Diuresis Efficacy in Ambulatory Congested Heart Failure Patients: Intra-patient Comparison of Three Diuretic Regimens (DEA-HF).

BACKGROUND: Limited evidence exists regarding efficacy and safety of diuretic regimens in ambulatory, congestion-refractory, chronic heart failure (CHF) patients. OBJECTIVE: To compare the potency and safety of commonly used diuretic regimens in CHF patients. METHODS: A prospective, randomized, open-label, crossover study conducted in NYHA class II-IV CHF patients, treated in an ambulatory day-care unit. Each patient received 3 different diuretic regimens: intravenous (IV) furosemide 250mg; IV furosemide 250mg plus oral metolazone 5mg; and IV furosemide 250mg plus IV acetazolamide 500mg. Treatments were administered once a week, in one of six randomized sequences. The primary endpoint was total sodium excretion, and the secondary was total urinary volume excreted, both measured for 6 hours post-treatment initiation. RESULTS: A total of 42 patients were recruited. Administration of furosemide plus metolazone resulted in the highest weight of sodium excreted, 4691 mg (95% CI: 4153-5229) compared to furosemide alone 3835 mg (95% CI: 3279-4392), P=0.015 and to furosemide plus acetazolamide 3584 mg (95% CI: 3020-4148), P=0.001. Furosemide plus metolazone resulted in 1.84 liters of urine (95% CI: 1.63-2.05), compared to 1.58 liters (95% CI: 1.37-1.8) P=0.039 collected following administration of furosemide plus acetazolamide and 1.71 liters (95% CI 1.49-1.93) following furosemide alone. The incidence of worsening renal function (WRF) was significantly higher when adding metolazone (41%) to furosemide compared to furosemide alone (17%) and to furosemide plus acetazolamide (2.6%), P<0.001. CONCLUSIONS: In ambulatory CHF patients, furosemide plus metolazone resulted in a significantly higher natriuresis compared to IV furosemide alone or furosemide plus acetazolamide.

Influence of socioeconomic status on rates of advanced heart failure therapies.

BACKGROUND: Socioeconomic deprivation is associated with a lower likelihood of referral for advanced heart failure (HF) evaluation, but it is not known whether it influences rates of advanced HF therapies independently of key hemodynamic measures and comorbidity following advanced HF evaluation in a universal healthcare system. METHODS: We linked data from a single-center Danish clinical registry of consecutive patients evaluated for advanced HF with patient-level information on socioeconomic status. Patients were divided into groups based on the level of education (low, medium, and high), combined degree of socioeconomic deprivation (low, medium, and high), and household income quartiles. Rates of the combined outcome of left ventricular assist device implantation or heart transplantation (advanced HF therapy) with death as a competing risk were estimated with cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, central venous pressure, cardiac index, and comorbidities. RESULTS: We included 629 patients, median age 53 years, of whom 77% were men. During a median follow-up of 5 years, 179 (28%) underwent advanced HF therapy. The highest level of education was associated with higher rates (high vs low, adjusted HR 1.81 95% CI 1.14-2.89, p = 0.01), whereas household income quartile groups (Q4 vs Q1, adjusted HR 1.37 95% CI 0.76-2.47, p = 0.30) or groups of combined socioeconomic deprivation (high vs low degree of deprivation, adjusted HR 0.86 95% CI 0.50-1.46, p = 0.56) were not significantly associated with rates of advanced HF therapy. CONCLUSIONS: Patients with a lower level of education might be disfavored for advanced HF therapies and could require specific attention in the advanced HF care center.

Use of inotropic agents in advanced heart failure: pros and cons.

BACKGROUND: Use of inotropic agents in advanced heart failure (HF) has over time been evaluated in several randomized, controlled clinical trials (RCTs). However, the evidence for both efficacy and safety is conflicting. SUMMARY: In this narrative review, the evidence for and role of inotropes in advanced HF are outlined. Readers are provided with a comprehensive overview of key-findings from 23 important RCTs comparing orally or intravenously administered inotropes. Clinically relevant pros and cons of inotropic regimens are summarized to guide the clinician in the management of advanced HF patients in different settings (e.g., out-patient, in-patient, and intensive care unit). Finally, future perspectives and potential new agents are discussed. KEY MESSAGES: Long-term use of inotropes in advanced HF is controversial and should only be considered in selected patients (e.g., as palliative or bridging strategy). However, short-term use continues to play a large role in hospitalized patients with cardiogenic shock or severe decompensated acute HF.

