Determinants of myocardial energetics and efficiency in symptomatic hypertrophic cardiomyopathy

Timmer, Stefan; Germans, Tjeerd; Götte, Marco J.W.; Rüssel, Iris K.; Dijkmans, Pieter A.; Lubberink, Mark; Berg, Jurriën Ten; Cate, Folkert J. ten; Lammertsma, Adriaan A.; Knaapen, Paul; Rossum, Albert C. van

doi:10.1007/s00259-009-1350-3

Cited by 28 publications

(20 citation statements)

References 42 publications

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“…This can result in abnormal patterns of LV mechanical torsion in vivo that decrease the efficiency of contraction and relaxation and thereby, chamber ejection and filling. Furthermore, both increased ATP turnover due to accelerated cross-bridge cycling and reduced LV mechanical efficiency would be expected to increase energy expenditure by myocytes, 41,42 which promotes apoptotic pathways 43 that lead to decreased myocyte survival and replacement of myocytes with fibrotic tissue. 44 The induction of LV fibrosis progressively stiffens the myocardium and impairs active fiber shortening and stretch.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Myosin Binding Protein C Insufficiency Leads to Early Onset of Mechanical Dysfunction

Desjardins

Chen

Coulton

et al. 2012

Circ: Cardiovascular Imaging

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Background Decreased expression of cardiac myosin binding protein C (cMyBPC) as a result of genetic mutations may contribute to the development of hypertrophic cardiomyopathy (HCM); however, the mechanisms that link cMyBPC expression and HCM development, especially contractile dysfunction, remain unclear. Methods and Results We evaluated cardiac mechanical function in vitro and in vivo in young mice (8–10 weeks of age) carrying no functional cMyBPC alleles (cMyBPC−/−) or 1 functional cMyBPC allele (cMyBPC±). Skinned myocardium isolated from cMyBPC−/− hearts displayed significant accelerations in stretch activation cross-bridge kinetics. Cardiac MRI studies revealed severely depressed in vivo left ventricular (LV) magnitude and rates of LV wall strain and torsion compared with wild-type (WT) mice. Heterozygous cMyBPC± hearts expressed 23±5% less cMyBPC than WT hearts but did not display overt hypertrophy. Skinned myocardium isolated from cMyBPC± hearts displayed small accelerations in the rate of stretch induced cross-bridge recruitment. MRI measurements revealed reductions in LV torsion and circumferential strain, as well reduced circumferential strain rates in early systole and diastole. Conclusions Modest decreases in cMyBPC expression in the mouse heart result in early-onset subtle changes in cross-bridge kinetics and in vivo LV mechanical function, which could contribute to the development of HCM later in life.

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Section: Discussionmentioning

confidence: 99%

Cardiac Myosin Binding Protein C Insufficiency Leads to Early Onset of Mechanical Dysfunction

Desjardins

Chen

Coulton

et al. 2012

Circ: Cardiovascular Imaging

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“…Myocardial activity generates the total power, which itself is fueled by O 2 consumption. Therefore, if we define the steady hydraulic work done as the useful mechanical work for the circulation, cardiac mechanical efficiency can be defined as the ratio of the steady hydraulic power to the total power generated by myocardial O 2 consumption 94,100 . For the left ventricle it has been hypothesized that physiological working conditions achieve maximal cardiac efficiency rather than maximal output power 17 .…”

Section: Physiology and Mechanics Of The Rvmentioning

confidence: 99%

Methods for Measuring Right Ventricular Function and Hemodynamic Coupling with the Pulmonary Vasculature

Bellofiore

Chesler

2013

Ann Biomed Eng

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The right ventricle (RV) is a pulsatile pump, the efficiency of which depends on proper hemodynamic coupling with the compliant pulmonary circulation. The RV and pulmonary circulation exhibit structural and functional differences with the more extensively investigated left ventricle (LV) and systemic circulation. In light of these differences, metrics of LV function and efficiency of coupling to the systemic circulation cannot be used without modification to characterize RV function and efficiency of coupling to the pulmonary circulation. In this article, we review RV physiology and mechanics, established and novel methods for measuring RV function and hemodynamic coupling, and findings from application of these methods to RV function and coupling changes with pulmonary hypertension. We especially focus on non-invasive measurements, as these may represent the future for clinical monitoring of disease progression and the effect of drug therapies.

