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Aim β-blockers are the first line of treatment in patients with congenital long QT syndrome (cLQTS) (class I or II recommendation) in order to prevent malignant arrhythmias. Hence, we examined long-term β-blocker adherence and associated risk factors among patients with cLQTS. Methods and results Danish patients with cLQTS claiming a prescription for any β-blocker after their cLQTS diagnosis were identified using data from nationwide registries and specialized inherited cardiac disease clinics (1995–2017). Patients were followed for up to 5 years. Treatment breaks >60 days were assessed (i.e. proxy for reduced adherence). Multivariable Cox regression was used to identify risk factors associated with breaks of >60 days in β-blocker treatment. Overall, 500 out of 633 (79%) patients with cLQTS claimed at least one prescription for any β-blocker after cLQTS diagnosis. During follow-up, 38.4% had a treatment break. Risk factors significantly associated with treatment breaks were implantable cardioverter defibrillator (ICD) [hazard ratio (HR) = 1.65, 95% confidence interval (CI): 1.08–2.53], β-blocker side effects (HR = 2.69, 95% CI: 1.75–4.13), and psychiatric disease (HR = 1.63, 95% CI: 1.04–2.57). In contrast, patients presenting with ventricular tachycardia/syncope as cLQTS disease manifestation were less likely to have a treatment break compared with asymptomatic patients (HR = 0.55, 95% CI: 0.33–0.92). Conclusion Reduced β-blocker adherence was common with more than a third of patients having a treatment break >60 days after cLQTS diagnosis. Patients with psychiatric disease, self-reported β-blocker side effects, and an ICD were more likely to display reduced adherence, whereas a severe cLQTS disease manifestation was associated with optimal β-blocker adherence.

AimsWhile 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.ObjectiveTo 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 resultsECGs 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.ConclusionsVentricular 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.

AimsReduced 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 resultsAll 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.ConclusionApproximately, 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. AimsReduced 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 resultsAll 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.ConclusionApproximately, 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.

BackgroundThere are no methods for classifying patients with ischemic heart disease (IHD) based on the entire spectrum of pre-existing diseases. Such methods might be clinically useful due to the marked differences in presentation and course of disease.MethodsA population-based cohort study from a Danish secondary care setting of patients with IHD (2004-2016) and subjected to a coronary angiography (CAG) or coronary computed tomography angiography (CCTA). Data sources were The Danish National Patient Registry, in-hospital laboratory data, and genetic data from Copenhagen Hospital Biobank. Comorbidities included diagnoses assigned prior to presentation of IHD. Patients were clustered by means of the Markov Clustering Algorithm using the entire spectrum of registered multimorbidity. The two prespecified outcomes were: New ischemic events (including death from IHD causes) and death from non-IHD causes. Patients were followed from date of CAG/CCTA until one of the two outcomes occurred or end of follow-up, whichever came first. Biological and clinical appropriateness of clusters was assessed by comparing risks (estimated from Cox proportional hazard models) in clusters and by phenotypic and genetic enrichment analyses, respectively.FindingsIn a cohort of 72,249 patients with IHD (mean age 63.9 years, 63.1% males), 31 distinct clusters (C1-31, 67,136 patients) were identified. Comparing each cluster to the 30 others, seven clusters (9,590 patients) had statistically significantly higher or lower risk of new ischemic events (five and two clusters, respectively). 18 clusters (35,982 patients) had a higher or lower risk of death from non-IHD causes (12 and six clusters, respectively). All clusters at increased risk of new ischemic events, associated with risk of death from non-IHD causes as well. Cardiovascular or inflammatory diseases were commonly enriched in clusters (13), and distributions for 24 laboratory test results differed significantly across clusters. Clusters enriched for cerebrovascular diseases were generally not at increased risk of the two outcomes. Polygenic risk scores were increased in a total of 15 clusters (48.4%).ConclusionsClustering of patients with IHD based on pre-existing comorbidities identified subgroups of patients with significantly different clinical outcomes and presented a tool to rank pre-existing comorbidities based on their association with clinical outcomes. This novel method may support better classification of patients and thereby differentiation of treatment intensity depending on expected outcomes in subgroups.

BackgroundPatients 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 ResultsAll 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 defibrillator 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.ConclusionsOne in 3 patients with BrS were treated with a nonrecommended BrS drug after BrS diagnosis, and a BrS diagnosis did not change prescription patterns. More awareness of nonrecommended drug use among patients with BrS is needed. BackgroundPatients 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 ResultsAll 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 defibrillator 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.ConclusionsOne in 3 patients with BrS were treated with a nonrecommended BrS drug after BrS diagnosis, and a BrS diagnosis did not change prescription patterns. More awareness of nonrecommended drug use among patients with BrS is needed.

AimsThyroid 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 resultsIn 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 63.88 g (ADD >175 mg).ConclusionAmong 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.

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.

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]; 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.

