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Aims We sought to determine if myocardial energetics could distinguish obesity cardiomyopathy as a distinct entity from dilated cardiomyopathy. Methods and results Sixteen normal weight participants with dilated cardiomyopathy (DCMNW), and 27 with DCM and obesity (DCMOB), were compared to 26 normal weight controls (CTLNW). All underwent cardiac magnetic resonance imaging and 31P spectroscopy to assess function and energetics. Nineteen DCMOB underwent repeat assessment after a dietary weight loss intervention. Adenosine triphosphate (ATP) delivery through creatine kinase (CK flux) was 55% lower in DCMNW than in CTLNW (P = 0.004), correlating with left ventricular ejection fraction (LVEF, r = 0.4, P = 0.015). In contrast, despite similar LVEF (DCMOB 41 ± 7%, DCMNW 38 ± 6%, P = 0.14), CK flux was two-fold higher in DCMOB (P < 0.001), due to higher rate through CK [median k f 0.21 (0.14) vs. 0.11 (0.12) s−1, P = 0.002]. During increased workload, the CTLNW heart increased CK flux by 97% (P < 0.001). In contrast, CK flux was unchanged in DCMNW and fell in DCMOB (by >50%, P < 0.001). Intentional weight loss was associated with positive left ventricular remodelling, with reduced left ventricular end-diastolic volume (by 8%, P < 0.001) and a change in LVEF (40 ± 9% vs. 45 ± 10%, P = 0.002). This occurred alongside a fall in ATP delivery rate with weight loss (by 7%, P = 0.049). Conclusions In normal weight, DCM is associated with reduced resting ATP delivery. In obese DCM, ATP demand through CK is greater, suggesting reduced efficiency of energy utilization. Dietary weight loss is associated with significant improvement in myocardial contractility, and a fall in ATP delivery, suggesting improved metabolic efficiency. This highlights distinct energetic pathways in obesity cardiomyopathy, which are both different from dilated cardiomyopathy, and may be reversible with weight loss. [ABSTRACT FROM AUTHOR]

Cardiac proton spectroscopy (1H‐MRS) is widely used to quantify lipids. Other metabolites (e.g. creatine and choline) are clinically relevant but more challenging to quantify because of their low concentrations (approximately 10 mmol/L) and because of cardiac motion. To quantify cardiac creatine and choline, we added water‐suppression cycling (WSC) to two single‐voxel spectroscopy sequences (STEAM and PRESS). WSC introduces controlled residual water signals that alternate between positive and negative phases from transient to transient, enabling robust phase and frequency correction. Moreover, a particular weighted sum of transients eliminates residual water signals without baseline distortion. We compared WSC and the vendor's standard 'WET' water suppression in phantoms. Next, we tested repeatability in 10 volunteers (seven males, three females; age 29.3 ± 4.0 years; body mass index [BMI] 23.7 ± 4.1 kg/m2). Fat fraction, creatine concentration and choline concentration when quantified by STEAM‐WET were 0.30% ± 0.11%, 29.6 ± 7.0 μmol/g and 7.9 ± 6.7 μmol/g, respectively; and when quantified by PRESS‐WSC they were 0.30% ± 0.15%, 31.5 ± 3.1 μmol/g and 8.3 ± 4.4 μmol/g, respectively. Compared with STEAM‐WET, PRESS‐WSC gave spectra whose fitting quality expressed by Cramér‐Rao lower bounds improved by 26% for creatine and 32% for choline. Repeatability of metabolite concentration measurements improved by 72% for creatine and 40% for choline. We also compared STEAM‐WET and PRESS‐WSC in 13 patients with severe symptomatic aortic or mitral stenosis indicated for valve replacement surgery (10 males, three females; age 75.9 ± 6.3 years; BMI 27.4 ± 4.3 kg/m2). Spectra were of analysable quality in eight patients for STEAM‐WET, and in nine for PRESS‐WSC. We observed comparable lipid concentrations with those in healthy volunteers, significantly reduced creatine concentrations, and a trend towards decreased choline concentrations. We conclude that PRESS‐WSC offers improved performance and reproducibility for the quantification of cardiac lipids, creatine and choline concentrations in healthy volunteers at 3 T. It also offers improved performance compared with STEAM‐WET for detecting altered creatine and choline concentrations in patients with valve disease. [ABSTRACT FROM AUTHOR]

