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In the last two years, the COVID-19 pandemic has undeniably changed everyday life and significantly reshaped the healthcare systems. Besides the direct effect on daily care leading to significant excess mortality, several collateral damages have been observed during the pandemic. The impact of the pandemic led to staff shortages, disrupted education, worse healthcare professional well-being, and a lack of proper clinical training and research. In this review we highlight the results of these important changes and how can the healthcare systems can adapt to prevent unprecedented events in case of future catastrophes.

Aims There is little evidence of the impact of syncope in implantable cardioverter-defibrillator (ICD) patients in routine community hospital care. This single-centre retrospective study sought to evaluate the incidence and prognostic significance of syncope in consecutive ICD patients. Methods and results Data were collected on consecutive patients undergoing first ICD implantation between January 2009 and December 2019. The primary endpoints were the first occurrence of all-cause syncope, all-cause mortality, and all-cause hospitalization. Multivariate Cox proportional hazard models were used to identify risk factors associated with syncope and to analyse the subsequent risk of mortality and hospitalization. 1003 patients (58% primary prevention) were included in the final analysis. During a mean follow-up of 1519 ± 1055 days, 106 (10.6%) experienced syncope, 304 died (30.3%), and 477 (47.5%) were hospitalized for any cause. In an analysis adjusted for baseline variables, the first occurrence of syncope was associated with a significantly increased risk of mortality (HR 2.82, P < 0.001) and the first occurrence of hospitalization (HR 2.46, P = 0.002). Conclusion Syncope in ICD recipients is common and associated with a poor prognosis irrespective of baseline variables and ICD programming. The occurrence of syncope is associated with a significant increase in the risk of mortality and hospitalization.

Purpose: Myocardial fibrosis, measured using cardiovascular magnetic resonance extracellular volume (ECV), is associated with adverse outcome in heart failure with preserved ejection fraction (HFpEF), but the mechanisms by which myocardial fibrosis exerts this deleterious effect are unclear. We aimed to determine whether myocardial fibrosis causes changes in cardiovascular structure and function, circulating biomarkers and functional status.Methods: Mediation analyses of data from the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial were conducted using the Baron and Kenny approach under a structural equation modelling framework to estimate average causal mediation effects, in order to determine whether changes in myocardial ECV, absolute myocardial extracellular matrix volume, and myocardial cellular volume (the mediator variables) following antifibrotic therapy, caused changes in cardiovascular structure and function, circulating biomarkers and functional status (the outcome variables).Results: Regression of myocardial fibrosis correlated with improvements in functional status (6-minute walk test distance [r=-0.28, p=0.021] and KCCQ clinical summary score [r=-0.23, P=0.045]). Pirfenidone had significant effects on the mediator variables, but the only outcome variable that demonstrated a treatment effect was left ventricular ejection fraction (LVEF) (p=0.011). The estimated average causal mediation effects of myocardial ECV, absolute myocardial extracellular matrix volume and absolute myocardial cellular volume on LVEF were 6.1%, 21.5%, and 13.7% respectively, none of which were significant (p=0.608, p=0.123 and p=0.186 respectively).Conclusion: Regression of myocardial fibrosis was associated with improvements in functional status. The small improvement in LVEF associated with pirfenidone was not mediated by myocardial fibrosis regression.(PIROUETTE; NCT02932566).

Background For patients with heart failure, prescription of loop diuretics (LD) and of higher doses are associated with an adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM). Methods Associations between outcomes and both furosemide-equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were classified as (i) dose↑ (FED increase by ≥ 50% or newly initiated); (ii) dose↓ (FED decrease by ≥ 50%); (iii) stable dose (change in FED by Results Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22], p = 0.003). Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% were dose↓; 26% were stable dose and 14% were dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of the primary outcome (HR 2.42 [95% CI 1.19–4.93], p = 0.015), while dose↑ had the worst prognosis (HR 2.76 [95% CI 1.27–6.03], p = 0.011). Results were similar for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with an improved outcome (HR 0.43 [95% CI 0.28–0.65], p Conclusions In patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never receive LD have an excellent prognosis. Graphical abstract

Within the abstract, the following phrase in the ‘Methods’ section “According to FED trajectory, patients were classified as (i) dose (FED increase by ≥ 50% or newly initiated);” was corrected to read “According to FED trajectory, patients were classified as (i) dose ↑ (FED increase by ≥ 50% or newly initiated);”. In the ‘Results’ section of the abstract, the sentence “Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22, p = 0.003].” was corrected to “Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04–1.22], p = 0.003).” Finally, in Table 1, the LVEF, % for Dose↓ patients was given incorrectly whenit should have been “28 (22-34)” and the N value has been corrected from “263” to “282”. The original article has been corrected.