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

Introduction: Pharmacotherapy with proarrhythmic or QT prolonging properties are known to augment the risk of malignant arrhythmias (e.g. TdP). We examined TdP risk drug usage prior to OHCA and how it may be associated with shockable rhythm and survival. Methods: Patients ≥18 years with an OHCA of cardiac origin were identified from the Danish Cardiac Arrest Registry (2001-2014). From nationwide registries TdP risk drug usage before OHCA according to CredibleMeds was assessed. We performed multivariable logistic regression to determine factors associated with TdP risk drug usage among OHCA patients and how usage may affect OHCA related factors (e.g. shockable rhythm or survival). Age and sex controls were identified (matching 1:5). Results: Overall, 10139 OHCA patients were identified, of which 43% were in treatment with a TdP risk drug 0-30 days before OHCA compared with 15% from the control population. Furthermore, this was significantly more than 61-90 days before OHCA (37%). Most common prescribed drugs with known risk of TdP were citalopram (31.1%), methadone (16.4%), and fluconazole (8.2%). OHCA patients in treatment with a TdP risk drug at the time of event had a significantly higher burden of comorbidities compared with OHCA patients not in treatment (e.g. cancer [19.3% and 8.7%], COPD [20.0% and 6.6%], psychiatric disease [21.9% and 13.5%], p Conclusion: Almost half of OHCA patients were in treatment with TdP risk drugs before OHCA. Subsequently, TdP risk drug usage did not modify the likelihood of presenting with a shockable rhythm as first recorded rhythm. However, this could partly be due to the large burden of comorbidities. Figure: Factors associated with TdP risk drug usage (adjusted for below mentioned factors).

Cardiology relies on a huge amount of data derived from clinical observations, case-specific considerations and randomised controlled trials. At best, medical intervention relieves symptoms and reduces disease consequences or complications. Rarely, it redirects the cause. However, an accelerated array of opportunities within a digital and molecular discourse may mark a medical era which acknowledges individual variation rather than accepts a pragmatic pooling of similarities. This review aims at providing a brief overview of academic achievements, clinical considerations and translational perspectives related to precision cardiology.

Considerable interindividual variability in response to cardiovascular pharmacotherapy exists with drug responses varying from being efficacious to inadequate to induce severe adverse events. Fueled by advancements and multidisciplinary collaboration across disciplines such as genetics, bioinformatics, and basic research, the vision of personalized medicine, rather than a one-size-fits-all approach, may be within reach. Pharmacogenetics offers the potential to optimize the benefit-risk profile of drugs by tailoring diagnostic and treatment strategies according to the individual patient. To date, a multitude of studies has tried to delineate the effects of gene-drug interactions for drugs commonly used to treat cardiovascular-related disease. The focus of this review is on how genetic variability may modify drug responsiveness and patient outcomes following therapy with commonly used cardiovascular drugs including clopidogrel, warfarin, statins, and β-blockers. Also included are examples of how genetic studies can be used to guide drug discovery and examples of how genetic information may be deployed in clinical decision making.

During the past year, the field of cardiovascular genomics has witnessed publication of an unprecedented number of outstanding articles. In addition to large-scale investigations of original hypotheses (eg, pleiotropic effects of height loci on coronary artery disease [CAD]), our community has welcomed seminal functional genomics studies using gene editing, induced pluripotent stem cells (iPSC), and total RNA sequencing. Taken together, these studies have produced valuable insights into mechanisms underlying the observed associations with cardiovascular disease (CVD). The mission of the Functional Genomics and Translational Biology (FGTB) Council of the American Heart Association (http://www.my.americanheart.org/fgtbcouncil) is to advance new discoveries in the fields of genetics, omics-based approaches, and translational biology, as well as to facilitate their application in cardiovascular health and disease. By creating a multidisciplinary collaborative environment, this Council integrates scientific knowledge from molecules to populations and contributes to the global goal of building healthier lives, free of CVDs and stroke. The Early Career Committee of the FGTB Council collectively selected studies that we believe to be the major advances published in 2015. In this Special Report, we summarize 10 articles that cover a variety of disciplines represented on the FGTB and highlight their particular significance to the cardiovascular field. Through interactions with the host genes and environmental exposures, gut bacteria have previously been shown to influence metabolic and inflammatory processes although the specific contributions to disease risk had remained elusive because of the lack of large-scale human studies. In the past year, Fu et al1 began to peel back the layers of uncertainty surrounding the role of the gut microbes in CVD. Using fecal samples from the LifeLines DEEP cohort, they have profiled the gut microbiome of 893 participants by 16s ribosomal RNA sequencing and identified novel …

Background: Dilated cardiomyopathy (DCM) has been associated with hundreds of genetic variants across 62 genes. These associations are now being questioned by large control populations in which these variants are found with high allele frequencies. Hypothesis: We hypothesized that genetic variants previously associated with DCM are overrepresented in the population-based ExAC database when taking the prevalence of the disease into account. Hence, we aimed to identify potentially false-positive variants previously associated with DCM. Methods: We identified all previously DCM associated variants in The Human Gene Mutation Database (HGMD). We then systematically searched for these in the ExAC database containing exome data on 61.000 individuals. In addition, we performed a PolyPhen-2 prediction on all variants, including those not found in the ExAC database. Results: We identified 148 (31%) out of 473 variants previously associated with DCM in ExAC. These variants included eight stop-gain variants, eight splice variants and 132 missense variants. The 148 variants affected 7.928 alleles corresponding to a genotype prevalence of 1:7 in the ExAC population. Thirty-five variants were found in 25 or more alleles, corresponding to a DCM genotype prevalence of 1:8 Furthermore, we identified all variants previously associated with DCM in 14 genes; hereof 4 genes only contained variants above our estimated allele frequency (25:61000). Polyphen-2 analysis predicted 53 (36%) variants to be benign in the ExAC population compared with 53 (16%) among variants not found in ExAC (p Conclusion: In conclusion, we identified much higher genotype prevalence of previously DCM associated variants than expected in the exome data from ExAC. More importantly we found 4 genes in which all previously identified variants were found with relative high allele frequencies, questioning the association of these genes with the monogenic form of DCM.