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Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.

Background and Aims Incidence and types of secondary tricuspid regurgitation (TR) are not well defined in atrial fibrillation (AFib) and sinus rhythm (SR). Atrial secondary TR (A-STR) is associated with pre-existing AFib; however, close to 50% of patients with A-STR do not have AFib. The aim of this study was to assess incidence, types, and outcomes of ≥ moderate TR in AFib vs. SR. Methods Adults with and without new-onset AFib without structural heart disease or ≥ moderate TR at baseline were followed for the development of ≥ moderate TR. Tricuspid regurgitation types were pacemaker, left-sided valve disease, left ventricular (LV) dysfunction, pulmonary hypertension (PH), isolated ventricular, and A-STR. Results Among 1359 patients with AFib and 20 438 in SR, 109 and 378 patients developed ≥ moderate TR, respectively. The individual types of TR occurred more frequently in AFib related to the higher pacemaker implantation rates (1.12 vs. 0.19 per 100 person-years, P <.001), larger right atrial size (median 78 vs. 53 mL, P <.001), and higher pulmonary pressures (median 30 vs. 28 mmHg, P <.001). The most common TR types irrespective of rhythm were LV dysfunction-TR and A-STR. Among patients in SR, those with A-STR were older, predominantly women with more diastolic abnormalities and higher pulmonary pressures. All types of secondary TR were associated with all-cause mortality, highest in PH-TR and LV dysfunction-TR. Conclusions New-onset AFib vs. SR conferred a higher risk of the individual TR types related to sequelae of AFib and higher pacemaker implantation rates, although the distribution of TR types was similar. Secondary TR was universally associated with increased mortality. [ABSTRACT FROM AUTHOR]

Aims: Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high‐risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high‐risk arrhythmogenic gene variants in DCM patients. Methods and results: In this multicentre study, DCM patients with available genetic testing were analysed. The following arrhythmic markers, present at baseline or within 1 year of enrolment, were tested: unexplained syncope, rapid non‐sustained ventricular tachycardia (NSVT), ≥1000 premature ventricular contractions/24 h or ≥50 ventricular couplets/24 h. LMNA, FLNC, RBM20, and desmosomal pathogenic or likely pathogenic gene variants were considered high‐risk arrhythmogenic genes. The study endpoint was a composite of sudden cardiac death and major ventricular arrhythmias (SCD/MVA). We studied 742 DCM patients (45 ± 14 years, 34% female, 410 [55%] with left ventricular ejection fraction [LVEF] <35%). During a median follow‐up of 6 years (interquartile range 1.6–12.1), unexplained syncope and NSVT were the only arrhythmic markers associated with SCD/MVA, and the combination of the two markers carried a significant additive risk of SCD/MVA, incremental to LVEF and New York Heart Association class. The probability of identifying an arrhythmogenic genotype rose from 8% to 30% if both early syncope and NSVT were present. Conclusion: In DCM patients, the combination of early detected NSVT and unexplained syncope increases the risk of life‐threatening arrhythmic outcomes and can aid the identification of carriers of malignant arrhythmogenic genotypes. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) affects an estimated 1:500 individuals and is largely considered to be a disease of the sarcomere. However, disease-causative genetic variants in PLN -encoded phospholamban and JPH2 -encoded junctophilin-2 cause HCM via perturbations in intracellular calcium handling (ICH). Given recent case reports describing asymmetric left ventricular hypertrophy (LVH) in patients with arrhythmogenic cardiomyopathy (ACM)-predisposing genetic variants in PKP2 -encoded plakophilin-2, a gene known to play a role in ICH, we sought to examine the prevalence and clinical impact of an HCM phenotype in PKP2-ACM patients. In this retrospective study, review of 771 genotype-positive ACM patients evaluated between 01/2015 and 04/2024 was used to identify those with a pathogenic/likely pathogenic (P/LP) variant in PKP2. Pertinent demographic, electrocardiographic, imaging and outcome data was extracted from the electronic medical record. HCM was defined by the presence of maximal end-diastolic wall thickness of >15 mm anywhere in the left ventricle. Advanced heart failure (HF) and major VA outcomes [sudden cardiac arrest (SCA), sustained VT, and appropriate implantable cardioverter-defibrillator (ICD) shocks] were analyzed. Collectively, an HCM phenotype was observed in 9 (7.8%) of the 115 P/LP variant-positive patients (mean age 38±36; 51 (44%) male, and 57 with a ACM phenotype). Of note sigmoid subtype HCM was noted in 8/9 (89%) and left ventricular outflow tract obstruction present in 7/9 (78%; mean gradient of 57±48 mmHg). In comparison to PKP2-ACM patients without HCM, PKP2-HCM patients with HCM were older and less likely to have a family history of any cardiomyopathy (Table). Interestingly, in the patients with a positive phenotype, non-sustained VT and major VA outcomes were less prevalent in the HCM patients (Table). Nearly 8% of individuals with a P/LP variant in PKP2 have a concomitant HCM phenotype. Whether this observation reflects abnormal calcium handling in the setting of PKP2 haploinsufficiency or selection bias in the setting of the combined prevalence of HCM (1:500) and PKP2 loss-of-function (1:695) requires further studies. [ABSTRACT FROM AUTHOR]

Background: Sarcoidosis is a disease characterized by non-caseating granulomas and may affect any organ system. Cardiac involvement may lead to conduction abnormalities, heart failure, or malignant ventricular arrhythmias. As sarcoidosis may present with heterogeneous manifestations, a detailed past medical history may provide clues that help guide further workup. We present a rare case of a patient with undiagnosed oral sarcoidosis who subsequently experienced cardiac arrest from cardiac involvement., Case Summary: A 43-year-old male with a history of palpitations and periodontitis consistent with oral sarcoidosis presents after experiencing sudden cardiac arrest. He was subsequently diagnosed with cardiac and pulmonary sarcoidosis. With contemporary management (both immunosuppression and antiarrhythmics), he has not experienced any recurrent arrhythmias., Discussion: In the setting of cardiac arrest and non-ischaemic cardiomyopathy, a careful clinical history and targeted cardiac testing may help clinicians determine when to consider cardiac sarcoidosis as a diagnosis. While oral sarcoidosis is a very rare condition, this case highlights how infrequent manifestations of sarcoidosis may be encountered in the clinical setting., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)