Fatunde, Olubadewa A.

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Mayo Clinic Background/Introduction Syncope is a common presentation in heart failure (HF) patients. However, the associations between syncope and prognosis in HF patients with the cardiac implantable electronic device (CIED) have not been demonstrated. It is unclear whether syncope increases all-cause mortality in HF patients with CIED. Purpose We aimed to examine the association between syncope and all-cause mortality in the largest cohort of HF with reduced ejection fraction (HFrEF), mid-ranged ejection fraction (HFmEF), and preserved ejection fraction (HFpEF) patients with and without CIED. Methods A retrospective cohort of patients with HF and syncope at our hospital between 2010 and 2015 were identified, and 1:1 propensity was matched with a control group of HF patients without syncope. A chart review was conducted. The multivariate Cox regression model was applied to estimate the association between syncope and the all-cause mortality endpoint. Results 3,449 HF patients were diagnosed with syncope (mean age, 72.8±14.5 years; 41.5% women), and the propensity-matched control HF patients without syncope (n=3,449) aged 72.8±14.3 years, and 42.5% women were selected. Cardiac implantable electronic devices were implanted more in HF patients with syncope (32.5% versus 13.7%, p<0.001). Implantable cardioverter defibrillators were implanted more in HF patients with syncope (15.6% versus 8.3%, p<0.001) as well as pacemakers (16.9% versus 7.5%, p<0.001) and cardiac resynchronization therapy devices (6.9% versus 4.8%, p=0.015). Among HF patients with CIED, syncope significantly increased the risk of all-cause mortality in HFrEF patients (hazard ratio [HR]=1.479, 95% confidence interval [CI]: 1.197-1.828, p<0.001) but not in HFpEF (HR=0.980, 95%CI: 0.793-1.210, p=0.849)(Figure 1). Syncope also tended to increase the risk of all-cause mortality in HFmEF patients with CIED but was not significant (HR=1.193, 95%CI: 0.762-1.865, p=0.762)(Figure 1). Among HF patients without CIED, syncope did not increase the risk of all-cause mortality in HFrEF (HR=0.923, 95%CI: 0.806-1.057, p=0.247), HFmEF (HR=1.074, 95%CI: 0.848-1.360, p=0.554), or HFpEF (HR=0.964, 95%CI: 0.883-1.052, p=0.406). Conclusions Syncope significantly increased the risk of all-cause mortality in HFrEF patients but not in HFmEF or HFpEF patients with CIED. The association of syncope and increased mortality in HFrEF patients with CIED suggests that syncope may be a marker and a factor of mortality and warrants further investigation.

AbstractIntroductionBrugada syndrome is an inherited arrhythmic disease associated with major arrhythmic events (MAE). The importance of primary prevention of sudden cardiac death (SCD) in Brugada syndrome is well recognized; however, ventricular arrhythmia risk stratification remains challenging and controversial. We aimed to assess the association of type of syncope with MAE via systematic review and meta‐analysis.MethodsWe comprehensively searched the databases of MEDLINE and EMBASE from inception to December 2021. Included studies were cohort (prospective or retrospective) studies that reported the types of syncope (cardiac, unexplained, vasovagal, and undifferentiated) and MAE. Data from each study were combined using the random‐effects, generic inverse variance method of DerSimonian and Laird to calculate the odds ratio (OR) and 95% confidence intervals (CIs).ResultsSeventeen studies from 2005 to 2019 were included in this meta‐analysis involving 4355 Brugada syndrome patients. Overall, syncope was significantly associated with an increased risk of MAE in Brugada syndrome (OR = 3.90, 95% CI: 2.22–6.85, p < .001, I2 = 76.0%). By syncope type, cardiac (OR = 4.48, 95% CI: 2.87–7.01, p < .001, I2 = 0.0%) and unexplained (OR = 4.71, 95% CI: 1.34–16.57, p = .016, I2 = 37.3%) syncope was significantly associated with increased risk of MAE in Brugada syndrome. Vasovagal (OR = 2.90, 95% CI: 0.09–98.45, p = .554, I2 = 70.9%) and undifferentiated syncope (OR = 2.01, 95% CI: 1.00–4.03, p = .050, I2 = 64.6%, respectively) were not.ConclusionOur study demonstrated that cardiac and unexplained syncope was associated with MAE risk in Brugada syndrome populations but not in vasovagal syncope and undifferentiated syncope. Unexplained syncope is associated with a similar increased risk of MAE compared to cardiac syncope.