Background For patients with heart failure, prescription of loop diuretics (LD) and higher doses are associated with adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM). Methods Associations between outcomes and both furosemide equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were divided in i) dose↑ (FED increase by ≥50% or newly initiated); ii) dose↓ (FED decrease by ≥50%); iii) stable dose (change in FED by Results Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20mg increase: 1.12 [95% CI 1.04-1.22, p=0.003]. Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% dose↓; 26% stable dose and 14% dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of primary outcome (HR 2.42 [95% CI: 1.19-4.93], p=0.015), while dose↑ had the worst prognosis (HR 2.76 [95% C.I. 1.27-6.03], p=0.011). The results were consistent for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with improved outcome (HR 0.43 [95% C.I. 0.28-0.65], p Conclusions In a large cohort of patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never require LD have an excellent prognosis.

Aims Specialist cardiology care is associated with a prognostic benefit in patients with HF with reduced ejection fraction (HFrEF) admitted with decompensated heart failure (HF). However, up to one third of patients admitted with HF and normal ejection fraction (HFnEF) do not receive specialist cardiology input. Whether this has prognostic implications is unknown. Methods Data on patients hospitalised with HFnEF from two tertiary centres were analysed. The primary outcome measure was all-cause mortality during follow-up. The secondary outcome was in-hospital mortality. Results A total of 1,413 patients were included in the study. Of these, 23% (n=322) did not receive in-hospital specialist cardiology input. Patients seen by a cardiologist were less likely to have hypertension (73% vs 79%, p=0.03) and respiratory comorbidities (25% vs 31%, p=0.02) compared to those who did not receive specialist input. Similarly, clinical presentation was more severe for those who received specialist input (NYHA III/IV 83% vs 75% respectively, p=0.003; moderate-to-severe peripheral oedema 65% vs 54%, p Conclusion In-hospital cardiology specialist input has no long-term prognostic advantage in patients with HFnEF but it is independently associated with reduced in-hospital mortality.

Background Neutrophil–lymphocyte ratio (NLR) is an easily obtained inflammatory biomarker. Recently it has emerged as baseline NLR is independently associated with incident cardiovascular (CV) events and all-cause mortality. However, its role in acute myocarditis (AM) has not been evaluated. Purpose The aim of the present study was to investigate the prognostic value of NLR in patients with AM. Methods All consecutive patients with a diagnosis of AM admitted to two tertiary referral cardiac centres (King's College Hospital, London, UK and Azienda Sanitaria Universitaria Giuliano-Isontina, Trieste, Italy) between October 2006 and June 2020 were included in the study. Diagnosis was confirmed by either cardiac magnetic resonance or endomyocardial biopsy. The outcome measure was all-cause mortality. Patients were divided into two groups according to NLR value defined in previous studies (i.e, 2.5). Results A total of 260 patients with AM were included in the study. Baseline characteristics were comparable in both groups. Approximately two thirds of patients were males (n=175, 67%) with a mean age of 45±16 years. Main clinical presentation was predominantly infarct-like (n=189, 73%), followed by heart failure (HF) (n=46, 18%) and arrhythmic (n=25, 10%). Patients admitted with a HF presentation were more prevalent in the group with elevated NLR, while no difference was found in the other clinical presentations. For all patients, ECG features were comparable between groups. However, patients with elevated NLR presented with slightly lower LVEF (54±11% vs 49±13% respectively, p=0.001). Higher NLR was associated with worse prognosis (Figure 1, p=0.02). Conclusions The NLR is a promising and accessible inflammatory biomarker. In patients with AM, elevated NLR is associated with worse prognosis. Further research is advocated to confirm these data in larger populations.

