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Left ventricular diastolic function in hypertrophic cardiomyopathy
1Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
Insights
Impaired diastolic function in hypertrophic cardiomyopathy affects left ventricular filling and can cause symptoms like dyspnea. Calcium channel blockers, particularly verapamil, show promise in improving relaxation and filling dynamics.
Area of Science:
- Cardiology
- Cardiovascular Physiology
Background:
- Hypertrophic cardiomyopathy (HCM) is characterized by impaired left ventricular (LV) diastolic function due to hypertrophy and stiffness.
- This dysfunction leads to altered LV filling, reduced distensibility, increased LV filling pressures, and coronary microcirculation compression.
Purpose of the Study:
- To explore the mechanisms underlying impaired LV diastolic function in HCM.
- To evaluate the impact of calcium channel blockers on LV diastolic function and filling in HCM patients.
Main Methods:
- The study reviews factors affecting passive elastic properties and active relaxation of the LV in HCM.
- It discusses inactivation-dependent and load-dependent mechanisms of impaired relaxation.
- The effects of calcium channel blockers (verapamil, diltiazem, nifedipine) on LV function were examined.
Main Results:
- Reduced LV distensibility contributes to symptoms such as fatigue, dyspnea, and angina.
- Impaired relaxation involves increased intracellular calcium and prolonged contractile protein interaction, alongside potential myocardial ischemia.
- Calcium channel blockers favorably influence LV relaxation and filling; verapamil improves stroke volume without increasing end-diastolic pressure.
Conclusions:
- Impaired diastolic function is central to HCM pathophysiology and clinical presentation.
- Verapamil and diltiazem are effective in improving LV diastolic function and filling patterns in HCM.
- Targeting diastolic dysfunction with specific calcium channel blockers offers therapeutic potential for HCM patients.
Abstract:
Impaired diastolic function of the hypertrophied and stiffened left ventricle is a characteristic feature of hypertrophic cardiomyopathy (Figure 1). Altered left ventricular filling dynamics and reduced left ventricular distensibility or increased left ventricular diastolic chamber stiffness are associated with reduced left ventricular stroke volume, increased left ventricular filling pressures and compressive effects on the coronary microcirculation. These factors contribute importantly to the clinical presentation of many patients, including symptoms of fatigue, dyspnea and angina pectoris. Reduced distensibility results both from factors determining the passive elastic properties of the ventricular chamber (including severity of hypertrophy, fibrosis and cellular disarray) and from factors influencing the rate and extent of active left ventricular relaxation (Figure 2). The factors contributing to impaired relaxation in hypertrophic cardiomyopathy are mediated via either inactivation dependent or load-dependent mechanisms. In laboratory animals, compromise of myocardial inactivation results in a persistent increase in intracellular calcium concentration and in prolonged interaction of the contractile proteins. Additionally, there is evidence for an increased number of active receptors for calcium antagonists and, lastly, for myocardial ischemia (Figure 3). Load-dependent mechanisms include diminished wall tension at the opening of the mitral valve, changes in afterload, contractility and coronary flow. Other factors are nonuniform and asynchronous regional ventricular function due to differing increases in thickness of the ventricular walls and ischemia (Figure 4). Calcium channel blockers exert a favorable influence on left ventricular relaxation and filling (Figure 5); verapamil and diltiazem are preferable to nifedipine. Verapamil increases left ventricular stroke volume without an increase in the end-diastolic pressure (Figure 6), reduces regional asynchrony if present, and leads to a more homogeneous regional diastolic filling (Figure 4).(ABSTRACT TRUNCATED AT 250 WORDS)