Abstract Funding Acknowledgements Type of funding sources: None. Background The prevalence of Type-1 Brugada pattern in Caucasians and Asians have been estimated to be 20 and 180 per 100,000. However, the prevalence of Type-1 Brugada pattern in African Americans has never been studied. Purpose This study aims to identify the prevalence of Type-1 Brugada pattern in African Americans. Methods Medical records of African American patients ages 18 years old or older with at least one 12-lead electrocardiogram (ECG) performed at 16 hospitals from 5 states in a single healthcare system between January 1, 2011 to December 31, 2020 were included. The search engine software was used to identify patients with keywords (Brugada pattern, Brugada ECG, Brugada Type-1, or Brugada syndrome) documented in the electronic medical record. The 12-lead ECGs were retrospectively analyzed by 2 cardiologists. Any inconsistencies were reviewed by a third cardiac electrophysiologist. Type-1 Brugada pattern was diagnosed according to the recent Heart Rhythm Society Expert Consensus Statement. Results Among 43,116 African American patients, (46.9% males), 6 patients (mean age 44.8±13.9 years, 100% males) had Type-1 Brugada pattern documented on at least one 12-lead ECG. The prevalence of Type-1 Brugada pattern in this large patient population of African American was 13.9 per 100,000. None of the patients had major arrhythmic event at 6.7±4.7 years follow-up. Conclusions The prevalence of Type-1 Brugada pattern in African American is lower than Caucasian and Asian populations. The risk of major arrhythmic event of Type-1 Brugada pattern in African American appears to be low; however longer follow-up data is needed.

Introduction: Multiple supervised machine learning (ML) models have been used to assess the outcomes in patients who underwent transcatheter aortic valve replacement (TAVR) procedure, however, supervised ML requires significant expert time for annotation and labeling. Unsupervised ML can provide insight into the dataset without this process. Hypothesis: We hypothesized that unsupervised k-means ML can identify distinct phenogroups in TAVR patients that can predict prognosis without a priori knowledge. Methods: A retrospective study of patients who underwent TAVR (Jan 2012-Dec 2017) at Mayo Clinic sites was performed. Baseline demographics, EKG, cardiac computed tomography, and echocardiographic data were abstracted. Variables with ≥ 20% missing data were excluded. Prior to the k-means clustering algorithm, principal component analysis was used for dimensionality reduction. Input variables were analyzed according to k-means determined clusters. Kaplan-Meier survival analysis was used to assess the survival of each cluster. Results: A total of 1071 consecutive patients were included in the final analysis. A total of 141 unique variables were used. The mean age was 80.7±8.6 years, 58.2% were male. Patients were divided into 2 distinct phenogroups. In the two phenogroups, cluster 0 (n=639) has significantly better survival than cluster 1 (n= 432) (log-rank p=0.0002) (Figure 1). Cluster 1 has features of low flow-low gradient (LFLG) hemodynamic profile, including lower systolic blood pressure, mean aortic valve gradient, peak aortic valve velocity, and worse LV ejection fraction. Conclusions: Unsupervised ML can identify distinct phenotype features with prognostic significance in TAVR patients. Our results suggest that patients with LFLG hemodynamic features are intrinsically different from other TAVR patients and require more attention to avoid adverse outcomes.

Introduction: Peripheral arterial disease (PAD) increases cardiovascular (CV) morbidity and mortality, but remains underdiagnosed and undertreated. Several trials support low-dose rivaroxaban in PAD treatment, although this has yet to be widely adopted in clinical practice. The effect of warfarin and direct oral anticoagulants (DOACs) on comprehensive PAD outcomes warrants further study. Hypothesis: Anticoagulant therapy, particularly DOACs, improves CV outcomes in PAD. Methods: We conducted a retrospective study of patients who underwent ankle-brachial index testing (ABI) from 1996 – 2020 at Mayo Clinic. We included patients with PAD defined by abnormal ABI (<1.0 or >/=1.4). Prolonged (>6 months) DOAC or warfarin use was compared to no anticoagulant therapy. Multivariable (MV) regression, controlling for baseline CV risk factors, was used. Results: 21,891 patients had abnormal ABI readings; 3,093 were on warfarin and 267 were on DOAC for any indication. Anticoagulation improved mortality, with DOACs superior to warfarin. DOACs improved critical limb ischemia (CLI)/amputation in univariate analysis, although this was not significant in MV. Patients with poorly compressible vessels (ABI >/=1.4) had increased limb outcomes compared to reduced ABI (<1.0). Ischemic stroke and myocardial infarction occurred more frequently in those on anticoagulation, but the risk was less for DOACs vs. warfarin. Notably, both anticoagulant groups had greater baseline comorbidity than the non-anticoagulant group; the DOAC and warfarin groups were similar. Major bleeding (6.7%) was increased in both anticoagulant groups, but less so with DOACs and this was similar to the bleeding risk seen with aspirin (HR 1.20). Conclusion: Anticoagulant therapy improved mortality in a large cohort of PAD patients. The risk of limb events appears improved in those on DOACs. DOACs showed improved risk profiles compared to warfarin regarding CV and bleeding outcomes.

