Arrhythmias in Congenital Heart Disease: a Nationwide Cohort Study.

BACKGROUND: As more patients with congenital heart disease (CHD) survive into adulthood, the population of adults with CHD is expanding. This trend is accompanied by an increasing incidence of complications, including arrhythmias. However, the long-term risk of arrhythmias remains sparsely investigated. METHODS: In this observational cohort study, all Danish patients with CHD born from 1977 to 2024 were identified using registries and followed from date of birth until the occurrence of arrhythmia, emigration, death, or end of follow-up (March 2024). The risk of arrhythmias was assessed among patients with CHD and compared to age- and sex-matched controls from the background population. RESULTS: A total of 45,820 patients with CHD (50.9% men) were identified and matched with 183,280 controls from the background population. During a median follow-up of 21.5 years, 2.6% of patients with CHD and 0.2% of controls developed arrhythmias - corresponding to incidence rates (IR) of 1.2 (95%CI 1.2-1.3) and 0.1 (95%CI 0.1-0.1) per 1,000 PY, respectively, and a hazard ratio (HR) of 16.4 (95%CI 14.4-18.7). The most common arrhythmias in patients with CHD were advanced atrioventricular block (IR 0.4 [95%CI 0.4-0.4] per 1,000 PY) and atrial flutter/fibrillation (IR 0.5 [95%CI 0.5-0.6] per 1,000 PY). Patients with malformations of the heart chambers, transposition of the great arteries, tetralogy of Fallot, and atrioventricular septal defect were at the highest risk of arrhythmias. Moreover, the risk of arrhythmias among those with ASD was not negligible. In patients with CHD, arrhythmia was associated with a significantly higher risk of death (HR of 6.9 [95%CI 5.9-8.1]). CONCLUSIONS: Patients with CHD are at significantly higher risk of arrhythmias than the background population, and those with complex CHD are at particularly high risk. In patients with CHD, arrhythmia is associated with an increased risk of death. Additional studies are warranted to investigate how we can improve the diagnosis and management of arrhythmias in CHD.

Excess long-term risk of adverse outcomes in heart failure patients with high and low levels of NT-proBNP: A 7-year follow-up study (NorthStar Trial).

Background: This study investigated excess risk in patients with heart failure with reduced left ventricular ejection fraction (HFrEF) with or without elevated levels of NT-proBNP (N-terminal pro-brain natriuretic peptide). Methods: Patients with HFrEF from the NorthStar cohort (n = 1120) were matched on age, sex, and presence of AF (atrial fibrillation/flutter) to five controls without HFrEF from The Danish National Patient Registries. Patients were compared with controls before and after stratification according to baseline NT-proBNP levels, with cutoffs defined as

Therapeutic Effects of Heart Failure Medical Therapies on Standardized Kidney Outcomes: Comprehensive Individual Participant-Level Analysis of 6 Randomized Clinical Trials.

Background: Kidney outcomes have been variably defined using non-standardized composite endpoints in key heart failure (HF) trials, thus introducing complexity in their interpretation and cross-trial comparability. We examined the effects of steroidal mineralocorticoid receptor antagonists (MRAs), the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan, and sodium-glucose cotransporter-2 (SGLT2) inhibitors on composite kidney endpoints using uniform definitions in 6 contemporary HF trials. Methods: Individual participant-level data from trials of steroidal MRAs (EMPHASIS-HF, TOPCAT Americas), ARNI (PARADIGM-HF, PARAGON-HF), and SGLT2 inhibitors (DAPA-HF, DELIVER) were included. The standardized composite kidney endpoint was defined as a sustained decline (a reduction in estimated glomerular filtration rate (eGFR) confirmed by a subsequent measurement at least 30 days later) in eGFR by 40%, 50%, or 57%, end-stage kidney disease, or renal death. eGFR was recalculated in a standardized manner using the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Results: Among 28,690 participants across the 6 trials (median age 69 years [IQR, 62-76]; 9,656 [33.7% ] women), the proportion experiencing the composite kidney endpoint with a more stringent definition of a sustained decline in kidney function (eGFR threshold of 57%) ranged from 0.3% to 3.3%. The proportion of patients experiencing this endpoint with a less stringent definition (eGFR threshold of 40%) ranged from 1.0% and 10.0%. The steroidal MRAs doubled the risk of the composite kidney endpoint when applying the least stringent definition compared with placebo, but these effects were less apparent and no longer significant with application of more stringent definitions. ARNI appeared to consistently reduce the occurrence of the composite kidney endpoints irrespective of specific eGFR threshold applied. The potential benefits of SGLT2-inhibitors on the composite kidney endpoints appeared more apparent when defined by more stringent eGFR thresholds, although none of these effects individually were statistically significant. Conclusions: When applying standardized stringent kidney endpoint definitions, steroidal MRAs, ARNI, and SGLT2-inhibitors have either neutral or beneficial effects on kidney outcomes in HF. Applying less stringent definitions increased event rates but included acute declines in eGFR that might not ultimately reflect long-term effects on kidney disease progression.

