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Aims Implantable device‐based sensor measurements including heart sounds, markers of ventilation, and thoracic impedance have been shown to predict heart failure (HF) hospitalizations. We sought to assess how these parameters changed prior to COVID‐19 (Cov‐19) and how these compared with those presenting with decompensated HF or pneumonia. Methods and results This retrospective analysis explores patterns of changes in daily measurements by implantable sensors in 10 patients with Cov‐19 and compares these findings with those observed prior to HF (n = 88) and pneumonia (n = 12) hospitalizations from the MultiSENSE, PREEMPT‐HF, and MANAGE‐HF trials. The earliest sensor changes prior to Cov‐19 were observed in respiratory rate (6 days) and temperature (5 days). There was a three‐fold to four‐fold greater increase in respiratory rate, rapid shallow breathing index, and night heart rate compared with those presenting with HF or pneumonia. Furthermore, activity levels fell more in those presenting with Cov‐19, a change that was often sustained for some time. In contrast, there were no significant changes in 1st or 3rd heart sound (S1 and S3) amplitude in those presenting with Cov‐19 or pneumonia compared with the known changes that occur in HF decompensation. Conclusions Multi‐sensor device diagnostics may provide early detection of Cov‐19, distinguishable from worsening HF by an extreme and fast rise in respiratory rate along with no changes in S3.

Aims This study aims to characterize the range of implantable device‐based sensor values including heart sounds, markers of ventilation, thoracic impedance, activity, and heart rate for patients with heart failure (HF) when patients were deemed to be in clinically stable periods against the time course of acute decompensation and recovery from HF events. Methods and results The MultiSENSE trial followed 900 patients implanted with a COGNIS CRT‐D for up to 1 year. Chronic, ambulatory diagnostic sensor data were collected and evaluated during clinically stable periods (CSP: unchanged NYHA classification, no adverse events, and weight change ≤2.27 kg), and in the timeframe leading up to and following HF events (HF admissions or unscheduled visits with intravenous HF treatment). Physiologic sensor data from 1667 CSPs occurring in 676 patients were compared with those data leading up to and following 192 HF events in 106 patients. Overall, the mean age was 66.6 years, and the population were predominantly male (73%). Patients were primarily in NYHA II (67%), with a mean LVEF of 29.6% and median NT‐proBNP of 754.5 pg/mL. Sensor values during CSP were poorer in patients who had HF events during the study period than those without HF events, including first heart sound (S1: 2.18 ± 0.84 mG vs. 2.62 ± 0.95 mG, P = 0.002), third heart sound (S3: 1.13 ± 0.36 mG vs. 0.91 ± 0.30 mG, P

This chapter discusses the ‘classical causes’ of heart failure. Heart failure is the common endpoint of a diverse range of cardiovascular and non-cardiovascular conditions. The list of potential causes of this syndrome continues to expand as the knowledge of the pathophysiology of heart failure increases. In western societies, coronary heart disease and hypertension are the commonest causes of heart failure. However, valvular heart disease, arrhythmias, and alcohol are also frequently implicated. The prevalence of heart failure secondary to coronary heart disease has increased in recent years, due in part to improved survival following acute myocardial infarction. The chapter then highlights the importance of establishing an aetiology of heart failure. Establishing the aetiology of heart failure is important, but it is often challenging for the clinician. Several causes of heart failure frequently coexist and determining the primary aetiology can be difficult: one cause may obviously dominate, but frequently patients may have multiple contributing aetiologies.

Aims None of the existing studies on adherence have directly measured levels of all medications (or their metabolites) in patients with heart failure (HF). Methods and results We used liquid chromatography–tandem mass spectrometry to measure the presence of prescribed drugs (diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists) in the urine of patients reviewed 4–6 weeks after hospitalization with HF. Patients were unaware that adherence was being assessed. Of the 341 patients studied, 281 (82.4%) were adherent, i.e. had all prescribed drugs of interest detectable in their urine. Conversely, 60 patients (17.6%) were partially or completely non-adherent. Notably, 24 of the 60 were non-adherent to only diuretic therapy and only seven out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed HF drugs. There were no major differences in baseline characteristics between adherent and non-adherent patients. Conclusion Non-adherence, assessed using a single spot urine measurement of drug levels, was confirmed in one of five patients evaluated 4–6 weeks after hospitalization with HF.

Objectives To compare the relationship between the third heart sound (S3) measured by implantable cardiac devices (devS3) and auscultation (ausS3) and evaluate their prognostic power for predicting heart failure events (HFEs). Methods In the MultiSENSE study, devS3 was measured daily with continuous values while ausS3 was assessed at study visits with discrete grades. They were compared between patients with and without HFEs at baseline and against each other directly. Cox proportional hazard models were developed between follow-up visits (FUs) and over the whole study. Simulations were performed on devS3 to match limitations of auscultation. Results Nine hundred patients were studied, of whom 106 patients experienced 192 HFEs. Two S3 sensing modalities correlated with each other but at baseline only devS3 differentiated patients with or without HFEs (p Conclusions S3 measured from implantable cardiac devices has stronger prognostic power to predict episodes of future HF events than that of auscultation.

These are the clinical practice guidelines from the European Society of Cardiology for the diagnosis and treatment of acute and chronic heart failure, from 2021.

