing muscle mass (i.e., alcohol injected into the coronary arteries) is a well-established therapy for patients not able to tolerate the surgery. Pathologists see Am. J. Card. 99: 563, 2007 and especially Heart 92: 1773, 2006 (coagulation necrosis of the coronary arteries themselves). As you'd expect, heart block may be unavoidable.

* Forme frustes? There are several genes (sarcomeres, mitochondria) which produce rare genetic cardiomyopathies. In the Framingham study, about person in 30 has unexplained, mild left ventricular hypertrophy and of these, one in 5 is heterozygous for one of these (Circ. 113: 2697, 2006); we await full data on the prevalence of these mutations in those without hypertrophy, but this is worth watching.

* The name of Reggie Lewis will always be associated with hypertrophic cardiomyopathy. However, this was not found on ultrasonography in life, or at autopsy. The extensive scarring described at autopsy sounds much more like "cocaine heart". During the litigation, which finally ended in 2005, there was a great deal of lawyering by attorneys for his family about Lewis's failing and/or refusing to take drug tests for cocaine. Of course, we'll never know for certain.



RESTRICTIVE-INFILTRATIVE-OBLIERATIVE ("stiff heart"; usually amyloid)

Most older people get some amyloids of various compositions (known and unknown) in their atria and aortas. All about amyloid and the heart: J. Clin. Path. 58: 125, 2005.

If amyloid involves the myocardium extensively, the muscles cannot contract. This is the usual cause of "restrictive cardiomyopathy" in the developed world.

One way to spot this is that the atria tend to be abnormally dilated, but the cardiac silhouette and diameter at autopsy normal-size. Think why.

As you'd expect, this is infamously difficult to treat using medications (South. med. J. 99: 1390, 2006), and since the pathophysiology different fundamentally from other causes of heart muscle failure, "the usual medications" tend to make matters worse.

* Amyloid hearts bounce; I was shown this once. Don't try it; it's disrespectful.

* Fabry's storage disease produces a restrictive cardiomyopathy, and sometimes a very severe case of sarcoidosis or hemochromatosis can do the same. There are a few poorly-understood restrictive cardiomyopathies of childhood, with collagen rather than amyloid.

* A small minority of hypertrophic cardiomyopathy patients (with the same genes as the classic presentation) have a stiff heart with little hypertrophy (J. Am.Coll. Card. 49: 2419, 2007); the prognosis is of course worse than in the classic syndrome.

Some "restrictive cardiomyopathy" patients in the developed nations, both children and adults, get an idiopathic interstitial fibrosis that makes the heart stiffer.

{07937} amyloid heart
{07940} amyloid heart
{07943} amyloid heart

Amyloid WebPath photo

Amyloid Congo Red birefringence WebPath photo

SECONDARY CARDIOMYOPATHIES: Hemochromatosis (dysrhythmogenic!), pheochromocytoma ("catecholamine heart", with single-fiber necrosis/apoptosis as in cocaine heart and perhaps after burns), chemotherapy (doxo- and daunorubicin; "Adriamycin"; flabby dilated heart), Pompe's glycogenosis, other glycogen storage diseases (glycogen synthetase deficiency NEJM 357: 1507, 2007), Duchenne's & Friedreich's (as above), end-stage HIV infection (Br. Med. J. 309: 1605, 1994).

Fabry's is worth knowing, because it can mimic hypertrophic or restrictive cardiomyopathy, and is treatable with enzyme replacement (Circulation 105: 1407, 2002).

Adriamycin is hated for producing a characteristic dilated cardiomyopathy. You may see pale-blue-staining myocardial cells without sarcomeres ("adria-cytes"). Adriamycin damages the mitochondria and somehow complexes with iron, producing free radical injury to the surrounding muscle tissue (J. Clin. Inv. 117: 3730, 2007).

I'm not big on the term ISCHEMIC CARDIOMYOPATHY for the fibrosis of the heart that's sustained many little infarcts, since the disease is not primarily the muscle. You may hear it used, though.

Normal myocardium
WebPath photo

{07039} von Gierke's disease
{07958} hemochromatosis
{07967} Fabry's
{08053} pheochromocytoma heart
{08078} radiation atherosclerosis
{08081} radiation pericarditis

Hemochromatosis
WebPath photo

* CADAVERIC SPASM

This is instantaneous, permanent stoppage of the heart, due to extreme pain or fright.