Endometriosis and Long-Term Cardiovascular Risk: A Nationwide Danish study.

BACKGROUND AND AIMS: Endometriosis, a systemic gynecological disease affecting 10% of women in reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiovascular outcomes are scarce, prompting this study to address the knowledge-gap. METHODS: Using Danish nationwide registries, women diagnosed with endometriosis (1977-2021) were identified and matched with controls in a 1:4 ratio based on year of birth. The primary outcome was a composite of acute myocardial infarction and ischemic stroke. The secondary outcomes were arrhythmias, heart failure, and mortality. RESULTS: In total, 60,508 women with endometriosis and 242,032 matched controls were included (median age 37.3 years). Women with endometriosis were more comorbid and used more medications than controls. The incidence rates of the composite outcomes were 3.2 (95% confidence interval [CI] 3.2-3.3) and 2.7 (95% CI 2.7-2.8) per 1000 person-years among women with and without endometriosis, respectively. Women with endometriosis had a significantly higher associated rate of the composite outcome compared with controls (unadjusted hazard ratio [HR] 1.18 [95% CI 1.14-1.23], adjusted HR 1.15 [95% CI 1.11-1.20]). Likewise, women with endometriosis were also at significantly increased associated risk of arrhythmias (unadjusted HR 1.24 [95% CI 1.20-1.28], adjusted HR 1.21 [95% CI 1.17-1.25]) and heart failure (unadjusted HR 1.16 [95% CI 1.09-1.22], adjusted HR 1.11 [95% CI 1.05-1.18]) but at decreased risk of mortality (unadjusted HR 0.95 [95% CI 0.92-0.97], adjusted HR 0.93 [95% CI 0.91-0.96]). CONCLUSIONS: Women with endometriosis have a higher associated long-term risk of cardiovascular outcomes compared with controls. Despite subtle absolute risk-differences, the high prevalence of endometriosis underscores the importance of these findings.

Temporal trends in infection-related hospitalizations among patients with heart failure: A Danish nationwide study from 1997 to 2017.

BACKGROUND: Despite improved survival, hospitalization is still common among patients with heart failure (HF). OBJECTIVE: This study aimed to examine temporal trends in infection-related hospitalization among HF patients and compare it to temporal trends in the risk of HF hospitalization and death. METHODS: Using Danish nationwide registers, we included all patients aged 18 to 100 years, with HF diagnosed between January 1, 1997 and December 31, 2017, resulting in a total population of 147.737 patients. The outcomes of interest were primarily infection-related hospitalization and HF hospitalization and secondarily all-cause mortality. The Aalen Johansen's estimator was used to estimate 5-year absolute risks for the primary outcomes. Additionally, cox analysis was used for adjusted analyses. RESULTS: The population had a median age of 74 [64, 82] years and 57.6 % were males. Patients with HF had a higher risk of infection over time 16.4 % (95% CI 16.0-16.8) in 1997 to 2001 vs 24.5% (95% CI 24.0-24.9) in 2012 to 2017. In contrast, they had a lower risk of HF hospitalization 26.5% (95% CI 26.1-27.0) in 1997 to 2001 vs 23.2% (95% CI 22.8-23.7) in 2012 to 2017. The risk of infection stratified by infection type showed similar trends for all infection types and marked the risk of pneumonia infection as the most significant in all subintervals. CONCLUSION: In the period from 1997 to 2017, we observed patients with HF had an increased risk of infection-related hospitalization, driven by pneumonia infections. In contrast, the risk of HF hospitalization decreased over time.

