Specialized heart failure clinics versus primary care: Extended registry-based follow-up of the NorthStar trial.

BACKGROUND: Whether continued follow-up in specialized heart failure (HF) clinics after optimization of guideline-directed therapy improves long-term outcomes in patients with HF with reduced ejection fraction (HFrEF) is unknown. METHODS AND RESULTS: 921 medically optimized HFrEF patients enrolled in the NorthStar study were randomly assigned to follow up in a specialized HF clinic or primary care and followed for 10 years using Danish nationwide registries. The primary outcome was a composite of HF hospitalization or cardiovascular death. We further assessed the 5-year adherence to prescribed neurohormonal blockade in 5-year survivors. At enrollment, the median age was 69 years, 24,7% were females, and the median NT-proBNP was 1139 pg/ml. During a median follow-up time of 4.1 (Q1-Q3 1.5-10.0) years, the primary outcome occurred in 321 patients (69.8%) randomized to follow-up in specialized HF clinics and 325 patients (70.5%) randomized to follow-up in primary care. The rate of the primary outcome, its individual components, and all-cause death did not differ between groups (primary outcome, hazard ratio 0.96 [95% CI, 0.82-1.12]; cardiovascular death, 1.00 [0.81-1.24]; HF hospitalization, 0.97 [0.82-1.14]; all-cause death, 1.00 [0.83-1.20]). In 5-year survivors (N = 660), the 5-year adherence did not differ between groups for angiotensin-converting enzyme inhibitors (p = 0.78), beta-blockers (p = 0.74), or mineralocorticoid receptor antagonists (p = 0.47). CONCLUSIONS: HFrEF patients on optimal medical therapy did not benefit from continued follow-up in a specialized HF clinic after initial optimization. Development and implementation of new monitoring strategies are needed.

Clinical cardiovascular phenotypes and the pattern of future events in patients with type 2 diabetes.

IMPORTANCE: Updated guidelines on diabetes recommend targeting sodium-glucose cotransporter-2 inhibitors (SGLT2i) at patients at risk of heart failure (HF) and glucagon-like peptide-1 receptor agonists (GLP1-RA) at those at greater risk of atherothrombotic events. OBJECTIVE: We estimated the risk of different cardiovascular events in patients with type 2 diabetes (T2D) and newly established cardiovascular disease. DESIGN, SETTING AND PARTICIPANTS: Patients with T2D and newly established cardiovascular disease from 1998 to 2016 were identified using Danish healthcare registers and divided into one of four phenotype groups: (1) HF, (2) ischemic heart disease (IHD), (3) transient ischemic stroke (TIA)/ischemic stroke, and (4) peripheral artery disease (PAD). The absolute 5-year risk of the first HF- or atherothrombotic event occurring after inclusion was calculated, along with the risk of death. MAIN OUTCOMES AND MEASURES: The main outcome was the first event of either HF or an atherothrombotic event (IHD, TIA/ischemic stroke or PAD) in patients with T2D and  new-onset cardiovascular disease. RESULTS: Of the 37,850 patients included, 40% were female and the median age was 70 years. Patients with HF were at higher 5-year risk of a subsequent HF event (17.9%; 95% confidence interval (CI) 17.1-18.8%) than an atherothrombotic event (15.8%; 15.0-16.6%). Patients with IHD were at higher risk of a subsequent atherothrombotic event (24.6%; 23.9-25.3%) than developing HF, although the risk of HF was still substantial (10.6%; 10.2-11.1%). Conversely, patients with PAD were at low risk of developing HF (4.4%; 3.8-5.1%) but at high risk of developing an atherothrombotic event (15.9%; 14.9-17.1%). Patients with TIA/ischemic stroke had the lowest risk of HF (3.2%; 2.9-3.6%) and the highest risk of an atherothrombotic event (20.6%; 19.8-21.4). CONCLUSIONS: In T2D, a patient's cardiovascular phenotype can help predict the pattern of future cardiovascular events.

Temporal trends in initiation of mineralocorticoid receptor antagonists and risk of subsequent withdrawal in patients with heart failure: a nationwide study in Denmark from 2003-2017.