Purpose: Phosphorus spectroscopy (31P‐MRS) is a proven method to probe cardiac energetics. Studies typically report the phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. We focus on another 31P signal: inorganic phosphate (Pi), whose chemical shift allows computation of myocardial pH, with Pi/PCr providing additional insight into cardiac energetics. Pi is often obscured by signals from blood 2,3‐diphosphoglycerate (2,3‐DPG). We introduce a method to quantify Pi in 14 min without hindrance from 2,3‐DPG. Methods: Using a 31P stimulated echo acquisition mode (STEAM) sequence at 7 Tesla that inherently suppresses signal from 2,3‐DPG, the Pi peak was cleanly resolved. Resting state UTE‐chemical shift imaging (PCr/ATP) and STEAM 31P‐MRS (Pi/PCr, pH) were undertaken in 23 healthy controls; pH and Pi/PCr were subsequently recorded during dobutamine infusion. Results: We achieved a clean Pi signal both at rest and stress with good 2,3‐DPG suppression. Repeatability coefficient (8 subjects) for Pi/PCr was 0.036 and 0.12 for pH. We report myocardial Pi/PCr and pH at rest and during catecholamine stress in healthy controls. Pi/PCr was maintained during stress (0.098 ± 0.031 [rest] vs. 0.098 ± 0.031 [stress] P =.95); similarly, pH did not change (7.09 ± 0.07 [rest] vs. 7.08 ± 0.11 [stress] P =.81). Feasibility for patient studies was subsequently successfully demonstrated in a patient with cardiomyopathy. Conclusion: We introduced a method that can resolve Pi using 7 Tesla STEAM 31P‐MRS. We demonstrate the stability of Pi/PCr and myocardial pH in volunteers at rest and during catecholamine stress. This protocol is feasible in patients and potentially of use for studying pathological myocardial energetics. [ABSTRACT FROM AUTHOR]

A 31-year-old woman underwent elective hysteroscopy and laparoscopy for investigation of primary infertility. The procedure was abandoned owing to intraoperative desaturation and reduced right-sided chest movement. Postoperative chest x-ray showed an opacified right hemithorax with tracheal deviation to the left. Retrospectively on direct questioning, she admitted to dry cough, mild dyspnoea and significant weight loss. Diagnostic thoracocentesis and contrast CT scan confirmed heavily blood-stained exudative pleural effusion but were otherwise non-diagnostic. After chest drain insertion, 4.6 litre drained but a hydropneumothorax developed upon drain removal, with no improvement on repeat drain insertion. Right video-assisted thoracic surgery was performed, converted to thoracotomy, with repair of diaphragmatic fenestrations, pleurectomy and decortication of trapped lung undertaken. Histological examination of samples of pleura and lung cortex was pathognomic of endometriosis. She was started on norethisterone with no recurrence to date. [ABSTRACT FROM AUTHOR]

Introduction: Obesity and heart failure with reduced ejection fraction (HFrEF) commonly coexist. However, the parallel observations that obesity is associated with improved survival in HFrEF, and that unintentional weight loss is a poor prognostic sign, are conflicting. Therefore, evidence is lacking regarding the role of intentional weight loss in HFrEF. In this study, we sought to investigate the impact of intentional weight loss in obese HFrEF on metabolic status, cardiac function and exercise capacity. Methods: 37 patients with stable idiopathic dilated cardiomyopathy (BMI 35±5kg/m2, LVEF 41±8%), and 23 matched controls (BMI 35±5kg/m2, LVEF 65±4%) underwent body composition analysis, quantification of abdominal visceral and hepatic fat, cardiac MR for geometry and systolic function, cardiopulmonary exercise testing and six minute walk test. All undertook a 12 month dietary intervention (1500kcal/day) before reassessment. Results: In obese controls, weight loss (-10±8%) led to a reduction in LV end diastolic volume (EDV by 6±4%, p=0.001) and LV mass (by 12±7%, p=0.001). In HFrEF, intentional weight loss (-7±6%) also led to reductions in LV EDV (by 8±10%, p=0.010), and LV mass (by 6±9%, p=0.047) and a significant improvement in LV systolic function (absolute LVEF +8±6%, p<0.001, figure 1 and table). Exercise capacity in HFrEF was maintained in weight loss (six minute walk test distance increase by 28±37m, p=0.057). Conclusion: Here we demonstrate in a prospective study that intentional weight loss is associated with substantial improvements in LV systolic function and prevents decline in exercise capacity. This suggests that weight loss may be an effective therapeutic strategy in HFrEF. [ABSTRACT FROM AUTHOR]

