{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 subtotal coronary occlusion.

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

Clinical 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 is being 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 terrible, lots of polys, fibers very dead; 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, or the dead fibers may persist for weeks

7 weeks

Nice scar.

* Today's standard for autopsy reports: "Acute" means polys, "Healing" means the polys are gone but there are monocytes, "Healed" means the monocytes 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

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).

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 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% stenosis of all 3 coronaries, often more

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 lymphocytic infiltrate ("Dallas criteria")

* 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). 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.).

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.

• "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"; 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 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).

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: The most interesting discovery in "heart pathology" in several years (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).