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Background Altered ventricular-vascular coupling (VVC) is a key mechanism in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Arterial elastance (Ea), an integral component of VVC, has a static and pulsatile component which could be affected by the physical differences in men and women. We hypothesised differences in height may explain some of the sex-differences in pulsatile load, which has been linked to the development of HFpEF. Methods We retrospectively analysed echocardiographic data from a large prospective community study of people aged >60 years. Height, arterial elastance (Ea), the pulsatile and static components of Ea (total arterial compliance (TAC) and systemic vascular resistance (SVR)), were calculated and compared between the sexes and across three groups: HFpEF, hypertensive (HTN) controls, and healthy controls. Results There were 142 HFpEF patients (73±7 years, 74% female), 725 HTN controls (70±7 years, 49% female) and 205 healthy controls (67±5 years, 59% female) (Table 1). There was a significant correlation between TAC and height in the participants as a group (r=0.218, p Height was only an independent predictor of TAC when controlling for sex in HTN controls (β=0.11, p=0.047). Women were shorter than men (p Conclusions Women have significantly higher Ea and lower TAC. In both men and women with hypertension, a taller stature was independently associated with reduced pulsatile arterial load and Ea. Women are more susceptible to the deleterious effects of low TAC, which may partly explain the sex differences in the prevalence of HFpEF. Conflict of Interest None

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 Conclusion VVC ratio, although ‘preserved’ at rest in HFpEF patients, was overtly impaired during exercise highlighting the importance of dynamic testing.

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.

BACKGROUND: Inorganic nitrate, abundant in leafy green vegetables and beetroot, is thought to have protective health benefits. Adherence to a Mediterranean diet reduces the incidence and severity of coronary artery disease, whereas supplementation with nitrate can improve submaximal exercise performance. Once ingested, oral commensal bacteria may reduce nitrate to nitrite, which may subsequently be reduced to nitric oxide during conditions of hypoxia and in the presence of "nitrite reductases" such as heme- and molybdenum-containing enzymes.OBJECTIVE: We aimed to explore the putative effects of inorganic nitrate and nitrite on mitochondrial function in skeletal muscle.METHODS: Mice were subjected to a nitrate/nitrite-depleted diet for 2 wk, then supplemented with sodium nitrate, sodium nitrite, or sodium chloride (1 g/L) in drinking water ad libitum for 7 d before killing. Skeletal muscle mitochondrial function and expression of uncoupling protein (UCP) 3, ADP/ATP carrier protein (AAC) 1 and AAC2, and pyruvate dehydrogenase (PDH) were assessed by respirometry and Western blotting. Studies were also undertaken in human skeletal muscle biopsies from a cohort of coronary artery bypass graft patients treated with either sodium nitrite (30-min infusion of 10 μmol/min) or vehicle [0.9% (wt:vol) saline] 24 h before surgery.RESULTS: Neither sodium nitrate nor sodium nitrite supplementation altered mitochondrial coupling efficiency in murine skeletal muscle, and expression of UCP3, AAC1, or AAC2, and PDH phosphorylation status did not differ between the nitrite and saline groups. Similar results were observed in human samples.CONCLUSIONS: Sodium nitrite failed to improve mitochondrial metabolic efficiency, rendering this mechanism implausible for the purported exercise benefits of dietary nitrate supplementation. This trial was registered at clinicaltrials.gov as NCT04001283.

Background Exercise‐induced pulmonary hypertension is common in heart failure with preserved ejection fraction ( HF p EF ). We hypothesized that this could result in pericardial constraint and diastolic ventricular interaction in some patients during exercise. Methods and Results Contrast stress echocardiography was performed in 30 HF p EF patients, 17 hypertensive controls, and 17 normotensive controls (healthy). Cardiac volumes, and normalized radius of curvature ( NRC ) of the interventricular septum at end‐diastole and end‐systole, were measured at rest and peak‐exercise, and compared between the groups. The septum was circular at rest in all 3 groups at end‐diastole. At peak‐exercise, end‐systolic NRC increased to 1.47±0.05 ( P HF p EF patients, confirming development of pulmonary hypertension. End‐diastolic NRC also increased to 1.54±0.07 ( P HF p EF patients, indicating septal flattening, and this correlated significantly with end‐systolic NRC (ρ=0.51, P =0.007). In hypertensive controls and healthy controls, peak‐exercise end‐systolic NRC increased, but this was significantly less than observed in HF p EF patients ( HF p EF , P =0.02 versus hypertensive controls; P NRC in both groups (hypertensive controls, +0.17±0.05, P =0.38; healthy, +0.06±0.03, P =0.93). In HF p EF patients, peak‐exercise end‐diastolic NRC also negatively correlated ( r =−0.40, P r =−0.36, P =0.08). Conclusions Exercise pulmonary hypertension causes substantial diastolic ventricular interaction on exercise in some patients with HF p EF , and this restriction to left ventricular filling by the right ventricle exacerbates the pre‐existing impaired Frank‐Starling response in these patients.