There are reports from the battlefield of soldiers found dead, or seen to die, with no injury, but with their muscles frozen in position. The cause was terror; the mechanism must be influx of calcium into skeletal and cardiac muscle, as in rigor mortis.

If cadaveric spasm really occurs, it must be rare. It makes for good stories, though. It's also the origin of the comforting untruth that, if you fall or jump off a building or something and see that you will surely die, your heart will stop before you hit the ground.

PERICARDIAL DISEASE (Lancet 363: 717, 2004)

Pericarditis From Chile In Spanish

PERICARDIAL EFFUSIONS

Many different situations result in accumulation of fluid (i.e., more than the usually few mL) in the pericardial sac. Viral pericarditis is often accompanied by a serous effusion; TB's effusion may also be serous.

However, to produce tamponade, it takes around 150 mL of fluid, and it must build up pressure rapidly (i.e., hemopericardium after ventricular rupture, penetrating trauma, or aortic dissection; pus in a suppurative pericarditis). If the fluid accumulates slowly, the pericardium can expand. I've seen a one-quart effusion that didn't seem to cause a problem.

On rotations, you'll learn how to do pericardiocentesis, and to place a pericardial window to keep the fluid "off the heart".

PERICARDITIS

Inflammation of the pericardium hurts. Patients typically get relief by leaning forward. You, the physician, will strain to hear the notoriously ephemeral "friction rubs" of this illness.

In sporadic pericarditis, the etiologic agent is probably some virus or immune phenomenon. It usually is self-limited; today people treat it with NSAIDs.

"Fibrinous pericarditis" (the familiar "bread and butter", or more realistically, "ketchup on bread" lesion) results from myocardial infarction (over a transmural infarct; Dressler's), uremia, radiation, lupus, rheumatic fever, surgery, and trauma. It may organize (obliterating the pericardial space, which isn't usually a big deal), or even calcify (perhaps limiting distensibility).

* One new cause is getting your first smallpox immunization (vaccinia myopericarditis, about 1:12,000 recipients): JAMA 289: 3283, 2003.

{18719} fibrinous pericarditis

Fibrinous pericarditis Great labels Romanian Pathology Atlas

Fibrinous pericarditis Classic gross appearance KU Collection

Fibrinous pericarditis Fibrin strands on right KU Collection

Fibrinous pericarditis WebPath photo

Fibrinous pericarditis WebPath photo

Fibrinous pericarditis WebPath photo

Fibrinous pericarditis WebPath photo

Pus in the pericardial space usually means bacterial infection. They usually got there by way of a nearby pneumonia or empyema, though there are other routes. Again, it may organize (a few adhesions, or "obliterative pericarditis"; or even calcify. TB in particular is infamous for causing troublesome scars. Old healed pericarditis (or TB, or asbestos, or "idiopathic") may become "constrictive" and cause problems.

Suppurative pericarditis
WebPath photo


"Hemorrhagic pericarditis" is due almost exclusively to TB and cancer. Caseous material in the pericardial sac is probably TB.

{03659} constrictive non-calcific pericarditis

Hemorrhagic pericarditis WebPath photo

Hemorrhagic pericarditis WebPath photo

* The "soldier's plaque" or "milk spot" on the visceral pericardium (i.e., the epicardial surface) is a focus of very slight thickening of the fibrous layer under the mesothelium. This mysterious finding is harmless. It was once attributed to packs worn during WWI, until some clever person noted that it's equally common in women. Today, somebody may tell you it represents "healed pericarditis", but it doesn't really look like scar.

CARDIAC TUMORS are rare.

The principal primary heart tumor is the MYXOMA, a lesion of endothelial origin that arises as a ball from the atrial septum and fills the left atrium. Grossly, it's a typically benign, soft tumor. Microscopically, there are lots of spindle cells and ground substance, and few vessels. Myxomas (familiarly called "wrecking balls") can plug the mitral valve (instant death), or cause emboli (under-recognized, Chest 107: 674, 1995).

Atrial myxoma are really tumors, not just organized atrial "ball-valve" thrombi of the sort seen in mitral valvular disease. They're clonal, and have a few antigenic markers.

