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BACKGROUND: Data concerning the long-term risk of heart failure (HF) in patients with takotsubo syndrome (TTS) are sparse. We compared the rates of death and hospitalization due to HF with matched individuals from the background population and patients with ST-segment elevation myocardial infarction (STEMI).METHODS: In this nationwide observational cohort study, all patients with first-time TTS (2011-2018) who were alive at discharge were identified by using data from Danish nationwide registries. These were matched for age and sex with individuals from the background population (1:4 matching) and with patients with STEMI who were alive at discharge (1:3 matching).RESULTS: A total of 881 patients with TTS who were alive at discharge were identified (median age 70 years; 89.4% men). During a mean follow-up of 2.9 years, the incidence rates of death, HF hospitalization, and TTS recurrence in survivors of TTS were 6.9, 0.9 and 1.1 events per 100 person-years. The corresponding absolute 3-year risks were 9.3%, 1.8% and 2.5%, respectively. Survivors of TTS had higher associated rates of death compared with the background population (hazard ratio [HR] 2.05 [95% CI, 1.62-2.60]) and survivors of STEMI (HR 1.69 [1.34-2.13]). Similarly, survivors of TTS had higher associated rates of hospitalization due to HF compared with the background population (HR 4.24 [1.88-9.53]), but lower rates compared with survivors of STEMI (HR 0.34 [0.20-0.56]). Propensity-score matched analyses yielded similar results.CONCLUSIONS: Survivors of TTS had significantly higher associated mortality rates than the background population and survivors of STEMI. Survivors of TTS had lower HF hospitalization rates than survivors of STEMI, but the rates were higher than those of the background population.

Background : N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations are independent prognostic markers in patients with heart failure and reduced ejection fraction (HFrEF). Whether a differential risk association between NT-proBNP plasma concentrations and risk of cardiovascular (CV) vs non-CV adverse events exists is not well known. Objective : To assess if there is a differential proportional risk of CV vs non-CV adverse events by NT-proBNP plasma concentrations. Methods : In this post hoc combined analysis of PARADIGM-HF and ATMOSPHERE trials, proportion of CV vs non-CV mortality and hospitalizations were assessed by NT-proBNP levels ( 3000 pg/mL) at baseline using Cox regression adjusting for traditional risk factors. Results : A total of 14,737 patients with mean age of 62 ± 8 years (24% history of atrial fibrillation [AF]) were studied. For CV deaths, the event rates per 1000 patient-years steeply increased from 33.8 in the ≤400 pg/mL group to 142.3 in the ≥3000 pg/mL group, while the non-CV death event rates modestly increased from 9.0 to 22.7, respectively. Proportion of non-CV deaths decreased across the 5 NT-proBNP groups (21.1%, 18.4%, 17.9%, 17.4%, and 13.7% respectively). Similar trend was observed for non-CV hospitalizations (46.4%, 42.6%, 42.9%, 42.0%, and 36.9% respectively). These results remained similar when stratified according to the presence of AF at baseline and prior HF hospitalization within last 12 months. Conclusions : The absolute CV event rates per patient years of follow-up were greater and had higher stepwise increases than non-CV event rates across a broad range of NT-proBNP plasma concentrations indicating a differential risk of CV events at varying baseline NT-proBNP values. These results have implications for future design of clinical trials.

