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Aims Reduced psychological health is associated with adverse patient outcomes and higher mortality. We aimed to examine if a Brugada syndrome (BrS) diagnosis and symptomatic disease presentation were associated with an increased risk of new-onset depression or anxiety and all-cause mortality. Methods and results All Danish patients diagnosed with BrS (2006–2018) with no history of psychiatric disease and available for ≥6 months follow-up were identified using nationwide registries and followed for up to 5 years after diagnosis. The development of clinical depression or anxiety was evaluated using the prescription of medication and diagnosis codes. Factors associated with developing new-onset depression or anxiety were determined using a multivariate Cox proportional hazards regression model. Disease manifestation was categorized as symptomatic (aborted cardiac arrest, ventricular tachycardia, or syncope) or asymptomatic/unspecified at diagnosis. A total of 223 patients with BrS and no history of psychiatric disease were identified (72.6% male, median age at diagnosis 46 years, 45.3% symptomatic). Of these, 15.7% (35/223) developed new-onset depression or anxiety after BrS diagnosis (median follow-up 5.0 years). A greater proportion of symptomatic patients developed new-onset depression or anxiety compared with asymptomatic patients [21/101 (20.8%) and 14/122 (11.5%), respectively, P = 0.08]. Symptomatic disease presentation (HR 3.43, 1.46–8.05) and older age (lower vs. upper tertile: HR 4.41, 1.42–13.63) were significantly associated with new-onset depression or anxiety. All-cause mortality in this group of patients treated according to guidelines was low (n = 4, 1.8%); however, 3/4 developed depression or anxiety before death. Conclusion Approximately, one-sixth of patients with BrS developed new-onset depression or anxiety following a diagnosis of BrS. Symptomatic BrS disease manifestation was significantly associated with new-onset d, Aims Reduced psychological health is associated with adverse patient outcomes and higher mortality. We aimed to examine if a Brugada syndrome (BrS) diagnosis and symptomatic disease presentation were associated with an increased risk of new-onset depression or anxiety and all-cause mortality. Methods and results All Danish patients diagnosed with BrS (2006-2018) with no history of psychiatric disease and available for >= 6 months follow-up were identified using nationwide registries and followed for up to 5 years after diagnosis. The development of clinical depression or anxiety was evaluated using the prescription of medication and diagnosis codes. Factors associated with developing new-onset depression or anxiety were determined using a multivariate Cox proportional hazards regression model. Disease manifestation was categorized as symptomatic (aborted cardiac arrest, ventricular tachycardia, or syncope) or asymptomatic/unspecified at diagnosis. A total of 223 patients with BrS and no history of psychiatric disease were identified (72.6% male, median age at diagnosis 46 years, 45.3% symptomatic). Of these, 15.7% (35/223) developed new-onset depression or anxiety after BrS diagnosis (median follow-up 5.0 years). A greater proportion of symptomatic patients developed new-onset depression or anxiety compared with asymptomatic patients [21/101 (20.8%) and 14/122 (11.5%), respectively, P = 0.08]. Symptomatic disease presentation (HR 3.43, 1.46-8.05) and older age (lower vs. upper tertile: HR 4.41, 1.42-13.63) were significantly associated with new-onset depression or anxiety. All-cause mortality in this group of patients treated according to guidelines was low (n = 4, 1.8%); however, 3/4 developed depression or anxiety before death. Conclusion Approximately, one-sixth of patients with BrS developed new-onset depression or anxiety following a diagnosis of BrS. Symptomatic BrS disease manifestation was significantly associated with new-onset depression or anxiety.