* Future pathologists: They light up with calretinin, in contrast to organized thrombi (Am. J. Clin. Path. 114: 754, 2000).

* Being genuine tumors, there's an important anti-oncogene deletion syndrome ("Carney complex", with lentigos and gland overfunctions too, and others: Am. J. Card. 79: 994, 1997). If you see a myxoma in the right atrium rather than the left, suspect a familial syndrome.

{07975} myxoma
{07982} myxoma

Atrial myxoma WebPath photo

Cardiac myxoma WebPath photo

Atrial Myxoma AFIP Wikimedia Commons

Atrial myxoma embolus AFIP Wikimedia Commons

Atrial myxoma
AFIP
Wikimedia Commons

People with tuberous sclerosis are prone to have small cardiac hamartomas ("rhabdomyomas"). These are seldom troublesome.

* The other pediatric tumor of the heart is the troublesome cardiac fibroma, which juts off the septum and interferes with outflow. Thankfully, it's rare.

I was amazed by my first PAPILLARY FIBROELASTOMA (J. Thor. Card. Surg. 112: 551, 1996; fatal AJFMP 19: 162, 1998) at a 1991 autopsy. It looked like a kooshball on the pulmonic valve. These form on any valve leaflet. Depending on location, they can cause embolic stoke (Clin. Card. 24: 346, 2001); look for them using transesophageal echocardiography. Series Circulation 103: 2687, 2001; surgery Ann. Thor. Surg. 80: 1712, 2005. Smaller, similar-looking lesions on the aortic leaflets called LAMBL'S EXCRESCENCES are supposed to be organized thrombi; they occasionally embolize too.

Lipomas ("lipomatous hypertrophy" / "massive fatty deposits") of the septum are occasionally seen (review AJFMP 17: 43, 1996); it can be left alone.

* "Cystic tumor of the AV node" is a hamartoma that mimics the ultimobranchial nests of the thyroid (Am. J. Clin. Path. 123: 369, 2005).

Cardiac rhabdomyoma
Rare fatal case
WebPath photo

{08029} lipomatous hypertrophy ("lipoma") of atrial septum

Primary cancers of the heart (i.e., sarcomas) are so rare that even Mayo's sees only about one a year; of course, they are deadly (Cancer 112: 2440, 2008.)

Metastases to the heart are usually from lung, breast, melanoma, lymphoma, leukemia, and choriocarcinoma. Any of these can be troublesome (heart block, muscle failure, effusion), but you will usually miss the diagnosis during life.

Metastatic melanoma
WebPath photo


Heart with metastatic melanoma
AFIP
Wikimedia Commons

LAST PHOTOS

{17416} tiger-stripes of fatty change in extreme anemia; remember this one?
{11480} thromboembolus caught in heart

PULSUS PARADOXUS OVERSIMPLIFIED

You need to understand this. In health, venous pressure drops slightly during inspiration because the decreased intrathoracic pressure draws venous blood into the chest. The pressure drop is less than 10 torr and is not obvious on palpation.

In health, arterial pressure drops slightly during inspiration because the greatly expanded pulmonary vascular bed takes up the right cardiac output, diminishing return to and output from the left.

In restrictive pericardial disease, the diaphragm pulling down on the pericardium pulls it even tighter. This further blocks venous return to the heart, so that venous pressure actually increases during inspiration. It also blocks arterial outflow from the heart, greatly accentuating the normal drop in arterial pressure during inspiration (>10 torr, should be obvious on palpation).

CPR contusion on epicardium Blood in the fat pad KCUMB Team

FINISHING UP

* The desires of the heart are as crooked as corkscrews.

--W.H. Auden

By now, one would have to be very naive to think that most of his or her neighbors (patients, whatever) don't prefer death to severe and expensive disability. This preference is showcased in a study (NEJM 330: 545, 1994) in which a group of older patients were told the (abysmal) odds of surviving CPR reasonably intact. The vast majority never-ever wanted it done to them. CPR doesn't work for trauma cases (why not?), and even in ischemic heart disease, the few cases where it does work are very likely to leave the "survivor" badly brain-damaged. Really, one's only hope is rapid defibrillation, which thankfully is now being emphasized (NEJM 348: 2626, 2003). When the geriatricians trashed "ER" for showing an excessively-high rate of good outcomes of CPR (NEJM 334: 1578, 1994), the producers shot back that it's the doctors' fault that patients hear about CPR from, and only from, Hollywood (no kidding, NEJM 334: 1578, 1994). As a physician, I welcome signs that the "keep them all alive as long as you can, you make more money" era is finally coming to an end. As a physician, I'm sorry that most of the impetus for change hasn't come from my fellow-physicians.