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“…Myocardial external efficiency (MEE) was calculated according to the equation depicted below (21,46). External work (EW) was defined as the product of SV derived by MRI and mean LVOTG plus MAP.…”

Section: Myocardial External Efficiencymentioning

confidence: 99%

“…The poorer prognosis of outflow tract obstruction in HCM is, at least in part, believed to be mediated by the induction of myocardial ischemia. Furthermore, myocardial energetics and efficiency are impaired in HCM (15,39,46). The latter may, in analogy with dilated cardiomyopathy, hold prognostic relevance (22,31,32).…”

mentioning

confidence: 99%

Effects of alcohol septal ablation on coronary microvascular function and myocardial energetics in hypertrophic obstructive cardiomyopathy

Timmer

Knaapen

Germans

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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This study investigated the effects of alcohol septal ablation (ASA) on microcirculatory function and myocardial energetics in patients with hypertrophic cardiomyopathy (HCM) and left ventricular outflow tract (LVOT) obstruction. In 15 HCM patients who underwent ASA, echocardiography was performed before and 6 mo after the procedure to assess the LVOT gradient (LVOTG). Additionally, [(15)O]water PET was performed to obtain resting myocardial blood flow (MBF) and coronary vasodilator reserve (CVR). Changes in LV mass (LVM) and volumes were assessed by cardiovascular magnetic resonance imaging. Myocardial oxygen consumption (MVo(2)) was evaluated by [(11)C]acetate PET in a subset of seven patients to calculate myocardial external efficiency (MEE). After ASA, peak LVOTG decreased from 41 ± 32 to 23 ± 19 mmHg (P = 0.04), as well as LVM (215 ± 74 to 169 ± 63 g; P < 0.001). MBF remained unchanged (0.94 ± 0.23 to 0.98 ± 0.15 ml·min(-1)·g(-1); P = 0.45), whereas CVR increased (2.55 ± 1.23 to 3.05 ± 1.24; P = 0.05). Preoperatively, the endo-to-epicardial MBF ratio was lower during hyperemia compared with rest (0.80 ± 0.18 vs. 1.18 ± 0.15; P < 0.001). After ASA, the endo-to-epicardial hyperemic (h)MBF ratio increased to 1.03 ± 0.26 (P = 0.02). ΔCVR was correlated to ΔLVOTG (r = -0.82; P < 0.001) and ΔLVM (r = -0.54; P = 0.04). MEE increased from 15 ± 6 to 20 ± 9% (P = 0.04). Coronary microvascular dysfunction in obstructive HCM is at least in part reversible by relief of LVOT obstruction. After ASA, hMBF and CVR increased predominantly in the subendocardium. The improvement in CVR was closely correlated to the absolute reduction in peak LVOTG, suggesting a pronounced effect of LV loading conditions on microvascular function of the subendocardium. Furthermore, ASA has favorable effects on myocardial energetics.

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Determinants of myocardial energetics and efficiency in symptomatic hypertrophic cardiomyopathy

Cited by 28 publications

References 42 publications

Cardiac Myosin Binding Protein C Insufficiency Leads to Early Onset of Mechanical Dysfunction

Cardiac Myosin Binding Protein C Insufficiency Leads to Early Onset of Mechanical Dysfunction

Methods for Measuring Right Ventricular Function and Hemodynamic Coupling with the Pulmonary Vasculature

Effects of alcohol septal ablation on coronary microvascular function and myocardial energetics in hypertrophic obstructive cardiomyopathy

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