Aims Acute myocarditis (AM) is a heterogeneous condition with variable estimates of survival. Contemporary criteria for the diagnosis of clinically suspected AM enable non-invasive assessment, resulting in greater sensitivity and more representative cohorts. We aimed to describe the demographic characteristics and long-term outcomes of patients with AM diagnosed using non-invasive criteria. Methods and Results A total of 199 patients with cardiac magnetic resonance (CMR)-confirmed AM were included. The majority (n=130, 65%) were male and the average age was 39±16 years. Half of patients were White (n=99, 52%) with the remainder from Black and Minority Ethnic (BAME) groups. The most common clinical presentation was with chest pain (n=156, 78%), with smaller numbers presenting with breathlessness (n=25, 13%) and arrhythmias (n=18, 9%). Patients admitted with breathlessness were sicker and more often required inotropes, steroids, and renal replacement therapy (p Conclusions AM is highly heterogeneous with an overall favourable prognosis. Three quarters of patients with AM present with chest pain and this is associated with a benign prognosis. AM presenting with life-threatening arrhythmias is associated with higher risk of adverse events.

BackgroundClozapine is associated with increased risk of myocarditis. However, many common side-effects of clozapine overlap with the clinical manifestations of myocarditis. As a result, there is uncertainty about which signs, symptoms and investigations are important in distinguishing myocarditis from benign adverse effects of clozapine. Clarity on this issue is important, since missing a diagnosis of myocarditis or discontinuing clozapine unnecessarily may both have devastating consequences.AimsTo examine the clinical characteristics of clozapine-induced myocarditis and to identify which signs and symptoms distinguish true myocarditis from other clozapine adverse effects.MethodA retrospective analysis of the record database for 247 621 patients was performed. A natural language processing algorithm identified the instances of patients in which myocarditis was suspected. The anonymised case notes for the patients of each suspected instance were then manually examined, and those whose instances were ambiguous were referred for an independent assessment by up to three cardiologists. Patients with suspected instances were classified as having confirmed myocarditis, myocarditis ruled out or undetermined.ResultsOf 254 instances in 228 patients with suspected myocarditis, 11.4% (n = 29 instances) were confirmed as probable myocarditis. Troponin and C-reactive protein (CRP) had excellent diagnostic value (area under the curve 0.975 and 0.896, respectively), whereas tachycardia was of little diagnostic value. All confirmed instances occurred within 42 days of clozapine initiation.ConclusionsSuspicion of myocarditis can lead to unnecessary discontinuation of clozapine. The ‘critical period’ for myocarditis emergence is the first 6 weeks, and clinical signs including tachycardia are of low specificity. Elevated CRP and troponin are the best markers for the need for further evaluation.

Heart failure (HF) can be considered a disease of older people. It is a leading cause of hospitalisation and is associated with high rates of morbidity and mortality in the over-65s. In 2012, an editorial in this journal detailed the latest HF research and guidelines, calling for greater integration of geriatricians in HF care. This current article reflects upon what has been achieved in this field in recent years, highlighting some future challenges and promising areas. It is written from the perspective of one such integrated team and explores the new role of cardiogeriatrician, working in a multidisciplinary team to deliver and improve care to increasingly complex, older, frail patients with multiple comorbidities who present with primary cardiology problems, especially decompensated HF. Geriatric liaison has improved the care of frail patients in orthopaedics, cancer services, stroke, acute medicine and numerous community settings. We propose that this vital role should now be extended to cardiology teams in general and to HF in particular.

Background On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures. Methods and results Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87–0.95; IRR 0.95, 95% CI 0.89–1.02; and IRR 0.87, 95% CI 0.83–0.93, respectively]. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97–1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88–0.96; out-of-hospital, IRR 1.04, 95% CI1.01–1.08). These trends were consistent irrespective of sex and age. Conclusions Among patients with established cardiovascular disease, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during lockdown compared with the same period in the preceding year, irrespective of age and sex., Graphical Abstract

Background: Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure. Methods: AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin

International audience; Iron deficiency (ID) is a comorbid condition frequently seen in patients with heart failure (HF). Iron has an important role in the transport of oxygen, and is also essential for skeletal and cardiac muscle, which depend on iron for oxygen storage and cellular energy production. Thus, ID per se, even without anaemia, can be harmful. In patients with HF, ID is associated with a poorer quality of life (QoL) and exercise capacity, and a higher risk of hospitalisations and mortality, even in the absence of anaemia. Despite its negative clinical consequences, ID remains under-recognised. However, it is easily diagnosed and managed, and the recently revised 2021 European Society of Cardiology (ESC) guidelines on HF provide specific recommendations for its diagnosis and treatment. Prospective randomised controlled trials in patients with symptomatic HF with reduced ejection fraction (HFrEF) show that correction of ID using intravenous iron (principally ferric carboxymaltose [FCM]) provides improvements in symptoms of HF, exercise capacity and QoL, and a recent trial demonstrated that FCM therapy following hospitalisation due to acute decompensated HF reduced the risk of subsequent HF hospitalisations. This review provides a summary of the epidemiology and pathophysiology of ID in HFrEF, and practical guidance on screening, diagnosing, and treating ID.