ObjectiveHeart failure is a prothrombotic state, and it has been hypothesised that thrombosis and embolism cause non-fatal and fatal events in heart failure and reduced ejection fraction (HFrEF). We sought to determine the effect of anticoagulant therapy on clinical outcomes in patients with HFrEF who are in sinus rhythm.MethodsWe conducted an updated systematic review and meta-analysis to examine the effect of anticoagulation therapy in patients with HFrEF in sinus rhythm. Our analysis compared patients randomised to anticoagulant therapy with those randomised to antiplatelet therapy, placebo or control, and examined the endpoints of all-cause mortality, (re)hospitalisation for worsening heart failure, non-fatal myocardial infarction, non-fatal stroke of any aetiology and major haemorrhage.ResultsFive trials were identified that met the prespecified search criteria. Compared with control therapy, anticoagulant treatment did not reduce all-cause mortality (risk ratio [RR] 0.99, 95% CI 0.90 to 1.08), (re)hospitalisation for heart failure (RR 0.97, 95% CI 0.82 to 1.13) or non-fatal myocardial infarction (RR 0.92, 95% CI 0.75 to 1.13). Anticoagulation did reduce the rate of non-fatal stroke (RR 0.63, 95% CI 0.49 to 0.81, p=0.001), but this was offset by an increase in the incidence of major haemorrhage (RR 1.88, 95% CI 1.49 to 2.38, p=0.001).ConclusionsOur meta-analysis provides evidence to oppose the hypothesis that thrombosis or embolism plays an important role in the morbidity and mortality associated with HFrEF, with the exception of stroke-related morbidity.

Funding Acknowledgements Type of funding sources: None. Background The insertable cardiac monitor (ICM) is an essential tool for the ambulatory diagnosis of arrhythmias. However, definitive diagnoses still rely on time-consuming, manual adjudication of electrograms (EGMs) transmitted to the patient care network. This EGM review burden may be minimized by automatically selecting a subset of EGMs for fast review without delaying the diagnosis. Purpose Develop EGM selection strategies to reduce the EGM review burden without delaying diagnoses. Methods A retrospective analysis of 1,000 randomly selected Abbott Confirm Rx devices with 90+ days of remote transmission history was performed, regardless of transmission frequency, and all EGMs were adjudicated as either true or false positive (TP, FP). Up to 3 EGMs per day per arrhythmia type were prioritized for review based on ventricular rate and episode duration, with rules specific to each arrhythmia type: atrial fibrillation (AF), tachycardia, bradycardia, and pause. The resulting reduction in EGM review burden and TP days (patient-days with at least 1 TP EGM), as well as any diagnostic delay from the first transmitted TP, were calculated relative to reviewing all transmitted EGMs. Results In this population and transmission period, at least one AF, tachycardia, bradycardia, and pause EGM was transmitted by 424, 343, 190, and 325 unique devices, respectively, with a total of 35,723, 12,239, 19,752, and 28,002 EGMs, and a total of 6,163, 1,572, 1,438, and 646 TP days. For these patients with ≥1 EGM, the median [IQR] EGM transmission rate was 2.6 [0.7, 11.6], 1.1 [0.4, 4.7], 2.1 [0.6, 10.7], and 3.4 [0.6, 29.9] EGMs/patient/month, respectively. The optimal EGM selection strategy reduced this EGM review burden by 43%, 67%, 76%, and 50%, while only missing 3.4%, 2.2%, 0.3%, and 0.2% of TP days, respectively. Ultimately, 97%, 99%, 99%, and 99% of devices with a TP AF, tachycardia, bradycardia, or pause EGM exhibited no diagnostic delay vs. reviewing all transmitted EGMs. Conclusion EGM prioritization rules for selecting up to 3 episodes/day significantly reduced EGM burden across all patients, not just "frequent fliers," with no delay-to-diagnosis in >97% of patients who exhibited a true arrhythmia. Implementing these rules on the patient care network may improve clinical workflow and ICM patient management. Abstract Figure.

Aim The aim of this study was to evaluate the haemodynamic correlates of heart sound (HS) parameters such as third HS (S3), first HS (S1), and HS-based systolic time intervals (HSTIs) from an implantable cardiac device. Methods and results Two unique animal models (10 swine with myocardial ischaemia and 11 canines with pulmonary oedema) were used to evaluate haemodynamic correlates of S1, S3, and HSTIs, namely, HS-based pre-ejection period (HSPEP), HS-based ejection time (HSET), and the ratio HSPEP/HSET during acute haemodynamic perturbations. The HS was measured using implanted cardiac resynchronization therapy defibrillator devices simultaneously with haemodynamic references such as left atrial (LA) pressure and left ventricular (LV) pressure. In the ischaemia model, S1 amplitude (r = 0.76 ± 0.038; P = 0.002), HSPEP (r = −0.56 ± 0.07; P = 0.002), and HSPEP/HSET (r = −0.42 ± 0.1; P = 0.002) were significantly correlated with LV dP/dtmax. In contrast, HSET was poorly correlated with LV dP/dtmax (r = 0.14 ± 0.14; P = 0.23). In the oedema model, a physiological delayed response was observed in S3 amplitude after acute haemodynamic perturbations. After adjusting for the delay, S3 amplitude significantly correlated with LA pressure in individual animals (r = 0.71 ± 0.07; max: 0.92; min: 0.17) as well as in aggregate (r = 0.62; P 25 mmHg, with a sensitivity = 58% and specificity = 90%. Conclusions The HS parameters such as S1, S3, and HSTIs measured using implantable devices significantly correlated with haemodynamic changes in acute animal models, suggesting potential utility for remote heart failure patient monitoring.

