Table 18.1 Nomenclature of bone tumors

Hypertrophic Cardiomyopathy

BASIC INFORMATION
DEFINITION
HCM includes a group of inherited conditions that produce hypertrophy of the myocardium in the absence of an alternate cause (e.g. aortic stenosis or hypertension). It is the most common cause of sudden cardiac death in young people and affects 1 in 500 of the population. The majority of cases are familial autosomal dominant, due to mutations in the genes encoding sarcomeric proteins (Fig. 14). The most common causes of HCM are mutations of the β-myosin heavy chain and myosin-binding protein C. Other mutations include troponin T and I, regulatory and essential myosin light chains, titin, α tropomyosin, α actin, α myosin heavy chain and muscle LIM protein (although over 400 mutations have been identified.) There are non-sarcomeric protein mutations in genes that control cardiac metabolism that result in glycogen storage diseases (Danon’s, Pompe’s and Fabry’s disease) that are indistinguishable from HCM.
SYNONYMS
Idiopathic hypertrophic subaortic stenosis (IHSS)
Hypertrophic obstructive cardiomyopathy (HOCM)
ASH
HCM
EPIDEMIOLOGY & DEMOGRAPHICS
• The disease occurs in two major forms:
1. A familial form, usually diagnosed in young patients and gene mapped to chromosome 14q
2. A sporadic form, usually found in elderly patients
• The prevalence of phenotypically expressed HCM in the adult general population is 1% (most common genetic cardiovascular disease)
PHYSICAL FINDINGS & CLINICAL PRESENTATION
• Harsh, systolic, diamond-shaped murmur at the left sternal border or apex that increases with Valsalva maneuver and decreases with squatting
• Paradoxic splitting of S2 (if left ventricular obstruction is present)
• S4
• Double or triple apical impulse
• Increased obstruction
1. Drugs: digitalis, ß-adrenergic stimulators (isoproterenol, dopamine, epinephrine), nitroglycerin, vasodilators, diuretics, alcohol
2. Hypovolemia
3. Tachycardia
4. Valsalva maneuver
5. Standing position
• Decreased obstruction

Fig. 14 Sarcomeric proteins implicated in hypertrophic cardiomyopathy.

1. Drugs: ß-adrenergic blockers, calcium channel blockers, disopyramide, a-adrenergic stimulators
2. Volume expansion
3. Bradycardia
4. Hand grip exercise
5. Squatting position
Signs
■ double apical pulsation (forceful atrial contraction producing a fourth heart sound)
■ jerky carotid pulse because of rapid ejection and sudden obstruction to left ventricular outflow during systole
■ ejection systolic murmur due to left ventricular outflow obstruction late in systole - it can be increased by manoeuvres that decrease after-load, e.g. standing or Valsalva, and decreased by manoeuvres that increase after-load and venous return, e.g. squatting
■ pan-systolic murmur due to mitral regurgitation (secondary to SAM)
■ fourth heart sound (if not in AF).

Fig. 14.1 Hypertrophic and dilated cardiomyopathy.
a Transverse echocardiogram of the left ventricle (LV) at the start of systole in hypertrophic cardiomyopathy shows a greatly thickened wall with a small end-diastolic diameter of the left ventricle (concentric hypertrophy).
b In dilated cardiomyopathy, the ventricle is dilated and the ventricular wall is thinned.

Fig. 14.2 Apical hypertrophic cardiomyopathy
a LV angiography demonstrates apical hypertrophy, which has caused typical apical obliteration of the left ventricle, producing a “spade-shaped” ventricle.
b Echocardiography shows massive thickening of the interventricular septum (IVS) and massive apical hypertrophy. RV = right ventricle, LV = left ventricle, RA = right atrium, LA = left atrium.