Identifying people who are at risk of being admitted to hospital (hospitalised) for heart failure and death, and particularly those who have not previously been hospitalised for heart failure, is a priority. We aimed to develop and externally validate a prognostic model involving contemporary deep phenotyping that can be used to generate individual risk estimates of hospitalisation for heart failure or all-cause mortality in patients with, or at risk of, heart failure, but who have not previously been hospitalised for heart failure.Between June 1, 2016, and May 31, 2018, 3019 consecutive adult patients (aged ≥16 years) undergoing cardiac magnetic resonance (CMR) at Manchester University National Health Service Foundation Trust, Manchester, UK, were prospectively recruited into a model development cohort. Candidate predictor variables were selected according to clinical practice and literature review. Cox proportional hazards modelling was used to develop a prognostic model. The final model was validated in an external cohort of 1242 consecutive adult patients undergoing CMR at the University of Pittsburgh Medical Center Cardiovascular Magnetic Resonance Center, Pittsburgh, PA, USA, between June 1, 2010, and March 25, 2016. Exclusion criteria for both cohorts included previous hospitalisation for heart failure. Our study outcome was a composite of first hospitalisation for heart failure or all-cause mortality after CMR. Model performance was evaluated in both cohorts by discrimination (Harrell's C-index) and calibration (assessed graphically).Median follow-up durations were 1118 days (IQR 950-1324) for the development cohort and 2117 days (1685-2446) for the validation cohort. The composite outcome occurred in 225 (7·5%) of 3019 patients in the development cohort and in 219 (17·6%) of 1242 patients in the validation cohort. The final, externally validated, parsimonious, multivariable model comprised the predictors: age, diabetes, chronic obstructive pulmonary disease, N-terminal pro-B-type natriuretic peptide, and the CMR variables, global longitudinal strain, myocardial infarction, and myocardial extracellular volume. The median optimism-adjusted C-index for the externally validated model across 20 imputed model development datasets was 0·805 (95% CI 0·793-0·829) in the development cohort and 0·793 (0·766-0·820) in the external validation cohort. Model calibration was excellent across the full risk profile. A risk calculator that provides an estimated risk of hospitalisation for heart failure or all-cause mortality at 3 years after CMR for individual patients was generated.We developed and externally validated a risk prediction model that provides accurate, individualised estimates of the risk of hospitalisation for heart failure and all-cause mortality in patients with, or at risk of, heart failure, before first hospitalisation. It could be used to direct intensified therapy and closer follow-up to those at increased risk.The UK National Institute for Health Research, Guerbet Laboratories, and Roche Diagnostics International.

Purpose of Review Palliative care is increasingly acknowledged as beneficial in supporting patients and families affected by heart failure, but policy documents have generally focused on the chronic form of this disease. We examined palliative care provision for those with acute heart failure, based on the recently updated National Consensus Project Clinical Practice Guidelines for Quality Palliative Care. Recent Findings The commonest reason for hospitalization in those > 65 years, acute heart failure admissions delineate crisis points on the unpredictable disease trajectory. Palliative care is underutilized, often perceived as limited to end-of-life care rather than determined by regular systematic needs assessment. No dominant paradigm of palliative care provision has emerged from the nascent evidence base related to this clinical cohort, underscoring the need for further research. Summary Embedding palliative support as mainstream to heart failure care from the point of diagnosis may better ensure treatment strategies for those admitted with acute heart failure remain consistent with patients’ preferences and values.

