Faculty Bibliography

BACKGROUND: Three competing theories about the mechanism of mitral coaptation in normal subjects were evaluated by color Doppler and vector flow mapping (VFM): (1) beginning of ventricular (LV) ejection, (2) "breaking of the jet" of diastolic LV inflow, and (3) returning diastolic vortices impacting the leaflets on their LV surfaces. METHODS AND RESULTS: We analyzed 80 color Doppler frames and 320 VFM measurements. In all 20 normal subjects, coaptation occurred before LV ejection, 78+/-16 ms before onset. On color Doppler frames the larger anterior, and smaller posterior vortices circle back and, in all cases, strike the ventricular surfaces of the leaflets. On the first closing-begins frame, for the first time, vortex velocity normal to the ventricular surface of the anterior leaflet (AML) is greater than that in the mitral orifice, and the angle of attack of LV vortical flow onto the AML is twice as high as the angle of flow onto the valve in orifice. Thus, at the moment coaptation begins, vortical flow strikes the mitral leaflet with higher velocity, and higher angle of attack than orifice flow, and thus with greater force. According to the "breaking of the jet" theory, one would expect to see de novo LV flow perpendicular to the leaflets beginning after transmitral flow terminates. Instead, the returning continuous LV vortical flow that impacts the valve builds continuously after the P-wave. CONCLUSIONS: Late diastolic vortices strike the ventricular surfaces of the mitral leaflets and contribute to valve coaptation, permitted by concomitant decline in transmitral flow.

Objective: Sarcomeric gene mutation carriers without overt left ventricular hypertrophy (G+/LVH-) can harbour subclinical changes in cardiovascular structure and function that precede the development of hypertrophic cardiomyopathy (HCM). We sought to investigate if circulating biomarkers of cardiovascular stress and collagen metabolism among G+/LVH- individuals, measured at rest and following exercise provocation, yield further insights into the underlying biology of HCM. Methods: We studied 76 individuals with overt HCM, 50 G+/LVH- individuals and 41 genotype-negative related controls enrolled in a cross-sectional, multicentre observational study (HCMNet). Biomarkers of cardiac stress (N-terminal pro-B-type natriuretic peptide, NT-proBNP; high-sensitivity troponin I, hsTnI; soluble ST2) and fibrosis (carboxy-terminal propeptide of procollagen type I; C-terminal telopeptide of type I collagen; galectin-3; periostin) were measured. Results: Individuals with overt HCM had elevated NT-proBNP and hsTnI compared with G+/LVH- subjects and controls at rest, along with an exaggerated increase in NT-proBNP and hsTnI in response to exercise. We found no detectable differences in resting or exercise-provoked biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with healthy controls despite subtle echocardiographic differences in cardiac structure and function. Conclusion: Dynamic exercise testing exaggerated resting differences in natriuretic peptides and troponin elevations among individuals with overt HCM. In contrast, we found no differences in biomarker profiles of cardiovascular stress and fibrosis among G+/LVH- individuals compared with controls even after maximal exercise provocation. Our findings highlight the need for continued investigation into early phenotypes of sarcomeric gene mutations and the evolution of HCM.

Evidence indicates that anatomical and physiological phenotypes of hypertrophic cardiomyopathy (HCM) stem from genetically mediated, inefficient cardiomyocyte energy utilization, and subsequent cellular energy depletion. However, HCM often presents clinically with normal left ventricular (LV) systolic function or hyperkinesia. If energy inefficiency is a feature of HCM, why is it not manifest as resting LV systolic dysfunction? In this Perspectives article, we focus on an idiosyncratic form of reversible systolic dysfunction provoked by LV obstruction that we have previously termed the 'lobster claw abnormality' - a mid-systolic drop in LV Doppler ejection velocities. In obstructive HCM, this drop explains the mid-systolic closure of the aortic valve, the bifid aortic pressure trace, and why patients cannot increase stroke volume with exercise. This phenomenon is characteristic of a broader phenomenon in HCM that we have termed dynamic systolic dysfunction. It underlies the development of apical aneurysms, and rare occurrence of cardiogenic shock after obstruction. We posit that dynamic systolic dysfunction is a manifestation of inefficient cardiomyocyte energy utilization. Systolic dysfunction is clinically inapparent at rest; however, it becomes overt through the mechanism of afterload mismatch when LV outflow obstruction is imposed. Energetic insufficiency is also present in nonobstructive HCM. This paradigm might suggest novel therapies. Other pathways that might be central to HCM, such as myofilament Ca2+ hypersensitivity, and enhanced late Na+ current, are discussed.

Mitral valve abnormalities were not part of modern pathological and clinical descriptions of hypertrophic cardiomyopathy in the 1950s, which focused on left ventricular (LV) hypertrophy and myocyte fiber disarray. Although systolic anterior motion (SAM) of the mitral valve was discovered as the cause of LV outflow tract obstruction in the M-mode echocardiography era, in the 1990s structural abnormalities of the mitral valve became appreciated as contributing to SAM pathophysiology. Hypertrophic cardiomyopathy mitral malformations have been identified at all levels. They occur in the leaflets, usually elongating them, and also in the submitral apparatus, with a wide array of malformations of the papillary muscles and chordae, that can be detected by transthoracic and transesophageal echocardiography and by cardiac magnetic resonance. Because they participate fundamentally in the predisposition to SAM, they have increasingly been repaired surgically. This review critically assesses imaging and measurement of mitral abnormalities and discusses their surgical relief.