AIMS: Despite landmark heart failure (HF) with reduced ejection fraction (HFrEF) trials showing effect of mineralocorticoid receptor antagonists (MRA) on the risk of death and HF hospitalization, it has been suggested that MRAs are underutilized or frequently withdrawn. This study sought to identify temporal trends in the initiation of MRAs and the subsequent risk of withdrawal and adherence of MRAs in HF patients treated with a renin-angiotensin system inhibitor and a beta-blocker in Denmark from 2003-2017. METHODS AND RESULTS: From nationwide registries, we identified patients receiving a diagnosis of HF. Use of MRA was identified by at least one prescription within 6 months after the diagnosis. The absolute risk of withdrawal with treatment was assessed with cumulative incidence, accounting for the competing risk of death. To estimate adherence, we calculated the proportion of days covered. We included 51 512 patients with incident HF. During the study period, 20 779 (40.3%) patients initiated MRA therapy. The incidence of withdrawal of MRA was 49.2% throughout the study period; 48.0% of the HF patients were adherent to the treatment. Among patients withdrawing treatment with MRA, the cumulative incidence of reinitiating was 36.6%. CONCLUSIONS: In a nationwide cohort of patients with HF, approximately half of the patients received MRA as third-line therapy within the first 6 months after diagnosis and approximately half of these withdrew MRA within 5 years. These findings warrant an increasing focus on retention to MRA treatment in a real-life setting.

Importance of diagnostic setting in determining mortality in patients with new-onset heart failure: temporal trends in Denmark from 1997 to 2017.

AIM: To investigate temporal trends in inpatient vs. outpatient diagnosis of new-onset heart failure (HF) and the subsequent risk of death and hospitalization. METHODS AND RESULTS: Using nationwide registers, 192 581 patients with a first diagnosis of HF (1997-2017) were included. We computed incidences of HF, age-standardized mortality rates, and absolute risks (ARs) of death and hospitalization (accounting for competing risk of death) to understand the importance of the diagnosis setting in relation to subsequent mortality and hospitalization. The overall incidence of HF was approximately the same (170/100 000 persons) every year during 1997-2017. However, in 1997, 77% of all first diagnoses of HF were made during a hospitalization, whereas the proportion was 39% in 2017. As inpatient diagnoses decreased, outpatient diagnoses increased from 23% to 61%. Outpatients had lower mortality and hospitalization rates than inpatients throughout the study period, although the 1-year age-standardized mortality rate decreased for each inpatient (24 to 14/100-person) and outpatient (11 to 7/100-person). One-year and five-year AR of death decreased by 11.1% and 17.0%, respectively, for all HF patients, while the risk of hospitalization for HF did not decrease significantly (1.13% and 0.96%, respectively). CONCLUSION: Between 1997 and 2017, HF changed from being primarily diagnosed during hospitalization to being mostly diagnosed in the outpatient setting. Outpatients had much lower mortality rates than inpatients throughout the study period. Despite a significant decrease in mortality risk for all HF patients, neither inpatients nor outpatients experienced a reduction in the risk of an HF hospitalization.

Rate of Heart Failure Following Atrial Fibrillation According to Presence of Family History of Dilated Cardiomyopathy or Heart Failure: A Nationwide Study.