Background Data on long-term cardiovascular outcomes in systemic lupus erythematosus (SLE) are sparse. Objectives This study sought to examine the long-term risk and prognosis associated with cardiovascular outcomes, including heart failure (HF), in patients with SLE. Methods Using Danish administrative registries, risks of outcomes were compared between SLE patients (diagnosed 1996 to 2018, no history of cardiovascular disease) and age-, sex-, and comorbidity-matched control subjects from the background population (matched 1:4). Furthermore, mortality following HF diagnosis was compared between SLE patients developing HF and age- and sex-matched non-SLE control subjects with HF (matched 1:4). Results A total of 3,411 SLE patients (median age: 44.6 years [25th to 75th percentile: 31.9 to 57.0 years]; 14.1% men) were matched with 13,644 control subjects. The median follow-up was 8.5 years (25th to 75th percentile: 4.0 to 14.4 years). Absolute 10-year risks of outcomes were: HF, 3.71% (95% confidence interval [CI]: 3.02% to 4.51%) for SLE patients, 1.94% (95% CI: 1.68% to 2.24%) for control subjects; atrial fibrillation, 4.35% (95% CI: 3.61% to 5.18%) for SLE patients, 2.82% (95% CI: 2.50% to 3.16%) for control subjects; ischemic stroke, 3.75% (95% CI: 3.06% to 4.54%) for SLE patients, 1.92% (95% CI: 1.66% to 2.20%) for control subjects; myocardial infarction, 2.17% (95% CI: 1.66% to 2.80%) for SLE patients, 1.49% (95% CI: 1.26% to 1.75%) for control subjects; venous thromboembolism, 6.03% (95% CI: 5.17% to 6.98%) for SLE patients, 1.68% (95% CI: 1.44% to 1.95%) for control subjects; and the composite of implantable cardioverter-defibrillator implantation/ventricular arrhythmias/cardiac arrest, 0.89% (95% CI: 0.58% to 1.31%) for SLE patients, 0.30% (95% CI: 0.20% to 0.43%) for control subjects. SLE with subsequent HF was associated with higher mortality compared with HF without SLE (adjusted hazard ratio: 1.50; 95% CI: 1.08 to 2.08). Conclusions SLE patients had a higher associated risk of HF and other cardiovascular outcomes compared with matched control subjects. Among patients developing HF, a history of SLE was associated with higher mortality.

Objectives The purpose of this study was to assess the efficacy and safety of dapagliflozin in patients taking or not taking an mineralocorticoid receptor antagonist (MRA) at baseline in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. Background MRAs and sodium glucose co-transporter 2 inhibitors each have diuretic activity, lower blood pressure, and reduce glomerular filtration rate (GFR). Therefore, it is important to investigate the safety, as well as efficacy, of their combination. Methods A total of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) were randomized to placebo or dapagliflozin 10 mg daily. The efficacy of dapagliflozin on the primary composite outcome (cardiovascular death or episode of worsening heart failure) and its components was examined according to MRA use, as were predefined safety outcomes. Results A total of 3,370 patients (71%) were treated with an MRA and they were younger (65 vs. 69 years of age), less often from North America (9% vs. 26%), had worse New York Heart Association functional class (35% vs. 25% in class III/IV), lower left ventricular ejection fraction (30.7% vs. 31.9%) and systolic blood pressure (120.3 vs. 125.5 mm Hg), but higher estimated GFR (67.1 vs. 62.6 ml/min/1.73 m2), than patients not taking an MRA. The benefit of dapagliflozin compared with placebo was similar in patients taking or not taking an MRA: hazard ratio: 0.74 (95% confidence interval [CI]: 0.63 to 0.87) versus 0.74 (95% CI: 0.57 to 0.95), respectively, for the primary endpoint (p value for interaction = 0.97); similar findings were observed for secondary endpoints. In both MRA subgroups, safety outcomes were similar in patients randomized to dapagliflozin or placebo. Conclusions Dapagliflozin was similarly efficacious and safe in patients with HFrEF taking or not taking an MRA, supporting the use of both drugs together. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124 )