Background Estimated plasma volume (ePV) can be calculated from haematocrit and body weight, and has been shown to correlate with PV measured using 125Iodine labelled human serum albumin. Comparing a patient's ePV to ideal PV (iPV), an estimate of a patient's relative congestion, called PV status (PVS), is possible. Higher PVS is associated with increased mortality in patients with heart failure (HF), and has been proposed as a simple, cheap, and non-invasive way of assessing congestion. Purpose Whether PVS is associated with invasively measured markers of congestion is unknown. We calculated PVS in patients with HF who had right heart catheterisation (RHC), and assessed any correlation between PVS and invasive measures of congestion. Methods We calculated PVS in consecutive patients who had RHC performed as part of transplant assessment. iPV was calculated as: iPV = c × weight (kg) where c=39 in males and c=40 in females. ePV was calculated using subjects' haematocrit and weight as follows: ePV = (1 − haematocrit) × [a + (b × weight in kg)], where haematocrit is a fraction, a=1530 in males and a=864 in females, and b=41 in males and b=47.9 in females. PVS was calculated as: PVS = PVS = (ePV − iPV) /iPV × 100%. Correlation between PVS and invasive wedge pressure, mean right atrial (RA) pressure, and NTproBNP were made using Pearson correlation. Results PV indices and RHC data were available for 61 patients, 43 (71%) were male. Median age was 55 [IQR 48, 58] years. 20 (33%), 24 (39%), and 15 (25%) were NYHA association class II, III, and IV respectively. The median NTproBNP was 1390 [IQR 512, 3612] pg/ml and median ejection fraction was 29 [IQR 20, 35] %. The median PVS was −5.9% (IQR −12.5, −1.6]. Median wedge and mean-RA pressures were 14 [7, 21] and 4 [1, 8] mmHg, respectively. Correlation between mean RA pressure and PVS is shown in the figure. There was no correlation between PVS and mean RA pressure (r=0.12, p=0.34) or wedge pressure (r=0.01, p=0.92). There was a weak correlation between NTproBNP and PVS (r=0.31, p=0.01) Correlation mean RA pressure and PVS Conclusion PVS did not correlate with the invasive measures of congestion, mean RA and wedge pressure, but was weakly correlated with NTproBNP. Although there were limited number of patients in this study, we question the conclusion that PVS is a marker of congestion, and whether it can be used clinically for this purpose.

ObjectivesUltra-small superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect cellular inflammation within tissues and may help non-invasively identify cardiac transplant rejection. Here, we aimed to determine the normal reference values for USPIO-enhanced MRI in patients with a prior cardiac transplant and examine whether USPIO-enhanced MRI could detect myocardial inflammation in patients with transplant rejection.MethodsTen volunteers and 11 patients with cardiac transplant underwent T2, T2* and late gadolinium enhancement 1.5T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months.ResultsTen patients with clinically stable cardiac transplantation were retained for analysis. Myocardial T2 values were higher in patients with cardiac transplant versus healthy volunteers (53.8±5.2 vs 48.6±1.9 ms, respectively; p=0.003). There were no differences in the magnitude of USPIO-induced change in R2* in patients with transplantation (change in R2*, 26.6±7.3 vs 22.0±10.4 s-1 in healthy volunteers; p=0.28). After 3 months, patients with transplantation (n=5) had unaltered T2 values (52.7±2.8 vs 52.12±3.4 ms; p=0.80) and changes in R2* following USPIO (29.42±8.14 vs 25.8±7.8 s-1; p=0.43).ConclusionStable patients with cardiac transplantation have increased myocardial T2 values, consistent with resting myocardial oedema or fibrosis. In contrast, USPIO-enhanced MRI is normal and stable over time suggesting the absence of chronic macrophage-driven cellular inflammation. It remains to be determined whether USPIO-enhanced MRI may be able to identify acute cardiac transplant rejection.Trial registration numberNCT02319278349 (https://clinicaltrials.gov/ct2/show/NCT02319278) Registered 03.12.2014 EUDraCT 2013-002336-24.

Aims: In recent years there has been an increase in the number of biomarkers in heart failure ( HF ). The clinical role for these novel biomarkers in combination is not clear. Methods and results: The following novel biomarkers were measured from 628 patients recently hospitalized with decompensated HF; mid-regional pro-adrenomedullin ( MR-proADM ), mid-regional pro-atrial natriuretic peptide ( MR-proANP ), copeptin, high-sensitivity cardiac troponin T ( hs-cTnT ), ST2, galectin-3, cystatin C, combined free light chains ( cFLC ) and high sensitivity C-reactive protein ( hsCRP ). The incremental prognostic value of these novel biomarkers was evaluated within an extensive model containing established predictors of mortality. During a mean ( SD ) follow-up of 3.2 ( 1.5 ) years, 290 ( 46% ) patients died. Elevated concentrations of all novel biomarkers were associated with an increased unadjusted risk of mortality but only two-thirds were independent predictors following multivariable analysis. Using dichotomized cut-points from receiver operating characteristic analysis, MR-proADM, hs-cTnT, cFLC, hsCRP, and ST2 remained independent predictors of mortality. Further dichotomization into low ( 0–2 elevated biomarkers ) or high ( at least three of the five biomarkers elevated ) risk groups provided greatest incremental prognostic value ( hazard ratio 2.20, 95% confidence interval 1.37–3.54; P = 0.001 ) and improved the performance of the model ( C-statistic 0.730 from 0.721, net reclassification index 32.5% ). Conclusion: The novel biomarkers included in this study added little, if any, incremental prognostic value on their own to a model containing established predictors of mortality. However, following dichotomization, five of the novel biomarkers provided incremental prognostic value. There was a clear gradient in the risk of death with increasing numbers of elevated novel biomarkers, with the presence of at least three identifying patients at greatest risk of mortality.