Background It is poorly understood why some patients with atrial fibrillation develop heart failure (HF) and others do not. We examined the rate of developing HF in patients with atrial fibrillation with and without first-degree family members with HF or dilated cardiomyopathy (DCM). Methods and Results Using Danish nationwide registries, patients born after 1942 diagnosed with atrial fibrillation in the period 2005 to 2015 were identified and followed for up to 5 years. Patients with pre-existing HF, DCM, and/or ischemic heart disease diagnoses were excluded. Exposure was defined as a first-degree relative with HF or DCM. The rate of developing the composite end point of HF or death, and the components, was estimated with multivariable Cox proportional hazard regression models. We included 10 605 patients. A total of 17% had a family member with DCM/HF. Having a family member with HF/DCM was associated with an increased 5-year risk of the composite of HF/death (cumulative incidence, 9.2% [95% CI, 7.8-10.7] versus 5.6% [95% CI, 5.0-6.1]; adjusted hazard ratio [HR] 1.36 [95% CI, 1.13-1.64]). (HF 8.4% [95% CI, 7.0-9.8] versus 4.5% [95% CI, 4.1-5.0]); (adjusted HR, 1.49 [95% CI, 1.22-1.82]). However, familial HF/DCM was not significantly associated with an increased 5-year risk and rate of death (0.8% [95% CI, 0.4-1.2] versus 1.1% [95% CI, 0.8-1.3]); (adjusted HR, 0.80 [95% CI, 0.46-1.39]). Conclusions In patients with incident atrial fibrillation without prior ischemic heart disease or HF diagnoses, 1 of 6 had a first-degree relative with HF, and having such a family history of HF/DCM was associated with an 87% increase in 5-year incidence of HF compared with those without.

Long-Term Mortality Associated With Use of Carvedilol Versus Metoprolol in Heart Failure Patients With and Without Type 2 Diabetes: A Danish Nationwide Cohort Study.

Background Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Methods and Results Using Danish nationwide databases between 2010 and 2018, we followed patients with new-onset HFrEF treated with either carvedilol or metoprolol for all-cause mortality until the end of 2018. Follow-up started 120 days after initial HFrEF diagnosis to allow initiation of guideline-directed medical therapy. There were 39 260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9355 (24%) had T2D. Carvedilol was used in 2989 (32%) patients with T2D and 10 411 (35%) of patients without T2D. Users of carvedilol had a lower prevalence of atrial fibrillation (20% versus 35%), but other characteristics appeared well-balanced between the groups. Totally 11 306 (29%) were deceased by the end of follow-up. We observed no mortality differences between carvedilol and metoprolol, multivariable-adjusted hazard ratio (HR) 0.97 (0.90-1.05) in patients with T2D versus 1.00 (0.95-1.05) for those without T2D, P for difference =0.99. Rates of new-onset T2D were lower in users of carvedilol versus metoprolol; age, sex, and calendar year adjusted HR 0.83 (0.75-0.91), P<0.0001. Conclusions In a contemporary clinical cohort of HFrEF patients with and without T2D, carvedilol was not associated with a reduction in long-term mortality compared with metoprolol. However, carvedilol was associated with lowered risk of new-onset T2D supporting the assertion that carvedilol has a more favorable metabolic profile than metoprolol.

Socioeconomic Disparities in Referral for Invasive Hemodynamic Evaluation for Advanced Heart Failure: A Nationwide Cohort Study.

BACKGROUND: Factors determining referral for advanced heart failure (HF) evaluation are poorly studied. We studied the influence of socioeconomic aspects on the referral process in Denmark, which has a taxpayer-funded national health care system. METHODS: We identified all patients aged 18 to 75 years with a first diagnosis of HF during 2010 to 2018. Hospitalized patients had to be discharged alive and were then followed for the outcome of undergoing a right heart catheterization (RHC) used as a surrogate marker of advanced HF work-up. RESULTS: Of 36 637 newly diagnosed patients with HF, 680 (1.9%) underwent RHC during the follow-up period (median time to RHC of 280 days [interquartile range, 73-914]). Factors associated with a higher likelihood of RHC included the highest versus lowest household income quartile (HR, 1.56 [95% CI, 1.19-2.06]; P=0.001), being diagnosed with HF at a tertiary versus nontertiary hospital (HR, 1.68 [95% CI, 1.37-2.05]; P<0.001) and during a hospitalization versus outpatient visit (HR, 1.67 [95% CI, 1.42-1.95]; P<0.001). Level of education, occupational status, and distance to tertiary hospital were not independently associated with RHC. Older age, cancer, and a psychiatric diagnosis were independently associated with a decreased probability of RHC. CONCLUSIONS: Higher household income, HF diagnosis during hospitalization, and first admission at a tertiary hospital were associated with increased likelihood of subsequent referral for RHC independent of other demographic and clinical variables. Greater attention may be required to ensure timely referral for advanced HF therapies in lower income groups.

