The Role of Cardiovascular Magnetic Resonance Imaging in Heart Failure

Cardiovascular imaging is key for the assessment of patients with heart failure. Today, cardiovascular magnetic resonance imaging plays an established role in the assessment of patients with suspected and confirmed heart failure syndromes, in particular identifying aetiology. Its role in informing prognosis and guiding decisions around therapy are evolving. Key strengths include its accuracy; reproducibility; unrestricted field of view; lack of radiation; multiple abilities to characterise myocardial tissue, thrombus and scar; as well as unparalleled assessment of left and right ventricular volumes. T2* has an established role in the assessment and follow-up of iron overload cardiomyopathy and a role for T1 in specific therapies for cardiac amyloid and Anderson–Fabry disease is emerging

Metabolic remodelling in hypertrophied and failing myocardium: a review

The energy starvation hypothesis proposes that maladaptive metabolic remodelling antedates, initiates and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signalling could help identify the role metabolic remodelling plays within HF and conditions known to transition toward HF, including 'pathological' hypertrophy. In this review, we discuss metabolic phenotype and metabolic signalling 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 remodelling that centre around metabolic flexibility, capacity (reserve) and efficiency, rather than around particular substrate preferences or transcriptomic profiles. We show that maladaptive metabolic remodelling takes multiple forms across multiple energy-handling domains. We suggest that lack of metabolic flexibility and reserve (substrate, oxidative and phosphotransfer) represent a final common denominator ultimately compromising efficiency and contractile reserve in stressful contexts

Metabolic remodelling in hypertrophied and failing myocardium: a review

The energy starvation hypothesis proposes that maladaptive metabolic remodelling antedates, initiates and maintains adverse contractile dysfunction in heart failure (HF). Better understanding of the cardiac metabolic phenotype and metabolic signalling could help identify the role metabolic remodelling plays within HF and conditions known to transition toward HF, including 'pathological' hypertrophy. In this review, we discuss metabolic phenotype and metabolic signalling 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 remodelling that centre around metabolic flexibility, capacity (reserve) and efficiency, rather than around particular substrate preferences or transcriptomic profiles. We show that maladaptive metabolic remodelling takes multiple forms across multiple energy-handling domains. We suggest that lack of metabolic flexibility and reserve (substrate, oxidative and phosphotransfer) represent a final common denominator ultimately compromising efficiency and contractile reserve in stressful contexts

Non-invasive investigation of myocardial energetics in cardiac disease using 31P magnetic resonance spectroscopy

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

Myocardial energetics in obesity: Enhanced ATP delivery through creatine kinase with blunted stress response

Background: Obesity is strongly associated with exercise intolerance and the development of heart failure. Whereas myocardial energetics and diastolic function are impaired in obesity, systolic function is usually preserved. This suggests that the rate of ATP delivery is maintained, but this has never been explored in human obesity. We hypothesized that ATP transfer rate through creatine kinase (CK) (kfCKrest) would be increased, compensating for depleted energy stores (phosphocreatine/ATP), but potentially limiting greater ATP delivery during increased workload. We hypothesized that these changes would normalize with weight loss. Methods: We recruited 80 volunteers (35 controls [body mass index 24±3 kg/m2], 45 obese [body mass index 35±5 kg/m2]) without coexisting cardiovascular disease. Participants underwent body composition analysis, magnetic resonance imaging of abdominal, liver, and myocardial fat content, left ventricular function, and 31P magnetic resonance spectroscopy to assess phosphocreatine/ATP and CK kinetics, at rest and during dobutamine stress. Obese volunteers were assigned to a dietary weight loss intervention, before reexamination. Results: At rest, although myocardial phosphocreatine/ATP was 14% lower in obesity (1.9±0.3 versus 2.2±0.2, P Conclusions: In the obese resting heart, the myocardial CK reaction rate is increased, maintaining ATP delivery despite reduced phosphocreatine/ATP. During increased workload, although the nonobese heart increases ATP delivery through CK, the obese heart does not; this is associated with reduced systolic augmentation and exercise tolerance. Weight loss reverses these energetic changes. This highlights myocardial energy delivery through CK as a potential therapeutic target to improve symptoms in obesity-related heart disease, and a fascinating modifiable pathway involved in the progression to heart failure, as well.</p

Very low calorie diets are associated with transient ventricular impairment before reversal of diastolic dysfunction in obesity

Objectives Very low calorie diets (VLCDs) are effective at clearing hepatic steatosis and improving insulin sensitivity. Whilst long-term weight loss is beneficial to the cardiovascular system, the acute elevation in fatty acids during caloric restriction is potentially detrimental to cardiac metabolism and function. We sought to investigate any cardiovascular changes occurring over the course of a modern VLCD regime, alongside the expected peripheral metabolic improvements. Methods 25 obese volunteers (BMI 36.8 ± 5.8 kg/m2) underwent magnetic resonance imaging, echocardiography, metabolic profiling, and bio-impedance analysis before 1 and 8 weeks following a VLCD (800 kcal/day). Results were compared to 15 age- and sex-matched controls. Results After 1 week of VLCD, despite only modest weight loss, significant drops occurred in liver fat and insulin resistance (HOMA-IR; by 14–50%, all p and#60; 0.01). In contrast, myocardial triglyceride content (MTGC) increased (by 48%, p = 0.030), and was associated with deterioration in both systolic (LVEF by 4%, p = 0.041) and diastolic function (e/e′ 8.6 ± 1.4 to 9.4 ± 1.7, p = 0.019). Aortic stiffness also increased by 35% (p = 0.015). At 8 weeks, liver steatosis and visceral fat were lower than baseline (by 20–55%, p and#60; 0.001), and peripheral metabolic improvements continued. MTGC also fell to below baseline (1.5 ± 0.6 vs 2.1 ± 1%, p = 0.05) with improved myocardial function (e/e′ 8.6 ± 1.4 to 7.5 ± 1.5, p = 0.003). Conclusions Whilst VLCDs result in dramatic improvements in insulin resistance, they are associated with transient but significant cardiovascular functional decline, which may have an impact on those with the coexisting cardiac disease. However, after 8 weeks, the diet was associated with normalisation of cardiac function, suggesting they may form a potential therapeutic intervention for diastolic dysfunction in obesity and diabetes