Myocardial efficiency is an important determinant of functional improvement after aortic valve replacement in aortic valve stenosis patients: a combined PET and CMR study

Güçlü, Ahmet; Knaapen, Paul; Harms, Hendrik J.; Vonk, Alexander B.A.; Stooker, Willem; Groepenhoff, Herman; Lammertsma, Adriaan A.; Rossum, Albert C. van; Germans, Tjeerd; Velden, Jolanda van der

doi:10.1093/ehjci/jev009

Cited by 31 publications

(31 citation statements)

References 32 publications

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“…These studies were also restricted by the absence of methods or by inaccurate methods to quantify stroke work, which evidently hampers any firm conclusion of how AS may affect myocardial efficiency. A more recent study found normal MVO 2 and reduced myocardial efficiency in 10 symptomatic AS patients with preserved LVEF compared with a younger control group (32% versus 49%) 28. Notably, myocardial efficiency for controls was substantially higher than that shown in previous reports (≈15–30%), and the reliability of this conclusion may be questioned 7…”

Section: Discussionmentioning

confidence: 93%

“…The pathophysiology of myocardial hypertrophy and the progression to LV failure in AS patients is a matter of ongoing debate,26, 27 and impaired MVO 2 capacity, limited substrate accessibility, and energy transfer or utilization have been proposed as responsible adverse mechanisms 5, 9, 28. However, clinical studies on MVO 2 and MEE during the progression from compensated hypertrophy to heart failure are lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Only a few minor studies have investigated MVO 2 in AS patients, and their conclusions are inconsistent 28, 29, 30, 31. These studies were also restricted by the absence of methods or by inaccurate methods to quantify stroke work, which evidently hampers any firm conclusion of how AS may affect myocardial efficiency.…”

Section: Discussionmentioning

confidence: 99%

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Myocardial Oxygen Consumption and Efficiency in Aortic Valve Stenosis Patients With and Without Heart Failure

Hansson

Sørensen

Harms

et al. 2017

JAHA

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BackgroundMyocardial oxygen consumption (MVO2) and its coupling to contractile work are fundamentals of cardiac function and may be involved causally in the transition from compensated left ventricular hypertrophy to failure. Nevertheless, these processes have not been studied previously in patients with aortic valve stenosis (AS).Methods and ResultsParticipants underwent 11C‐acetate positron emission tomography, cardiovascular magnetic resonance, and echocardiography to measure MVO2 and myocardial external efficiency (MEE) defined as the ratio of left ventricular stroke work and the energy equivalent of MVO2. We studied 10 healthy controls (group A), 37 asymptomatic AS patients with left ventricular ejection fraction ≥50% (group B), 12 symptomatic AS patients with left ventricular ejection fraction ≥50% (group C), and 9 symptomatic AS patients with left ventricular ejection fraction <50% (group D). MVO2 did not differ among groups A, B, C, and D (0.105±0.02, 0.117±0.024, 0.129±0.032, and 0.104±0.026 mL/min per gram, respectively; P=0.07), whereas MEE was reduced in group D (21.0±1.6%, 22.3±3.3%, 22.1±4.2%, and 17.3±4.7%, respectively; P<0.05). Similarly, patients with global longitudinal strain greater than −12% and paradoxical low‐flow, low‐gradient AS had impaired MEE (P<0.05 versus controls). The ability to discriminate between symptomatic and asymptomatic patients was superior for global longitudinal strain compared with MVO2 and MEE (area under the curve 0.98, 0.48, and 0.61, respectively; P<0.05).ConclusionsAS patients display a persistent ability to maintain normal MVO2 and MEE (ie, the ability to convert energy into stroke work); however, patients with left ventricular ejection fraction <50%; global longitudinal strain greater than −12%; or paradoxical low‐flow, low‐gradient AS demonstrate reduced MEE. These findings suggest that mitochondrial uncoupling contributes to the dismal prognosis in patients with reduced contractile function or paradoxical low‐flow, low‐gradient AS.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Myocardial Oxygen Consumption and Efficiency in Aortic Valve Stenosis Patients With and Without Heart Failure