Anthropometric measures and long-term mortality in non-ischaemic heart failure with reduced ejection fraction: Questioning the obesity paradox.

AIMS: Although body mass index (BMI) is the most commonly used anthropometric measure to assess adiposity, alternative indices such as the waist-to-height ratio may better reflect the location and amount of ectopic fat as well as the weight of the skeleton. METHODS AND RESULTS: The prognostic value of several alternative anthropometric measures was compared with that of BMI in 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) enrolled in DANISH. The association between anthropometric measures and all-cause death was adjusted for prognostic variables, including natriuretic peptides. Median follow-up was 9.5 years (25th-75th percentile, 7.9-10.9). Compared to patients with a BMI 18.5-24.9 kg/m2 (n = 363), those with a BMI ≥25 kg/m2 had a higher risk of all-cause and cardiovascular death, although this association was only statistically significant for a BMI ≥35 kg/m2 (n = 91) (all-cause death: hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.28-2.48; cardiovascular death: HR 2.46, 95% CI 1.69-3.58). Compared to a BMI 18.5-24.9 kg/m2, a BMI <18.5 kg/m2 (n = 24) was associated with a numerically, but not a significantly, higher risk of all-cause and cardiovascular death. Greater waist-to-height ratio (as an exemplar of indices not incorporating weight) was also associated with a higher risk of all-cause and cardiovascular death (HR for the highest vs. the lowest quintile: all-cause death: HR 2.11, 95% CI 1.53-2.92; cardiovascular death: HR 2.17, 95% CI 1.49-3.15). CONCLUSION: In patients with non-ischaemic HFrEF, there was a clear association between greater adiposity and higher long-term mortality. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00542945.

Burden of hospitalization during the first year following transcatheter and surgical aortic valve replacement.

BACKGROUND: Hospitalizations are a major burden for both patients and society but are potentially preventable. We examined the one-year hospitalization burden in patients undergoing transcatheter aortic valve replacement (TAVR) and compared hospitalization rates and patterns with those undergoing isolated surgical aortic valve replacement (SAVR). METHODS: Using Danish nationwide registries, we identified patients who underwent first-time TAVR and isolated SAVR (2008-2019), respectively. Subsequent hospitalizations were classified as cardiovascular or noncardiovascular according to discharge diagnosis codes. RESULTS: Patients undergoing TAVR (N = 4,921) were older and had more comorbidities than those undergoing SAVR (N = 5,220). There were 5,725 and 4,426 hospitalizations within the first year after discharge in the TAVR and SAVR group, respectively. During the one-year follow-up period post-TAVR, 46.6% were not admitted, 25.4% were admitted once, 12.6% twice, and 15.4% 3 times or more. The corresponding proportions in patients undergoing SAVR were 55.3%, 25.1%, 10.0%, and 9.5%, respectively. Among patients with ≥1 hospitalization following TAVR, 50.3% had a total length of all hospital stays between 1 and 7days, 19.0% 8-14days, 18.0% 15-30days, 9.9% 31-60days, and 2.8% ≥61days. The corresponding proportions for patients undergoing SAVR were 58.6%, 17.2%, 13.1%, 7.4%, and 3.7%, respectively. Compared with patients undergoing SAVR, those undergoing TAVR had a lower early (day0-30: HR 0.89 [95% CI, 0.80-0.98]), but a higher late hospitalization rate (day 31-365: 1.46 [1.32-1.60]). CONCLUSIONS: The 1-year hospitalization burden following TAVR is substantial. Compared with patients undergoing isolated SAVR, those undergoing TAVR had a lower early, but a higher late hospitalization rate - a difference that likely reflects unmeasured differences in the patient cohorts.

Frailty and Cardiovascular Health.