Background: Patients with chronic renal failure on hemodialysis carry a significant risk of infective endocarditis (IE), but data on whether these patients differ from other patients with IE in terms of comorbidity, microbiology, rates of surgery and mortality are sparse. Methods: Using Danish nationwide registries, all patients with IE diagnosed between February 1, 2010, and May 14, 2018 were identified and categorized into a “hemodialysis group” and a “non-hemodialysis group.” Patient groups were compared by comorbidities, microbiological etiology, cardiac surgery, and mortality. Risk factors associated with mortality were assessed in multivariable Cox regression analysis. Results: In total, 4,366 patients with IE were included with 226 (5.2%) patients in the hemodialysis group. Patients in the hemodialysis group were younger (66.0 years [IQR 53.8-74.9] vs 72.2 years [IQR 62.2-80.0]), had more comorbidities and were surgically treated less often (10.6% vs 20.8%), compared with patients from the nonhemodialysis group. Staphylococcus aureus was more than twice as prevalent (58.0% vs 26.5%). No difference in in-hospital mortality was found between the 2 groups (20.8% vs 18.5%), but 1- and 5-year mortality were significantly higher in the hemodialysis group than in the nonhemodialysis group (37.7% vs 17.7% and 72.1% vs 42.5%, respectively). In adjusted analysis, hemodialysis was associated with higher 1-year (HR = 2.71, 95% CI 2.07-3.55) and 5-year mortality (HR = 2.72, 95% CI 2.22-3.34) Conclusions: Patients with IE on chronic hemodialysis were younger, had more comorbidity, a higher prevalence of Staphylococcus aureus IE, and a higher mortality than patients without hemodialysis.

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., 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.

Aims While clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted. Objective To assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate. Methods and results ECGs recorded at the Copenhagen General Practitioners Laboratory (2001–15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [<60, 60–79, 80–99, and 100–110, > 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70–85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71–101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100–110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10–1.95) and 2.41 (CI: 1.94–3.00) respectively for new-onset HF, compared with 60–79 bpm. Similarly, patients with AF ventricular rates 100–110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13–1.82) and 1.34 (CI: 1.08–1.65) respectively for all-cause mortality, compared with 60–79 bpm. Conclusions Ventricular rates ≥100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality., Aims While clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted. Objective To assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate. Methods and results ECGs recorded at the Copenhagen General Practitioners Laboratory (2001-15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [ 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70-85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71-101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100-110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10-1.95) and 2.41 (CI: 1.94-3.00) respectively for new-onset HF, compared with 60-79 bpm. Similarly, patients with AF ventricular rates 100-110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13-1.82) and 1.34 (CI: 1.08-1.65) respectively for all-cause mortality, compared with 60-79 bpm. Conclusions Ventricular rates >= 100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality.

BACKGROUND: Patients with Brugada syndrome (BrS) are recommended to avoid drugs that may increase their risk of arrhythmic events. We examined treatment with such drugs in patients with BrS after their diagnosis. METHODS AND RESULTS: All Danish patients diagnosed with BrS (2006– 2018) with >12 months of follow-up were identified from nationwide registries. Nonrecommended BrS drugs were grouped into drugs to “avoid” or “preferably avoid” according to http://www.brugadadrugs.org. Cox proportional hazards analyses were performed to identify factors associated with any nonrecommended BrS drug use, and logistic regression analyses were performed to examine associated risk of appropriate implantable cardioverter defibrillator therapy, mortality, and a combined end point indicating an arrhythmic event of delayed implantable cardioverter defibrillator implantation, appropriate implantable cardioverter defibrillator therapy, and mortality. During a median follow-up of 6.8 years, 93/270 (34.4%) patients with BrS (70.4% male, median age at diagnosis 46.1 years [interquartile range, 32.6– 57.4]) were treated with ≥1 nonrecommended BrS drugs. No difference in any nonrecommended BrS drug use was identified comparing time before BrS diagnosis (12.6%) with each of the 5 years following BrS diagnosis (P>0.05). Factors associated with any nonrecommended BrS drug use after diagnosis were female sex (hazard ratio [HR]) 1.83 [95% CI, 1.15– 2.90]), psychiatric disease (HR, 3.63 [1.89– 6.99]), and prior use of any nonrecommended BrS drug (HR, 4.76 [2.45– 9.25]). No significant association between any nonrecommended BrS drug use and implantable cardioverter de-fibrillator therapy (n=20/97, odds ratio [OR], 0.7 [0.2– 2.4]), mortality (n=10/270, OR, 3.4 [0.7–19.6]), or the combined end point (n=38/270, OR, 1.7 [0.8– 3.7]) was identified. CONCLUSIONS: One in 3 patients with BrS were treated with a nonrecommended BrS drug after BrS diagnosis, and a BrS diagnosis did not change prescri

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.