Long-term prognosis following hospitalization for acute myocarditis - a matched nationwide cohort study.

OBJECTIVE: The aim of this study was to examine the long-term risk of heart failure (HF) and all-cause mortality, in patients discharged alive following hospitalization for myocarditis. Background. Prognosis in patients with apparently uncomplicated myocarditis is in general perceived as good, but data on long-term outcomes are sparse. Methods. From nationwide Danish registries we included patients without prior cardiac disease, discharged alive with a first-time diagnosis of myocarditis 1996-2016. Patients were matched 1:10 by age- and sex, with controls from the general population. Risk of HF hospitalization and death in cases and controls was compared by use of adjusted Cox regression analyses. Results. We identified 1557 patients with a first-time diagnosis of myocarditis, 72% men, median age 39 years. Patients with myocarditis had more hypertension, diabetes, and cancer, and received more pharmacotherapy prior to hospitalization compared to matched controls. During a mean follow-up of 8.5 years, the event rate of HF hospitalization was 8.7 vs. 2.2 per 1000 patient-years (py) in cases and controls; HR 4.59 (95% CI; 3.58-5.88) and for all-cause mortality, event rate 21.9 vs 11.2 per 1000 py; HR 2.10 (95% CI; 1.82-2.43). Among 784 patients with no events or HF medication one year after diagnosis, risk of HF hospitalization (HR 2.15; 95% CI; 1.18-3.92), and all-cause mortality (HR 1.62; 95% CI; 1.21-2.16) remained elevated compared to matched controls. Conclusion. Myocarditis in younger patients without prior cardiac disease was associated with a long-term excess risk of HF hospitalization, and death, even in patients free of events and HF medication 1 year after discharge.HighlightsMyocarditis ranges from chest discomfort to severe heart failure.In most patients, left ventricular ejection fraction recovers but the long-term adverse cardiac risk is unknown.Patients with myocarditis and no prior cardiac disease were at higher risk of death and heart failureRoutine follow-up may be warranted following an episode of acute myocarditis.

The mediating role of effective treatments in the relationship between income level and survival in patients with heart failure: a sex- and cohabitation-stratified study.

AIMS: Patients with heart failure and low income have a high mortality risk. We examined whether lower survival among low-income patients with heart failure could be explained by different use of ß -blockers, renin-angiotensin system inhibitors (RASi), and implanted devices compared with high-income patients. METHODS AND RESULTS: We linked Danish national registries to identify patients with new-onset heart failure between 2005 and 2016. A total of 18 308 patients was included in the main analysis. We collected information on medical treatment and device therapy after discharge. We investigated the remaining income disparity if everybody had the same probability of treatment as the high-income patients. We used causal mediation analysis to examine to what extent treatment differences mediate the association between income and 1-year mortality in strata defined by sex and cohabitation status. If low-income patients had the same probability of initiating ß-blockers and RASi treatment as high-income patients, low-income men who lived alone would increase initiation of treatment by 12.4% (CI: 10.0% to 14.9%) and as a result reduce their absolute 1-year mortality by 1.0% (CI: -1.4% to -0.5%). If low-income patients had the same probability of not having breaks in medical treatment and getting device therapy, as high-income patients, low-income patients would increase the probability of not having breaks in treatment between 1.8% and 5.8% and increase the probability of getting device therapy between 1.0% and 3.8%, across strata of sex and cohabitation status. CONCLUSION: Lower rates of treatment initiation appear to mediate the poorer survival seen among patients with heart failure and low income, but only in males living alone.

The risk of cardiac events in patients receiving immune checkpoint inhibitors: a nationwide Danish study.

