Aims:Myocardial response to stress echocardiography may be elicited physiologically, through exercise, or pharmacologically, often with dobutamine. Both have advantages but also limitations due to reduced exercise capacity or side-effects to stressor agent/lack of closeness to true pathophysiology of ischaemic cascade. We have combined low-dose dobutamine and exercise, creating a 'hybrid' protocol to utilize the advantages of both techniques and limit the drawbacks. The aim of the study was to evaluate its safety and feasibility. Methods and results:In the hybrid protocol, low-dose dobutamine infusion (up to 10 µg/kg/min) is enhanced by supine bicycle exercise at 3-min increments of workload of 25 W to achieve target heart rate (THR). We analysed safety and outcome data for all the patients who underwent this protocol from 2017 to 2022. Out of 835, 727 (87.1%) patients referred for evaluation of ischaemia underwent the hybrid protocol. The median age was 61 years old and 61% (442/727) were men. The median exercise time was 11 (9-13.5) min with a median maximum workload of 100 W (75-125). Out of 727, 670 (92.2%) achieved THR. Atropine was not used. Out of 727, 192 (26.4%) of studies were positive for ischaemia. Out of 122, 102 (83.6%) with positive stress who underwent invasive angiography had significant coronary disease. The incidence of complications was low: 1/727-severe arrhythmia, 5/727 (0.7%) developed a vasovagal episode, and 14/727 (1.9%) had a hypertensive response to exercise. Conclusion:Our findings suggest that this protocol is safe, feasible, and has a high success rate in achieving THR.

Sacubitril/valsartan is a first-in-class Angiotensin Receptor-Neprilysin inhibitor (ARNi) to be approved for the treatment of heart failure with reduced ejection fraction (HFrEF). The combination tablet has become a mainstay of treatment in the management of heart failure (HF) due to its composite inhibition of the neurohumoral system. There is growing support to show that sacubitril/valsartan may enhance glycaemic control through the augmentation of neprilysin substrates - in particular, glucagon-like peptide 1 (GLP-1). Given that HF and Diabetes Mellitus (DM) frequently coexist, with 44% of patients hospitalised with heart failure also having diabetes as a co-morbidity, it is plausible that sacubitril/valsartan may represent a novel way to address glucose intolerance in HF. However, the role of neprilysin in the degradation of GLP-1 raises important clinical considerations such as the risk of hypoglycaemia and potential drug-drug interactions in patients with and without concurrent DM. We review the current body of research addressing the effect of neprilysin inhibition on GLP-1 receptor signalling and discuss the implications for treatment of HF and DM.

We devised a medical education quality improvement (QI) project aimed at enhancing training in transthoracic echocardiography (TTE) for junior doctors at Harefield Hospital, Royal Brompton and Harefield NHS Foundation Trust. During the COVID-19 pandemic, junior doctors expressed a desire for further

We were presented with a 60-year-old SARS-CoV-2- (Covid-19) positive gentle-man who was transferred to our intensive care unit from a district general hospital. The patient was intubated and required mechanical ventilation prior to transfer for type 1 respiratory failure secondary to pneumonitis. His past medical history included hypertension and hypercholes-terolaemia. Admission blood tests dem-onstrated markedly elevated troponin I of 593 ng/L and C-reactive protein of 360 mg/L. D-dimer levels were elevated at 32 ng/L. Bedside echocardiogram showed a dilated right ventricle (base 45 mm, mid 42 mm) with severely impaired right ventricular

Background Phase analysis of gated single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy provides a measure of left ventricular dyssynchrony and may have applications for identifying patients suitable for cardiac resynchronisation therapy. Phase analysis is typically described in degrees of cardiac cycle, less intuitive to cardiologists familiar with ECGs. We assessed the relationship between time and degrees, to determine whether they are interchangeable. Methods and results 399 patients underwent normal stress-only SPECT myocardial perfusion imaging using Technetium-99m-tetrofosmin. Data analysis used QGS software (Cedars Sinai) calculating bandwidth and standard deviation. Heart rate, age, gender, stress modality, and ejection fraction were analyzed for their relation to phase variables. 13 patients were excluded for conduction abnormalities including right and left bundle branch block and ventricular pacing. Heart rate was strongly correlated to bandwidth and standard deviation measured in time, but unrelated when measured in degrees. Although bandwidth measured by time and degrees were strongly correlated with each other this relationship was not perfect (correlation coefficient 0.87, P < .001). The addition of heart rate to the model explained most of the residual variation between the two. The results for standard deviation were similar. Conclusion In patients with normal myocardial perfusion and QRS duration bandwidth measured by degrees is not directly interchangeable with time in milliseconds. However most of the variation is explainable by heart rate, which predominantly affects measures of time rather than degrees. We would propose that although the values are less intuitive to cardiologists, normal ranges for phase measured in degrees are potentially more robust.

