Effect of left ventricular size and shape upon the hemodynamics of subaortic stenosis

Klein, Michael D.; Lane, Francis J.; Gorlin, Richard

doi:10.1016/0002-9149(65)90379-6

Cited by 40 publications

(12 citation statements)

References 18 publications

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“…Associated histopathologic findings include enlarged, disorganized cardiomyocytes and increased amounts of myocardial fibrosis. HCM also perturbs heart function, with characteristically hyperdynamic contraction (2, 3) and impaired relaxation (4). Both the histopathologic and hemodynamic abnormalities of HCM contribute to patient symptoms (including exertional angina and shortness of breath) and increase the risk for atrial fibrillation, stroke, heart failure, and premature death (5).…”

mentioning

confidence: 99%

A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice

Green¹,

Wakimoto

Anderson³

et al. 2016

Science

581

558

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Hypertrophic cardiomyopathy (HCM) is an inherited disease of heart muscle that can be caused by mutations in sarcomere proteins. Clinical diagnosis depends on an abnormal thickening of the heart, but the earliest signs of disease are hyperdynamic contraction and impaired relaxation. Whereas some in vitro studies of power generation by mutant and wild-type sarcomere proteins are consistent with mutant sarcomeres exhibiting enhanced contractile power, others are not. We identified a small molecule, MYK-461, that reduces contractility by decreasing the adenosine triphosphatase activity of the cardiac myosin heavy chain. Here we demonstrate that early, chronic administration of MYK-461 suppresses the development of ventricular hypertrophy, cardiomyocyte disarray, and myocardial fibrosis and attenuates hypertrophic and profibrotic gene expression in mice harboring heterozygous human mutations in the myosin heavy chain. These data indicate that hyperdynamic contraction is essential for HCM pathobiology and that inhibitors of sarcomere contraction may be a valuable therapeutic approach for HCM.

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mentioning

confidence: 99%

A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice

Green¹,

Wakimoto

Anderson³

et al. 2016

Science

581

558

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“…These characteristics raise the potential for excessive ATP utilization and, consequently, boost energy demand, which could signal hypertrophic remodeling (8). These gains of function for the mutant form of myosin should not have been surprising, given that clinical measures of cardiac performance describe the HCM heart as hyperdynamic (9). Many of the mutations discovered in myosin’s motor domain have a tendency toward enhanced mechanical and/or ATPase capacities (10)—specifically, the R403Q, R453C, and R719W mutations studied by Green et al, in which arginine (R) at position 403, 453, and 719 is substituted with glutamine (Q), cysteine (C), and trypophan (W), respectively.…”

mentioning

confidence: 99%

Throttling back the heart's molecular motor

Warshaw

2016

Science

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“…Such mitral valve motion had irutially been demonstrated angiocardiographically (10,14,54), and appeared to compare well with earlier direct anatomical observations during operative interventions (4,6,55). The angiograpruc systolic operung of the mitral valve in HCM has recently been reconfirmed (9,11,13,33,37), but it is notable that it is infrequently seen, even though the echocardiograpruc SAM structures are easily detected and often have an amplitude equal to the diastolic operung of the mitral valve. Both left ventricular outflow tract obstruction (7,35,45,49) and mitral regurgitation in HCM have been attributed to the systolic anterior motion of the mitral valve leaflets (2,10,14,40,47,54).…”

Section: Discussionmentioning

confidence: 99%

“…in systole may result in abnormal traction on the mitral valve cusps with consequent systolic re-opening (37). To gain evidence of the assumed systolic motion of the papillary muscles, transverse cross-sections were performed.…”

Section: Discussionmentioning

confidence: 99%

The significance of systolic anterior motion (SAM) on the mitral valve echo pattern in hypertrophic cardiomyopathy

Gehrke

Goodwin

1978

Clinical Cardiology

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The systolic anterior motion (SAM) of valve structures in the mitral echogram in hypertrophic cardiomyopathy (HCM) has previously been considered to be anterior motion and re‐opening of mitral valve leaflets, causing left ventricular outflow tract (LVOT) obstruction and mitral regurgitation. Fifteen patients with HCM underwent cardiac catheterisation and were also examined by M‐scan and mechanical real‐time B‐scan techniques. In all patients SAM was seen during M‐scan echocardiography. The mitral valve leaflets were visualised during the entire cardiac cycle during real‐time B‐scanning without showing any re‐opening in systole. Thickened papillary muscles have been observed in 12 patients and prominent chordae tendineae moving in the opposite direction to the anterior mitral valve leaflet in 10 patients. Four patients with SAM did not show mitral regurgitation during left ventricular angiography. In two patients without fixed haemodynamic obstruction, a complete SAM touching the interventricular septum was observed with prolonged apposition in one case. These findings suggest that SAM is due to the motion of chordae tendineae and/or papillary muscles traversing the single dimensional ultrasonic beam in systole, thus producing single linear or multiple spotty echoes within SAM. The mechanism of the upward motion of the subvalvular mitral valve apparatus in systole appears to be due to forceful contraction of the apical left ventricular posterior wall. The observation of SAM in patients without HCM also indicates that its presence during single dimensional echocardiography is neither diagnostic nor specific for HCM, LVOT obstruction or mitral regurgitation, and contradicts the assumption that the anterior mitral valve leaflet plays a significant role in the mechanism of LVOT obstruction. The salient feature of all conditions associated with abnormal mitral subvalvular motion is hyperkinetic contraction of the apical left ventricular posterior wall. Hyperkinetic left ventricular ejection appears to be the main factor in the complex development of an LVOT gradient in hypertrophic cardiomyopathy.

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Effect of left ventricular size and shape upon the hemodynamics of subaortic stenosis

Cited by 40 publications

References 18 publications

A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice

A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice

Throttling back the heart's molecular motor

The significance of systolic anterior motion (SAM) on the mitral valve echo pattern in hypertrophic cardiomyopathy

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