BACKGROUND: Acquired long QT syndrome (aLQTS) is a serious unpredictable adverse drug reaction. Pharmacogenomic markers may predict risk.METHODS: Among 153 aLQTS patients (mean age 58 years [range, 14-88], 98.7% White, 85.6% symptomatic), computational methods identified proteins interacting most significantly with 216 QT-prolonging drugs. All cases underwent sequencing of 31 candidate genes arising from this analysis or associating with congenital LQTS. Variants were filtered using a minor allele frequency <1% and classified for susceptibility for aLQTS. Gene-burden analyses were then performed comparing the primary cohort to control exomes (n=452) and an independent replication aLQTS exome sequencing cohort.RESULTS: In 25.5% of cases, at least one rare variant was identified: 22.2% of cases carried a rare variant in a gene associated with congenital LQTS, and in 4% of cases that variant was known to be pathogenic or likely pathogenic for congenital LQTS; 7.8% cases carried a cytochrome-P450 (CYP) gene variant. Of 12 identified CYP variants, 11 (92%) were in an enzyme known to metabolize at least one culprit drug to which the subject had been exposed. Drug-drug interactions that affected culprit drug metabolism were found in 19% of cases. More than one congenital LQTS variant, CYP gene variant, or drug interaction was present in 7.8% of cases. Gene-burden analyses of the primary cohort compared to control exomes (n=452), and an independent replication aLQTS exome sequencing cohort (n=67) and drug-tolerant controls (n=148) demonstrated an increased burden of rare (minor allele frequency<0.01) variants in CYP genes but not LQTS genes.CONCLUSIONS: Rare susceptibility variants in CYP genes are emerging as potentially important pharmacogenomic risk markers for aLQTS and could form part of personalized medicine approaches in the future.

Aims Current treatment guidelines recommend implantable cardioverter-defibrillators (ICDs) in eligible patients with an estimated survival beyond 1 year. There is still an unmet need to identify patients who are unlikely to benefit from an ICD. We determined cause-specific 1-year mortality after ICD implantation and identified associated risk factors.Methods and results Using Danish nationwide registries (2000-2017), we identified 14 516 patients undergoing first-time ICD implantation for primary or secondary prevention. Risk factors associated with 1-year mortality were evaluated using multivariable logistic regression. The median age was 66 years, 81.3% were male, and 50.3% received an ICD for secondary prevention. The 1-year mortality rate was 4.8% (694/14 516). ICD recipients who died within 1 year were older and more comorbid compared to those who survived (72 vs. 66 years, P < 0.001). Risk factors associated with increased 1-year mortality included dialysis [odds ratio (OR): 3.26, confidence interval (CI): 2.37-4.49], chronic renal disease (OR: 2.14, CI: 1.66-2.76), cancer (OR: 1.51, CI: 1.15-1.99), age 70-79 years (OR: 1.65, CI: 1.36-2.01), and age >= 80 years (OR: 2.84, CI: 2.15-3.77). The 1-year mortality rates for the specific risk factors were: dialysis (13.8%), chronic renal disease (13.1%), cancer (8.5%), age 70-79 years (6.9%), and age >= 80 years (11.0%). Overall, the most common causes of mortality were related to cardiovascular diseases (62.5%), cancer (10.1%), and endocrine disorders (5.0%). However, the most common cause of death among patients with cancer was cancer-related (45.7%).Conclusion Among ICD recipients, mortality rates were low and could be indicative of relevant patient selection. Important risk factors of increased 1-year mortality included dialysis, chronic renal disease, cancer, and advanced age.