AIMS: The study aimed to estimate the risk of cardiac events in immune checkpoint inhibitor (ICI)-treated patients with lung cancer or malignant melanoma. METHODS AND RESULTS: The study included consecutive patients with lung cancer or malignant melanoma in 2011-17 nationwide in Denmark. The main composite outcome was cardiac events (arrhythmia, peri- or myocarditis, heart failure) or cardiovascular death. Absolute risks were estimated and the association of ICI and cardiac events was analysed in multivariable Cox models. We included 25 573 patients with lung cancer. Of these, 743 were treated with programmed cell death-1 inhibitor (PD1i) and their 1-year absolute risk of cardiac events was 9.7% [95% confidence interval (CI) 6.8-12.5]. Of the 13 568 patients with malignant melanoma, 145 had PD1i and 212 had cytotoxic T-lymphocyte-associated protein-4 inhibitor (CTLA-4i) treatment. Their 1-year risks were 6.6% (1.8-11.3) and 7.5% (3.7-11.3). The hazard rates of cardiac events were higher in patients with vs. without ICI treatment. Within 6 months from 1st ICI administration, the hazard ratios were 2.14 (95% CI 1.50-3.05) in patients with lung cancer and 4.30 (1.38-13.42) and 4.93 (2.45-9.94) in patients with malignant melanoma with PD1i and CTLA-4i, respectively. After 6 months, HRs were 2.26 (1.27-4.02) for patients with lung cancer and 3.48 (1.91-6.35) for patients with malignant melanoma and CTLA-4i. CONCLUSIONS: Among patients with lung cancer and malignant melanoma, ICI treated had increased rates of cardiac events. The absolute risks were higher in these data compared with previous pharmacovigilance studies (e.g. 1.8% peri-/myocarditis 1-year risk).

Risk Factors for Morbidity and Mortality Following Hospitalization for Pericarditis.

BACKGROUND: Viral or idiopathic pericarditis is a frequent condition, often considered benign, although prior studies have suggested that pericarditis is associated with both cardiovascular and noncardiovascular disease, for example, malignancy. OBJECTIVES: This study sought to assess mortality risk and morbidity patterns in patients with incident viral or idiopathic pericarditis. METHODS: In nationwide Danish registries, we identified patients discharged with a first-time diagnosis of pericarditis from 1996 to 2016. Patients with a severe underlying heart condition were excluded. The patients were matched 1:10 with individuals from the general population by sex and year of birth. We assessed 5-year mortality using Kaplan-Meier and Cox proportional hazards models adjusted for baseline comorbidities and identified subsequent hospital admissions. RESULTS: We identified 7,988 patients with pericarditis and 79,880 matched control individuals. The absolute 5-year survival probability was 92.9% and 95.8% in the pericarditis and control groups, respectively (adjusted hazard ratio: 1.31; 95% confidence interval: 1.13 to 1.52). The greatest difference in mortality was seen the first year, and it was primarily driven by the female part of the population. The incidence rate per 1,000 person-years of new-onset, admission-required diagnosis was higher in the pericarditis group both for cardiovascular and noncardiovascular diseases. CONCLUSIONS: We observed a higher mortality risk over 5 years in the pericarditis group, especially among the female patients, compared to matched control individuals. Furthermore, we observed a higher frequency of both cardiovascular and noncardiovascular hospital admissions, highlighting the need for focus on underlying morbidity in patients presenting with apparent viral or idiopathic pericarditis.

One-Year Mortality After Intensification of Outpatient Diuretic Therapy.

Background Mortality is increased following a hospitalization for decompensated heart failure (HF), during which diuretics are usually intensified. It is unclear how risk is affected after outpatient intensification of diuretic therapy for HF. Methods and Results From nationwide administrative registers, we identified all Danish patients who were diagnosed with HF from 2001 to 2016 and received angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and ß blocker within 120 days. Subsequent follow-up tracked progressive events of diuretic intensification and HF hospitalization. Intensification events were defined as new addition or doubling of loop diuretic or addition of thiazide to loop diuretic. These events were included in multivariable Cox regression models, calculating 1-year mortality hazard after each year since inclusion. Patients with an intensification event or hospitalization were risk set matched to 2 nonworsened HF controls and absolute 1-year mortality risks were calculated using Kaplan-Meier estimates. We included 74 990 patients, their median age was 71 years, and 36% were women. Intensification events were associated with significantly increased mortality at all times during follow-up. One-year mortality was 18.0% after an intensification event, 22.6% after HF hospitalization, and 10.4% for matched controls with neither. In a multivariable Cox model adjusted for age, sex, ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease, and diabetes mellitus, the hazard ratio for 1-year death after an intensification event was 1.75 (95% CI, 1.66-1.85), and it was 2.28 (95% CI, 2.16-2.41) after HF hospitalization. Conclusions In a nationwide cohort of patients with HF, outpatient intensification events were associated with almost 2-fold risk of mortality during the next year. Although HF hospitalization was associated with a higher risk, the need to intensify diuretics in the outpatient setting is a signal to review and intensify efforts to improve HF outcomes.