AIMS: Admission rates for acute decompensated heart failure (HF) declined during the COVID-19 pandemic. However, the impact of this reduction on hospital mortality is unknown. We describe temporal trends in the presentation of patients with acute HF and their in-hospital outcomes at two referral centres in London during the COVID-19 pandemic. METHODS AND RESULTS: A total of 1372 patients hospitalized for HF in two referral centres in South London between 7 January and 14 June 2020 were included in the study and their outcomes compared with those of equivalent patients of the same time period in 2019. The primary outcome was all-cause in-hospital mortality. The number of HF hospitalizations was significantly reduced during the COVID-19 pandemic, compared with 2019 (P < 0.001). Specifically, we observed a temporary reduction in hospitalizations during the COVID-19 peak, followed by a return to 2019 levels. Patients admitted during the COVID-19 pandemic had demographic characteristics similar to those admitted during the equivalent period in 2019. However, in-hospital mortality was significantly higher in 2020 than in 2019 (P = 0.015). Hospitalization in 2020 was independently associated with worse in-hospital mortality (hazard ratio 2.23, 95% confidence interval 1.34-3.72; P = 0.002). CONCLUSIONS: During the COVID-19 pandemic there was a reduction in HF hospitalization and a higher rate of in-hospital mortality. Hospitalization for HF in 2020 is independently associated with more adverse outcomes. Further studies are required to investigate the predictors of these adverse outcomes to help inform potential changes to the management of HF patients while some constraints to usual care remain.

Whereas multiple national, international, and trial registries for heart failure have been created, international standards for clinical assessment and outcome measurement do not currently exist. The working group’s objective was to facilitate international comparison in heart failure care, using standardized parameters and meaningful patient-centered outcomes for research and quality of care assessments. The International Consortium for Health Outcomes Measurement recruited an international working group of clinical heart failure experts, researchers, and patient representatives to define a standard set of outcomes and risk-adjustment variables. This was designed to document, compare, and ultimately improve patient care outcomes in the heart failure population, with a focus on global feasibility and relevance. The working group employed a Delphi process, patient focus groups, online patient surveys, and multiple systematic publications searches. The process occurred over 10 months, employing 7 international teleconferences. A 17-item set has been established, addressing selected functional, psychosocial, burden of care, and survival outcome domains. These measures were designed to include all patients with heart failure, whether entered at first presentation or subsequent decompensation, excluding cardiogenic shock. Sources include clinician report, administrative data, and validated patient-reported outcome measurement tools: the Kansas City Cardiomyopathy Questionnaire; the Patient Health Questionnaire-2; and the Patient-Reported Outcomes Measurement Information System. Recommended data included those to support risk adjustment and benchmarking across providers and regions. The International Consortium for Health Outcomes Measurement developed a dataset designed to capture, compare, and improve care for heart failure, with feasibility and relevance for patients and clinicians worldwide., Central Illustration, Highlights • ICHOM seeks to help standardize and align outcome measurement efforts globally. • Standardization and alignment of this sort does not exist for heart failure. • The heart failure working group developed a standard set of 17 outcomes to be measured. • ICHOM hopes this standardization effort will increase quality and value in heart failure care.

The past year has brought many new concepts and an abundance of new data on the nature, management, and outcome of heart failure. The pace of change is accelerating. We look forward to an exciting new decade of research. The prognosis of cardiovascular disease is determined to a large extent by the ability to delay or prevent the development and progression of heart failure.1 Accordingly, attention is shifting to earlier diagnosis of and intervention for heart failure. Patients with type-2 diabetes mellitus (T2DM)2 or coronary artery disease (CAD)3 have a relatively good prognosis unless plasma concentrations of natriuretic peptides are increased, indicating important cardiac or renal dysfunction. Adoption of a simple ‘Universal Definition’ of heart failure based on natriuretic peptides would facilitate early diagnosis and treatment but lead to an enormous increase in its prevalence and demand upon medical services.4 We need to prepare for the impending shock.

Myocardial fibrosis, measured using magnetic resonance extracellular volume (ECV), associates with adverse outcome in heart failure with preserved ejection fraction (HFpEF). In the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial, the novel anti-fibrotic agent pirfenidone reduced myocardial fibrosis. We sought to identify baseline characteristics that associate with myocardial fibrotic burden, the change in myocardial fibrosis over a year, and predict response to pirfenidone in patients with HFpEF. Amongst patients enrolled in the PIROUETTE trial (n = 107), linear regression models were used to assess the relationship between baseline variables and baseline myocardial ECV, with change in myocardial ECV adjusting for treatment allocation, and to identify variables that modified the pirfenidone treatment effect. Body mass index, left atrial reservoir strain, haemoglobin and aortic distensibility were associated with baseline ECV in stepwise modelling, and systolic blood pressure, and log N-terminal pro B-type natriuretic peptide were associated with baseline ECV in clinically-guided modelling. QRS duration, left ventricular mass and presence of an infarct at baseline were associated with an increase in ECV from baseline to week 52. Whilst QRS duration, presence of an infarct, global longitudinal strain and left atrial strain modified the treatment effect of pirfenidone when considered individually, no variable modified treatment effect on multivariable modelling. Baseline characteristics were identified that associate with myocardial fibrosis and predict change in myocardial fibrosis. No variables that independently modify the treatment effect of pirfenidone were identified (PIROUETTE, NCT02932566).