OBJECTIVE: To examine workforce attachment among patients with congenital long QT syndrome (cLQTS) following diagnosis and identify factors associated with workforce attachment.METHODS AND RESULTS: In this nationwide cohort study, all patients diagnosed with cLQTS in Denmark between 1996 and 2016 aged 18-60 years at diagnosis were identified using nationwide registries. Patients attached to the workforce at diagnosis were included. Attachment to the workforce 1 year after cLQTS diagnosis was examined and compared with a background population matched 1:4 on age, sex and employment status. Multiple logistic regression was performed to identify factors associated with 1-year workforce detachment among patients with cLQTS. 298 patients fulfilled the inclusion criteria. Six months after cLQTS diagnosis, 90.9% of patients with cLQTS were attached to the workforce compared with 95.0% in the background population (p=0.006 for difference). One year after diagnosis, 93.3% of patients with cLQTS were attached to the workforce compared with 93.8% in the background population (p=0.26). Among patients with cLQTS, a severe cLQTS disease manifestation was associated with workforce detachment 1 year after diagnosis (compared with asymptomatic patients; aborted cardiac arrest OR 20.4 (95% CI, 1.7 to 249.9); ventricular tachycardia/syncope OR 10.9 (95% CI, 1.1 to 110.5)). No other associated factors were identified.CONCLUSIONS: More than 90% of patients with cLQTS remained attached to the workforce 1 year after diagnosis, which was similar to a matched background population. Patients with a severe cLQTS disease manifestation were less likely to be attached to the workforce 1 year after diagnosis.

Background: International guidelines recommend work-up of relatives to autopsy negative sudden cardiac death victims, denoted as sudden unexplained death (SUD) and nonautopsied possible sudden cardiac death (pSCD) victims. This study assesses and compare baseline characteristics and clinical outcome at initial evaluation and during follow-up of relatives to SUD and pSCD victims. Methods: We retrospectively included data from systematic screening and routine follow-up of first-degree relatives to SUD and pSCD victims referred to our Unit for Inherited Cardiac Diseases, Copenhagen, 2005–2018. Victims with an antemortem known inherited cardiac disease were excluded. Results: We included 371 first-degree relatives from 187 families (120 SUD, 67 pSCD): 276 SUD relatives (age 33 ± 18 years, 54% men) and 95 pSCD relatives (age 40 ± 15 years, 51% men). The diagnostic yields of inherited cardiac diseases in SUD and pSCD families were 16% and 13%, respectively (p =.8). The diagnoses in SUD families were mainly channelopathies (68%), whereas pSCD families were equally diagnosed with cardiomyopathies, channelopathies, and premature ischemic heart disease. Ninety-three percent of diagnosed families were diagnosed at initial evaluation and 7% during follow-up (5.4 ± 3.3 years). During follow-up 34% of relatives with a diagnosed inherited cardiac disease had an arrhythmic event, compared to 5% of relatives without established diagnosis (p <.0001). Conclusions: Channelopathies dominated in SUD families whereas a broader spectrum of inherited diseases was diagnosed in pSCD families. Most affected relatives were diagnosed at initial evaluation. The event rate was low in relatives without an established diagnosis. Long-term clinical follow-up may not be warranted in all relatives with normal baseline-findings.

