Pathophysiology
Summary
In hypertrophic obstructive cardiomyopathy (HOCM), the interventricular septum displays the most pronounced myocardial hypertrophy, potentially leading to diastolic dysfunction and diastolic heart failure. This massive septal hypertrophy can obstruct blood flow out of the left ventricle, particularly below the aortic valve in the left ventricular outflow tract (LVOT). This obstruction is further exacerbated by the systolic anterior motion of the mitral valve and its contact with the hypertrophied septum. Such contact causes the anterior leaflet of the mitral valve to remain open during systole, resulting in mitral regurgitation.
The underlying etiology of HOCM is an autosomal dominant mutation in sarcomere proteins, notably beta-myosin heavy chain, myosin-binding protein C, and troponin T. These gain-of-function mutations promote increased myofilament activity and myocardial hypertrophy. Furthermore, they induce a disorganized proliferation of myofibrils. Such aberrant myofibrillar structures pave the way for abnormal conduction pathways, predisposing individuals to fatal arrhythmias like VT and VF. Alarmingly, HOCM tends to present itself before puberty and stands as the foremost cause of sudden death in young athletes.
Clinically, HOCM can present with a harsh systolic murmur and an S4 heart sound. Specific maneuvers affecting preload and afterload can significantly influence the intensity of the murmur. Valsalva and standing maneuvers decrease preload, leading to a higher degree of LVOT obstruction and an increase in murmur intensity. In contrast, supine leg raises and squatting increase preload, resulting in a decreased degree of LVOT obstruction and diminished murmur intensity. Furthermore, maneuvers that increase afterload contribute to a reduction in murmur intensity by slowing the movement of blood through the LVOT.
Treatment for HOCM often involves beta blockers and nondihydropyridine calcium channel blockers, which act to decrease HR, leading to increased time in diastole and enhanced left ventricular preload. This, in turn, decreases LVOT obstruction. Several drugs are specifically contraindicated in HOCM. For instance, drugs that decrease preload, such as diuretics and nitrates, can exacerbate LVOT obstruction. Dihydropyridine calcium channel blockers and drugs like increase contractility (e.g. digitalis) are also contraindicated. Additionally, vasodilatory drugs and nitroglycerine can increased blood velocity through the LVOT, thereby intensifying the obstruction. ACE inhibitors should also be avoided, as they can decrease both preload and afterload, worsening LVOT obstruction. Friedreich's ataxia, an autosomal recessive trinucleotide repeat disorder that manifests as ataxia and cardiomyopathy, is closely associated with HOCM. In fact, Friedreich's ataxia is the most common cause of death in these patients.
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FAQs
HOCM is a subtype of hypertrophic cardiomyopathy, a condition characterized by abnormal thickening of the heart muscle, specifically the interventricular septum. This hypertrophy can obstruct the blood flow from the left ventricle, leading to diastolic dysfunction and potentially heart failure. This condition is typically caused by an autosomal dominant mutation in sarcomere proteins, such as beta-myosin heavy chain, myosin-binding protein C, troponin T. The mutations often result in a gain-of-function, causing increased myofilament activity and hypertrophy, as well as disorganized myofibrillar proliferation.
In hypertrophic obstructive cardiomyopathy (HOCM), hypertrophy of the interventricular septum impedes the flow of blood from the left ventricle. This obstruction primarily occurs distal to the aortic valve in the left ventricular outflow tract (LVOT). Additionally, the systolic anterior motion of the mitral valve may cause it to contact the hypertrophied septum, further contributing to the obstruction in the LVOT.
HOCM typically presents with a unique, harsh crescendo-decrescendo systolic murmur, most audible at the left sternal border, which is a result of LVOT obstruction. The condition may also produce an S4 heart sound, trigger episodes of angina, and lead to syncope due to non-lethal arrhythmias or transient reductions in cardiac output. Notably, HOCM is a frequent cause of sudden cardiac death among young athletes.
In hypertrophic obstructive cardiomyopathy (HOCM), the intensity of the murmur correlates with the degree of left ventricular outflow tract (LVOT) obstruction. Maneuvers that reduce preload, such as the valsalva maneuver or standing, typically intensify the murmur by exacerbating LVOT obstruction. Conversely, maneuvers that elevate preload or afterload, including leg raising or squatting, tend to lessen the murmur by mitigating the degree of LVOT obstruction.
The mainstay of pharmacologic treatment for HOCM aims to decrease cardiac contractility, thereby reducing the velocity of blood flow across the LVOT. This is generally achieved through the use of beta-blockers and nondihydropyridine calcium channel blockers. Medications that either decrease preload, such as diuretics, nitrates, and dihydropyridine calcium channel blockers, or that increase cardiac contractility, like digitalis or milrinone, are generally contraindicated. These medications can worsen the degree of LVOT obstruction, thus exacerbating the clinical picture.
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