Background N-terminal pro-B-type natriuretic peptide (NT-proBNP), a non-active fragment of the prohormone proBNP, is produced by the heart and released in response to volume or pressure overload. NT-proBNP has proven to be a valuable biomarker in the diagnosis and prognosis of heart failure (HF), and NT-proBNP concentrations rise with worsening HF. HeartLogic, a multi-sensor composite index and alert algorithm, aggregates multiple physiologic trends associated with HF status, and proactively provides alerts for worsening HF with high sensitivity and low alert burden. Objective To compare NT-proBNP concentrations during periods IN or OUT of an active HeartLogic alert. Methods The MultiSENSE study enrolled 900 HF patients with an implanted COGNIS CRT-D, and followed them up to 1 year. Device software was modified to permit collection of chronic trends HeartLogic leveraged (heart sounds, heart rate, thoracic impedance, respiration and activity). Clinicians were blinded to individual sensors and results of HeartLogic during the study. Optional NT-proBNP tests were conducted when clinically needed (e.g., patients hospitalized with HF symptoms). HeartLogic index of the day before each of the NT-proBNP test dates was extracted. Based on HeartLogic alert state (i.e., IN alert vs OUT of alert), NT-proBNP concentrations were divided into two groups and compared using a one-way ANOVA. Results Of a total of 855 valid NT-proBNP tests in 741 patients with valid associated HeartLogic index, 180 NT-proBNP concentrations were measured in 150 patients while the HeartLogic alert state was IN alert, and 675 were measured in 616 patients while HeartLogic was OUT of alert. Figure 1 shows when HeartLogic was IN alert, the NT-proBNP concentrations (6957.9±10398.0 pg/ml) were significantly higher than those when HeartLogic was OUT of alert (1675.5±4403.1 pg/ml) (p Conclusion HF patients’ NT-proBNP concentrations were significantly elevated when HeartLogic was IN alert status, consistent with the HeartLogic algorithm capturing clinical worsening of HF status.

Heart failure (HF) is a clinical syndrome characterized by reduced exercise tolerance, dyspnoea and peripheral oedema, which is confirmed with imaging evidence of ventricular dysfunction and, if available, cardiac biomarkers. HF is one of the major cardiovascular causes of morbidity and mortality worldwide. It has a prevalence of 1–2%, rising with age to >10% in those over 70 years old. Pharmacological and device-based therapy for HF with reduced ejection fraction (HFrEF) has dramatically improved over the last 30 years, resulting in significantly better outcomes for patients, in terms of improvements in quality of life, and reduction in morbidity and mortality. However, some patients remain highly symptomatic despite these measures and for a select few, advanced therapies (e.g. mechanical circulatory support devices and cardiac transplantation) might be suitable. This article provides an overview of contemporary management of patients with HFrEF.

Acute heart failure syndromes consist of a spectrum of clinical presentations due to an impairment of some aspect of the cardiac function. They represent a final common pathway for a vast array of pathologies and may be either a de novo presentation or, more commonly, a decompensation of pre-existing chronic heart failure. Despite being one of the most common medical presentations, there are no definitively proven prognosis-modifying treatments. The mainstay of current therapy is oxygen and intravenous diuretics. However, within this spectrum of presentations, there is a crucial dichotomy which governs the ultimate treatment approach, i.e. the presence, or absence, of cardiogenic shock. Patients without cardiogenic shock may receive vasodilators, whilst shocked patients should be considered for treatment with inotropic therapy or mechanical circulatory support, when appropriate and where available.

After reading this article the reader should be familiar with: Current guidelines for implantable cardioverter defibrillator (ICD) use post myocardial infarction (MI) and ischaemic cardiomyopathy. Primary prevention ICD guidelines. Secondary prevention ICD guidelines. Non-sustained ventricular tachycardia in patients post MI and the use of ICDs. Programming ICDs.

A systematic search of Medline, EMBASE and CINAHL electronic databases was performed. Original research articles reporting all-cause mortality following surgery in patients with aortic regurgitation and severe left ventricular systolic dysfunction (LVSD) were identified. Nine of the 10 eligible studies were observational, single-center, retrospective analyses. Survival ranged from 86 to 100% at 30 days; 81 to 100% at 1 year and 68 to 84% at 5 years. Three studies described an improvement in mean left ventricular ejection fraction (LVEF) following aortic valve replacement (AVR) of 5-14%; a fourth study reported an increase in mean left ventricular ejection fraction (LVEF) of 9% in patients undergoing isolated AVR but not when AVR was combined with coronary artery bypass graft and/or mitral valve surgery. Three studies demonstrated improvements in functional New York Heart Association (NYHA) class following AVR. Additional studies are needed to clarify the benefits of AVR in patients with more extreme degrees of left ventricular systolic dysfunction (LVSD) and the potential roles of cardiac transplantation and transaortic valve implantation.

Peripartum cardiomyopathy (PPCM) is a rare condition with a diverse spectrum of potential outcomes, ranging from frequent complete recovery to fulminant heart failure and death. The pathogenesis of PPCM is not well understood, and relatively little is known about its incidence and prevalence. PPCM is often under-recognised in the clinical setting. Early investigation and diagnosis with subsequent expert management may improve outcomes. The development of registries will allow this condition to be better characterised and may help answer crucial questions regarding its optimal medical and surgical management. This paper reviews the potential approaches to improve outcomes in patients with PPCM.

Aims To investigate the relationship between angina pectoris and fatal and non-fatal clinical outcomes in heart failure with reduced and preserved ejection fraction (HF-REF and HF-PEF, respectively). Methods and results Of 7599 patients in the CHARM program, 5408 had ischaemic heart disease; 3855 had HF-REF (ejection fraction ≤45%) and 1553 had HF-PEF. These patients were separated into three groups: no history of angina, previous angina, and current angina. Three coronary outcomes were examined: fatal or non-fatal myocardial infarction (MI); MI or hospitalization for unstable angina (UA); and MI, UA or coronary revascularization. The composite heart failure outcome of cardiovascular death or heart failure hospitalization (HFH) was also analysed, along with its components and all-cause mortality. New York Heart Association functional class was worse in both HF-REF and HF-PEF patients with current angina compared with patients without angina (P

