May rapidly develop heart failure, arrhythmias, or may cause sudden death
There may be a murmur due to cardiac dilatation causing mitral regurgitation
May heal completely, or may progress to dilated cardiomyopathy years later
Grossly, hearts with active myocarditis are described as soft and flabby. The myocardium may be mottled and the heart may be dilated. Microscopically, viral myocarditis is characterized by a (nonspecific) lymphocytic infiltrate with myocyte necrosis.
Chagas disease – the protozoan bug is Trypanosoma cruzi
Important in South America – 80% with heart involvement – may be lethal or may go into chronic phase
Transmitted by insects such as reduvid bug
Microscopically see parasites within myocytes and mixed inflammation
T. Cruzi may also cause destruction of the myenteric plexus of the esophagus, duodenum, colon and ureter with subsequent dilatation of these viscera (megacolon).
Giant Cell Myocarditis
Has a rapid onset with a poor prognosis
Microscopically see myocardial necrosis with lymphocytes, plasma cells, eosinophils and giant cells
Has some overlap with sarcoidosis, but sarcoidosis has a more insidious onset
Some patients may recover completely or with some myocardial fibrosis
A variant is arrhythmogenic right ventricular dysplasia (cardiomyopathy) – a heritable defect that causes heart failure and may cause sudden death in young persons (see Robbins text)
Dilated CM is also known as congestive cardiomyopathy. Dilated CM may cause death either by heart failure or arrhythmia.
Causes of Dilated CM
Burned out myocarditis
EtOH or other toxicity
Peripartum CM occurs late in pregnancy or several weeks to months postpartum – poorly understood – possibly related to circulating anti-angiogenic factors
Genetic – 30% to 50% of cases, variable inheritance, mostly autosomal dominant, & variable defects - one is abnormal cytoskeletal protein like Duchenne & Becker muscular dystrophy
Mostly the cause is unknown
The progression from viral myocarditis to dilated cardiomyopathy has been demonstrated by serial myocardial biopsies. However, in most cases of DCM, the heart shows little or no residual inflammation.
Toxic causes of DCM are hard to prove – no good way to tell apart from other DCM.
The etiology of peripartum CM may be multifactorial, including factors such as hypertension, volume overload, poor nutrition, possible metabolic abnormalities or autoimmune phenomena; recent evidence suggests that it may be related to circulating anti-angiogenic factors (see Robbins text).
Morphology of Dilated CM
Rounded, dilated heart, 2 –3x expected weight
LV wall may be thinner due to dilatation
May see endocardial fibrosis, may see mural thrombus in chambers
Histology not too exciting – myocyte hypertrophy, some interstitial fibrosis, rarely some residual myocarditis
Has many names:
Idiopathic hypertrophic subaortic stenosis
Hypertrophic obstructive cardiomyopathy
Asymmetric septal hypertrophy
Features a heart that is normal in shape, but with marked wall thickening due to hypertrophy (esp LV) often with asymmetric thickening of the septum and narrowing of the LV cavity
The heart is hypercontractile without LV cavity dilatation
The problem is diastolic filling and LVOT obstruction
Has a better prognosis than DCM, but may cause angina, CHF, A-fib, mural thrombus, infective endocarditis of MV
Can affect children or adults
HCM is one of the most common causes of sudden death in young athletes
The septum may bulge into the left ventricular outflow tract. This acts in concert with the adjacent anterior leaflet of the mitral valve to produce left ventricular outflow tract obstruction. A harsh systolic ejection murmur may be present.
Late cardiac dilatation in the course of HCM may actually relieve the LVOT obstruction.
To diagnose HCM, it is necessary to rule out other causes of myocardial hypertrophy such as hypertension and aortic stenosis.
Sudden death may be due to blockage of the left ventricular outflow by the anterior leaflet of the mitral valve. The leaflet may be sucked into the LVOT by “venturi” action of the blood flowing through the narrowed passage.