Comparative outcomes in patients with preexisting heart failure to those without heart failure after out-of-hospital cardiac arrest: A nationwide registry study.

BACKGROUND: The knowledge of prognosis following out-of-hospital cardiac arrest (OHCA) in patients with heart failure heart failure (HF) is sparse. The objective of this study was to compare the outcome after OHCA among patients with and without HF. METHODS: We studied 45,293 patients who were included for the Danish cardiac arrest registry between 2001 and 2014. Patients were stratified into two groups based on the presence of HF prior to cardiac arrest. The primary outcome was 30-day survival and secondary outcome was anoxic brain damage or permanent nursing home admission at 1-year among 30-day survivors. RESULTS: Among the final 28,955 patients included, 6675 (23%) patients had prior HF and 22,280 (77%) patients had no prior HF. At 30 days, 616 (9.2%) patients survived among the patients with HF and 1916 (8.6%) among the patients without HF. There was a significant interaction between atrial fibrillation (AF) and HF for primary outcome and therefore it was assessed separately between the two study groups stratified based on AF. Among patients without AF a significantly higher odds of 30-day survival were observed among patients with HF (OR 2.69, 95% CI 2.34-3.08, P < 0.001), but no difference was observed among the patients from two study groups with no AF. No significant difference in risk for secondary outcome was observed among the two study groups. In multivariable average treatment effect modeling, all the results largely remain unchanged. CONCLUSIONS: Outcome following OHCA among patients with and without HF is found to be similar in this large Danish OHCA registry.

Arterial Thromboembolism in Patients With Atrial Fibrillation and CHA2DS2-VASc Score 1: A Nationwide Study.

BACKGROUND: Oral anticoagulation is suggested in patients with atrial fibrillation and a CHA2DS2-VASc score ≥1 (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, and sex score). To assess granular differences within CHA2DS2-VASc 1, the incidence of arterial thromboembolism according to CHA2DS2-VASc 1 subgroups was examined. METHODS: The Danish National Patient Registry and the Danish Prescription Registry were linked on a nationwide level to identify patients with atrial fibrillation from 2000 to 2021 without oral anticoagulation and categorized according to CHA2DS2-VASc score: CHA2DS2-VASc 0 (male and female subjects); CHA2DS2-VASc 1 (hypertension, heart failure, diabetes, vascular disease, and age 65-74 years); or CHA2DS2-VASc 2 (age ≥75 years without other risk factors). Female sex was not considered a risk factor in any risk group. The outcome was arterial thromboembolism (ischemic stroke, embolism of extremity, or transient cerebral ischemia). Study groups were compared using Cox regression analysis. RESULTS: We included 26 701 patients with a CHA2DS2-VASc 0 score; 22 915 with CHA2DS2-VASc 1 (1483 patients with heart failure, 9066 with hypertension, 843 with diabetes, 770 with vascular disease, and 10 753 who were 65 to 74 years of age); and 14 525 patients with CHA2DS2-VASc 2 (≥75 years of age without other risk factors). With a median of 1 year of observation time, the cumulative incidence of arterial thromboembolism was 0.6% (n=154 [95% CI, 0.6%-0.8%]), 1.4% (n=16 [95% CI, 0.8%-2.2%]), 1.9% (n=141 [95% CI, 1.6%-2.2%]), 1.7% (n=12 [95% CI, 0.9%-2.9%]), 2.0% (n=13 [95% CI, 1.1%-3.4%]), 2.3% (n=187 [95% CI, 2.0%-2.7%]), and 4.4% (n=533 [95% CI, 4.1%-4.8%]) for CHA2DS2-VASc 0, heart failure, hypertension, diabetes, vascular disease, age 65 to 74 years (CHA2DS2-VASc 1), and age ≥75 years (CHA2DS2-VASc 2), respectively. No statistically significant difference was identified among subgroups of CHA2DS2-VASc 1 (P=0.15 for difference). CONCLUSIONS: For patients with atrial fibrillation, all subgroups of CHA2DS2-VASc 1 were associated with lower incidence of arterial thromboembolism compared with age ≥75 years without other risk factors (ie, CHA2DS2-VASc 2) and a higher incidence compared with CHA2DS2-VASc 0. No statistically significant difference was identified between the subgroups of CHA2DS2-VASc 1. These findings support current recommendations that patients within this intermediate risk group could be identified with a similar risk of arterial thromboembolism.