Objectives This study aims to identify patients with nonischemic heart failure who are more likely to benefit from implantable cardioverter-defibrillator (ICD) implantation by use of established risk prediction models. Background It has been debated whether an ICD for primary prevention reduces mortality in patients with nonischemic heart failure. Methods The Seattle Heart Failure Model (SHFM) predicts all-cause mortality whereas the Seattle Proportional Risk Model (SPRM) predicts the proportion of sudden cardiac death (SCD) versus nonsudden death, with a higher score indicating a greater proportion of SCD. We report the effect of ICD implantation on all-cause mortality and SCD, according to median SPRM and SHFM scores in all 1,116 patients enrolled in the DANISH (Danish study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on mortality) trial. Results Among patients with an SPRM score above the median (n = 558), ICD implantation reduced all-cause mortality (hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.43 to 0.94), whereas patients with lower SPRM scores (n = 558) had no effect (HR: 1.08; 95% CI: 0.78 to 1.49, p for interaction = 0.04). The corresponding numbers for SHFM score above and below the median were HR: 0.84; 95% CI: 0.62 to 1.13 and HR: 0.82; 95% CI: 0.53 to 1.28, respectively (p for interaction = 0.980). In 177 patients with upper SPRM/upper SHFM, ICD implantation reduced all-cause mortality (HR: 0.45; 95% CI: 0.25 to 0.80) when compared to 381 patients with lower SPRM/upper SHFM (HR: 1.09; 95% CI: 0.76 to 1.55) (p for interaction Conclusions Nonischemic heart failure patients with high predicted relative likelihood of SCD, as estimated by higher SPRM score, seemed to benefit from ICD implantation. (DANISH [Danish ICD Study in Patients With Ditaled Cardiomyopathy]; NCT00542945)

Objectives: This study aimed to evaluate the incidence and causes of hospitalization in the year preceding death of patients with heart failure (HF). Background: Hospitalizations in HF are common, especially in the last period of the lives of patients with HF, but little is known about hospitalization burden and causes during this phase of the disease. Methods: From Danish nationwide registries, we identified patients who died in the period 2001–2016 after having experienced HF for at least 1 year, and examined hospitalizations during the last year of life in age- and sex-stratified analyses. Results: We included 32,157 patients. Median age at time of death was 81 years; 39% were women. A total of 26,561 (84%) patients were hospitalized at least once during the last year of life. The patients experienced a median of 2 (1 to 3) hospitalizations and spent 14 (3 to 31) days in the hospital. Of all hospitalizations (n = 80,362), 9,644 (12%) were due to HF, 14,738 (18%) due to other cardiovascular (CV) causes, and 51,696 (64%) due to non-CV causes (p < 0.001). The frequency of hospitalizations increased toward death, but the domination of non-CV causes remained consistent throughout the year, regardless of age and sex. If we included diagnoses covering renal insufficiency in the definition of HF hospitalizations, non-CV hospitalizations remained dominant (58%). Conclusions: During the last year alive, patients with HF were more often hospitalized due to non-CV causes rather than HF. These findings warrant more focus on a multidisciplinary approach toward end-of-life care in patients with HF.

Background The aim of the study was to investigate the associated risk of stroke after discharge of infective endocarditis (IE) in patients with stroke during IE admission compared with patients without stroke during IE admission. Methods Using Danish nationwide registries, we identified nonsurgically treated patients with IE discharged alive in the period from 1996 to 2016. The study population was grouped into (1) patients with stroke during IE admission and (2) patients without stroke during IE admission. Multivariable adjusted Cox proportional-hazard analysis was used to compare the associated risk of stroke between groups. Results We identified 4,284 patients with IE, of whom 239 (5.6%) had a stroke during IE admission. We identified differentials in the associated risk of stroke during follow-up between groups (P = .006 for interaction with time). The associated risk of stroke was higher in patients with stroke during IE admission with a 1-year follow-up, HR = 3.21 (95% CI 1.66-6.20), compared with patients without stroke during IE admission. From 1 to 5 years of follow-up, we identified no difference in the associated risk of stroke between groups, HR = 0.91 (95% CI 0.33-2.50). Conclusions Patients with nonsurgically treated IE with a stroke during IE admission were at significant higher associated risk of subsequent stroke within the first year of follow-up as compared with patients without a stroke during IE admission. This risk difference was not evident beyond 1 year of discharge. These findings underline the need for identification of causes and mechanisms of recurrent strokes after IE to develop preventive means.