HCM can be managed medically better than DCM.
Causes of Hypertrophic CM
Has a genetic basis in all cases. Most are familial and typically autosomal dominant with variable expression; the rest are sporadic
Often genetic errors are in coding for contractile proteins; >100 mutations known
Investigation of family members of patients with HCM is indicated.
Morphology of Hypertrophic CM
Thickened LV wall at the expense of the cavity, often with asymmetric septal thickening and bulge of septum into LVOT
Heart may be normal in shape (may look normal on a routine chest X-ray), but 2-3x expected weight
Anterior leaflet of MV is thickened, and there may be a “friction lesion” on the LVOT
Histology shows myocyte hypertrophy, some interstitial fibrosis, and sometimes myofiber disarray, especially in septum
Myofibrillar disarray within cardiac myocytes in HCM can be seen with electron microscopy.
This is a disorder of ventricular compliance – The heart is normal in shape but stiff
Constrictive pericarditis is clinically similar – heart is mechanically prevented from contracting well
Causes of Restrictive CM
Things that infiltrate and stiffen the myocardium:
Some storage diseases
Endomyocardial fibrosis (a tropical disease of unknown cause)
Things that thicken and stiffen the myocardium and endocardium:
Endocardial fibroelastosis (in children - occurs with some types of congenital heart disease and rarely occurs alone)
Loeffler endomyocarditis (assoc. with eosinophilia or eosinophilic leukemia)
Endomyocardial fibrosis (a tropical disease of unknown cause)
Idiopathic restrictive CM – myocardium shows patchy or diffuse fibrosis
In RCM the heart is about normal size and the myocardium is firm (“waxy” in amyloidosis).
~2500/year worldwide; ~7 in 2013 at Riley
Acute cellular rejection is a form of lymphocytic myocarditis – controllable with drugs
Transplant arteriopathy is a long term complication (aka graft vascular disease, graft arteriosclerosis) – years to a decade or more – may cause sudden death
Acute cellular rejection is cell mediated and is controllable by drugs such as cyclosporine. Transplant vasculopathy on the other hand, may be mediated more by humoral means, and as yet is not controllable by drugs.
Congenital Heart Disease (CHD)
Def: Abnormality of heart or great vessels present at birth (although may be discovered as an adult)
Usually refers to structural abnormalities such as abnormal chamber and vessel relationships, abnormal connections (holes), obstructions, absence or maldevelopment of structures, and other anatomic abnormalities
By convention, usually does not include congenital tumors, infections, cardiomyopathies
Ranges from trivial (bicuspid aortic valve) to lethal (absent left ventricle)
If severe, causes delayed development, failure to thrive, increased susceptibility to infectious diseases in childhood, cardiac failure, and rarely sudden cardiac death
Increased risk for endocarditis (generally true for any structural abnormality, congenital or acquired; i.e. prosthetic valve)
Increased risk during pregnancy for women with CHD
Hyperviscosity due to polycythemia
Nearly twice as many children die from CHD in the U.S. as from all forms of childhood cancer combined (Am. Heart Association, 2005)
Causes of CHD
Usually unknown - probably multifactorial (may see discordance of CHD in identical twins!)