Perioperative Atrial Fibrillation and One-year Clinical Outcomes in Patients Following Major Emergency Abdominal Surgery.

The prevalence and impact of perioperative atrial fibrillation (AF) during an admission for major emergency abdominal surgery are sparsely examined. Therefore, this study aimed to compare the 30-day and 1-year outcomes (AF-related hospitalization, stroke, and all-cause mortality) in patients with and without perioperative AF to their major emergency abdominal surgery. All patients without a history of AF who underwent major emergency abdominal surgery from 2000 to 2019 and discharged alive were identified using Danish nationwide registries. Patients with and without perioperative AF (defined as new-onset AF during the index hospitalization) were matched 1:4 on age, gender, year of surgery, and type of surgery. The cumulative incidences and hazard ratios of outcomes were assessed using a multivariable Cox regression analysis comparing patients with and without perioperative AF. A total of 2% of patients were diagnosed with perioperative AF. The matched cohort comprised 792 and 3,168 patients with and without perioperative AF, respectively (median age 78 years [twenty-fifth to seventy-fifth percentile 70 to 83 years]; 43% men). Cumulative incidences of AF-related hospitalizations, stroke, and mortality 1 year after discharge were 30% versus 3.4%, 3.4% versus 2.7%, and 35% versus 22% in patients with and without perioperative AF, respectively. The 30-day outcomes were similarly elevated among patients with perioperative AF. Perioperative AF during an admission for major emergency abdominal surgery was associated with higher 30-day and 1-year rates of AF-related hospitalization and mortality and similar rates of stroke. These findings suggest that perioperative AF is a prognostic marker of increased morbidity and mortality in relation to major emergency abdominal surgery and warrants further investigation.

Long-Term Incidence of Ischemic Stroke After Transient Ischemic Attack: A Nationwide Study From 2014 to 2020.

BACKGROUND: The short-term incidence of ischemic stroke after a transient ischemic attack (TIA) is high. However, data on the long-term incidence are not well known but are needed to guide preventive strategies. METHODS: Patients with first-time TIA (index date) in the Danish Stroke Registry (January 2014-December 2020) were included and matched 1:4 with individuals from the background population and 1:1 with patients with a first-time ischemic stroke on the basis of age, sex, and calendar year. The incidences of ischemic stroke and mortality from index date were estimated by Aalen-Johansen and Kaplan-Meier estimators, respectively, and compared between groups using multivariable Cox regression. RESULTS: We included 21 500 patients with TIA, 86 000 patients from the background population, and 21 500 patients with ischemic stroke (median age, 70.8 years [25th-75th percentile, 60.8-78.7]; 53.1% males). Patients with TIA had more comorbidities than the background population, yet less than the control stroke population. The 5-year incidence of ischemic stroke after TIA (6.1% [95% CI, 5.7-6.5]) was higher than the background population (1.5% [95% CI, 1.4-1.6], P<0.01; hazard ratio, 5.14 [95% CI, 4.65-5.69]) but lower than the control stroke population (8.9% [95% CI, 8.4-9.4], P<0.01; hazard ratio, 0.58 [95% CI, 0.53-0.64]). The 5-year mortality for patients with TIA (18.6% [95% CI, 17.9-19.3]) was higher than the background population (14.8% [95% CI, 14.5-15.1], P<0.01; hazard ratio, 1.26 [95% CI, 1.20-1.32]) but lower than the control stroke population (30.1% [95% CI, 29.3-30.9], P<0.01; hazard ratio, 0.41 [95% CI, 0.39-0.44]). CONCLUSIONS: Patients with first-time TIA had an ischemic stroke incidence of 6.1% during the 5-year follow-up period. After adjustment for relevant comorbidities, this incidence was approximately 5-fold higher than what was found for controls in the background population and 40% lower than for patients with recurrent ischemic stroke.

