Morten Krogh Christiansen

The evidence supporting beta-blocker therapy after myocardial infarction was established before the introduction of modern coronary reperfusion therapy and secondary prevention strategies. In an open-label, randomized trial with blinded end-point evaluation, conducted in Denmark and Norway, we assigned patients who had had a myocardial infarction and who had a left ventricular ejection fraction of at least 40%, in a 1:1 ratio, to receive long-term beta-blocker therapy within 14 days after the event or no beta-blocker therapy. The primary end point was a composite of death from any cause or major adverse cardiovascular events (new myocardial infarction, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias). A total of 5574 patients underwent randomization and were included in the main analyses - 2783 in the beta-blocker group and 2791 in the no-beta-blocker group. After a median follow-up of 3.5 years (interquartile range, 2.2 to 4.6), a primary end-point event had occurred in 394 patients (14.2%) in the beta-blocker group and in 454 patients (16.3%) in the no-beta-blocker group (hazard ratio, 0.85; 95% confidence interval [CI], 0.75 to 0.98; P = 0.03). Death from any cause occurred in 4.2% of the patients in the beta-blocker group and in 4.4% of those in the no-beta-blocker group; myocardial infarction occurred in 5.0% and 6.7%, respectively (hazard ratio, 0.73; 95% CI, 0.59 to 0.92), unplanned coronary revascularization in 3.9% and 3.9%, ischemic stroke in 1.6% and 1.3%, heart failure in 1.5% and 1.9%, and malignant ventricular arrhythmias in 0.5% and 0.6%. No apparent differences in safety outcomes were observed between the groups. Among patients with a myocardial infarction and a left ventricular ejection fraction of at least 40%, beta-blocker therapy led to a lower risk of death or major adverse cardiovascular events than no beta-blocker therapy. (Funded by the Health South-East research program in Norway and others; BETAMI-DANBLOCK ClinicalTrials.gov numbers, NCT03646357 and NCT03778554.).

Aims: We aimed to investigate the risk of sinus node dysfunction (SND) indicating cardiac pacing and mortality in first-degree relatives to patients with a pacemaker implanted on this indication and assess the effect of onset-age on disease risk. Methods and results: In this nationwide register-based study, we used the Danish Civil Registration Registry to establish family structures and merged data with the Danish National Patient Registry and the Danish Pacemaker and ICD Registry containing information on all pacemakers implanted due to SND in Denmark. We followed 6 027 090 individuals born after 1954 in the period between 1982 and 2022 (180 775 041 person-years) among whom 2.477 pacemakers were implanted due to SND. The adjusted rate ratio (RR) of pacemaker-treated SND was 2.9 (2.4–3.6) for individuals having any father, mother, or sibling with a pacemaker implanted on this indication compared with the general population (derived cumulative incidence at the age of 68 years: 0.79 and 0.27%, respectively). This risk was inversely proportional to implantation age in the index person [≤60 years: RR = 5.5 (3.4–9.0)]. Overall, mortality was similar between individuals having a father, mother, or sibling with SND and the general population, but higher for relatives to index persons with an early onset [≤60 years: RR = 1.22 (1.05–1.41)]. Conclusion: First-degree relatives to SND patients are at increased risk of SND with risk being inversely associated with pacemaker implantation age in the index person. Mortality in first-degree relatives was comparable with the general population, although subgroup findings suggest an increased mortality among individuals with a family history of early-onset SND.