Identification of Patients with New-Onset Heart Failure and Reduced Ejection Fraction in Danish Administrative Registers.

BACKGROUND: In Danish administrative registers, ejection fraction (EF) is not recorded, which is a considerable limitation for correct subclassification of patients with heart failure (HF). We hypothesized that a diagnosis of HF combined with the recorded prescription of both renin-angiotensin system (RAS) inhibitors and beta- blockers (RASi+BB) within 120 days could identify patients with HF and reduced ejection fraction (EF ≤40%) (HFrEF). METHODS: On two sites, we identified all patients with a first-time registration of HF as primary hospital discharge diagnosis (ICD-10: I50) between June 1, 2016, and May 31, 2018 in inpatient or outpatient settings. Patients were included if they survived the initial 120 days after discharge. Reviewing patient records, we identified patients with HFrEF, based on EF ≤ 40% and reported HF symptoms. We registered the use of RASi+BB at 120 days and calculated sensitivity, specificity and predictive values. RESULTS: A total of 704 consecutive patients with a primary diagnosis of HF were included, of whom 541 (77%) fulfilled the HFrEF criteria. Patients with HFrEF confirmed from patient records were younger (median age 73 compared to 79 years) and less frequently women (31% compared to 56%) compared to non-HFrEF patients. At baseline, 24 (4%) of HFrEF patients were treated with RASi+BB compared to 22 (14%) of non-HFrEF patients. At 120 days, 460 (85%) of HFrEF patients received RASi+BB as compared to 25 (15%) of non-HFrEF patients. This resulted in a positive predictive value of 95%, sensitivity of 85% and specificity of 85%. CONCLUSION: In Denmark, the ICD-10 HF diagnosis combined with recorded RASi+BB treatment by 120 days after discharge has high positive predictive value and can accurately be used to identify patients with HFrEF.

Add-on therapy in metformin-treated patients with type 2 diabetes at moderate cardiovascular risk: a nationwide study.

BACKGROUND: In randomised clinical trials, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors reduced cardiovascular events in patients with type 2 diabetes (T2D) at high cardiovascular risk, as compared to standard care. However, data comparing these agents in patients with T2D who are at moderate risk is sparse. METHODS: From Danish national registries, we included patients with T2D previously on metformin monotherapy, who started an additional glucose-lowering agent [GLP-1 RA, SGLT-2 inhibitor, dipeptidyl peptidase-4 (DPP-4) inhibitor, sulfonylurea (SU), or insulin] in the period 2010-2016. Patients with a history of cardiovascular events [heart failure (HF), myocardial infarction (MI) or stroke] were excluded. Patients were followed for up to 2 years. Cause-specific adjusted Cox regression models were used to compare the risk of hospitalisation for HF, a composite endpoint of major adverse cardiovascular events (MACE) (MI, stroke or cardiovascular death), and all-cause mortality for each add-on therapy. Patients who initiated DPP-4 inhibitors were used as reference. RESULTS: The study included 46,986 T2D patients with a median age of 61 years and of which 59% were male. The median duration of metformin monotherapy prior to study inclusion was 5.3 years. Add-on therapy was distributed as follows: 13,148 (28%) GLP-1 RAs, 2343 (5%) SGLT-2 inhibitors, 15,426 (33%) DPP-4 inhibitors, 8917 (19%) SUs, and 7152 (15%) insulin. During follow-up, 623 (1.3%, range 0.8-2.1%) patients were hospitalised for HF-hazard ratios (HR) were 1.11 (95% CI 0.89-1.39) for GLP-1 RA, 0.84 (0.52-1.36) for SGLT-2 inhibitors, 0.98 (0.77-1.26) for SU and 1.54 (1.25-1.91) for insulin. The composite MACE endpoint occurred in 1196 (2.5%, range 1.5-3.6%) patients, yielding HRs of 0.82 (0.69-0.97) for GLP-1 RAs, 0.79 (0.56-1.12) for SGLT-2 inhibitors, 1.22 (1.03-1.49) for SU and 1.23 (1.07-1.47) for insulin. 1865 (3.9%, range 1.9-9.0%) died from any cause during follow-up. HRs for all-cause mortality were 0.91 (0.78-1.05) for GLP-1 RAs, 0.79 (0.58-1.07) for SGLT-2 inhibitors, 1.13 (0.99-1.31) for SU and 2.33 (2.08-2.61) for insulin. CONCLUSION: In a nationwide cohort of metformin-treated T2D patients and no history of cardiovascular events, the addition of either GLP-1 RA or SGLT-2 inhibitor to metformin treatment was associated with a similar risk of hospitalisation for HF and death, and a lower risk of MACE for GLP-1 RA when compared with add-on DPP-4 inhibitors. By contrast, initiation of treatment with SU and insulin were associated with a higher risk of MACE. Additionally, insulin was associated with an increased risk of all-cause mortality and hospitalisation for HF.