Aim: Angina pectoris is common in patients with heart failure and reduced ejection fraction (HF-REF) but its relationship with outcomes has not been well defined. This relationship was investigated further in a retrospective analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Methods and results: Four thousand, eight hundred and seventy-eight patients were divided into three categories: no history of angina and no chest pain at baseline (Group A; n = 1240), past history of angina but no chest pain at baseline (Group B; n = 1353) and both a history of angina and chest pain at baseline (Group C; n = 2285). Outcomes were examined using Kaplan–Meier and Cox regression survival analysis. Compared with Group A, Group C had a higher risk of non-fatal myocardial infarction or unstable angina (HR: 2.36, 1.54–3.61; P < 0.001), this composite plus coronary revascularization (HR: 2.54, 1.76–3.68; P < 0.001), as well as HF hospitalization (HR: 1.35, 1.13–1.63; P = 0.001), over a median follow-up period of 33 months. There was no difference in cardiovascular or all-cause mortality. Group B had a smaller increase in risk of coronary events but not of heart failure hospitalization. Conclusion: Patients with HF-REF and ongoing angina are at an increased risk of acute coronary syndrome and HF hospitalization. Whether these patients would benefit from more aggressive medical therapy or percutaneous revascularization is not known and merits further investigation.

Cardiac transplantation can be a life-saving treatment for selected patients with heart failure. However, despite advances in immunosuppressive therapy, acute allograft rejection remains a significant cause of morbidity and mortality. The current ‘gold standard’ for rejection surveillance is endomyocardial biopsy, which aims to identify episodes of rejection prior to development of clinical manifestations. This is an invasive technique with a risk of false-positive and false-negative results. Consequently, a wide variety of noninvasive alternatives have been investigated for their potential role as biomarkers of rejection. This article reviews the evidence behind proposed alternatives such as imaging techniques, electrophysiological parameters and peripheral blood markers, and highlights the potential future role for biomarkers in cardiac transplantation as an adjunct to biopsy.

Aim: Our understanding of heart failure in younger patients is limited. The Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) database, which consisted of 24 prospective observational studies and 7 randomized trials, was used to investigate the clinical characteristics, treatment, and outcomes of younger patients. Methods and Results: Patients were stratified into six age categories: < 40 (n = 876), 40–49 (n = 2638), 50–59 (n = 6894), 60–69 (n = 12 071), 70–79 (n = 13 368), and ≥80 years (n = 6079). Of 41 926 patients, 2.1, 8.4, and 24.8% were younger than 40, 50, and 60 years of age, respectively. Comparing young ( < 40 years) against elderly (≥80 years), younger patients were more likely to be male (71 vs. 48%) and have idiopathic cardiomyopathy (63 vs. 7%). Younger patients reported better New York Heart Association functional class despite more severe left ventricular dysfunction (median ejection fraction: 31 vs. 42%, all P < 0.0001). Comorbidities such as hypertension, myocardial infarction, and atrial fibrillation were much less common in the young. Younger patients received more disease-modifying pharmacological therapy than their older counterparts. Across the younger age groups ( < 40, 40–49, and 50–59 years), mortality rates were low: 1 year 6.7, 6.6, and 7.5%, respectively; 2 year 11.7, 11.5, 13.0%; and 3 years 16.5, 16.2, 18.2%. Furthermore, 1-, 2-, and 3-year mortality rates increased sharply beyond 60 years and were greatest in the elderly (≥80 years): 28.2, 44.5, and 57.2%, respectively. Conclusion: Younger patients with heart failure have different clinical characteristics including different aetiologies, more severe left ventricular dysfunction, and less severe symptoms. Three-year mortality rates are lower for all age groups under 60 years compared with older patients.

It is well established that organized care of heart failure patients, including specialist management by cardiologists, improves patient outcomes. In response to this, other national training bodies (the UK and the USA) have developed heart failure subspecialty curricula within their Cardiology Training Curricula. In addition, European Society of Cardiology (ESC) subspecialty curricula exist for Interventional Cardiology and Heart Rhythm Management. The purpose of this heart failure curriculum is to provide a framework which can be used as a blueprint for training across Europe. This blueprint mirrors other ESC curricula. Each section has three components: the knowledge required, the skills which are necessary, and the professionalism (attitudes and behaviours) which should be attained. The programme is designed to last 2 years. The first year is devoted to the specialist heart failure module. The second year allows completion of the optional modules of advanced imaging, device therapy for implanters, cardiac transplantation, and mechanical circulatory support. The second year can also be devoted to continuation of specialist heart failure training and/or research for those not wishing to continue with the advanced modules.

Non-ischaemic cardiomyopathy (NICM) is a common cause of heart failure. If no cause is identified it is termed idiopathic dilated cardiomyopathy (IDCM). Guideline-recommended therapy can improve left ventricular systolic function (LVSF). Although criteria for defining myocardial recovery exist, its

Although peripartum cardiomyopathy (PPCM) is associated with mortality and morbidity, improvement in cardiac function – termed myocardial recovery – can occur. No study has systematically reviewed myocardial recovery in PPCM and its independent predictors. A systematic review was performed of

Aims Microvolt T-wave alternans (MTWA) testing identifies beat-to-beat fluctuations in T-wave morphology, which have been linked to ventricular arrhythmias. However, clinical studies have produced conflicting results and data in heart failure (HF) have been limited. The aim of this study was to determine the prevalence and incremental prognostic value of spectral MTWA testing in an unselected cohort of patients recently hospitalized with HF. Methods and results Consecutive admissions with confirmed HF were recruited, and survivors were invited to attend 1 month post-discharge for MTWA testing. A total of 648 of 1003 enrolled patients returned for MTWA testing (58% male, mean age 71 years). Forty-nine per cent were ineligible due to AF, pacemaker dependency, or inability to exercise. Of the 330 MTWA test results, 30% were positive, 24% negative, and 46% indeterminate. Overall, 268 deaths occurred during a median follow-up of 3.1 (interquartile range 1.9–3.9) years. Of the ineligible patients, 48% died vs. 35% of eligible patients (P < 0.001). Of those patients with positive, negative, and indeterminate tests, 27, 35, and 40%, respectively, died (P = 0.12). Even when analysed as non-negative (positive/indeterminate) vs. negative, there was still no between-group difference in mortality (P = 0.95). MTWA results categorized as positive, negative, or indeterminate showed no incremental prognostic value in a multivariable model, which included BNP. Paradoxically, when compared in a binary fashion with a non-negative result, a negative test was an independent predictor of death, as was ineligibility for MTWA testing. Conclusion Spectral MTWA testing was not widely applicable and failed to predict mortality, and so cannot be endorsed as a risk stratification tool in HF.