Hypertrophic cardiomyopathy is the most common genetic heart disease. Once considered relentless, untreatable and deadly, it has become a highly treatable disease with contemporary management. Hypertrophic cardiomyopathy is one of cardiology's "great masqueraders". Mistakes and delays in diagnosis abound. Hypertrophic cardiomyopathy commonly "masquerades" as asthma, anxiety, mitral prolapse, and coronary artery disease. However, once properly diagnosed, patients with hypertrophic cardiomyopathy can be effectively managed to improve both symptoms and survival. This review highlights some of the misconceptions regarding hypertrophic cardiomyopathy. Providers at all levels should have awareness of hypertrophic cardiomyopathy to promptly diagnose and properly manage these individuals.

HCM is the most common inherited heart condition occurring in 1:500 individuals in the general population. Left ventricular outflow obstruction at rest or after provocation occurs in 2/3 of HCM patients and is a frequent cause of limiting symptoms. Pharmacologic therapy is the first-line treatment for obstruction, and should be aggressively pursued before application of invasive therapy. Beta-blockade is given first, and up-titrated to decrease resting heart rate to between 50 and 60 beats per minute. However, beta-blockade is not expected to decrease resting gradients; its effect rests on decreasing the rise in gradient that accompanies exercise. For patients who fail beta-blockade the addition of oral disopyramide in adequate dose often will decrease resting gradients and offer meaningful relief of symptoms. Disopyramide vagolytic side effects, if they occur, can be greatly mitigated by simultaneous administration of oral pyridostigmine. This combination allows adequate dosing of disopyramide to achieve therapeutic goals. Verapamil utility in obstructive HCM with high resting gradients is limited by its vasodilating effects that can, infrequently, worsen gradient and symptoms. As such, we tend to avoid it in patients with high gradients and limiting heart failure symptoms. In a head-to-head comparison of intravenous drug administration in individual obstructive HCM patients the relative efficacy for lowering gradient was disopyramide > beta-blockade > verapamil. Severe symptoms in non-obstructive HCM are caused by fibrosis or severe myocyte disarray, and often by very small LV chamber size. Severe symptoms caused by these anatomic and histologic abnormalities, in the absence of obstruction, are less amenable to current pharmacotherapy. New pharmacotherapeutic approaches to HCM are on the horizon, that are to be evaluated in formal therapeutic trials.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), akinetic apical aneurysms are associated with ventricular tachycardia, heart failure, apical thrombus, and mortality. The cause of apical aneurysms remains unresolved, and there is controversy about prevalence and significance of mid-left ventricular (LV) obstruction, often present in these patients. The aim of this study was to test the hypothesis that low velocities in patients with aneurysms are due to near complete cessation of mid-LV flow, characteristically marked by a Doppler signal void. METHODS: This was a retrospective analysis of 39 patients with HCM with segmental hypertrophy of the mid left ventricle and complete systolic emptying at the mid-LV level. The severity of dynamic obstruction was evaluated by measuring the time during which cross-sectional mid-LV cavity area was <1 cm(2). Presence or absence of an LV Doppler midsystolic signal void was determined. RESULTS: Akinetic apical aneurysms were present in 21 patients. The duration of two-dimensional mid-LV short-axis complete emptying was longer in patients with akinetic apical aneurysms (194 +/- 45 vs 148 +/- 63 msec, P = .013), nearly 50% of systole. Midsystolic signal voids were seen only in patients with akinetic apical aneurysms (P < .001), present in 86%. In patients with akinetic aneurysms, there was a strong correlation between the duration of the systolic signal void and the proportion of systole with complete emptying <1 cm(2) (r = 0.704; P = .001). Complete emptying <1 cm(2) for >/=38% of systole was associated with akinetic aneurysm (odds ratio, 9.35; P < .004). CONCLUSION: Patients with akinetic apical aneurysm HCM have near complete cessation of flow across severe dynamic mid-LV obstruction for nearly 50% of systole. This explains how the adverse effects of obstruction may occur without high velocities on echocardiography.

BACKGROUND: Anatomic features of obstructive hypertrophic cardiomyopathy are septal hypertrophy, elongated mitral leaflets, and anterior displacement of the papillary muscles. In addition to extended myectomy, the resect-plicate-release operation adds horizontal plication of the anterior mitral leaflet (AML) and release of the anterolateral papillary muscle (APM) in selected patients. The aim of this study was to test the hypotheses that (1) preoperative findings would be associated with procedures applied, (2) anatomic corrections would be observable postoperatively, and (3) there would be consistently good physiologic outcomes. METHODS: A retrospective study was conducted of patients with obstructive hypertrophic cardiomyopathy who had adequate echocardiograms before and 9.5 +/- 12 months after the resect-plicate-release operation was performed from 2006 to 2012. RESULTS: Seventy-seven patients underwent myectomy, 50 AML plication, and 50 APM release. Patients who underwent plication had longer AMLs (32 +/- 4 vs 28 +/- 4 mm; P < .004). Anterior extension of the APM was more common with papillary muscle release (86% vs 62%, P < .04). Twenty-seven (35%) had septal thickness