Purpose: Phosphorus spectroscopy ( 31 P-MRS) is a proven method to probe cardiac energetics. Studies typically report the phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio. We focus on another 31 P signal: inorganic phosphate (Pi), whose chemical shift allows computation of myocardial pH, with Pi/PCr providing additional insight into cardiac energetics. Pi is often obscured by signals from blood 2,3-diphosphoglycerate (2,3-DPG). We introduce a method to quantify Pi in 14 min without hindrance from 2,3-DPG., Methods: Using a 31 P stimulated echo acquisition mode (STEAM) sequence at 7 Tesla that inherently suppresses signal from 2,3-DPG, the Pi peak was cleanly resolved. Resting state UTE-chemical shift imaging (PCr/ATP) and STEAM 31 P-MRS (Pi/PCr, pH) were undertaken in 23 healthy controls; pH and Pi/PCr were subsequently recorded during dobutamine infusion., Results: We achieved a clean Pi signal both at rest and stress with good 2,3-DPG suppression. Repeatability coefficient (8 subjects) for Pi/PCr was 0.036 and 0.12 for pH. We report myocardial Pi/PCr and pH at rest and during catecholamine stress in healthy controls. Pi/PCr was maintained during stress (0.098 ± 0.031 [rest] vs. 0.098 ± 0.031 [stress] P = .95); similarly, pH did not change (7.09 ± 0.07 [rest] vs. 7.08 ± 0.11 [stress] P = .81). Feasibility for patient studies was subsequently successfully demonstrated in a patient with cardiomyopathy., Conclusion: We introduced a method that can resolve Pi using 7 Tesla STEAM 31 P-MRS. We demonstrate the stability of Pi/PCr and myocardial pH in volunteers at rest and during catecholamine stress. This protocol is feasible in patients and potentially of use for studying pathological myocardial energetics., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Cardiac metabolism and function are intrinsically linked. High-energy phosphates occupy a central and obligate position in cardiac metabolism, coupling oxygen and substrate fuel delivery to the myocardium with external work. This insight underlies the widespread clinical use of ischaemia testing. However, other deficits in high-energy phosphate metabolism (not secondary to supply-demand mismatch of oxygen and substrate fuels) may also be documented, and are of particular interest when found in the context of structural heart disease. This review introduces the scope of deficits in high-energy phosphate metabolism that may be observed in the myocardium, how to assess for them, and how they might be interpreted., Competing Interests: Conflicts of Interests: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/cdt-20-275). The series “The use of advanced cardiac MRI in heart failure and cardiac hypertrophy” was commissioned by the editorial office without any funding or sponsorship. AJML and OJR served as the unpaid Guest Editors of the series. AJML reports other from Bayer, personal fees from Boehringer Ingelheim, outside the submitted work. SN reports grants from British Heart Foundation, during the conduct of the study; grants from Cytokinetics, personal fees from Cytokinetics, personal fees from Pfizer, grants from Boehringer Ingelheim, outside the submitted work. MAP reports grants from British Heart Foundation No. FS/15/80/31803, outside the submitted work. The other authors have no other conflicts of interest to declare., (2020 Cardiovascular Diagnosis and Therapy. All rights reserved.)

The energy starvation hypothesis proposes that maladaptive metabolic remodeling antedates, initiates, and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signaling could help identify the role metabolic remodeling plays within HF and the conditions known to transition toward HF, including "pathological" hypertrophy. In this review, we discuss metabolic phenotype and metabolic signaling in the contexts of pathological hypertrophy and HF. We discuss the significance of alterations in energy supply (substrate utilization, oxidative capacity, and phosphotransfer) and energy sensing using observations from human and animal disease models and models of manipulated energy supply/sensing. We aim to provide ways of thinking about metabolic remodeling that center around metabolic flexibility, capacity (reserve), and efficiency rather than around particular substrate preferences or transcriptomic profiles. We show that maladaptive metabolic remodeling takes multiple forms across multiple energy-handling domains. We suggest that lack of metabolic flexibility and reserve (substrate, oxidative, and phosphotransfer) represents a final common denominator ultimately compromising efficiency and contractile reserve in stressful contexts., (Copyright © 2017 the American Physiological Society.)