Incidence of New-Onset and Worsening Heart Failure Before and After the COVID-19 Epidemic Lockdown in Denmark: A Nationwide Cohort Study.

BACKGROUND: The Danish government ordered a public lockdown on March 12, 2020, because of the coronavirus disease 2019 (COVID-19) pandemic. We investigated the immediate consequences of such a lockdown for patients with heart failure (HF). METHODS: Using the Danish nationwide administrative databases, we investigated the incidence of new-onset HF and hospitalizations for worsening HF before and after the lockdown (January 1 to March 11 versus March 12 to March 31) in 2020 versus 2019. We also investigated the mortality for all patients with HF and in COVID-19-infected patients with HF. RESULTS: Rates of new-onset HF between January 1 and March 11 were comparable for 2020 and 2019 (1.83 versus 1.78 per 10 000 person-years; P=0.19), while hospitalizations for worsening HF were slightly higher in 2020 versus 2019 (1.04 versus 0.93 per 1000 person-years; P=0.02). In the lockdown period, rates of new-onset HF diagnoses (1.26 versus 2.25 per 1000 person-years) and of hospitalizations for worsening HF (0.63 versus 0.99 per 1000 person-years) were significantly lower in 2020 versus 2019 (P for both, <0.0001). Mortality was similar before and after the national lockdown for the population with HF. We observed 90 HF patients with diagnosed COVID-19 infection, of whom 37% (95% CI, 23%-50%) died within 15 days. CONCLUSIONS: The number of patients hospitalized with worsening HF or diagnosed with new-onset HF was markedly reduced after lockdown but has not yet impacted mortality in HF patients at a population-based level. However, these data raise concerns for a potential undertreatment of HF currently that may impact prognosis in the longer term.

Readmission and death in patients admitted with new-onset versus worsening of chronic heart failure: insights from a nationwide cohort.

AIMS: To examine the rates of all-cause mortality and heart failure (HF) readmission in patients hospitalized with decompensated HF according to HF duration - new-onset HF and worsening of chronic HF. METHODS AND RESULTS: In this nationwide observational cohort study, 17 176 patients were included at first hospital admission for HF in the period 2013-2015 using data from Danish nationwide registries. In total, 8860 (51.6%) patients were admitted with new-onset HF and 8316 (48.4%) with worsening of chronic HF. Patients with worsening of chronic HF were characterized by a greater comorbidity burden compared with patients with new-onset HF. The rates of outcomes were examined by multivariable Cox regression models, adjusted for age, sex, and comorbidity. Worsening of chronic HF was associated with a higher rate of the composite endpoint of all-cause mortality or HF readmission [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.31-1.43], all-cause mortality (HR 1.22, 95% CI 1.16-1.28), and HF readmission (HR 1.81, 95% CI 1.69-1.93) compared with new-onset HF. There was an interaction between atrial fibrillation (AF), HF duration, and outcome: in worsening of chronic HF, the rate of the composite endpoint was higher in patients with AF compared with those without (HR 1.12, 95% CI 1.07-1.19), whereas in new-onset HF, the rate of the composite endpoint was lower in patients with AF compared with those without (HR 0.91, 95% CI 0.85-0.96) (P-value for interaction <0.001). CONCLUSIONS: Among patients hospitalized with decompensated HF, worsening of chronic HF was associated with poorer outcomes compared with new-onset HF.