A 61-year old gentleman with a past medical history of type-2 diabetes mellitus presented to hospital with breathlessness and ankle swelling for 1 week. He reported no chest pain. Resting electrocardiogram revealed sinus rhythm with non-specific ST segment changes, and his high sensitivity troponin T was elevated. An echocardiogram demonstrated severe left ventricular systolic dysfunction. Coronary angiography revealed severe multi-vessel coronary artery disease. …

Patients with left ventricular assist devices (LVADs) are at high risk of sustained ventricular arrhythmias, but these may be remarkably well tolerated and the association with sudden death is unclear. Many patients who receive an LVAD already have an implantable cardioverter defibrillator (ICD). While it is standard practice to reactivate a previously implanted ICD in an LVAD recipient, this should include discussion of the revised risks and benefits of ICD therapy following LVAD implantation. In particular, patients should be warned that they might receive a significant number of ICD shocks that may not be life saving. When ICDs are reactivated, device programming should minimize the risk of repeated shocks for non-sustained or well-tolerated ventricular arrhythmias. Implantation of a primary prevention ICD after implantation of an LVAD is not supported by current evidence, poses potential risks, and should be the subject of a clinical trial before it becomes standard practice.

Background The third heart sound (S3) is regarded as one of the earliest signs of heart failure (HF) and is typically assessed via auscultation clinically. The embedded accelerometer sensor in implantable devices can pick up the mechanical vibration caused by S3. We compared the device-measured S3 amplitude (devS3) to auscultated S3 volume grades (audS3). Methods In the MultiSENSE study, ambulatory HF patients implanted with a CRT-D were enrolled and followed up for 1 year. DevS3 amplitude was trended daily. Clinicians were asked to auscultate for S3 intensity on a graded scale (None/Low/Moderate/Loud) at baseline and each regular follow-up. Clinicians were blinded to the devS3 data at the time of assessment. We compared devS3 on the day of assessment in patients with different level of audS3 intensity. ANOVA test was used to compare the mean S3 amplitudes among groups and unpaired t-tests for between-group comparison. Conclusion This demonstrates that device-measured S3 amplitude reflects auscultated S3 heart sound volume grades. Since device-measured S3 is an objective measure on a continuous scale as opposed to auscultation which is subjectively categorized, it could avoid inter-observer auscultation variability and enables monitoring of this clinical variables in ambulatory HF patients. Result A total of 5211 auscultation reports were obtained from the 900 patients in the study. AudS3 intensity was None in 4709, Low in 391, Moderate in 108, and Loud in 3 reports (moderate and loud were combined for this analysis). Figure represents the devS3 amplitude (mean ± standard error) on the day of the follow-up as a function of the audS3 grades reported, the mean devS3 values for None, Low, and Moderate/Loud audS3 was 0.96 ± 0.01 mG, 1.02 ± 0.02 mG, and 1.27± 0.06 mG respectively. Both ANOVA test and unpaired tests between groups were significant and remained significant after adjusting for repeated measures.

Background A multisensor algorithm has been demonstrated to predict heart failure (HF) events in patients with implanted devices with high sensitivity and low false positive rate. However, it is not known how the individual sensors change from hospital admission to discharge and whether it can be indicative of readmissions or death within 30 days. Methods The MultiSENSE study followed 900 HF patients with CRT-D for up to 1 year. Devices were modified to enable the collection of first (S1) and third (S3) heart sounds, thoracic impedance (TI), respiratory rate (RR), rapid shallow breathing index (RSBI), night heart rate (nHR), and activity. All hospitalizations were adjudicated by an independent committee. Hospitalizations with HF as a primary cause (HFH) were identified. HFH with an admission outside of the customized data collection were excluded due to lack of sensor data. Each HFH was classified as unresolved if it was followed by all-cause hospitalization or death within 30 days of discharge; otherwise, it was classified as resolved. For each type of HFH, daily sensor values on the day before admission and the day before discharge were compared with a pairwise t-test. The changes in each sensor were compared between the resolved and the unresolved group via t-test. Significant difference in comparisons was defined as that with p Results Out of 149 HFHs, 109 were determined as resolved and 40 as unresolved. Additional HFHs were excluded if sensor data at admission or discharge was not available (see Figure). Admission-to-discharge differences for resolved HFHs showed improvement in S3, S1, TI, and RR; no change in RSBI and nHR, and reduction in activity. Admission-to-discharge differences for unresolved HFHs showed improvement in TI; no change in S3, S1, RR, nHR; worsening in RSBI, and reduction in activity. Changes in RSBI were significantly different between the two groups of HFHs. Conclusions Worsening in RSBI during hospitalization identified a group of patients with either early HF readmissions or death.

