Dietary nitrate reduces skeletal muscle oxygenation response to physical exercise : a quantitative muscle functional MRI study

© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.Peer reviewedPublisher PD

Healthcare professional’s guide to cardiopulmonary exercise testing

Cardiopulmonary exercise testing (CPEX) is a valuable clinical tool that has proven indications within the fields of cardiovascular, respiratory and pre-operative medical care. Validated uses include investigation of the underlying mechanism in patients with breathlessness, monitoring functional status in patients with known cardiovascular disease and pre-operative functional state assessment. An understanding of the underlying physiology of exercise, and the perturbations associated with pathological states, is essential for healthcare professionals to provide optimal patient care. Healthcare professionals may find performing CPEX to be daunting, yet this is often due to a lack of local expertise and guidance with testing. We outline the indications for CPEX within the clinical setting, present a typical protocol that is easy to implement, explain the key underlying physiological changes assessed by CPEX, and review the evidence behind its use in routine clinical practice. There is mounting evidence for the use of CPEX clinically, and an ever-growing utilisation of the test within research fields; a sound knowledge of CPEX is essential for healthcare professionals involved in routine patient care

The pathophysiology of diastolic heart failure

Whilst resting disturbances of both diastolic and long-axis systolic function are observed in patients with heart failure who have normal left ventricular ejection fraction, recent evidence suggests that dynamic disturbances in cardiac function occur during exercise. A paradoxical slowing of left ventricular active relaxation during exercise limits cardiac filling and therefore stroke volume and appears to be due to the combination of cardiac energetic impairment and disturbed ventricular-vascular coupling

Dynamic changes of the extracellular matrix after acute tako-tsubo cardiomyopathy

Funding Tenovus Scotland. Grant number G13/10.Peer reviewedPublisher PD

Cardiac metabolism — A promising therapeutic target for heart failure

Both heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) are associated with high morbidity and mortality. Although many established pharmacological interventions exist for HFrEF, hospitalization and death rates remain high, and for those with HFpEF (approximately half of all heart failure patients), there are no effective therapies. Recently, the role of impaired cardiac energetic status in heart failure has gained increasing recognition with the identification of reduced capacity for both fatty acid and carbohydrate oxidation, impaired function of the electron transport chain, reduced capacity to transfer ATP to the cytosol, and inefficient utilization of the energy produced. These nodes in the genesis of cardiac energetic impairment provide potential therapeutic targets, and there is promising data from recent experimental and early-phase clinical studies evaluating modulators such as carnitine palmitoyltransferase 1 inhibitors, partial fatty acid oxidation inhibitors and mitochondrial-targeted antioxidants. Metabolic modulation may provide significant symptomatic and prognostic benefit for patients suffering from heart failure above and beyond guideline-directed therapy, but further clinical trials are needed

Modification of myocardial substrate utilisation: a new therapeutic paradigm in cardiovascular disease

ABSTRACT Therapies that aim to modify cardiac substrate utilisation are designed to increase metabolic efficiency. Although the main energy supply for the heart is generally provided by the oxidation of fatty acids, the heart is a metabolic omnivore and able to consume glucose as well as lactate and amino acids in varying proportions. A shift from fatty acid oxidation to glucose oxidation leads to lower oxygen consumption per unit of ATP produced. This concept of reduced oxygen utilisation underlies the use of metabolic modulating agents to treat chronic stable angina. Furthermore, the model of an energystarved heart now forms the basis for our understanding of both ischaemic and non-ischaemic heart failure. Potential alterations in substrate utilisation and thus myocardial efficiency underlie the use of metabolic agents in heart failure. This is achieved by either promoting glucose or reducing the utilisation of fatty acids. Such a shift results in a relatively greater production of ATP per unit of oxygen consumed. With an ongoing demand for treatment options in ischaemic heart disease and a growing epidemic of heart failure, new treatment modalities beyond contemporary therapy need consideration

Reference values for mitral and tricuspid annular dimensions using two-dimensional echocardiography

Only limited data are available from which normal ranges of mitral annular (MA) and tricuspid annular (TA) dimensions have been established. Normative data are important to assist the echocardiographer in defining the mechanism of atrioventricular valve regurgitation and to inform surgical planning. This study was conceived to establish normal MA and TA dimensions. Consecutive healthy subjects over the age of 60 were randomly recruited from the community as part of a screening project within South Birmingham. MA and TA dimensions in end-systole and end-diastole were evaluated in the parasternal and apical acoustic windows views using transthoracic echocardiography. Gender (males (M) and females (F))-specific dimensions were then assessed. A total of 554 subjects were screened and 74 with pathology considered to have an effect on annular dimensions were excluded from analysis. The mean age of the remaining 480 subjects was 70±7 years and the majority were female (56%). Dimensions were larger in men than in women and greater at end-diastole than end-systole (both P<0.05). Mean MA diameters at end-systole in the parasternal long axis view (cm) were 3.44 cm (M) and 3.11 cm (F) and at end-diastole 3.15 cm (M) and 2.83 cm (F) respectively. Mean TA diameters (cm) at end-systole in the apical 4 chamber view were 2.84 (M) and 2.80 (F) and at end-diastole 3.15 (M) and 3.01 (F) respectively. The reference ranges derived from this study differ from current published standards and should help to improve distinction of normal from pathological findings, in identifying aetiology and defining the mechanism of regurgitation

Effect of selective heart rate slowing in heart failure with preserved ejection fraction

Background Heart failure with preserved ejection fraction (HFpEF) is associated with significant morbidity and mortality but is currently refractory to therapy. Despite limited evidence, heart rate reduction has been advocated, on the basis of physiological considerations, as a therapeutic strategy in HFpEF. We tested the hypothesis that heart rate reduction improves exercise capacity in HFpEF. Methods and Results We conducted a randomized, crossover study comparing selective heart rate reduction with the If blocker ivabradine at 7.5 mg twice daily versus placebo for 2 weeks each in 22 symptomatic patients with HFpEF who had objective evidence of exercise limitation (peak oxygen consumption at maximal exercise [GraphicO2 peak] <80% predicted for age and sex). The result was compared with 22 similarly treated matched asymptomatic hypertensive volunteers. The primary end point was the change in GraphicO2 peak. Secondary outcomes included tissue Doppler–derived E/e′ at echocardiography, plasma brain natriuretic peptide, and quality-of-life scores. Ivabradine significantly reduced peak heart rate compared with placebo in the HFpEF (107 versus 129 bpm; P<0.0001) and hypertensive (127 versus 145 bpm; P=0.003) cohorts. Ivabradine compared with placebo significantly worsened the change in GraphicO2 peak in the HFpEF cohort (-2.1 versus 0.9 mL·kg−1·min−1; P=0.003) and significantly reduced submaximal exercise capacity, as determined by the oxygen uptake efficiency slope. No significant effects on the secondary end points were discernable. Conclusion Our observations bring into question the value of heart rate reduction with ivabradine for improving symptoms in a HFpEF population characterized by exercise limitation

Hypoxic modulation of exogenous nitrite-induced vasodilation in humans

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