Introduction: Syncope was reported to be associated with sudden cardiac death in heart failure patients regardless of the etiology of syncope. We attempted to use unsupervised machine learning to identify the prognostically distinct phenotypes in a large population of heart failure patients presenting with syncope. Hypothesis: Unsupervised machine learning can identify prognostically distinct phenotypes in a large population of heart failure patients presenting with syncope. Methods: Patients with a diagnosis of systolic or diastolic heart failure and syncope at Mayo Clinic sites were identified for baseline and follow-up data. Variables with ≥ 20% missing data were excluded; a total of 57 variables were used for k-means clustering analysis. Patients were grouped according to 4 distinct k-means determined clusters for statistical analysis. Results: A total of 3,557 patients with proper follow-up and echocardiography data were included in the final analysis. The median follow-up duration was 36.3 months, and 2908 (81.7%) patients died. Cluster 2 (n= 680) was identified as the cluster with the highest mortality (92%), which contained patients with high proportions of cardiovascular comorbidities, especially chronic kidney disease. The Kaplan-Meier survival curves are shown in Figure 1. In multivariate Cox regression analysis, the presence of CKD independently predicts mortality (HR 1.62, 95%CI 1.50-1.76, p <0.0001) after adjusting for age and sex. Conclusions: Unsupervised machine learning identified patients with CKD, CAD and DM are high-risk phenotypes in heart failure patients with syncope, and can be used to guide future studies in this highly heterogeneous, unexplored population.

Introduction: Catheter ablation of the arrhythmogenic substrate reduces the recurrence of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillator (ICD). However, the all-cause mortality benefit in this population is unclear. Hypothesis: Prophylactic ablation of the arrhythmogenic substrate decreases all-cause mortality and prevents the recurrence of VT/ventricular fibrillation (VF) in patients with ischemic cardiomyopathy. Methods: We searched the MEDLINE and EMBASE databases from inception through May 2021. We included randomized controlled trials that compared all-cause mortality and ventricular arrhythmia recurrence in patients with ischemic cardiomyopathy who underwent ICD implantation with and without prophylactic ablation. The data from each study was combined using a fixed effects model to calculate the hazard ratio and 95% confidence interval (CI). Results: Four randomized controlled trials during 2007-2020 involving 505 patients (249 patients with and 256 patients without prophylactic VT ablation) were included in our meta-analysis. Compared with control, prophylactic VT ablation did not decrease the all-cause mortality (pooled hazard ratio = 0.94, 95% CI 0.54-1.63, p = 0.818, I2 = 5.8%). However, prophylactic VT ablation significantly decreased appropriate ICD therapy (pooled hazard ratio = 0.58, 95% CI 0.41-0.82, p = 0.002, I 2 = 26.1%) and VT/VF recurrence (pooled hazard ratio = 0.70, 95% CI 0.52-0.93, p = 0.015, I 2 = 0.0%). Conclusions: Prophylactic VT ablation in patients with ischemic cardiomyopathy did not decrease all-cause mortality; however, it did lead to decreased appropriate ICD therapy and VT/VF recurrence.

Abstract Recent advances in treatment have transformed the management of cancer. Despite these advances, cardiovascular disease remains a leading cause of death in cancer survivors. Cardio-oncology has recently evolved as a subspecialty to prevent, diagnose, and manage cardiovascular side effects of antineoplastic therapy. An emphasis on optimal management of comorbidities and close attention to drug interactions are important in cardio-oncologic care. With interdisciplinary collaboration among oncologists, cardiologists, and pharmacists, there is potential to prevent and reduce drug-related toxicities of treatments. The cytochrome P450 (CYP450) family of enzymes and the P-glycoprotein (P-g) transporter play a crucial role in drug metabolism and drug resistance. Here we discuss the role of CYP450 and P-g in drug interactions in the field of cardio-oncology, provide an overview of the cardiotoxicity of a spectrum of cancer agents, highlight the role of precision medicine, and encourage a multidisciplinary treatment approach for patients with cancer.

As many novel cancer therapies continue to emerge, the field of Cardio-Oncology (or onco-cardiology) has become crucial to prevent, monitor and treat cancer therapy-related cardiovascular toxicity. Furthermore, given the narrow therapeutic window of most cancer therapies, drug-drug interactions are prevalent in the cancer population. Consequently, there is an increased risk of affecting drug efficacy or predisposing individual patients to adverse side effects. Here we review the role of cytochrome P450 (CYP450) enzymes in the field of Cardio-Oncology. We highlight the importance of cardiac medications in preventive Cardio-Oncology for high-risk patients or in the management of cardiotoxicities during or following cancer treatment. Common interactions between Oncology and Cardiology drugs are catalogued, emphasizing the impact of differential metabolism of each substrate drug on unpredictable drug bioavailability and consequent inter-individual variability in treatment response or development of cardiovascular toxicity. This inter-individual variability in bioavailability and subsequent response can be further enhanced by genomic variants in CYP450, or by modifications of CYP450 gene, RNA or protein expression or function in various ‘omics’ related to precision medicine. Thus, we advocate for an individualized approach to each patient by a multidisciplinary team with clinical pharmacists evaluating a treatment plan tailored to a practice of precision Cardio-Oncology. This review may increase awareness of these key concepts in the rapidly evolving field of Cardio-Oncology.