Background: Individuals with both atrial fibrillation (AF) and myocardial infarction (MI) have higher mortality compared with individuals with only 1 condition. Whether mortality differs according to the temporal order of AF and MI is unclear. Methods and Results: We included participants from the FHS (Framingham Heart Study) from 1960 and onwards. We assessed the hazard ratio (HR) of new‐onset AF and MI, and mortality according to MI and AF status (prevalent and interim) using multivariable‐adjusted Cox proportional hazards models. Interim diseases were modeled as time‐varying variables. For the analysis of new‐onset AF, 10 923 participants (55% women; mean±SD age, 54±8 years) were included. For new‐onset MI, 10 804 participants (55% women; mean±SD age, 54±8 years) were included. Compared with no MI, the hazard of new‐onset AF was higher in participants with prevalent (HR, 1.60 [95% CI, 1.32–1.94]) and interim MI (HR, 3.96 [95% CI, 3.18–4.91]). Both ST‐segment–elevation MI and non–ST‐segment–elevation MI were associated with new‐onset AF. Interim AF, not prevalent AF, was associated with higher hazard rate of new‐onset MI (HR, 2.21 [95% CI, 1.67–2.92]). Interim AF was associated with both ST‐segment–elevation MI and non–ST‐segment–elevation MI. Mortality was significantly greater among participants with AF and MI compared with participants with 1 of the 2, regardless of temporal order. Conclusions: We report a bidirectional association between AF and MI, which was observed for both non–ST‐segment–elevation MI and ST‐segment–elevation MI. Participants with both AF and MI had considerably higher mortality compared with participants with only 1 of the 2 conditions, regardless of order.

Background: Rare genetically inherited forms of sinus node dysfunction (SND) have been described but the significance of a family history of SND and the associated prognosis remains unknown. Purpose: To investigate the risk of SND indicating pacemaker implantation and mortality in first-degree relatives to patients who received a pacemaker because of SND, and to assess the effect of age of onset on disease risk. Methods: This was a nationwide retrospective register-based cohort study including all Danish citizens born after 1954. SND was defined to be present when a first pacemaker was implanted on this indication. To establish family structures, we retrieved data from the Danish civil registration registry which contains information on parental links and merged them with the Danish Pacemaker and ICD registry which contains information on all pacemaker implanted because of SND in Denmark. Using Poisson regression, we compared the rates of SND and the risk of all-cause mortality in first-degree relatives of SND patients with the rates in the general population between January 1st 1982 and August 31st 2022. Analyses were adjusted for selected diagnosis- and procedure codes from the Danish National Patient Registry, including hypertension, diabetes mellitus, heart failure, coronary artery disease, atrial fibrillation or flutter, valvular heart disease, stroke, and cardiac surgery. Results: We included 6,027,090 individuals among whom 2,477 first pacemakers were implanted due to SND in the time period. The adjusted rate ratio (RR) of SND was 2.9 (95% CI 2.4-3.6), p<0.001, for individuals having any father, mother or sibling with SND compared with the general population. This risk was increased in first-degree relatives across all ages of SND onset in the index person but substantially higher if SND onset in the index person occurred ≤50 years (adjusted RR=7.1 (95% CI 3.5-14.3), p<0.001). Comparable risks of SND were observed for first-degree relatives to mothers, fathers and siblings with SND as well as for men and women. Overall, mortality was similar between individuals having any father, mother or sibling with SND and the general population (adjusted RR=1.02 (0.97-1.08), p=0.45). However, there was a trend towards an increased mortality among first-degree relatives to index persons with an early onset. Conclusions: First-degree relatives to SND patients are at increased risk of SND with risk being inversely associated with age of onset in the index person. Overall, mortality in first-degree relatives was comparable to the general population, suggesting a benign prognosis in the vast majority of cases with genetically inherited SND.Table 1Figure 1

Aims: Obesity is a major risk factor for atrial fibrillation (AF). Compared with stable weight, gaining weight was associated with a higher risk of incident AF in observational studies. The results, however, are conflicting regarding weight loss and risk of AF. This study aimed to assess the association between 5-year weight changes and risk of incident AF. Methods and results: The study was based on participants from the Danish Diet, Cancer, and Health Cohort. Body mass index (BMI) was assessed at a baseline examination and at a second examination 5 years later. Diagnoses of AF and co-morbidities were retrieved from the Danish National Patient Registry. In total, 43 758 participants without prior AF were included. The median age was 61 years and 54% were female. During a median follow-up of 15.7 years, 5312 individuals had incident AF (incidence rate 8.6/1000 person-years). Compared with stable weight, weight gain between 2.5 and 5 BMI units (kg/m2) was associated with a higher risk of AF [hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.09–1.41]. Weight gain of 5 or more BMI units (kg/m2) was associated with a HR of 1.95 (95% CI 1.48–2.56) of incident AF. However, there was no statistically significant association between weight loss and risk of AF. Conclusion: Five-year weight gain was associated with greater risk of AF compared with stable weight in the Danish Diet, Cancer, and Health Cohort. There was no statistically significant association between weight loss and risk of AF.