Symptoms
■ many are asymptomatic and are detected through family screening of an affected individual or following a routine ECG examination
■ chest pain, dyspnoea, syncope or pre-syncope (typically with exertion), cardiac arrhythmias and sudden death are seen
■ sudden death occurs at any age but the highest rates (up to 6-7% per annum) occur in adolescents or young adults. Risk factors for sudden death are discussed below
■ dyspnoea occurs due to impaired relaxation of the heart muscle or the left ventricular outflow tract obstruction that occurs in some patients. The systolic cavity remains small until the late stages of disease when progressive dilatation may occur. If a patient develops atrial fibrillation there is often a rapid deterioration in clinical status due to the loss of atrial contraction and the tachycardia - resulting in elevated left atrial pressure and acute pulmonary oedema.
ETIOLOGY
• Autosomal dominant trait with variable penetrance caused by mutations in any of 1 to 10 genes, each encoding proteins of cardiac sarcomere
• Sporadic occurrence
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
• Coronary atherosclerosis
• Valvular dysfunction
• Pericardial abnormalities
• Chronic pulmonary disease
• Psychogenic dyspnea
WORKUP
• Chest x-ray examination, ECG, echocardiography
• Medical history with emphasis in the following manifestations:
1. Dyspnea
2. Syncope (usually seen with exercise)
3. Angina (decreased angina in recumbent position)
4. Palpitations
• 24-hours Holter monitor to screen for potential lethal arrhythmias (principal cause of syncope or sudden death in obstructive cardiomyopathy)
IMAGING STUDIES
• Chest x-ray examination: normal or cardiomegaly
• ECG is abnormal in 77% to 97% of patients: left ventricular hypertrophy, abnormal Q waves in anterolateral and inferior leads
• Two-dimensional echocardiography is used to establish the diagnosis. Findings include: ventricular hypertrophy, ratio of septum thickness to left ventricular wall thickness >1.3:1, increased ejection fraction.
• Magnetic resonance imaging may be of diagnostic value when echocardiographic studies are technically inadequate. MRI is also useful in identifying segmental LVH undetectable by echocardiography.
TREATMENT
NONPHARMACOLOGIC THERAPY
Advise avoidance of alcohol; alcohol use (even in small amounts) results in increased obstruction of the left ventricular outflow tract.
ACUTE GENERAL Rx
• Propranolol 160 to 240 mg/day. The beneficial effects of ß-blockers on symptoms (principally dyspnea and chest pain) and exercise tolerance appear to be largely a result of a decrease in the heart rate with consequent prolongation of diastole and increased passive ventricular filling. By reducing the inotropic response, ß-blockers may also lessen myocardial oxygen demand and decrease the outflow gradient during exercise, when sympathetic tone is increased.
• Verapamil also decreases left ventricular outflow obstruction by improving filling and probably reducing myocardial ischemia.
• IV saline infusion in addition to propranolol or verapamil is indicated in patients with CHF.
• Disopyramide is a useful antiarrhythmic.
• Use antibiotic prophylaxis for surgical procedures.
• Avoid use of digitalis, diuretics, nitrates, and vasodilators.
• Encouraging results have been reported on the use of DDD pacing for hemodynamic and symptomatic benefit in patients with drugresistant hypertrophic obstructive cardiomyopathy.
• Implantable defibrillators are a safe and effective therapy in HCM patients prone to ventricular arrhythmias. Their use is strongly warranted for patients with prior cardiac arrest or sustained spontaneous ventricular tachycardia.
DISPOSITION
HCM is not a static disease. Some adults may experience subtle regression in wall thickness while others (approximately 5% to 10%) paradoxically evolve into an end stage resembling dilated cardiomyopathy and characterized by cavity enlargement, LV wall thinning, and diastolic dysfunction. Patients with HCM are at increased risk of sudden death, especially if there is onset of symptoms during childhood. Adult patients can be considered low risk if they have no symptoms or mild symptoms and also if they have none of the following:
• A family history of premature death caused by hypertrophic cardiomyopathy
• Nonsustained ventricular tachycardia during Holter monitoring
• A marked outflow tract gradient
• Substantial hypertrophy (>20 mm)
• Marked left atrial enlargement
• Abnormal blood pressure response during exercise
REFERRAL
• Surgical treatment (myotomymyectomy) is reserved for patients who have both a large outflow gradient (=50 mm Hg) and severe symptoms of heart failure that are unresponsive to medical therapy. The risk of sudden death from arrhythmias is not altered by surgery.
• Nonsurgical reduction of interventricular septum represents a new, controversial, and unproven therapeutic approach that can be used in patients with HCM that has proved refractory to pharmacologic treatment. This technique involves the injection of ethanol in the septal perforator branch of the left anterior descending coronary artery, producing a controlled myocardial infarction of the interventricular septum and thereby reducing the left ventricular outflow tract gradient. This method can lead to sustained improvement in both subjective and objective measures of exercise capacity but is associated with a high incidence of heart block, often requiring permanent pacing in about one fourth of patients.