The incidence of frailty and cardiovascular disease (CVD) increases as the population ages. There is a bidirectional relationship between frailty and CVD, and both conditions share several risk factors and underlying biological mechanisms. Frailty has been established as an independent prognostic marker in patients with CVD. Moreover, its presence significantly influences both primary and secondary prevention strategies for adults with CVD while also posing a barrier to the inclusion of these patients in pivotal clinical trials and advanced cardiac interventions. This review discusses the current knowledge base on the relationship between frailty and CVD, how managing CVD risk factors can modify frailty, the influence of frailty on CVD management, and future directions for frailty detection and modification in patients with CVD.

Education and Age in Return to Work After Ischemic Stroke: A Danish Nationwide Registry-based Cohort Study.

OBJECTIVES: To investigate return to work and workforce detachment in ischemic stroke, including the association with age and level of education. METHODS: Patients in the workforce aged 18 to 60 with first-time ischemic stroke between 1997 and 2017 were identified in Danish registers and followed for 5 years. The cumulative incidence of return to work and subsequent workforce detachment was computed overall and stratified according to age group and education level. Cox regression analysis was used for multivariate analysis. RESULTS: A total of 28,325 patients were included (median age 52.3 (interquartile range (IQR) 46.1 to 56.6) and 64.3% male). After 1 year, 62.0% were in the workforce, highest in age group 18 to 30 (80.0%) and lowest in patients aged 51 to 60 (58.5%). One-year cumulative incidence of return to work overall was 73.4% (20,475), highest in the young age group (87.0%, 76.7%, 74.5%, and 71.3% for age group 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high education (80.3%, 72.1%, and 71.3% for long higher, basic or vocational education, respectively). One-year cumulative incidence of subsequent workforce detachment was 25.6% (5248), lowest in young age (22.4%, 23.1%, 24.1%, and 27.2% for age groups 18 to 30, 31 to 40, 41 to 50, and 51 to 60, respectively) and high level of education (13.0%, 28.4%, and 27.2% for long higher, basic, and vocational education, respectively). During the full follow-up, 10,855 (53.0%) left the workforce again. CONCLUSIONS: A high proportion of patients returned to work within 1 year, but more than half left the workforce again. Young age and long education were associated with a higher incidence of return to work and lower subsequent workforce detachment.

Effect of Implantable Cardioverter-defibrillators in Nonischemic Heart Failure According to Background Medical Therapy: Extended Follow-up of the DANISH Trial.

BACKGROUND: The Heart Failure Collaboratory (HFC) score integrates types and dosages of guideline-directed pharmacotherapies for heart failure (HF) with reduced ejection fraction (HFrEF). We examined the effects of cardioverter-defibrillator (ICD) implantation according to the modified HFC (mHFC) score in 1116 patients with nonischemic HFrEF from the Danish Study to Assess the Efficacy of ICDs in Patients with Nonischemic Systolic HF on Mortality (DANISH). METHODS AND RESULTS: Patients were assigned scores for renin-angiotensin-system inhibitors, beta-blockers and mineralocorticoid receptor antagonists (0, no use; 1, < 50% of maximum dosage; 2, ≥ 50% of maximum dosage). The maximum score was 6, corresponding to ≥ 50% of maximum dosage for all therapies. The median baseline mHFC score was 4, and the median follow-up was 9.5 years. Compared with an mHFC score of 3-4, an mHFC score of 1-2 was associated with a higher rate of all-cause death (mHFC = 1-2: adjusted HR 1.67 [95% CI, 1.23-2.28]; mHFC = 3-4, reference; mHFC = 5-6: adjusted HR 1.07 [95% CI, 0.87-1.31]). ICD implantation did not reduce all-cause death compared with control (reference) (HR 0.89 [95% CI, 0.74-1.08]), regardless of mHFC score (mHFC = 1-2: HR 0.98 [95% CI, 0.56-1.71]; mHFC = 3-4: HR 0.89 [95% CI,0.66-1.20]; mHFC = 5-6: HR 0.85 [95% CI, 0.64-1.12]; Pinteraction, 0.65). Similarly, ICD implantation did not reduce cardiovascular death (HR 0.87 [95% CI, 0.70-1.09]), regardless of mHFC score (Pinteraction, 0.59). The ICD group had a lower rate of sudden cardiovascular death (HR, 0.60 [95% CI,0.40-0.92]); this association was not modified by mHFC score (Pinteraction, 0.35). CONCLUSIONS: Lower mHFC scores were associated with higher rates of all-cause death. ICD implantation did not result in an overall survival benefit in patients with nonischemic HFrEF, regardless of mHFC score.