Background Respiratory distress is common in heart failure (HF) and a primary driver for HF hospitalizations. Minute Ventilation (MV), a product of respiratory rate and tidal volume, is known to be elevated in HF patients due to ventilation/perfusion (V/Q) mismatch. However, it is not known if changes in MV accurately reflect emergence of rapid shallow breathing patterns in ambulatory patients preceding a HF event. Methods The MultiSENSE trial enrolled 900 patients implanted with a COGNIS CRT-D and followed them up to 1 year. Device software was modified to permit collection of chronic diagnostic sensor data including impedance based respiration rate (RR) and tidal volume (TV), which was used to compute MV (= RR*TV) and Rapid Shallow Breathing Index (RSBI = RR/TV), and activity (XL). Daily averages were separately computed over entire 24 hours as well as during resting epochs. HF events (HFEs) were independently adjudicated and defined as HF admissions or unscheduled visits with intravenous HF treatment. Relative changes preceding HFEs were computed between a baseline 30–60 days prior to HFEs (BL) and 3-day pre-HFE (ST) as (ST-BL)/BLx100% and reported as mean +/- SEM. Significance was tested using Wilcoxon signed-rank test. Results 900 patients followed for a year experienced 192 HFEs. Using 24-hour averages, significant changes were observed in RR, TV and RSBI indicating the emergence of rapid shallow breathing pattern leading up to HFE. MV average over 24 hours showed nonsignificant decrease coincident with decreased patient activity but showed no change when daily averaging was limited to resting epochs. In contrast, RR, TV and RSBI were significantly changed even at rest in directions consistent with the emergence of rapid shallow breathing pattern. Conclusion Device measured rapid shallow breathing is significantly elevated in the three day epoch preceding HFEs, whereas minute ventilation is not, in both 24-hour as well as resting period daily averages. Automatic ambulatory longitudinal monitoring of changes in rapid shallow breathing patterns may enable better monitoring for emerging respiratory distress in HF patients.

The B-type natriuretic peptides (BNPs) now have a well-established role in the diagnosis of heart failure. There is also a wealth of evidence on their ability as prognostic markers in patients with heart failure. The other potential role of BNPs is in the arena of therapy monitoring, although much less is known regarding this putative application. This review summarizes what evidence there is both for and against using BNPs to monitor heart failure patients.

The angiotensin receptor-like 1 (APJ) and its novel ligand, apelin, share similarities in structure and anatomical distribution with that of angiotensin II and the angiotensin II type 1 receptor. However, apelin has positive inotropic, vasodilatory and diuretic properties. Differential expression and synthesis of apelin and the APJ receptor in normal and failing hearts suggest that the apelin system may contribute to the pathophysiology of human heart failure and has potential therapeutic use in treatment of heart failure.

This study examined the trends in the relative contributions of cardiovascular and noncardiovascular mortality to total mortality according to use of beta-blockers in clinical trials of patients with heart failure with reduced ejection fraction (HF-REF).With the increasingly widespread use of disease-modifying therapies, particularly beta-blockers, in HF-REF, the proportion of patients dying from cardiovascular causes is likely to be decreasing.In a systematic review, 2 investigators independently searched online databases to identify clinical trials including400 patients with chronic heart failure published between 1986 and 2014 and that adjudicated cause of death. Trials were divided into 3 groups on the basis of the proportion of patients treated with a beta-blocker (33% [low], 33% to 66% [medium], and66% [high]). Percentages of total deaths adjudicated as cardiovascular or noncardiovascular were calculated by weighted means and weighted standard deviations. Weighted Student t tests were used to compare results between groups.Sixty-six trials met the inclusion criteria with a total of 136,182 patients and 32,140 deaths. There was a sequential increase in the percentage of noncardiovascular deaths with increasing beta-blocker use from 11.4% of all deaths in trials with low beta-blocker use to 19.1% in those with high beta-blocker use (p0.001).In trials of patients with HF-REF, the proportion of deaths adjudicated as cardiovascular has decreased. Cardiovascular mortality, and not all-cause mortality, should be used as an endpoint for trials of new treatments for HF-REF.

The apelin-APJ system is a novel neurohormonal pathway, with studies to date suggesting that it may be of pathophysiologic relevance in heart failure and may indeed be a viable therapeutic target in this syndrome. This interest is driven primarily by the demonstration of its vasodilator, inotropic, and aquaretic actions as well as its apparent antagonistic relationship with the renin-angiotensin system. However, its promise is heightened further by the observation that, unlike other and more established cardioprotective pathways, it appears to be down-regulated in heart failure, suggesting that augmentation of this axis may have a powerful effect on the heart failure syndrome. We review the literature regarding the apelin-APJ system in heart failure and suggest areas requiring further research.

Objectives This study investigated the prevalence and potential incremental prognostic value of combined free light chains (cFLCs) in patients recently hospitalized with decompensated heart failure (HF). Background Inflammatory pathways are recognized in the pathogenesis and progression of HF. Free light chain (FLC) elevation is conventionally associated with monoclonal gammopathies, including multiple myeloma. Polyclonal increases in both kappa and lambda FLCs occur in autoimmune and other chronic inflammatory conditions. Recently, a novel assay for measuring kappa and lambda immunoglobulin FLCs together, known as combined free light chain (cFLC) has been developed. Methods Six hundred twenty-eight patients recently hospitalized with decompensated HF were studied. cFLCs were measured by turbidimetry using an immunoassay. The incremental prognostic value of cFLCs for mortality was evaluated using Cox proportional hazard models including 22 established predictors of outcome in HF. Results Of 628 patients, 290 (46%) died during a follow-up of 3.2 ± 1.5 years. Two hundred seventy patients (43%) had elevated cFLCs. There was a clear gradient in the risk of death according to cFLC quartile, with those in the top quartile having an unadjusted risk of mortality more than twice that of those in the lowest quartile (hazard ratio: 2.38; p < 0.0001). After multivariable analysis, cFLC remained an independent predictor of mortality, with an almost 50% higher adjusted risk for those in the top compared with bottom quartile. Older age, lower body mass index, New York Heart Association classification III/IV, previous myocardial infarction, current smoking and B-type natriuretic peptide, bilirubin, high-sensitivity C-reactive protein, glycated hemoglobin, and lymphocyte concentrations were also independent predictors of mortality. Conclusions cFLCs are an independent predictor of mortality in patients recently hospitalized with decompensated HF. Further work is required to assess the effects of HF therapies on cFLC concentrations and whether or not directly targeting this marker of inflammation improves prognosis for patients with HF.