Aim To determine the risk of adverse outcomes across the spectrum of glycated haemoglobin (HbA1c) levels among hospitalized COVID-19 patients with and without diabetes. Materials and methods Danish nationwide registries were used to study the association between HbA1c levels and 30-day risk of all-cause mortality and the composite of severe COVID-19 infection, intensive care unit (ICU) admission and all-cause mortality. The study population comprised patients hospitalized with COVID-19 (3 March 2020 to 31 December 2020) with a positive polymerase chain reaction (PCR) test and an available HbA1c ≤ 6 months before the first positive PCR test. All patients had at least 30 days of follow-up. Among patients with diabetes, HbA1c was categorized as <48 mmol/mol, 48 to 53 mmol/mol, 54 to 58 mmol/mol, 59 to 64 mmol/mol (reference) and >64 mmol/mol. Among patients without diabetes, HbA1c was stratified into <31 mmol/mol, 31 to 36 mmol/mol (reference), 37 to 41 mmol/mol and 42 to 47 mmol/mol. Thirty-day standardized absolute risks and standardized absolute risk differences are reported. Results We identified 3295 hospitalized COVID-19 patients with an available HbA1c (56.2% male, median age 73.9 years), of whom 35.8% had diabetes. The median HbA1c was 54 and 37 mmol/mol among patients with and without diabetes, respectively. Among patients with diabetes, the standardized absolute risk difference of the composite outcome was higher with HbA1c < 48 mmol/mol (12.0% [95% confidence interval {CI} 3.3% to 20.8%]) and HbA1c > 64 mmol/mol (15.1% [95% CI 6.2% to 24.0%]), compared with HbA1c 59 to 64 mmol/mol (reference). Among patients without diabetes, the standardized absolute risk difference of the composite outcome was greater with HbA1c < 31 mmol/mol (8.5% [95% CI 0.5% to 16.5%]) and HbA1c 42 to 47 mmol/mol (6.7% [95% CI 1.3% to 12.1%]), compared with HbA1c 31 to 36 mmol/mol (reference). Conclusions Patients with COVID-1

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 27481 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.

Objective. To examine the long-term rates of heart failure (HF) and other adverse cardiovascular (CV) outcomes in a nationwide cohort of patients diagnosed with granulomatosis with polyangiitis (GPA) compared with the general population. Methods. Using Danish nationwide registries, patients with newly diagnosed GPA were identified and matched 1:4 by age, sex, and comorbidities with subjects from the general population. Outcomes were compared using Cox regression. Due to violation of the proportional hazard assumption, landmark analyses for the first year and from 1 year were performed. Results. Of the 1923 patients with GPA, 1781 patients (median age 59 yrs, 47.9% men) were matched with 7124 subjects from the general population. The median follow-up was 6.4 years. The absolute 10-year risk of HF was 6.8% (95% CI 5.5–8.2%) for patients with GPA and 5.9% (5.3–6.6%) for the general population. During the first year after diagnosis, GPA was associated with a significantly higher rate of HF (hazard ratio [HR] 3.60, 95% CI, 2.28–5.67) and other adverse outcomes, including atrial fibrillation/flutter (HR 6.50, 95% CI 4.43–9.55) and ischemic stroke (HR 3.24, 95% CI 1.92–5.48), compared with the general population. After the first year, GPA was not associated with higher rates of HF or other CV outcomes compared with the general population, except atrial fibrillation/flutter (HR 1.38, 95% CI 1.12-1.70). Conclusion. During the first year after diagnosis, the rates of HF and other CV outcomes were higher in patients with GPA compared with the general population. However, after the first year, the rates of HF and other CV outcomes, except atrial fibrillation/flutter, were similar to those in the general population.

BACKGROUND: Physical and mental well-being after critical illness may be objectified by the ability to work. We examined return to work among patients with myocardial infarction (MI) by cardiogenic shock (CS) status.METHODS: Danish nationwide registries were used to identify patients with first-time MI by CS status between 2005 and 2015, aged 18-63 years, working before hospitalization and discharged alive. Multiple logistic regression models were used to compare groups.RESULTS: We identified 19 799 patients with MI of whom 653 had CS (3%). The median age was similar for patients with and without CS (53 years, interquartile range 47-58). One-year outcomes in patients with and without CS were as follows: 52% vs. 83% returned to work, 41% vs. 16% did not and 6% vs. 1% died. The adjusted odds ratio (OR) of returning to work was 0.53 [95% confidence limit (CI): 0.42-0.66]. In patients with CS, males and patients surviving OHCA were more likely to return to work (OR: 1.83, 95% CI: 1.15-2.92 and 1.55, 95% CI: 1.00-2.40, respectively), whereas prolonged hospitalization (OR: 0.38, 95% CI: 0.22-0.65) and anoxic brain damage (OR: 0.36, 95% CI: 0.18-0.72) were associated with lower likelihood of returning to work.CONCLUSION: In patients with MI discharged alive, approximately 80% of those without CS returned to work at 1-year follow-up in contrast to 50% of those with CS. Among patients with CS, male sex and OHCA survivors were markers positively related to return to work, whereas prolonged hospitalization and anoxic brain damage were negatively related markers.