Traditional risk factors for cardiovascular disease (CVD) have been thoroughly investigated. We aimed to investigate the impact of comorbid cardiovascular risk factors and diseases on length of stay (LOS) and mortality in patients presenting with acute coronary syndromes (ACS).We examined prevalence of CVD, LOS and mortality from 25,287 consecutive admissions for ACS from seven hospitals across North West England between 2000 and 2013 using the ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) protocol using ICD-10 and OPCS-4 coding systems.Mean LOS was 7.0days and there were 9653 (38.2%) deaths in the ACS cohort over the 13-year period. Hypertension and hyperlipidaemia were associated with decreased LOS (6.95 and 4.8days respectively, P0.001) and mortality (36.8% and 19.4% respectively, P0.001), as was angina pectoris (5.4days and 33.5%, P0.001). Type 2 diabetes was associated with increased LOS and mortality (7.8days, P0.05; 44.4%, P0.001), whereas type 1 diabetes was associated with increased mortality only (7.0days, P=0.42; 41.3%, P0.001). Other concomitant CVD was associated with an increased LOS and mortality: peripheral vascular disease (8.6days, P0.05; 53%, P0.001), atrial fibrillation (10.9days, P0.001; 63.5%, P0.001), cerebrovascular disease (15.9days, P0.001; 76%, P0.001), heart failure (11days, P0.001; 69.9%, P0.001), and ischaemic heart disease (6.7days, P0.001; 38.7%, P0.05).CVD risk factors have a significant and varied impact on LOS and mortality in patients with ACS and it may be inappropriate to group them when assessing in-hospital risk. These factors should be used to identify patients at an increased risk of prolonged admissions and death post-ACS, and services should be directed accordingly.

Background Classical risk factors for cardiovascular disease such as hypertension and diabetes, and their association with myocardial infarction (MI), have been thoroughly investigated. However, more research is needed to investigate the correlation between these risk factors and the impact on length of stay (LOS) and mortality in patients presenting with MI, which was the aim of this study. Methods We reviewed anonymous patient data including demographics, LOS, prevalence of cardiovascular comorbidities, and mortality during 25,287 consecutive admissions for MI from seven hospitals in the North West of England between 1 January 2000 and 31 March 2013. The ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) protocol, using ICD-10 and OPCS-4 coding systems, was used to track patient data. LOS and mortality of MI patients with and without cardiovascular comorbidities was compared by multinomial logistic regression. P values Results Of 25,287 patients admitted with MI over the study period, mean (± SD) age was 66.6 ± 14.3 and 64.2% were male. The mean (± SD) LOS was 7.0 ± 16.2 days and there were a total of 9,653 (38.2%) deaths. The classical cardiovascular risk factors hypertension and hyperlipidaemia were associated with a decreased LOS and mortality (7.0 and 4.8 days respectively, P Conclusion Cardiovascular risk factors and concomitant disease have a significant impact on LOS and mortality in patients presenting with MI. The presence of these diseases should be used to identify patients at an increased risk of prolonged admissions and death post MI, and services should be directed accordingly.

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.

In the developed world, there has been a substantial increase over several decades in the prevalence of congestive heart failure (CHF), partly as a result of demographic changes. Overall, 1–2% of the adult population has CHF and this increases to ≥10% in the over 70s age group.1 However, hospitalization rates due to CHF are falling,2 and length of hospital stay and in-hospital mortality have also fallen.3 It could be argued that effective outpatient management of CHF through dedicated heart failure clinics, specialist nurses, and general practitioners has played a key role in these positive trends. However, given the significant patient morbidity and the inpatient costs associated with CHF, methods to reduce hospital readmission rates are imperative to alleviate an already overstretched system. Rahimi and colleagues4 present the development and assessment of an easy-to-use, android-based monitoring system to empower patients and reduce readmission rates in a cohort from the Seamless User-centred Proactive Provision Of Risk-stratified Treatment for Heart Failure (SUPPORT-HF) study. Patients were provided with internet-enabled tablets that were connected to commercially available sensors to record blood pressure, heart rate, and weight, and provide alerts to patients to see their doctor or healthcare provider when physiological parameters were perturbed. Although this particular self-management study focused primarily on patient uptake of monitoring … [↵][1]*Corresponding author. Tel: +44 1603 592376, Fax: +44 1603 593752, Email: m.frenneaux{at}uea.ac.uk [1]: #xref-corresp-1-1