Aims: Alcohol intake is a well-established risk factor for atrial fibrillation (AF). However, evidence on the effects of changes in alcohol intake to primary AF prevention is sparse. The aim of this study was to examine the association between 5-year changes in alcohol intake and the risk of incident AF. Methods and results: This study was based on the Danish cohort study Diet, Cancer and Health. Lifestyle factors were assessed using questionnaires at a recruitment research examination and a second examination 5 years later. Diagnoses of AF and comorbidities were retrieved from the Danish National Patient Registry. 43 758 participants without prior AF were included. The median age was 61 (25th–75th percentile 58–66) years and 54% were female. Over a median follow-up time of 15.7 years, 5312 participants had incident AF (incidence rate 8.6/1000 person-years). Compared with stable intake, increases in alcohol intake to ≥21 drinks/week from ≤6.9 drinks/week (HR: 1.38, 95% CI: 1.09–1.72) or 14–20.9 drinks/week (HR: 1.27, 95% CI: 1.01–1.59) at baseline were associated with a higher risk of AF. In contrast, we did not observe a statistically significant association between reductions in alcohol intake and the risk of AF. Conclusion: A 5-year increase in alcohol intake was associated with a greater risk of AF compared with a stable low/moderate intake.

Purpose of review: Recent advances in genetics have facilitated the calculation of polygenic risk scores (PRSs) based on common genetic risk variants of coronary artery disease (CAD). Here, we provide an explanation of the genetic basis for PRSs and review recent literature investigating PRSs and the clinical utility for different aspects of CAD. Recent findings: CAD-based PRSs are strongly associated with atherosclerosis burden in the coronary arteries and other vascular beds. In multiple studies, PRSs have proven to be a measure of CAD risk, more powerful than most established risk factors alone, that can be used from early life to stratify individuals into varying trajectories of lifetime risk. When implemented in risk stratification models for primary prevention of cardiovascular disease, PRSs provide modest improvements in discrimination (C-index generally increasing 0–4% points) and reclassification, but yield significant clinical benefit as a risk enhancer. Additionally, data suggest possible value of PRSs for aiding decisions in other aspects of diagnostics and treatment in CAD. Summary: Once genotyped, the genetic information may be used to calculate an infinite number of PRSs and contribute to personalize medicine providing clinical value for risk stratification, diagnostics and treatment in CAD as well as in other diseases.

Background: The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown.Methods and Results: Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32–45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in theLMNAgene (n=5).LMNAvariant carriers all had a family history of either AVB and/or sudden cardiac death.Conclusions: In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in theLMNAgene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members.

Objective Rare cases of genetically inherited atrioventricular block (AVB) have been reported; however, the heredity of AVB remains unknown. We aimed to assess the heredity of AVB. Design, setting and participants Using data from the Danish Civil Registration Registry, we established a nationwide cohort of individuals with parental links. Data were merged with information from the Danish Pacemaker and Implantable Cardioverter Defibrillator Registry, containing information on all pacemaker implantations performed in Denmark during the study period, to identify patients who received a first-time pacemaker because of AVB. Results A total of 4 648 204 individuals had parental links and a total of 26 880 consecutive patients received a first-time pacemaker due to AVB. Overall, the adjusted rate ratio (RR) of pacemaker implantation due to AVB was 2.1 (95% CI 1.8 to 2.5) if a father, mother or sibling had AVB compared with the risk in the general population. The adjusted RR was 2.2 (1.7–2.9) for offspring of mothers with AVB, 1.9 (1.5–2.4) for offspring of fathers with AVB and 3.5 (2.3–5.4) for siblings to a patient with AVB. The risk increased inversely proportionally with the age of the index case at the time of pacemaker implantation. The corresponding adjusted RRs were 15.8 (4.8–52.3) and 10.0 (3.3–30.4) if a mother or father, respectively, had a pacemaker implantation before 50 years. Conclusion and relevance First-degree relatives to a patient with AVB carry an increased risk of AVB with the risk being strongly inversely associated with the age of the index case at pacemaker implantation. These findings indicate a genetic component in the development of AVB in families with an early-onset disease.