Around 5% chromosomal (Trisomies, Turner’s)
A major known cause is sporadic genetic abnormalities such as single gene mutations or small chromosomal losses (examples include Noonans, DiGeorge, numerous others)
May be seen in many malformation associations (VATER, polysplenia)
Rare infectious cause (rubella)
Note: Robbins 9th edition has a good overview on gene defects that cause congenital heart defects (p. 532)
Major CHD Defects Can Be Lumped into 3 Categories
Cyanotic - when blood from the right side of the heart (deoxygenated blood) enters the left side without going through the lungs (right to left shunt)
Noncyanotic - when blood from the left side of the heart enters the right side (left to right shunt)
“Other” (i.e. no shunts, example - obstructions)
Right to Left Shunts
Cause cyanosis from early infancy (blue baby)
May be complicated by paradoxical emboli
Left to Right Shunts
No (initial) cyanosis (pink baby)
Causes pressure (or volume) overload of the pulmonary circulation
Eventually can reverse shunt direction and become cyanotic (see below)
Is a switch from noncyanotic to cyanotic CHD due to reversal of shunt flow
Due to right ventricular hypertrophy and pulmonary vascular changes after prolonged pulmonary HTN
Too late to surgically repair since pulmonary vascular changes become irreversible
Not the same as Eisenmenger’s complex
CHD with Right to Left Shunt (Cyanotic)
Tetralogy of Fallot (if sufficient pulmonary outflow restriction)
Hypoplastic left heart syndrome probably should be considered as cyanotic
Note: All the cyanotic types start with a T except the last one.
CHD with Left to Right Shunt (Noncyanotic)
ASD (increased pulmonary blood volume more than pressure)
AV septal defect (AV canal)
Note: All the noncyanotic types have a D.
Atrial Septal Defect (ASD)
90% are “secundum” (at foramen ovale) - the rest are rare
Not the same as patent FO (present in up to 1/3 of normals)
Shunts left to right (noncyanotic)
May be asymptomatic for a long time (30 yo) or a life time
Increased lung volume of flow more than pressure
May eventually get volume hypertrophy of right ventricle, <10% develop irreversible pulmonary HTN
Ventricular Septal Defect (VSD)
Most common cardiac anomaly
Frequently associated with other cardiac defects - about 30% isolated
The interval between group A strep pharyngitis and RF = 1 to 5 weeks – average is about 3 weeks
Acute RF and poststreptococcal glomerulonephritis usually do not coexist
Severity of joint involvement is inversely proportional to heart involvement
In acute RF, heart involvement is typically not symptomatic unless there is heart failure or pericarditis
Mitral regurgitation may develop quickly (due to restricted mobility of leaflets or ventricular dilatation), but stenosis takes years
Sydenham’s chorea – a late manifestation of RF, female > male
May last for a week to >2 years!
Chorea is never seen with arthritis, but may coexist with carditis
Hypotonia and emotional disturbances are typical
PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus) (see Wall Street Journal, December 13, 2011)
Includes obsessive compulsive disorder, tics, anxiety, irritability, hyperactivity, anorexia and urinary problems
May resolve with antibiotics, but may return & worsen if exposed to strep again
May be a version of Sydenham’s
Subcutaneous nodules – attached to tendon sheaths – extensor surfaces & over bony prominences of upper & lower extremities & mastoid. Histologically → Aschoff bodies
Erythema marginatum – red margin progresses as center clears, see on trunk and proximal limbs
RF complications may include pleural pain, pneumonia, abdominal pain, and appendicitis secondary to vasculitis
Appendix II – Kawasaki Syndrome (Mucocutaneous Lymph Node Syndrome)
Kawasaki syndrome is rare, but it is the leading cause of acquired heart disease in children in the United States (great exam question?).
Kawasaki syndrome is an arteritis involving medium and small arteries, often unfortunately the coronary arteries.
The mucocutaneous lymph node syndrome in children is manifested by fever, conjunctival and oral erythema and erosion, erythema of the palms and soles, a skin rash often with desquamation, and enlargement of the cervical lymph nodes. It is usually self-limited.
Approximately 20% develop cardiovascular sequelae ranging from coronary artery ectasia to aneurysm formation to giant (>7 to 8 mm) aneurysm formation.
Death may occur in the acute phase of the disease or shortly thereafter due to coronary artery rupture or thrombosis, or aneurysms may persist after resolution of the acute disease and cause death years later.
The cause of Kawasaki’s is unknown, but it is probably a form of autoimmunity triggered by a variety of infections, most likely viral, in genetically susceptible individuals.