Importance of heart failure duration for development of pulmonary hypertension in advanced heart failure.

BACKGROUND AND OBJECTIVES: Pulmonary vascular resistance (PVR) is critical when evaluating candidacy for advanced heart failure (HF) therapies, but risk factors for elevated PVR are not well studied. We hypothesized that HF duration would be associated with elevated PVR. METHODS: Danish single-center registry of consecutive in- and outpatients undergoing right heart catheterization as part of advanced HF work up. The relation between HF duration and PVR was estimated by regression analysis. Finally, the relation between PVR and long-term mortality was assessed by Cox proportional hazards regression and Kaplan-Meier analyses. RESULTS: A total of 549 patients (77% men, median age 54 (43-61) years, median HF duration 1.6 years (0.1-7.1)) were included. Univariate linear regression displayed an association between longer HF duration and increasing PVR (p = 0.014). PVR > 3 WU was present in 92 patients (17%) who were older (median p < 0.001) and had longer HF duration (p = 0.03). HF duration (per 1 year increase) did not predict PVR > 3 WU after adjustment for covariables (OR 1.00; p = 0.99). During a mean follow-up time of 4.5 years, there were 240 (44%) deaths. Increasing PVR was associated with elevated all-cause mortality risk (adjusted HR 1.24; p < 0.001). PVR > 3 WU was associated with higher mortality (adjusted HR 1.49; p = 0.027). CONCLUSION: Longer duration of HF was associated with higher PVR in patients with advanced HF, but this association disappeared in multivariate analyses. Longer HF duration per se likely does not cause elevated PVR and should not discourage evaluation for heart transplantation.

Long-term cardiovascular outcomes among immigrants and non-immigrants in cardiac resynchronization therapy: a nationwide study.

AIMS: To date, potential differences in outcomes for immigrants and non-immigrants with a cardiac resynchronization therapy (CRT), in a European setting, remain underutilized and unknown. Hence, we examined the efficacy of CRT measured by heart failure (HF)-related hospitalizations and all-cause mortality among immigrants and non-immigrants. METHODS AND RESULTS: All immigrants and non-immigrants who underwent first-time CRT implantation in Denmark (2000-2017) were identified from nationwide registries and followed for up to 5 years. Differences in HF related hospitalizations and all-cause mortality were evaluated by Cox regression analyses. From 2000 to 2017, 369 of 10 741 (3.4%) immigrants compared with 7855 of 223 509 (3.5%) non-immigrants with a HF diagnosis underwent CRT implantation. The origins of the immigrants were Europe (61.2%), Middle East (20.1%), Asia-Pacific (11.9%), Africa (3.5%), and America (3.3%). We found similar high uptake of HF guideline-directed pharmacotherapy before and after CRT and a consistent reduction in HF-related hospitalizations the year before vs. the year after CRT (61% vs. 39% for immigrants and 57% vs. 35% for non-immigrants). No overall difference in 5-year mortality among immigrants and non-immigrants was seen after CRT [24.1% and 25.8%, respectively, P-value = 0.50, hazard ratio (HR) = 1.2, 95% confidence interval (CI): 0.8-1.7]. However, immigrants of Middle Eastern origin had a higher mortality rate (HR = 2.2, 95% CI: 1.2-4.1) compared with non-immigrants. Cardiovascular causes were responsible for the majority of deaths irrespective of immigration status (56.7% and 63.9%, respectively). CONCLUSION: No overall differences in efficacy of CRT in improving outcomes between immigrants and non-immigrants were identified. Although numbers were low, a higher mortality rate among immigrants of Middle Eastern origin was identified compared with non-immigrants.

Temporal changes in incidence, treatment strategies and 1-year re-admission rates in patients with atrial fibrillation/flutter under 65 years of age: A Danish nationwide study.