New York Heart Association functional class and implantable cardioverter-defibrillator in non-ischaemic heart failure with reduced ejection fraction: Extended follow-up of the DANISH trial.

AIMS: Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure, a left ventricular ejection fraction of ≤35%, and New York Heart Association (NYHA) class II-III. However, the evidence regarding the benefit of primary prevention ICD is less consistent in patients with NYHA class III. We investigated the long-term effects of primary prevention ICD implantation according to NYHA class in an extended follow-up study of the DANISH trial. METHODS AND RESULTS: The DANISH trial randomized 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) to ICD implantation or usual care. Outcomes were analysed according to NYHA class at baseline (NYHA class II and III/IV). The primary outcome was all-cause mortality. Of the 1116 patients randomized in the DANISH trial, 597 (53.5%) were in NYHA class II at baseline, 505 (45.3%) in NYHA class III, and 14 (1.3%) in NYHA class IV. During a median follow-up of 9.5 years, NYHA class III/IV, compared with NYHA class II, were associated with a greater long-term rate of all-cause mortality (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.20-1.93) and cardiovascular death (HR 1.95 [1.47-2.60]). ICD implantation, compared with usual care, did not reduce the long-term rate of all-cause mortality (all participants: HR 0.89 [95% CI 0.74-1.08]; NYHA class II: HR 0.85 [0.64-1.13]; NYHA class III/IV: HR 0.89 [0.69-1.14]; pinteraction = 0.78) or cardiovascular death (all participants: HR 0.87 [95% CI 0.70-1.09]; NYHA class II: HR 0.78 [0.54-1.12]; NYHA class III/IV: HR 0.89 [0.67-1.19]; pinteraction = 0.58), irrespective of NYHA class. Similarly, NYHA class did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (all participants: HR 0.60 [95% CI 0.40-0.92]; NYHA class II: HR 0.73 [0.40-1.36]; NYHA class III/IV: HR 0.52 [0.29-0.94]; pinteraction = 0.39). CONCLUSIONS: In patients with non-ischaemic HFrEF, ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce sudden cardiovascular death, regardless of baseline NYHA class. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00542945.

Dapagliflozin and Timing of Prior Heart Failure Hospitalization: A Patient-Level Meta-Analysis of DAPA-HF and DELIVER.

BACKGROUND: Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable." OBJECTIVES: The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure). METHODS: A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death. RESULTS: In total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; Pinteraction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category. CONCLUSIONS: The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.

Long-term Rate of Ventricular Arrhythmia in Autoimmune Disease.

AIMS: Although selected autoimmune diseases (AIDs) have been linked to an increased risk of ventricular arrhythmias (VAs), data on the long-term rate of VAs across the spectrum of AIDs are lacking. The aim of our study was to investigate the long-term rate of VAs (a composite of ventricular tachycardia, ventricular fibrillation, ventricular flutter, or cardiac arrest) in individuals with a history of 28 different AIDs. METHODS: Individuals diagnosed with an AID (2005-2018) were identified through Danish nationwide registries. Each patient with AID was matched with four individuals from the background population by age and sex. Multivariable Cox regression was used to compare the rate of VAs between the AIDs and background population, overall and according to individual AIDs. RESULTS: In total, 186,733 patients diagnosed with AIDs were matched with 746,932 individuals without AIDs (median age 55 years; 63% female; median follow-up 6.0 years). The 5-year cumulative incidence of VAs was 0.5% for patients with AIDs and 0.3% for matched individuals. Patients with any AIDs had a higher associated rate of VAs than matched individuals (HR 1.39 [95% CI, 1.29-1.49]). The highest HR was observed in patients with systemic sclerosis (3.86 [95% CI, 1.92-7.75]). The higher rate of VAs in patients with AIDs, compared with individuals from the background population, was more pronounced in patients without ischemic heart disease or heart failure/cardiomyopathy compared to those with these conditions (Pinteraction < 0.05). CONCLUSIONS: Despite a low cumulative incidence, patients with a history of AIDs had a higher relative rate of VAs than matched individuals.