Background: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19–associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Methods: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19–associated AM. Results: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19–associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia ( P =0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P Conclusions: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

Large randomized controlled trials (RCTs) have led to major changes in the treatment of patients with heart failure and reduced left ventricular ejection fraction (HFrEF) and these advances are included in the recent European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) guidelines issued in 2021 and 2022, respectively. According to both guidelines, treatment of patients with HFrEF is based on the administration of four classes of drugs that reduce the primary endpoint of cardiovascular death and HF hospitalizations in RCTs: angiotensin-converting enzyme or angiotensin receptor neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter 2 inhibitors. Specific sequences of treatment are not recommended but emphasis is given to reaching treatment with all four drugs as early as possible. Further treatments are considered in selected patients including ivabradine, hydralazine nitrates, digoxin, and the new agent vericiguat. Specific treatments, mostly new, for cardiovascular and non-cardiovascular comorbidities are also given. The aim of this article is to compare the two recent guidelines issued by the ESC and ACC/AHA/HFSA and show the few differences and the many consistent recommendations, now more numerous given the evidence available for many new treatments.

To develop a suite of quality indicators (QIs) for the evaluation of the quality of care for adults with heart failure (HF).We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care for the management of HF by constructing a conceptual framework of HF care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. The Working Group comprised experts in HF management including Task Force members of the 2021 European Society of Cardiology (ESC) Clinical Practice Guidelines for HF, members of the Heart Failure Association (HFA), Quality Indicator Committee and a patient representative. In total, 12 main and 4 secondary QIs were selected across five domains of care for the management of HF: (1) structural framework, (2) patient assessment, (3) initial treatment, (4) therapy optimization, and (5) assessment of patient health-related quality of life.We present the ESC HFA QIs for HF, describe their development process and provide the scientific rationale for their selection. The indicators may be used to quantify and improve adherence to guideline-recommended clinical practice and thus improve patient outcomes.

IMPORTANCE: Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed when they are older than 60 years (ie, late-onset DCM). OBJECTIVE: To investigate the prevalence, type, and prognostic impact of disease-associated rare variants in patients with late-onset DCM. DESIGN, SETTING, AND PARTICIPANTS: A population of patients with late-onset DCM who had undergone genetic testing in 7 international tertiary referral centers worldwide were enrolled from March 1990 to August 2020. A positive genotype was defined as the presence of pathogenic or likely pathogenic (P/LP) variants. MAIN OUTCOMES AND MEASURES: The study outcome was all-cause mortality. RESULTS: A total of 184 patients older than 60 years (103 female [56%]; mean [SD] age, 67 [6] years; mean [SD] left ventricular ejection fraction, 32% [10%]) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin-truncating variants were the most prevalent (present in 46 [25%] of the total population and accounting for 46 [69%] of all genotype-positive patients). During a median (interquartile range) follow-up of 42 (10-115) months, 23 patients (13%) died; 17 (25%) of these were carriers of P/LP variants, while 6 patients (5.1%) were genotype-negative. CONCLUSIONS AND RELEVANCE: Late-onset DCM might represent a distinct subgroup characterized by and a high genetic variation burden, largely due to titin-truncating variants. Patients with a positive genetic test had higher mortality than genotype-negative patients. These findings support the extended use of genetic testing also in older patients.