Chronic heart failure (CHF) is a clinical syndrome defined by the presence of symptoms (primarily breathlessness, fatigue and fluid retention), objective evidence of cardiac dysfunction, and in cases where the diagnosis is in doubt, a response to treatment directed towards it. It is not only important to investigate to ascertain the diagnosis, but also to identify the aetiology (as this might be reversible) and to give some indication of the prognosis of the condition. The treatment of CHF has been revolutionalized by large randomized controlled clinical trials studying the effects of antagonism of the renin-angiotensin-aldosterone and sympathetic nervous systems, as well as more recently, device therapy. These therapies now form the cornerstones in the management of the condition, and prognosis for this syndrome has improved as a result. However, cardiac transplantation remains an option for patients who remain severely symptomatic, and at high risk, despite optimal medical and appropriate device therapy.

Background— The aim of our study was to investigate the relationship between coronary artery disease (CAD), angina, and clinical outcomes in patients with heart failure and preserved ejection fraction enrolled in the irbesartan in patients with heart failure and preserved systolic function (I-Preserve) trial. Methods and Results— The mean follow-up period for the 4128 patients enrolled in I-Preserve was 49.5 months. Patients were divided into 4 mutually exclusive groups according to history of CAD and angina: patients with no history of CAD or angina (n=2008), patients with no history of CAD but a history of angina (n=649), patients with a history of CAD but no angina (n=468), and patients with a history of CAD and angina (n=1003); patients with no known CAD or angina were the reference group. After adjustment for other prognostic variables using Cox proportional-hazard models, patients with CAD but no angina were found to be at higher risk of all-cause mortality (hazard ratio [HR], 1.58 [1.22–2.04]; P P P =0.02) and sudden death (HR, 1.83 [1.24–2.69]; P P Conclusions— Patients with heart failure and preserved ejection fraction and CAD are at higher risk of all-cause mortality and sudden death when compared with those without CAD. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00095238.

Background Right heart catheterization long has been a routine investigation in advanced heart failure, and its measurements have been linked variably to prognosis. However, in the modern era, newer potential markers of prognosis are coming to light. This study reconsiders the use of right heart catheterization data and compares their use to that of N-terminal pro-brain natriuretic peptide (NT-proBNP), a neurohormone linked with prognosis in chronic heart failure. Methods We assessed prospectively the prognostic potential of baseline right heart catheterization data in 97 consecutive patients with advanced heart failure referred to the Scottish Cardiopulmonary Transplant Unit for consideration of cardiac transplantation. Patients underwent baseline routine investigation, including right heart catheterization and blood draws for NT-proBNP analysis. Patients were observed for a median of 370 days. Results The primary end-point of all-cause mortality was reached in 17 patients (17.5%), and the secondary end-point of all-cause mortality or urgent cardiac transplantation was reached in 21 (21.6%) patients. Univariate predictors of all-cause mortality included pulmonary artery systolic pressure (PASP), pulmonary artery wedge pressure (PAWP), and NT-proBNP concentration greater than their median values. Univariate predictors of the secondary end-point included right atrial pressure, PASP, PAWP, and NT-proBNP concentration greater than their median values, and left ventricular ejection fraction, cardiac output, and cardiac index less than their median values. In multivariate analyses, however, only NT-proBNP concentration remained an independent predictor of all-cause mortality. Both NT-proBNP concentration and PAWP were independent predictors of all-cause mortality and of the need for urgent cardiac transplantation. Conclusion Baseline data from routine right heart catheterization are of limited prognostic use in advanced heart failure. A baseline NT-proBNP concentration is a superior, non-invasive method of risk stratification in this era of measuring neurohormones.

Aim: Apelin is an endogenous vasodilator and inotrope, plasma concentrations of which are reduced in advanced heart failure (HF). We determined the prognostic significance of plasma concentrations of apelin in advanced HF. Patients & methods: Plasma concentrations of apelin were measured in 182 patients with advanced HF secondary to left ventricular systolic dysfunction. The predictive value of apelin for the primary end point of all-cause mortality was assessed over a median follow-up period of 544 (IQR: 196–923) days. Results: In total, 30 patients (17%) reached the primary end point. Of those patients with a plasma apelin concentration above the median, 14 (16%) reached the primary end point compared with 16 (17%) of those with plasma apelin levels below the median (p = NS). NT-proBNP was the most powerful prognostic marker in this population (log rank statistic: 10.37; p = 0.001). Conclusion: Plasma apelin concentrations do not predict medium to long-term prognosis in patients with advanced HF secondary to left ventricular systolic dysfunction.

Aims: Effective cardiac resynchronization therapy may depend upon the distance between left ventricular (LV) and right ventricular (RV) pacing leads. We assessed the influence of lead separation upon circulating NT-proBNP. Materials & methods: In total, 132 patients underwent assessment, including NT-proBNP assay, before and after cardiac resynchronization therapy. 3D lead separation was calculated from postero-anterior and lateral chest radiography. Results: Lead separation correlated with NT-proBNP reduction (r = 0.25; p = 0.004). Circulating NT-proBNP only fell in those with lead separation in the upper two quartiles. Deteriorating NT-proBNP occurred in 44 patients. Lead separation was less in these patients compared with those with an improvement (corrected 3D lead separation: 148.0 ± 5.38 and 170.5 ± 4.21 mm, respectively; p = 0.0018). Conclusion: Left ventricular–right ventricular lead separation correlates with postcardiac resynchronization therapy improvements in circulating NT-proBNP, a powerful marker of heart failure status and prognosis. Attention should be paid to achieving maximal lead separation at implantation.