Objectives The aim of this study was to investigate the impact of atrial fibrillation (AF) and antithrombotic treatment on the prognosis in patients with heart failure (HF) as well as vascular disease. Background HF, vascular disease, and AF are pathophysiologically related, and understanding antithrombotic treatment for these conditions is crucial. Methods In hospitalized patients with HF and coexisting vascular disease (coronary artery disease or peripheral arterial disease) followed from 1997 to 2009, AF status was categorized as prevalent AF, incident AF, or no AF. Risk of thromboembolism (TE), myocardial infarction (MI), and serious bleeding was assessed by Cox regression models (hazard ratio [HR] with 95% confidence interval [CI]) with antithrombotic therapy and AF as time-dependent variables. Results A total of 37,464 patients were included (age, 74.5 ± 10.7 years; 36.3% females) with a mean follow-up of 3 years during which 20.7% were categorized as prevalent AF and 17.2% as incident AF. Compared with vitamin K antagonist (VKA) in prevalent AF, VKA plus antiplatelet was not associated with a decreased risk of TE (HR: 0.91; 95% CI: 0.73 to 1.12) or MI (HR: 1.11; 95% CI: 0.96 to 1.28), whereas bleeding risk was significantly increased (HR: 1.31; 95% CI: 1.09 to 1.57). Corresponding estimates for incident AF were HRs of 0.77 (95% CI: 0.56 to 1.06), 1.07 (95% CI: 0.89 to 1.28), and 2.71 (95% CI: 1.33 to 2.21) for TE, MI, and bleeding, respectively. In no AF patients, no statistical differences were seen between antithrombotic therapies in TE or MI risk, whereas bleeding risk was significantly increased for VKA with and without single-antiplatelet therapy. Conclusions In AF patients with coexisting HF and vascular disease, adding single-antiplatelet therapy to VKA therapy is not associated with additional benefit in thromboembolic or coronary risk, but notably increased bleeding risk.

Despite improvement in treatment, heart failure (HF) is associated with a median survival of 5 years. However, HF is a heterogeneous disease, and more knowledge on mortality rates and HF progression is warranted in subgroups. We sought to assess risk of death and HF progression (HF hospitalization

Prevalent diabetes mellitus (DM) is associated with higher risk of death and recurrent heart failure hospitalization (HFH) in patients with HF. However, little is known about the prognosis in HF patients developing DM after HF diagnosis. We examined the risk of death and HFH in HF patients with

Objectives: This study investigated the association between the use of evidence-based medicine (EBM) for heart failure (HF) and risk of workforce detachment. Background: The ability to work can be a marker of functional capacity and quality of life. Methods: We examined a nationwide cohort of patients in the workforce 1 year after first hospitalization for HF. EBM was defined as treatment with β-blockers and renin angiotensin system inhibitors. The fraction of target dose (0-1) for each drug was calculated. The sum of the fractions gave each patient a score between 0 and 2. Patients were stratified into 4 groups according to this score: group 4 score = 2 (target dose of both drugs); group 3 score 1; group 2 score ≤1 to >0.5; and group 1 score ≤0.5. The risk of subsequent workforce detachment was estimated in cause specific Cox regression models. Results: One year after first HF hospitalization, 10,185 patients were part of the workforce, and 7,561 (74%) were in treatment with at least 1 of the components of EBM. During a median follow-up of 727 days, 2,698 individuals (36%) became detached from the workforce. Patients receiving more EBM had a significantly lower risk of workforce detachment compared with those receiving less EBM (group 4 hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; group 3 HR: 0.85; 95% CI: 0.77 to 0.94; and group 2 HR 0.92; 95% CI: 0.83 to 1.02), all compared to group 1. Conclusions: Patients in the workforce 1 year after first HF hospitalization and treated with target or near-target doses of EBM were associated with a significantly lower risk of subsequent workforce detachment.

In response to our article [(1)][1], Dr. Ayturk and colleagues emphasize that the type of stent might affect the risk of stent thrombosis and consequently the need of prolonged dual antiplatelet therapy with aspirin and clopidogrel. We agree that the subject is complex, but physicians should