AIM: To examine temporal changes in incidence rates of atrial fibrillation/flutter (AF), treatment strategies, and AF readmission rates in patients <65 years. METHODS: Using Danish nationwide registries, we identified patients <65 years with a first-time AF diagnosis from 2000 to 2018. The cohort was categorized according to calendar periods; 2000-2002, 2003-2006, 2007-2010, 2011-2014, and 2015-2018. In this retrospective cohort study the incidence rate (IR) of AF per 100,000 person years (PY), catheter ablation, electrical cardioversion, use of pharmacotherapy, and AF readmission, were investigated in the first year following AF diagnosis. RESULTS: We identified 60,917 patients; 8150 (13.4%) in 2000-2002, 11,898 (19.5%) in 2003-2006, 13,560 (22.3%) in 2007-2010, 14,167 (23.3%) in 2011-2014, and 13,142 (21.6%) in 2015-2018. Apart from 2015 to 2018, a stepwise increase in the crude IR of AF was observed across calendar periods; 2000-2002: 78.7 (95% CI 77.0;80.4), 2003-2006: 86.3 (84.7;87.8), 2007-2010: 97.9 (96.3;99.6), 2011-2014: 102.3 (100.7;104.0), 2015-2018: 93.6 (92.0;95.2). Over the studied time-periods, we found a stepwise increase in the cumulative incidence of catheter ablation (1.2% to 7.6%) electrical cardioversion (2.0% to 8.7%) and treatment with oral anticoagulant therapy (OAC) (28.5% to 47.8%) within the first year of diagnosis. No temporal differences in incidence of 1-year AF readmission were identified (AF-readmissions: 2000-2002: 32.7%, 2003-2006: 31.1%, 2007-2010: 32.2%, 2011-2014: 32.1% and 2015-2018: 31.7%). CONCLUSION: The incidence rate of AF in patients <65 years increased from 2000 to 2018, as did the use of catheter ablation, electrical cardioversion and OAC in the first year following AF diagnosis. 1-year AF readmission incidence remained stable around 32% over the study period.

Diuretic treatment before and after transcatheter aortic valve implantation: A Danish nationwide study.

OBJECTIVES: We examined loop diuretic treatment before and 1-year after transcatheter aortic valve implantation (TAVI), as a proxy for changes in symptom severity and secondly assessed how changes in loop diuretics related to mortality risk. BACKGROUND: Randomized clinical trials suggest that approximately one third of patients undergoing TAVI do not achieve symptom relief, but "all-comer" data are lacking. METHODS: Using Danish nationwide registries, we identified all citizens, who underwent TAVI from 2008 to 2019 and were alive at 1-year post-discharge. Loop diuretic treatment pre-TAVI and at 1-year post-TAVI were assessed and grouped as receiving 1) no-loop diuretics; 2) low: 1-40 mg of furosemide (or equivalent bumetanide) daily; 3) intermediate: 41-120 mg of furosemide daily; or 4) high: >120 mg furosemide daily. RESULTS: Among the 4431 patients undergoing TAVI, 2173 (49%) patients were not treated with loop diuretics at the time of TAVI, 918 (21%) had low-loop diuretics, 881 (20%) had intermediate-loop diuretics, and 459 (10%) had high-loop diuretics. At 1-year post-TAVI, 893 (20%) patients had increased, 1010 (23%) had reduced, and 2528 (57%) had unchanged loop diuretic treatment. The cumulative 5-year risk of death in patients surviving one year, was 61% (95% CI: 56.4% to 65.3%) in patients with increased and 47% (95% CI: 44.9% to 49.9%) in patients with reduced/unchanged loop diuretic treatment, respectively. In multivariable Cox proportional hazard analysis, increased loop diuretic treatment was associated with a higher risk of death compared with reduced/unchanged loop diuretic treatment (Hazard ratio: 1.4; 95% CI: 1.22 to 1.52). CONCLUSIONS: Among patients undergoing TAVI, surviving one year, one fifth of patients had increased loop diuretic treatment, and a little over one fifth had reduced loop diuretic treatment 1-year post-procedure. In patients with increased diuretic treatment, the risk of death was higher compared to those with reduced/unchanged loop diuretic treatment.

Incidence of thyroid dysfunction following initiation of amiodarone treatment in patients with and without heart failure: a nationwide cohort study.