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 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]

AIMS: We examined if a congenital long QT syndrome (cLQTS) diagnosis and severity of cLQTS disease manifestation was associated with increased risk of depression, anxiety, and all-cause mortality.METHODS AND RESULTS: All patients with known cLQTS in Denmark were identified using nationwide registries and specialized inherited cardiac disease clinics (1994-2016) and followed for up to 3 years after their cLQTS diagnosis. Risk factors for depression, anxiety, and all-cause mortality were determined using multivariable Cox proportional-hazards regression. An age- and sex-matched control population was identified (matching 1:4). Overall, 589 patients with cLQTS were identified of which 119/589 (20.2%) developed depression or anxiety during follow-up compared with 302/2356 (12.8%) from the control population (P < 0.001). Severity of cLQTS disease manifestation was identified for 324/589 (55%) of patients with cLQTS; 162 were asymptomatic, 119 had ventricular tachycardia (VT)/syncope, and 43 had aborted sudden cardiac death (aSCD). In multivariable models, patients with aSCD, VT/syncope, or unspecified cLQTS disease manifestation had a higher risk of developing depression or anxiety compared with the control population (hazard ratio [HR]=2.4, 95% confidence interval [CI]: 1.1-5.1; HR = 1.9, 95% CI: 1.2-3.0; HR = 1.6, 95% CI: 1.1-2.3, respectively). Asymptomatic patients had similar risk of developing depression or anxiety as the control population (HR = 1.2, 95% CI: 0.8-1.9). During follow-up, 10/589 (1.7%) patients with cLQTS died compared with 27/2356 (1.1%) from the control population (P = 0.5). Furthermore, 4/10 who died had developed depression or anxiety.CONCLUSION: A severe cLQTS disease manifestation was associated with a greater risk of depression or anxiety. All-cause mortality for patients with cLQTS was low.

AimsInsulin resistance associates with development of metabolic syndrome and risk of cardiovascular disease. The link between insulin resistance and cardiovascular disease is complex and multifactorial. Confirming the genetic link between insulin resistance, type 2 diabetes, and coronary artery disease, as well as the extent of coronary artery disease, is important and may provide better risk stratification for patients at risk. We investigated whether a genetic risk score of 53 single nucleotide polymorphisms known to be associated with insulin resistance phenotypes was associated with diabetes and burden of coronary artery disease.Methods and resultsWe genotyped patients with a coronary angiography performed in the capital region of Denmark from 2010-2014 and constructed a genetic risk score of the 53 single nucleotide polymorphisms. Logistic regression using quartiles of the genetic risk score was performed to determine associations with diabetes and coronary artery disease. Associations with the extent of coronary artery disease, defined as one-, two- or three-vessel coronary artery disease, was determined by multinomial logistic regression.We identified 4,963 patients, of which 17% had diabetes and 55% had significant coronary artery disease. Of the latter, 27%, 14% and 14% had one, two or three-vessel coronary artery disease, respectively. No significant increased risk of diabetes was identified comparing the highest genetic risk score quartile with the lowest. An increased risk of coronary artery disease was found for patients with the highest genetic risk score quartile in both unadjusted and adjusted analyses, OR 1.21 (95% CI: 1.03, 1.42, p = 0.02) and 1.25 (95% CI 1.06, 1.48, pConclusionsAmong patients referred for coronary angiography, only a strong genetic predisposition to insulin resistance was associated with risk of coronary artery disease and with a greater disease burden.

AIMS: The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.METHODS AND RESULTS: We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1-1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10-20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05).CONCLUSION: We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.