Hansson

Sørensen

Harms

et al. 2017

JAHA

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“…This suggests that LV unloading improves coupling between mitochondrial energy production and stroke work, a finding which is supported by increasing myocardial efficiency in patients with AS who undergo AVR. 36 However, despite this evident relationship between afterload and myocardial efficiency, there was no overall improvement in MEE for patients treated with metoprolol ( Figures 2F and 4F). This may be explained by the fact that we investigated patients with asymptomatic AS who in contrast to AS patients with heart failure may have a normal or near-normal MEE.…”

Section: Effects Of Metoprolol On Cardiac Energeticsmentioning

confidence: 93%

“…35 Similarly, the transition from compensated hypertrophy to failure in patients with AS is characterized by reduced myocardial efficiency caused by an increase in total MVO 2 (ie, MVO 2 ×LV mass) and an inability to maintain stroke work. 10,36 Thus, a combination of hemodynamic and metabolic overload contributes to the onset of heart failure in patients with AS.…”

Section: Effects Of Metoprolol On Cardiac Energeticsmentioning

confidence: 99%

Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients

Hansson

Sørensen

Harms

et al. 2017

Circ: Cardiovascular Imaging

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Background— Currently, no pharmacological treatment can modify the natural history of aortic valve stenosis (AS). This underlines the critical need to explore novel treatment strategies, which could postpone or prevent the need for aortic valve replacement in patients with asymptomatic AS. The objectives of this study were to investigate whether metoprolol reduce the hemodynamic and metabolic burden imposed by AS. Methods and Results— In a double-blinded design, 40 patients with moderate-severe asymptomatic AS (aortic valve area, 0.5±0.1 cm 2 /m 2 ; peak gradient, 53±19 mm Hg) were randomized to placebo or metoprolol treatment for 22 weeks. Patients were evaluated by echocardiography, cardiovascular magnetic resonance, and 11 C-acetate positron emission tomography. Compared with placebo, metoprolol (100±53 mg/d) decreased heart rate; mean difference (95% confidence interval) −8 minute − 1 (−13, −3; P =0.003) and increased ejection time 26 ms (2, 50; P =0.03). Furthermore, metoprolol reduced aortic valve peak −7 mm Hg (−13, 0; P =0.05) and mean −4 mm Hg (−7, −1; P =0.03) gradients, without affecting stroke volume 3 mL/m 2 (−2, 8; P =0.16). Valvuloarterial impedance (ie, global afterload) and myocardial oxygen consumption were reduced by −11% and −12% ( P =0.03 and 0.01), respectively; and decreased heart rate correlated with lower valvuloarterial impedance, myocardial oxygen consumption, and improved myocardial efficiency defined as stroke work/myocardial oxygen consumption ( r =0.63–0.65; all P <0.01). There were 2 adverse cardiovascular events in the metoprolol group and none in the placebo group. Conclusions— In patients with asymptomatic AS, metoprolol increases systolic ejection time and reduces aortic valve gradients, global afterload, and myocardial oxygen requirements. Thus, metoprolol displays favorable hemodynamic and metabolic effects and could improve outcome in patients with asymptomatic AS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02076711.

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Assessment of wall stresses and mechanical heart power in the left ventricle: Finite element modeling versus Laplace analysis

Gsell

Augustin

Prassl

et al. 2018

Numer Methods Biomed Eng

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Laplace estimates of LV wall stress are able to provide a rough approximation of global mean stress in the circumferential-longitudinal plane of the LV. However, according to FE results, spatial heterogeneity of stresses in the LV wall is significant, leading to major discrepancies between local stresses and global mean stress. Assessment of mechanical power with Laplace methods is feasible, but these are inferior in accuracy compared with FE models. The accurate assessment of stress and power density distribution in the LV wall is only feasible based on patient-specific FE modeling.

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Myocardial efficiency is an important determinant of functional improvement after aortic valve replacement in aortic valve stenosis patients: a combined PET and CMR study

Abstract: MEE is significantly reduced in patients with AVS-induced hypertrophy. Improved MEE is an important predictor of AVR-induced improvement of exercise capacity in AVS patients. Future investigation is needed to confirm our observations in a large prospective, multicenter clinical trial.

Cited by 31 publications

References 32 publications

Myocardial Oxygen Consumption and Efficiency in Aortic Valve Stenosis Patients With and Without Heart Failure

Myocardial Oxygen Consumption and Efficiency in Aortic Valve Stenosis Patients With and Without Heart Failure

Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients

Assessment of wall stresses and mechanical heart power in the left ventricle: Finite element modeling versus Laplace analysis

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