In a large Danish nationwide study, we examined the risk of ventricular arrhythmias, which are serious and potentially life-threatening conditions, in patients with and without a history of autoimmune diseases. Patients with a history of any autoimmune disease had a higher risk of experiencing ventricular arrhythmias compared with age- and sex-matched individuals from the background population. This association was observed for most of the autoimmune diseases when examined individually. The higher rate of ventricular arrhythmias in patients with autoimmune diseases, compared with individuals from the background population, was relatively more pronounced in patients without a history of ischemic heart disease or heart failure/cardiomyopathy compared with individuals with a history of these conditions.

Temporal Trends in the Initiation of Dialysis Among Patients With Heart Failure With or Without Diabetes: A Nationwide Study From 2002 to 2016.

BACKGROUND: The incidence and distribution of acute and chronic dialysis among patients with heart failure (HF), stratified by diabetes, remain uncertain. We hypothesized that with improved survival and rising comorbidities, the demand for dialysis would increase over time. METHODS AND RESULTS: Patients with incident HF, aged 18 to 100 years, between 2002 and 2016, were identified using Danish nationwide registers. Primary outcomes included acute and chronic dialysis initiation, HF-related hospitalization, and all-cause mortality. These outcomes were assessed in 2002 to 2006, 2007 to 2011, and 2012 to 2016, stratified by diabetes. We calculated incidence rates (IRs) per 1000 person-years and hazard ratios (HR) using multivariable Cox regression. Of 115 533 patients with HF, 2734 patients received acute dialysis and 1193 patients received chronic dialysis. The IR was 8.0 per 1000 and 3.5 per 1000 person-years for acute and chronic dialysis, respectively. Acute dialysis rates increased significantly among patients with diabetes over time, while no significant changes occurred in those without diabetes, chronic dialysis, HF-related hospitalization, or overall mortality. Diabetes was associated with significantly higher HRs of acute and chronic dialysis, respectively, compared with patients without diabetes (HR, 2.07 [95% CI, 1.80-2.39] and 2.93 [95% CI, 2.40-3.58] in 2002 to 2006; HR, 2.45 [95% CI, 2.14-2.80] and 2.86 [95% CI, 2.32-3.52] in 2007 to 2011; and 2.69 [95% CI, 2.33-3.10] and 3.30 [95% CI, 2.69-4.06] in 2012 to 2016). CONCLUSIONS: The IR of acute and chronic dialysis remained low compared with HF-related hospitalizations and mortality. Acute dialysis rates increased significantly over time, contrasting no significant trends in other outcomes. Diabetes exhibited over 2-fold increased rates of the outcomes. These findings emphasize the importance of continued monitoring and renal care in patients with HF, especially with diabetes, to optimize outcomes and prevent adverse events.

Estimated Glomerular Filtration Rate and Implantable Cardioverter-Defibrillator in Nonischemic Systolic Heart Failure: Extended Follow-Up of DANISH.

BACKGROUND: Patients with heart failure and chronic kidney disease (CKD) may have an increased risk of death from causes competing with arrhythmic death, which could have implications for the efficacy of implantable cardioverter-defibrillators (ICDs). We examined the long-term effects of primary prophylactic ICD implantation, compared with usual care, according to baseline CKD status in an extended follow-up study of DANISH (Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality). METHODS AND RESULTS: In the DANISH trial, 1116 patients with nonischemic heart failure with reduced ejection fraction were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (estimated glomerular filtration rate ≥/<60 mL/min per 1.73 m2) at baseline. In total, 1113 patients had an available estimated glomerular filtration rate measurement at baseline (median estimated glomerular filtration rate 73 mL/min per 1.73 m2), and 316 (28%) had CKD. During a median follow-up of 9.5 years, ICD implantation, compared with usual care, did not reduce the rate of all-cause mortality (no CKD, HR, 0.82 [95% CI, 0.64-1.04]; CKD, HR, 1.02 [95% CI, 0.75-1.38]; Pinteraction=0.31) or cardiovascular death (no CKD, HR, 0.77 [95% CI, 0.58-1.03]; CKD, HR, 1.05 [95% CI, 0.73-1.51]; Pinteraction=0.20), irrespective of baseline CKD status. Similarly, baseline CKD status did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (no CKD, HR, 0.57 [95% CI, 0.32-1.00]; CKD, HR, 0.65 [95% CI, 0.34-1.24]; Pinteraction=0.70). CONCLUSIONS: ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce the rate of sudden cardiovascular death, regardless of baseline kidney function in patients with nonischemic heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.