Objectives Cardiovascular disease accounts for 42% of male and 51% of female mortality within Europe. Kyrgyzstan, population of almost 6 million, has amongst the highest rates within Europe, second only to Uzbekistan for female cardiovascular disease mortality (588 per 100,000). We attempted to identify established cardiovascular disease prevalence within a rural community in Kyrgyzstan using portable echocardiography. Design Free open access echocardiography (VIVID-I, GE, USA) was offered to all adults in Batken district. Routine echocardiographic views were obtained and analysis performed using EchoPac Clinical Workstation (GE, USA). Mild valvular regurgitation, mild LV hypertrophy, patent foramen ovales and mild atrial enlargement were considered mild abnormalities; compensated ischaemic or valvular heart disease – moderate abnormalities, and decompensated congenital, ischaemic or valvular disease – severe abnormalities. Results One hundred and twenty five adults (48 male, 77 female), mean age 53 ± 16 years, underwent echocardiography. Only 16% of participants had no significant abnormality, 46% had mild disease, 25% moderate, compensated disease and 13% had severe disease. Nine percent had congenital heart disease including one tetralogy of Fallot and one Ebstein’s anomaly. Average LV function was normal, however, 19 participants had EF < 50%. Forty percent of participants had a new diagnosis warranting formal follow-up, 12% a new diagnosis of heart failure. Conclusion Using portable echocardiography, we identify a higher than reported prevalence of cardiovascular disease in rural Kyrgyzstan. Absence of portable tools and specialists for early diagnosis might lead to presentation in an advanced stage of disease when little can be done to improve mortality. Embracing remote access diagnostics is essential for disease identification within rural communities.

BACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS. The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION. The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING. For detailed information per study, see Acknowledgments.

OBJECTIVES The study sought to compare the relative discrimination of various cardiopulmonary exercise testing (CPX) variables between cardiac and respiratory disease. CI) CrossMarkBACKGROUND CPX testing is used in many cardiorespiratory diseases. However, discrimination of cardiac and respiratory dysfunction can be problematic. Anaerobic threshold (AT) and oxygen-uptake to work-rate relationship (VO2/WR slope) have been proposed as diagnostic of cardiac dysfunction, but multiple variables have not been compared.METHODS A total of 73 patients with chronic obstructive pulmonary disease (COPD) (n = 25), heart failure with reduced ejection fraction (HFrEF) (n = 40), or combined COPD and HFrEF (n = 8) were recruited and underwent CPX testing on a bicycle ergometer. Following a familiarization test, each patient underwent a personalized second test aiming for maximal exercise after 10 min. Measurements from this test were used to calculate area under the receiver-operator characteristic curve (AUC).RESULTS Peak VO2 was similar between the 2 principal groups (COPD 17.1 4.6 ml/min/kg; HFrEF 16.4 +/- 3.6 ml/min/kg). Breathing reserve (AUC: 0.91) and percent predicted oxygen uptake efficiency slope (OUES) (AUC: 0.87) had the greatest ability to discriminate between COPD and HFrEF. VO2/WR slope performed significantly worse (AUC: 0.68). VO2 at the AT did not discriminate (AUC for AT as percent predicted peak VO2: 0.56). OUES and breathing reserve remained strong discriminators when compared with an external cohort of healthy matched controls, and were comparable to B-type natriuretic peptide.CONCLUSIONS Breathing reserve and OUES discriminate heart failure from COPD. Despite it being considered an important determinant of cardiac dysfunction, the AT could not discriminate these typical clinical populations while the VO2/WR slope showed poor to moderate discriminant ability. (Identifying an Ideal Cardiopulmonary Exercise Test Parameter [PVA]; NCT01162083) (C) 2016 by the American College of Cardiology Foundation.

BACKGROUND:In at-risk patients with left ventricular dysfunction, implantable cardioverter defibrillators (ICDs) prolong life. Implantable cardioverter defibrillators are increasingly implanted for primary prevention and therefore into lower risk patients. Trial data have demonstrated the benefit of these devices but does not provide an estimate of potential lifespan-gain over longer time periods, e.g. a patient's lifespan. METHODS:Using data from landmark ICD trials, lifespan-gain was plotted against baseline annual mortality in the individual trials. Lifespan-gain was then extrapolated to a time-horizon of >20 years while adjusting for increasing 'competing' risk from ageing and non-sudden cardiac death (pump failure). RESULTS:At 3 years, directly observed lifespan-gain was strongly dependent on baseline event rate (r = 0.94, P < 0.001). However, projecting beyond the duration of the trial, lifespan-gain increases rapidly and non-linearly with time. At 3 years, it averages 1.7 months, but by 10 years up to 9-fold more. Lifespan-gain over time horizons >20 years were greatest in lower risk patients (∼5 life-years for 5% baseline mortality, ∼2 life-years for 15% baseline mortality). Increased competing risks significantly reduce lifespan-gain from ICD implantation. CONCLUSION:While high-risk patients may show the greatest short-term gain, the dramatic growth of lifespan-gain over time means that it is the lower risk patients, e.g. primary prevention ICD implantation, who gain the most life-years over their lifetime. Benefit is underestimated when only trial data are assessed as trials can only maintain randomization over limited periods. Lifespan-gain may be further increased through advances in ICD device programming.