AIMS: Thyroid dysfunction is considered the most frequent complication to amiodarone treatment, but data on its occurrence outside clinical trials are sparse. The present study aimed to examine the incidence of thyroid dysfunction following initiation of amiodarone treatment in a nationwide cohort of patients with and without heart failure (HF). METHODS AND RESULTS: In Danish registries, we identified all patients with first-time amiodarone treatment during the period 2000-18, without prior thyroid disease or medication. The primary outcome was a composite of thyroid diagnoses and initiation of thyroid drugs. Outcomes were assessed at 1-year follow-up, and for patients free of events in the first year, in a landmark analysis for the subsequent 5 years. We included 43 724 patients with first-time amiodarone treatment, of whom 16 939 (38%) had HF. At 1-year follow-up, the cumulative incidence and adjusted hazard ratio (HR) of the primary outcome were 5.3% and 1.37 (95% confidence interval 1.25-1.50) in patients with a history of HF and 4.2% in those without HF (reference). In the 1-year landmark analysis, the subsequent 5-year cumulative incidences and adjusted HRs of the primary outcome were 5.3% (reference) in patients with 1-year accumulated dose <27.38 g [corresponding to average daily dose (ADD <75 mg)], 14.0% and HR 2.74 (2.46-3.05) for 27.38-45.63 g (ADD 75-125 mg), 20.0% and HR 4.16 (3.77-4.59) for 45.64-63.88 g (ADD 126-175 mg), and 24.5% and HR 5.30 (4.82-5.90) for >63.88 g (ADD >175 mg). CONCLUSION: Among patients who initiated amiodarone treatment, around 5% had thyroid dysfunction at 1-year follow-up, with a slightly higher incidence in those with HF. A dose-response relationship was observed between the 1-year accumulated amiodarone dose and the subsequent 5-year cumulative incidence of thyroid dysfunction.

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.

Use of torsades de pointes risk drugs among patients with out-of-hospital cardiac arrest and likelihood of shockable rhythm and return of spontaneous circulation: A nationwide study.

AIM: Treatment with certain drugs can augment the risk of developing malignant arrhythmias (e.g. torsades de pointes [TdP]). Hence, we examined the overall TdP risk drug use before out-of-hospital cardiac arrest (OHCA) and possible association with shockable rhythm and return of spontaneous circulation (ROSC). METHODS: Patients ≥18 years with an OHCA of cardiac origin from the Danish Cardiac Arrest Registry (2001-2014) and TdP risk drug use according to www.CredibleMeds.org were identified. Factors associated with TdP risk drug use and secondly how use may affect shockable rhythm and ROSC were determined by multivariable logistic regression. RESULTS: We identified 27,481 patients with an OHCA of cardiac origin (median age: 72 years [interquartile range 62.0, 80.0 years]). A total of 37% were in treatment with TdP risk drugs 0-30 days before OHCA compared with 33% 61-90 days before OHCA (p < 0.001). Most commonly used TdP risk drugs were citalopram (36.1%) and roxithromycin (10.7%). Patients in TdP risk drug treatment were older (75 vs 70 years) and more comorbid compared with those not in treatment. Subsequently, TdP risk drug use was associated with less likelihood of the presenting rhythm being shockable (odds ratio [OR] = 0.63, 95% confidence interval [CI]:0.58-0.69) and ROSC (OR = 0.73, 95% CI:0.66-0.80). CONCLUSION: TdP risk drug use increased in the time leading up to OHCA and was associated with reduced likelihood of presenting with a shockable rhythm and ROSC in an all-comer OHCA setting. However, patients in TdP risk drug treatment were older and more comorbid than patients not in treatment.

Association Between Inappropriately Dosed Anticoagulation Therapy With Stroke Severity and Outcomes in Patients With Atrial Fibrillation.

