The study of myocardial metabolism and its role in the pathophysiology of early diabetic cardiomyopathy

The human myocardium is a metabolic omnivore and utilises fatty acids, glucose, ketones, amino acids and lactate to produce energy. Altered metabolism results in cardiac muscle dysfunction and can play a potentially significant role in development of heart failure. Metabolic modulators like Perhexiline are potentially significant new treatments in the management of heart failure and coronary artery disease. Diabetes is a metabolic disorder that results in altered high energy phosphate kinetics in the myocardium. We demonstrate that microvascular disease plays little role in the development of impaired cardiac energetics in young patients with uncomplicated type 1 diabetes. We have shown an increase in left ventricular torsion in these patients with normal ejection fraction. Coronary microvascular disease and rotational deformation delay play a significant role in the development of increased torsion in these individuals which counteracts the early diastolic dysfunction. Furthermore the left atrial contribution to left ventricular filling is increased in these individuals. We demonstrate that Perhexiline has a differential action on insulin sensitivity in subjects with and without diabetes. It also increased plasma ketones and triglycerides in these patients. Finally we demonstrate that Perhexiline can be safely used and provides good relief of symptoms when used clinically in subjects with refractory angina and heart failure

The pathophysiology of heart failure with preserved ejection fraction: from molecular mechanisms to exercise haemodynamics

The pathophysiology of HfpEF is complex. In this review we discuss the molecular aspects of HfpEF as well as the profoundly disturbed haemodynamics with particular focus on exercise haemodynamic abnormalities

(31)P magnetic resonance spectroscopy to measure in vivo cardiac energetics in normal myocardium and hypertrophic cardiomyopathy:Experiences at 3T

(31)P magnetic resonance spectroscopy (MRS) allows measurement of in vivo high-energy phosphate kinetics in the myocardium. While traditionally (31)P cardiac spectroscopy is performed at 1.5T, cardiac MRS at higher field strength can theoretically increase signal to noise ratio (SNR) and spectral resolution therefore improving sensitivity and specificity of the cardiac spectra. The reproducibility and feasibility of performing cardiac spectroscopy at 3T is presented here in this study in healthy volunteers and patients with hypertrophic cardiomyopathy

Left ventricular torsion and strain patterns in heart failure with normal ejection fraction are similar to age-related changes

We used speckle tracking echocardiography (STE) to make a comparison between the effects of ageing and of heart failure with normal ejection fraction (HfnEF) on left ventricular (LV) torsion and strain patterns

Potential of metabolic agents as adjunct therapies in heart failure

Heart failure continues to have a significant morbidity and mortality rate despite several recent advances in treatment such as additional neurohumoral blockades and cardiac resynchronization therapy. There is emerging evidence that, irrespective of etiology, heart failure is associated with an energetic disorder and that this may contribute to the pathogenesis of the syndrome. Recently, a number of studies have suggested that some metabolic agents may have potential as adjunctive therapy in patients with heart failure. These agents cause a shift of myocardial-substrate utilization away from free fatty acids toward glucose. Free fatty acid utilization consumes more oxygen to generate an equivalent amount of energy compared with glucose. Some of these agents are also effective antianginals, presumably by reducing the myocardial oxygen requirement. In this review we will discuss some of the current issues and progresses relating to metabolic manipulation in heart failure

Insights into how to conduct a clinical trial in the UK

New researchers may find starting and conducting clinical studies in the UK complicated and time-consuming. In this article, we describe our collective experiences and provide some pointers on how to navigate through the various committees and regulatory bodies. The article is intended to aid junior researchers in understanding the study process and to provide them with some insight on how to get through this complex system successfully

Myocardial contractile inefficiency and dyssynchrony in heart failure with preserved ejection fraction and narrow QRS complex

Using speckle-tracking imaging (STI), the aims of this study were to assess dyssynchrony and quantify the myocardial energy wasted by contractility in delayed segments by determining the longitudinal strain delay index (LSDi) in patients with heart failure with preserved ejection fraction (HFpEF)

Increased atrial contribution to left ventricular filling compensates for impaired early filling during exercise in heart failure with preserved ejection fraction

The role of left atrial (LA) function on exercise remains poorly understood in heart failure with preserved ejection fraction (HfpEF) despite its key role in optimizing left ventricular (LV) diastolic function. We used resting and exercise radionuclide ventriculography to investigate the role of LA function in the pathophysiology of HfpEF

Impaired heart rate recovery and chronotropic incompetence in patients with heart failure with preserved ejection fraction

This study assessed the chronotropic response to exercise and heart rate (HR) recovery after exercise in a carefully phenotyped group of patients with heart failure with preserved left ventricular ejection fraction (HfpEF) and a control group of similar age and gender distribution