Aims Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both ‘direct’, through infection, and ‘indirect’, through changes in healthcare. Methods and results We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0). Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60–100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2–3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths. Conclusion Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic., Graphical Abstract Graphical Abstract

Aims Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed after 60 years of age (i.e. late-onset DCM). The aim is to investigate the prevalence, type, and prognostic impact of disease-associated rare variants in late-onset DCM patients. Methods and results We analysed a population of late-onset DCM patients who had undergone genetic testing in seven international tertiary referral centres worldwide. A positive genotype was defined as the presence of ‘pathogenic’ or ‘likely pathogenic’ (P/LP) variants. The study outcome was all-cause mortality. 184 patients over age 60 years (56% females, mean age 67 ± 6 years, mean left ventricular ejection fraction 32 ± 10%) were studied. Sixty-six patients (36%) were carriers of a P/LP variant. Titin truncating variants (TTNtv) were the most prevalent (present in 25% of the total population and accounting for 69% of all genotype-positive patients). During a median follow-up of 42 months (interquartile range: 10–115), 23 patients (13%) died; 17 of these (25%) were carriers of P/LP variants while six patients (5.1%) were genotype-negative (P Conclusions In the largest series worldwide, to date, of patients with late-onset DCM, we found a high prevalence of female sex and a high genetic mutation burden, largely due to TTNtv. Patients with a positive genetic test had higher mortality than genotype-negative patients. These findings support the extended use of genetic testing also in the elderly.

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.

Aims Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population. Methods and results The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5–5.3, P = 0.018) for OSS and 2.8 (0.3–5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3–5.6, P = 0.028) for OSS and 2.9 (0.2–5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM. Conclusion In iron-deficient patients with HF and left ventricular ejection fraction, Graphical Abstract

In heart failure with preserved ejection fraction (HFpEF), the occurrence of myocardial fibrosis is associated with adverse outcome. Whether pirfenidone, an oral antifibrotic agent without hemodynamic effect, is efficacious and safe for the treatment of HFpEF is unknown. In this double-blind, phase 2 trial ( NCT02932566 ), we enrolled patients with heart failure, an ejection fraction of 45% or higher and elevated levels of natriuretic peptides. Eligible patients underwent cardiovascular magnetic resonance and those with evidence of myocardial fibrosis, defined as a myocardial extracellular volume of 27% or greater, were randomly assigned to receive pirfenidone or placebo for 52 weeks. Forty-seven patients were randomized to each of the pirfenidone and placebo groups. The primary outcome was change in myocardial extracellular volume, from baseline to 52 weeks. In comparison to placebo, pirfenidone reduced myocardial extracellular volume (between-group difference, −1.21%; 95% confidence interval, −2.12 to −0.31; P = 0.009), meeting the predefined primary outcome. Twelve patients (26%) in the pirfenidone group and 14 patients (30%) in the placebo group experienced one or more serious adverse events. The most common adverse events in the pirfenidone group were nausea, insomnia and rash. In conclusion, among patients with HFpEF and myocardial fibrosis, administration of pirfenidone for 52 weeks reduced myocardial fibrosis. The favorable effects of pirfenidone in patients with HFpEF will need to be confirmed in future trials. In a double-blind, randomized phase 2 trial, treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the oral antifibrotic agent pirfenidone reduced myocardial fibrosis.

Ferric derisomaltose (FDI) is an intravenous (IV) high-dose iron formulation approved in\ud the US for the treatment of iron deficiency anemia in adults who are intolerant of/have\ud had an unsatisfactory response to oral iron, or who have non-dialysis-dependent chronic\ud kidney disease (NDD-CKD). FERWON-NEPHRO was a randomized, open-label, multicenter clinical trial evaluating the safety and efficacy of a single infusion of FDI 1,000 mg\ud versus up to 5 doses of iron sucrose (IS) 200 mg (recommended cumulative dose, 1,000\ud mg) over 8 weeks in patients with NDD-CKD and iron deficiency anemia. Of 1,525 patients\ud included in the safety analysis, 244 (16%) had a history of heart failure (HF). Overall, the\ud rate of serious or severe hypersensitivity reactions was low and did not differ between\ud treatment groups. Cardiovascular adverse events (AEs) were reported for 9.4% of\ud patients who had HF and 4.2% who did not. Time to first cardiovascular AE was longer\ud following administration of FDI compared with IS (hazard ratio: 0.59 [95% CI: 0.37,\ud 0.92]; p=0.0185), a difference that was similar in patients with or without HF (p=0.908 for\ud interaction). Patients achieved a faster hematological response (assessed by changes in\ud hemoglobin and ferritin concentrations, and increase in transferrin saturation) with FDI\ud versus IS. In conclusion, in patients with NDD-CKD, a single infusion of FDI was safe,\ud well tolerated, and was associated with fewer cardiovascular AEs and a faster hematological response, compared to multiple doses of IS. These effects were similar for patients with and without HF.