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

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

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

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

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

The impact of methodological and temporal variation on infarct size quantification in acute myocardial infarction with late enhancement CMR

Funding This project was funded by a grant from the MRC(UK).Peer reviewedPublisher PD

Ventricular-vascular coupling in heart failure with preserved ejection fraction: A systematic review and meta-analysis

Background: Heart failure with preserved ejection fraction (HFpEF) is a complex disease underlined by impaired ventricular-vascular coupling (VVC). Objectives: To evaluate the VVC ratio in HFpEF patients at rest and during exercise and compare it to the healthy and heart failure with reduced ejection fraction (HFrEF) controls. Methods: PubMed and EMBASE databases were searched for trials that matched the inclusion criteria. Random-effects models were used to estimate the pooled mean difference with 95% confidence interval using Open Meta[Analyst] software. Results: A total of 13 trials met the inclusion criteria. Although VVC ratio was comparable between HFpEF and healthy controls at rest, it was significantly lower in HFrEF compared to HFpEF. During exercise, there was a significant decline in VVC ratio in HFpEF (-0.119, 95% CI (-0.183 to -0.055), p<0.001). Conclusion: VVC ratio, although ‘preserved’ at rest in HFpEF patients, was overtly impaired during exercise highlighting the importance of dynamic testing

Radial dyssynchrony assessed by cardiovascular magnetic resonance in relation to left ventricular function, myocardial scarring and QRS duration in patients with heart failure

Radial dyssynchrony is almost universal in patients with heart failure. This vies against the notion that a lack of response to CRT is related to a lack of dyssynchrony

Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy

We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a–j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4′,4′-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer

MOLLI T1 mapping versus T2 W-SPAIR at 3T : myocardial area at risk measurements and the influence of microvascular obstruction

Funding Information: This study was supported by a Medical Research Council (UK) grant, as a sub-study of Nitrites in Acute Myocardial Infarction, NCT01388504.Peer reviewe