Long-Term Risk of VTE in Sarcoidosis: A Nationwide Cohort Study.

BACKGROUND: Chronic inflammation is increasingly recognized as a risk factor for VTE, but unlike other inflammatory diseases including systemic lupus erythematosus and rheumatoid arthritis, data on the risk of VTE in patients with sarcoidosis are sparse. RESEARCH QUESTION: Do patients with sarcoidosis have a higher long-term risk of VTE (pulmonary embolism or DVT, and each of these individually) compared with the background population? STUDY DESIGN AND METHODS: Using Danish nationwide registries, patients aged ≥ 18 years with newly diagnosed sarcoidosis (two or more inpatient/outpatient visits, 1996-2020) without prior VTE were matched 1:4 by age, sex, and comorbidities with individuals from the background population. The primary outcome was VTE. RESULTS: We included 14,742 patients with sarcoidosis and 58,968 matched individuals (median age, 44.7 years; 57.2% male). The median follow-up was 8.8 years. Absolute 10-year risks of outcomes for patients with sarcoidosis vs the background population were the following: VTE, 2.9% vs 1.6% (P < .0001), pulmonary embolism, 1.5% vs 0.7% (P < .0001), and DVT, 1.6% vs 1.0% (P < .0001), respectively. In multivariable Cox regression, sarcoidosis was associated with an increased rate of all outcomes in the first year after diagnosis (VTE: hazard ratio [HR], 4.94; 95% CI, 3.61-6.75) and after the first year (VTE: HR, 1.65; 95% CI, 1.45-1.87) compared with the background population. These associations persisted when excluding patients with a history of cancer and censoring patients with incident cancer during follow-up. Three-month mortality was not significantly different between patients with VTE with and without sarcoidosis (adjusted HR, 0.84; 95% CI, 0.61-1.15). INTERPRETATION: In this nationwide cohort study, sarcoidosis was associated with a higher long-term risk of VTE compared with a matched background population.

Heart failure with preserved ejection fraction, red cell distribution width, and sacubitril/valsartan.

AIMS: Red cell distribution width (RDW) is a strong prognostic marker in patients with heart failure (HF) and reduced ejection fraction and other conditions. However, very little is known about its prognostic significance in HF with preserved ejection fraction. We examined the relationship between RDW and outcomes and the effect of sacubitril/valsartan, compared with valsartan, on RDW and clinical outcomes in PARAGON-HF. METHODS AND RESULTS: PARAGON-HF enrolled patients with a left ventricular ejection fraction of ≥45%, structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary endpoint was a composite of total HF hospitalizations and cardiovascular deaths. Median RDW at randomization was 14.1% (interquartile range 13.5-15.0%). Patients with higher RDW levels were more often men and had more comorbidity, a higher heart rate and NT-proBNP concentration, more advanced New York Heart Association class, and worse Kansas City Cardiomyopathy Questionnaire scores. There was a graded relationship between quartiles of RDW at randomization and the primary endpoint, with a significantly higher risk associated with increasing RDW, even after adjustment for NT-proBNP and other prognostic variables {Quartile 1, reference; Quartile 2, rate ratio 1.03 [95% confidence interval (CI) 0.83 to 1.28]; Quartile 3, 1.25 [1.01 to 1.54]; Quartile 4, 1.70 [1.39 to 2.08]}. This association was seen for each of the secondary outcomes, including cardiovascular and all-cause death. Compared with valsartan, sacubitril/valsartan reduced RDW at 48 weeks [mean change -0.09 (95% CI -0.15 to -0.02)]. The effect of sacubitril/valsartan vs. valsartan was not significantly modified by RDW levels at randomization. CONCLUSIONS: RDW, a routinely available and inexpensive biomarker, provides incremental prognostic information when added to established predictors. Compared with valsartan, sacubitril/valsartan led to a small reduction in RDW.