*Transgenic pigs are now being bred as heart donors: Br. Med. J. 312: 657, 1996. Since then, there has been a great deal of work, but with publications only in the super-specialty literature. Stay tuned.



You'll hear in ACLS about ELECTROMECHANICAL DISSOCIATION, i.e., the EKG is fine and the heart isn't pumping. In other words, dead with a normal EKG. What would cause this? HINT: Pulmonary emboli, tamponade, no venous return to the heart because of bleeding or widespread vasodilatation, ruptured septum, no calcium. Understand the "why" of each? Can you think of others? Since the only one that you're going to be able to treat during CPR is "no calcium", you'll give calcium by vein. Don't expect....

In our sleep, pain that cannot forget falls drop by drop upon the heart. And in our own despair, against our will, comes wisdom through the awful grace of God.

-- Aeschylus, "Agamemnon"
tr. by Robert F. Kennedy in his extremporaneous eulogy for Martin Luther King

* A final, personal note: The heart is a source for metaphor. My favorite quotations concerning the heart include Jeremiah 17: 9-10 and 31:33 and Koran 91:4. See also the Katha Upanishad for a classic description of the metaphysical heart. And of all the experiences in clinical medicine, the one that this pathologist misses the most is the sound of the beating heart.

BIBLIOGRAPHY / FURTHER READING

I urge anyone interested in learning more about pathology of the heart to consult these standard textbooks.

Robbins and Cotran Pathologic Basis of Disease
Rosai and Ackerman's Surgical Pathology
Rubin's Pathology: Clinicopathologic Foundations of Medicine
Silver's Cardiovascular Pathology
Silverberg's Surgical Pathology
Abbott's Atlas of Congenital Cardiac Disease


In my notes, the most helpful current journal references are embedded in the text. Students using these during lecture strongly prefer this. And because the site is constantly being updated, numbered endnotes would be unmanageable. What's available online, and for whom, is always changing. Most public libraries will be happy to help you get an article that you need. Good luck on your own searches, and again, if there is any way in which I can help you, please contact me at scalpel_blade@yahoo.com. No texting or chat messages, please. Ordinary e-mails are welcome. Health and friendship!

Visitors to www.pathguy.com reset Jan. 30, 2005:

Drop by and meet Ed

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Teaching Pathology

PathMax -- Shawn E. Cowper MD's pathology education links
Ed's Autopsy Page
Notes for Good Lecturers
Small Group Teaching
Socratic Teaching
Preventing "F"'s
Classroom Control
"I Hate Histology!"
Ed's Physiology Challenge
Pathology Identification Keys ("Kansas City Field Guide to Pathology")
Ed's Basic Science Trivia Quiz -- have a chuckle!
Rudolf Virchow on Pathology Education -- humor
Curriculum Position Paper -- humor
The Pathology Blues
Ed's Pathology Review for USMLE I
Part I
Part II

EXAMINING THE LIVING CARDIOVASCULAR SYSTEM
Correlations with Pathology
Ed Friedlander MD "the pathology guy"

A group of you asked, in lieu of continuing into "lung", to integrate pathology and the changes you have learned about on physical exam. Pathologists are the big integrators and "why"-folks in most medical schools, so here goes....
0. Turn off the TV 1. Inspect 2. Palpate 3. Percuss 4. Auscultate
Valsalva: Reduces, then increases, preload
Leg lift: Increases preload
Handgrip: Increases afterload

Inspection! Apex impulse. Where? How big? Any others? Dextrocardia / situs inversus. Cyanosis? Jugular venous distention? Anything else?

Jugular venous pulse peaks demystified (see also South. Med. J. 100: 1022, 2007....

Big "A"'s: think of high pulmonary vascular resistance ("pulmonary hypertension", why?
Big "V"'s: Tricuspid regurgitation (why)?