BACKGROUND:Cardiopulmonary exercise testing allows for assessment of cardiac and respiratory limitation, but is often affected by patient effort. Indices of oxygen kinetics, including the oxygen uptake efficiency slope (OUES), oxygen uptake-work-rate slope (VO2-WR slope) and the heart rate-oxygen uptake slope (HR-VO2 slope) are relatively effort independent but may be affected by patient characteristics. The objective of this study is to identify the impact of factors, such as age, gender, body size, respiratory function, smoking and beta-blockade on these parameters, as well as generate predictive equations. METHODS:1708 volunteers from the population-based Study of Health in Pomerania underwent an incremental bicycle exercise protocol. Markers of oxygen kinetics were calculated. Participants with structural heart disease, echocardiographic or lung function pathology were excluded, leaving 577 males and 625 females. Age, height, weight, smoking, forced expiratory volume in 1 s (FEV1) and beta-blockers were analysed for their influencing power by gender. Quantile regression analysis determined the reference equations for each parameter. RESULTS:Age, gender, height, weight and FEV1 (but not percent predicted FEV1) are strongly related to OUES. Participants using beta-blockers and male smokers had significantly lower OUES values. VO2-WR slope was minimally affected by age, gender, weight and FEV1. Gender, height, weight and beta-blocker use, but not FEV1 and smoking status, were related to the HR-VO2 slope whilst age was only related in females. CONCLUSIONS:Markers of oxygen kinetics are differentially affected by patient characteristics. This study provides normal reference values for these variables thereby facilitating interpretation of oxygen uptake kinetics in health and disease.

BackgroundThe test-retest reliability for multiple cardiopulmonary exercise test (CPX) variables has not been compared in a single study and the influence of different diseases on test-retest reliability has not been examined. We investigated different measures of test-retest reliability for multiple variables and compared them by category of cardiac or respiratory disease.MethodsPatients with chronic obstructive airways disease (n = 24), heart failure (n = 43), or severe mitral valve disease (n = 26) were recruited into a prospective study. Each patient underwent two bicycle ergometer tests; the first, a familiarization test, with a 10 W/min ramp, and the second a personalized ramp based on the results of the familiarization test to elicit maximal effort within 8-10 min. Intraclass correlation coefficients (ICC) and coefficients of variation between the two tests were calculated. Influence of potential modifiers was assessed using repeated measures analysis of variance.ResultsPeak VO2 (ICC 0.95, 95% CI 0.94-0.97), oxygen uptake efficiency slope (ICC 0.93, 95% CI 0.90-0.95), O-2 pulse (ICC 0.96, 95% CI 0.94-0.97), and the VE/VCO2 ratio at the nadir (ICC 0.92, 95% CI 0.89-0.95) all showed excellent test-retest reliability, with within-subject coefficients of variation <0.12. VO2 at the anaerobic threshold (ICC 0.84, 95% CI 0.78-0.89) and the VE/VCO2 slope (ICC 0.88, 95% CI 0.79-0.93) showed good test-retest reliability, although inferior to peak VO2. Age, gender, body mass index, disease aetiology, protocol change, and intertest interval did not affect the reliability of most variables.ConclusionsCPX showed high test-retest reliability; certain variables such as peak VO2 and oxygen uptake efficiency slope outperform others. These results identify which variables are most suitable for serial testing of patients with three common disease aetiologies owing to their superior reproducibility.

Prescription and adherence to medical therapy for heart failure are disappointing despite convincing randomized controlled trial (RCT) evidence for angiotensin-converting enzyme inhibition, beta-blockade, and aldosterone antagonism. In this study, we report an imbalanced approach amongst clinicians, who describe focusing during patient consultations on perceived risks of therapy rather than survival benefits. Only one-half of clinicians mention increased lifespan, and very few suggest to the patient how large this gain might be. We calculate from the available RCT data that, for patients whose lifespan is limited by heart failure, triple therapy triples lifespan.