Background Oral anticoagulation (OAC) is effective for stroke prevention in patients with atrial fibrillation. However, some patients experience stroke despite OAC therapy, and knowledge about the impact of prior treatment quality is lacking. Methods and Results Patients with atrial fibrillation on OAC therapy who had a first-time ischemic stroke were identified in the Danish Stroke Registry (2005-2018). Patients treated with vitamin K antagonist (VKA) therapy were compared according to the international normalized ratio just before stroke (international normalized ratio <2 [subtherapeutic], international normalized ratio 2-3 [therapeutic], international normalized ratio >3 [supratherapeutic]), and patients on underdosed, appropriately dosed, and overdosed direct OAC (DOAC) therapy were compared. Stroke severity was determined using the Scandinavia Stroke Scale (0-58 points), and the risk of very severe stroke (0-14 points) was analyzed by multivariable logistic regression. One-year mortality was determined using multivariable Cox regression. A total of 2319 patients with atrial fibrillation and stroke were included; 1196 were taking a VKA (subtherapeutic [46%], therapeutic [43%], supratherapeutic [11%]), and 1123 were taking DOAC (underdosed [23%], appropriately dosed [60%], and overdosed [17%]). Subtherapeutic and supratherapeutic VKA therapy (compared with therapeutic) and underdosed DOAC therapy (compared with appropriate and underdosed DOAC) patients were older, more often women, and more comorbid. Subtherapeutic VKA therapy was associated with very severe stroke (odds ratio [OR], 2.06 [95% CI, 1.28-3.31]), whereas supratherapeutic VKA therapy was not (OR, 1.24 [95% CI, 0.60-2.57]) compared with therapeutic VKA therapy. Patients on subtherapeutic and supratherapeutic VKA therapy had a higher 1-year mortality (hazard ratio [HR], 1.66 [95% CI, 1.29-2.13]); HR, 1.55 [95% CI, 1.08-2.22], respectively) than those on therapeutic VKA therapy. Treatment with underdosed or overdosed DOAC therapy was not associated with very severe stroke (OR, 1.27 [95% CI, 0.76-2.15]; OR, 0.73 [95% CI, 0.37-1.43], respectively) and was not associated with 1-year mortality (HR, 1.09 [95% CI, 0.83-1.44]; HR, 0.82 [95% CI, 0.57-1.18], respectively) than appropriate DOAC. Conclusions Half of the patients with atrial fibrillation with stroke were on inappropriate OAC therapy. Subtherapeutic VKA was associated with worse stroke severity and higher mortality rate than therapeutic VKA therapy. Neither underdosed nor overdosed DOAC was associated with worse outcomes in adjusted models compared with appropriately dosed DOAC. This study supports DOAC as a first-line therapy over VKA.

Long-term Risk of Death and Hospitalization in Patients With Heart Failure and Takotsubo Syndrome: Insights From a Nationwide Cohort.

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.

The burden of cardiovascular outcomes in heart failure patients with new-onset, prevalent, and without type 2 diabetes.

BACKGROUND: The prognostic importance of new-onset type 2 diabetes (T2D) in heart failure (HF) remains unknown. We aimed to describe the cardiovascular outcome profile in HF patients with new-onset, no and prevalent T2D. METHODS: We constructed a cohort of patients with first HF admission between 1998 and 2016 from nationwide Danish registers. Outcomes were ischemic event, HF event, and death from other causes. The landmarking approach and the Aalen Johansen estimator were used together to estimate 5-year absolute and 5-year relative risk of the outcomes in HF patients with new-onset, no and prevalent T2D. Risk among subgroups were investigated by stratification. RESULTS: A total of 139 264 HF patients were included between 1998 and 2016, of which 29 078 patients had prevalent T2D. A total of 11 819 developed new-onset T2D. The 5-year risks of ischemic event in new-onset, no, and prevalent T2D were: 17.9% [17.2; 18.6], 18.8% [18.6; 19.0], and 26.1% [25.6; 26.7]. The 5-year risks of HF event were: 31.5% [30.6; 32.3], 30.7% [30.5; 31.0], and 33.6% [33.0; 34.2]. For other causes of death, the 5-year risks were: 20.9% [20.2; 21.7], 18.6% [18.4; 18.8], and 18.9% [18.4; 19.3]. The 5-year risk ratios of HF event or death from other causes versus ischemic event were: 2.9 [2.8; 3.1], 2.6 [2.6; 2.7], and 2.0 [2.0; 2.1] in patients with new-onset, no, and prevalent T2D. CONCLUSIONS: In patients with new-onset T2D, death from other causes were more likely to occur than an ischemic event, whereas in patients with prevalent T2D and no T2D, ischemic events were more common.