Estimating CVP is very helpful. Be sure you can recognize Kussmaul's sign in the neck veins in tamponade (and explain how it happens -- nice case Lancet 371: 1810, 2008)

Palpation! Right ("sternal") lift or heave. Big apex beat is "left lift" or "left heave". Thrill -- palpable murmur. Feel PMI and carotids simultaneously. Position of PMI can be measured; duration has most to do with actual hypertrophy.

Percussion!: Bring your sharpie marker. Don't expect this to tell you as much or as well as a chest x-ray.

Auscultation!: Bell (S3 and S4; mitral stenosis) vs. diaphragm (everything else). The Littman diaphragm, lightly applied, supposedly hears the low pitches as well as the bell. You decide. "I can't tell you, professor, I am listening to diastole!" Inching along. Sitback and put your elbows on your knees. Roll over on your left side and lean back against me.
S1. What is it? Can anybody hear T1?
S2. What is it? P2 is delayed a bit during inspiration. Learning to tell if a sound is split. Exaggerated split (i.e., P2 is always a little too late): increased pulmonary vascular resistance (why?), left-to-right shunt (why?), right bundle branch block (why?) Paradoxical split (i.e., A2 is always a little too late and/or P2 a bit early); left bundle branch block (why?), some normal folks. Loud A2: systemic hypertension. Loud P2: Pulmonary hypertension.
S3: Waves-in-the-wall, the heart as kettledrum? "Tennessee". When do you hear it? Why?
S4: Atrial sound. "Kentucky". When do you hear it? Why?

Ejection click: Little wiggles in the aortic and/or pulmonary valve leaflets as they open.
Opening snap: Litle wiggles in the stiff leaflets of a tight mitral valve. Midsystolic click: Barlow posterior leaflet being pulled tense, less when you increase preload.
Murmurs mean turbulence. Volume of sound is proportionate to force and volume of turbulent flow.

Grade 1: Cardiologist found it.
Grade 2: Resident found it.
Grade 3: Medical student found it.
Grade 4: Thrill.
Grade 5: Feel thrill through sportshirt.
Grade 6: Family heard it when they turned off the TV.

Systolic murmurs:

"Innocent murmur" -- jocks, teens, young adults, hyperdynamic pulses; left sternal border, 1/6 or 2/6, nonradiating, normal splitting of S2, no respiratory variation
"Benign murmur" -- the cardiologist told you it's got an anatomic basis not worth pursuing
Hypertrophic cardiomyopathy: Softer when preload is increased (why?)
VSD, mitral regurgitation: Louder when afterload is increased (why?)
Right-sided murmur: Varies notably with respiration
Venous hum: Compress the neck veins.

Diastolic murmurs: always deserve your serious attention.

Continuous murmurs: patent ductus (why?), fistulas (why?), mammary souffle (why?)

Friction rub: Fibrin-coated surfaces of epicardiumon pericardium (or visceral on parietal pleura). Ephemeral.

Blood pressure: Korotkoff sounds. "Auscultatory gap", and why you need to have a finger on the pulse of the wrist. Wide cuffs for big arms (avoids factitious hypertension).

Pulses: Rhythm. Respiratory arrhythmia. Regularly irregular or irregularly irregular. Pulsus alternans (easiest to detect using a cuff, "the heart rate suddenly doubled!") bespeaks left CHF, why? Absent doralis pedis. Carotid bruits. Other bruits. Jerky pulse (think hypertrophic cardiomyopathy, why?) Hyperkinetic. Waterhammer (Corrigan) pulse. Thready pulse. "Pulsus paradoxus" (everybody has a slight decrease, >10 torr is abnormal, how to measure it). Capillary refill (2 sec. rule). Check those leg veins to detect coarctation of the aorta. Why you don't want to use your thumb to palpate a pulse.

Other stuff: Barrel chest. Marfanoids. Ehlers-Danlos. Pectus. Erythema marginatum. Xanthomas. Osler's nodes. Roth spots. Vessel changes (narrowed light reflex, AV nicking, copper wires, silver wires) of (hyaline) arteriolar sclerosis. Splinter hemorrhages (uh huh...) Hepatojugular reflux. Edema (+1 pit goes away fast, +2 5 sec +3 1 min +4 5 min, or thereabouts). Non-pitting edema (lymph, real vein trouble). Homan's sign. Varicose veins; Trendelenberg test, tourniquet test.

Pathological Chess

Taser Video 83.4 MB 7:26 min