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The present study tested the hypothesis that metformin treatment may increase myocardial efficiency (stroke work/myocardial oxygen consumption) in insulin-resistant patients with heart failure and reduced ejection fraction (HFrEF) without diabetes.

Myocardial deformation assessed by speckle tracking echocardiography (STE) is increasingly used for diagnosis, monitoring and prognosis in patients with clinical and pre-clinical cardiovascular diseases. Feature tracking cardiac magnetic resonance (FT-CMR) also allows myocardial deformation analysis. To clarify whether the two modalities can be used interchangeably, we compared myocardial deformation analysis by FT-CMR with STE in patients with a variety of cardiovascular diseases and healthy subjects. We included 40 patients and 10 healthy subjects undergoing cardiac magnetic resonance and echocardiographic examination for left ventricular volumetric assessment. We studied patients with heart failure and reduced ejection fraction (n = 10), acute perimyocarditis (n = 10), aortic valve stenosis (n = 10), and previous heart transplantation (n = 10) by global longitudinal (GLS), radial (GRS) and circumferential strain (GCS). Myocardial deformation analysis by FT-CMR was feasible in all but one participant. While GLS, GRS and GCS measured by FT-CMR correlated overall with STE (r = 0.74 and p < 0.001, r = 0.58 and p < 0.001, and r = 0.76 and p < 0.001), the correlations were not consistent within subgroups. GLS was systematically lower, whereas GRS and GCS were higher by FT-CMR compared to STE (p = 0.04 and p < 0.0001). Inter- and intra-observer reproducibility were comparable for FT-CMR and STE overall and across subgroups. In conclusion, myocardial deformation can be evaluated using FT-CMR applied to routine cine-CMR images in patients with a variety of cardiovascular diseases. However, correlation between FT-CMR and STE was modest and agreement was not optimal due to systematic bias regarding GLS and GCS. Consequently, FT-CMR and STE should not be used interchangeably for myocardial strain evaluation.

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.

Background This study evaluated myocardial oxygen consumption (MVO 2 ) and myocardial external efficiency (MEE) in patients with cardiac amyloidosis (CA). Furthermore, we compared MEE and MVO 2 in subjects with light chain amyloidosis versus transthyretin (ATTR) amyloidosis. Methods and Results The study population comprised 40 subjects: 25 patients with confirmed CA and 15 control subjects. All subjects underwent an 11 C‐acetate positron emission tomography. Furthermore, the CA patients underwent comprehensive echocardiography and right heart catheterization during a symptom‐limited, semi‐supine exercise test. MEE was calculated from 11 C‐acetate positron emission tomography as the ratio of left ventricular (LV) stroke work and the energy equivalent of MVO 2 . Myocardial work efficiency was calculated as echocardiography‐derived work pressure product divided by three‐dimensional LV mass. CA patients had significantly lower LV‐ejection fraction (54±13% versus 63±4%, P <0.05) and LV‐global longitudinal strain (LVGLS) (12±4% versus 19±2%, P <0.0001) and a more restrictive filling pattern (E/e′‐ratio 18 [12–25] versus 8 [7–9], P <0.0001) than controls. MEE was severely reduced (13±5% versus 22±5%, P <0.0001) whereas total MVO 2 was higher (18±6 mL/min versus 13±3 mL/min, P <0.01) in CA patients than controls. MEE decreased with increasing New York Heart Association symptom burden ( P <0.0001). We found a good relationship between MEE and peak exercise systolic performance (LVGLS: R 2 =0.60, P <0.0001; myocardial work efficiency: R 2 =0.48, P <0.0001; cardiac index: R 2 =0.52, P <0.0001) and between MEE and myocardial blood flow ( R 2 =0.44, P <0.0001). Conclusion Myocardial oxidative metabolism is disturbed in CA patients with increased total MVO 2 and reduced MEE. MEE correlated significantly with echocardiographic derived systolic parameters such as myocardial work efficiency and LVGLS that might be used as surrogate MEE markers.

Background. Myocardial external efficiency (MEE) is defined as the ratio of kinetic energy associated with cardiac work [forward cardiac output (FCO)*mean systemic pressure] and the chemical energy from oxygen consumed (MVO 2 ) by the left ventricular mass (LVM). We developed a fully automated method for estimating MEE based on a single 11 C-acetate PET scan without ECG-gating.Methods and Results. Ten healthy controls, 34 patients with aortic valve stenosis (AVS), and 20 patients with mitral valve regurgitation (MVR) were recruited in a dual-center study. MVO 2 was calculated using washout of 11 C -acetate activity. FCO and LVM were calculated automatically using dynamic PET and parametric image formation. FCO and LVM were also obtained using cardiac magnetic resonance (CMR) in all subjects. The correlation between MEE PET-CMR and MEE PET was high (r 5 0.85, P < 0.001) without significant bias. MEE PET was 23.6 ± 4.2% for controls and was lowered in AVS (17.2 ± 4.3%, P < 0.001) and in MVR (18.0 ± 5.2%, P 5 0.004). MEE PET was strongly associated with both NYHA class (P < 0.001) and the magnitude of valvular dysfunction (mean aortic gradient: P < 0.001, regurgitant fraction: P 5 0.009).Conclusion. A single 11 C-acetate PET yields accurate and automated MEE results on different scanners. MEE might provide an unbiased measurement of the phenotypic response to valvular disease. (J Nucl Cardiol 2018;25:1937-44.)

Although analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [(11)C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.

Non-invasive measurements of MEE using C-acetate PET are highly repeatable. A PET-only approach did not differ significantly from CMR/PET and might facilitate further clinical research due to lower costs and broader applicability.