Risk of heart failure in type 2 diabetes complicated by incident ischaemic heart disease and end-stage renal disease.

AIMS: To evaluate the risk of heart failure (HF) in patients with type 2 diabetes (T2D) complicated by development of intercurrent ischaemic heart disease (IHD), end-stage renal disease (ESRD), or both, compared to patients with T2D and no IHD and ESRD. METHODS AND RESULTS: From Danish nationwide registries, we identified all patients with new-onset T2D with no history of HF between 1998 and 2015. Landmark analyses were used to estimate the 5-year absolute risk of HF at several follow-up times, and accounted for the occurrence of IHD and ESRD, identified before HF. The Aalen-Johansen estimator was used to account for censoring and the competing risk of death. A total of 285 024 patients with new-onset T2D were included. During follow-up, 19 960 developed incident HF. Among patients with T2D free of HF 5 years after T2D diagnosis, patients without IHD and ESRD had the lowest 5-year risk of HF [4.02%; 95% confidence interval (CI) 3.90-4.15), those with T2D complicated by IHD [11.51%; relative risk (RR) 2.86; 95% CI 2.72-3.02; P < 0.001] or ESRD (8.11%; RR 2.02; 95% CI 1.39-2.93; P < 0.001) an intermediate risk, and those with both IHD and ESRD (19.76%; RR 4.92; 95% CI 3.43-7.05; P < 0.001) the highest risk. CONCLUSION: Patients with T2D complicated by development of intercurrent IHD, ESRD, or both, showed a significantly higher risk of HF compared to those who did not develop IHD and ESRD. An effective way to delay or prevent the development of HF in patients with T2D may be to prevent IHD and ESRD.

Favorable five-year outcomes for heart failure diagnosed in younger patients without severe comorbidity.

BACKGROUND: Heart failure (HF) is widely associated with a median survival of 5 years. However, population level data on survival and HF progression has been limited for key subgroups. We assessed survival and HF progression, defined as hospitalization or outpatient diuretic intensification in patients ≤70 years without severe comorbidity, who received relevant medical therapy. METHODS: From administrative registers, we identified all Danish patients ≤70 years diagnosed with HF 2000-2012 without severe comorbidity, survived for 120 days to receive angiotensin converting enzyme inhibitors (ACE-I)/angiotensin receptor blocker (ARB) and beta blocker. Risk of death or progression of HF was assessed with Kaplan-Meier and Aalen Johansen estimators, respectively. Cox regression models were used to identify factors associated with risk of death. RESULTS: We included 19,985 patients, median age 61, 25% women - 1/3 of all HF patients ≤70 years. We excluded 237 patients who died within 120 days and 21,065 due to severe comorbidity. Five-year cumulative incidence of all-cause death was 14% (95%-confidence interval [CI]:13-14). Risk of death was increased for patients first diagnosed in hospital compared to outpatient clinics (hazard ratio: 1.51, 95%-CI:1.38-1.65, p < 0.001). Five-year cumulative incidence of HF hospitalization: 18% (95%-CI, 18-19) and intensification of diuretic therapy: 14% (95%-CI, 14-15). CONCLUSIONS: In patients ≤70 years without severe comorbidity, five-year mortality was only 14% and almost 2/3 were alive after 5 years without evident HF progression. Discussion of prognosis should be tailored to age and health status to provide realistic expectations for patients newly diagnosed and treated with recommended therapies for HF.