ObjectiveDiscussions about statin efficacy in cardiovascular prevention are always based on data from blinded randomized controlled trials (RCTs) comparing statin to placebo; however, discussion of side effects is not. Clinicians often assume symptoms occurring with statins are caused by statins, encouraging discontinuation. We test this assumption and calculate an evidence-based estimate of the probability of a symptom being genuinely attributable to the statin itself.MethodsWe identified RCTs comparing statin to placebo for cardiovascular prevention that reported side effects separately in the two arms.ResultsAmong 14 primary prevention trials (46,262 participants), statin therapy increased diabetes by absolute risk of 0.5% (95% CI 0.1-1%, p = 0.012), meanwhile reducing death by a similar extent: -0.5% (-0.9 to -0.2%, p = 0.003). In the 15 secondary prevention RCTs (37,618 participants), statins decreased death by 1.4% (-2.1 to -0.7%, p < 0.001). There were no other statin-attributable symptoms, although asymptomatic liver transaminase elevation was 0.4% more frequent with statins across all trials. Serious adverse events and withdrawals were similar in both arms.ConclusionsOnly a small minority of symptoms reported on statins are genuinely due to the statins: almost all would occur just as frequently on placebo. Only development of new-onset diabetes mellitus was significantly higher on statins than placebo; nevertheless only 1 in 5 of new cases were actually caused by statins. Higher statin doses produce a detectable effect, but even still the proportion attributable to statins is variable: for asymptomatic liver enzyme elevation, the majority are attributable to the higher dose; in contrast for muscle aches, the majority are not.

BACKGROUND:We examined the prognostic utility of rate of change in serum albumin over time in chronic heart failure (CHF), as well as the utility of multivariate dynamic risk modelling. METHODS AND RESULTS:The survival implication of ∆albumin was analysed in 232 systolic CHF patients and validated in 212 patients. A multivariate dynamic risk score predicated on the rate of change in 6 simple indices including albumin was calculated and related to mortality. In derivation patients, 50 (22%) deaths occurred over 13 months. Greater rates of decline in albumin related to higher mortality (HR 0.55, 95% CI 0.41-0.73, P<0.0001) independently, incrementally and more accurately than other covariates including baseline albumin. A rate of attenuation >0.4 g/dL/month optimally forecasted death and was associated with a 5-fold escalated risk of mortality (HR 5.13, 95% CI 2.92-9.00, P<0.0001). Similar results were seen in the validation cohort. On multivariate dynamic risk modelling, survival at 1-year worsened with higher scores-a score ≥ 3 was associated with a 12-fold greater risk of death than a score of 0, a 6-fold higher risk of death than a score of 1, and a 4-fold enhanced risk of mortality than a score of 2. CONCLUSION:Attenuations in serum albumin over time relate to increased mortality in CHF, and a risk model predicated on the rate of change in 6 simple indices can identify patients at a 12-fold enhanced risk of death over the coming year.

Plasma volume (PV) expansion drives systemic congestion in chronic heart failure (CHF) and is a plausible substrate for exercise limitation. Because no simply means of quantifying PV in CHF exists, we derived an index of relative PV status (PVS) and tested its relation to exercise performance in CHF

Background: Patients trying life-preserving agents such as beta-blockers may be discouraged by listings of harmful effects provided in good faith by doctors, drug information sheets, and media. We systematically review the world experience of side-effect information in blinded, placebo-controlled beta-blockade in heart failure. We present information for a physician advising a patient experiencing an unwanted symptom and suspecting the drug.Methods: We searched Medline for double-blinded randomized trials of beta-blocker versus placebo in heart failure reporting side-effects. We calculated, per 100 patients reporting the symptom on beta-blockade, how many would have experienced it on placebo: the "proportion of symptoms non-pharmacological".Results: 28 of the 33 classically-described side-effects are not significantly more common on beta-blockers than placebo.Of the 100 patients developing dizziness on beta-blockers, 81 (95% CI 73-89) would have developed it on placebo. For diarrhoea this proportion is 82/100 (70-95), and hyperglycaemia 83/100 (68-98). For only two side-effects is this under half (i.e. predominantly due to beta-blocker): bradycardia (33/100, CI 21-44) and intermittent claudication (41/100, 2-81).At least 6 so-called side-effects are less common on beta-blocker than placebo, including depression (reduced by 35%, p < 0.01) and insomnia (by 27%, p - 0.01).Conclusions: Clinicians might reconsider whether it is scientifically and ethically correct to warn a patient that a drug might cause them a certain side-effect, when randomized controlled trials show no significant increase, or indeed a significant reduction. A better informed consultation could, in patients taking beta-blockers, alleviate suffering. In patients who might otherwise not take the drug, it might prevent deaths. (C) 2013 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.