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Objective: To determine the prevalence, penetrance, and disease expression of cardiomyopathy-related genetic variants in an unselected, richly phenotyped Mayo Clinic population in the setting of preemptive sequencing, with return of incidental findings following the American College of Medical Genetics and Genomics recommendations., Patients and Methods: We analyzed a quaternary medical center-based biobank cohort (n=983) for reportable variants in 15 cardiomyopathy genes. Prioritization of genetic variants was performed using an internally developed pipeline to identify potentially reportable variants. Prioritized variants were then manually curated. The correlation of likely pathogenic/pathogenic (LP/P) variants with clinical phenotypes and outcomes was established. Artificial intelligence-enabled electrocardiographic predictions of reduced left ventricular ejection fraction and hypertrophic cardiomyopathy were applied to genotype-positive (G+) participants., Results: Of the 983 patients, 11 (1%) were G+, with 11 LP/P variants found in the MYBPC3, DSG2, MYH7, DSP, and PKP2 genes. All G+ participants underwent electrocardiography, and 10 (90%) underwent echocardiography. Most patients (10 [90%]) did not have a prior diagnosis of cardiomyopathy. Definitive disease penetrance (heart failure or cardiomyopathy) was present in 4 (36%), while 3 (27%) had possible penetrance (structural heart disease identified by echocardiography). Arrhythmias and/or cardiac conduction disease was present in 4 of 11 G+ individuals (36%). Artificial intelligence-electrocardiography was positive for hypertrophic cardiomyopathy or reduced left ventricular ejection fraction in 5 of the G+ participants (45%), of whom 4 (80%) had definitive or possible disease penetrance., Conclusion: Cardiomyopathy-associated LP/P variants are present in a small subset of a quaternary medical center population, and disease penetrance in G+ individuals is high in the form of cardiac structural abnormalities and heart failure., (Copyright © 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) is characterized by heterogeneity in susceptibility to the disease and severity of illness. Understanding inter-individual variation has important implications for not only allocation of resources but also targeting patients for escalation of care, inclusion in clinical trials, and individualized medical therapy including vaccination. In addition to geographic location and social vulnerability, there are clear biological differences such as age, sex, race, presence of comorbidities, underlying genetic variation, and differential immune response that contribute to variability in disease manifestation. These differences may have implications for precision medicine. Specific examples include the observation that androgens regulate the expression of the enzyme transmembrane protease, serine 2 which facilitates severe acute respiratory syndrome coronavirus 2 viral entry into the cell; therefore, androgen deprivation therapy is being explored as a treatment option in males infected with COVID-19. An immunophenotyping study of COVID-19 patients has shown that a subset develop T cytopenia which has prompted a clinical trial that is testing the efficacy of interleukin-7 in these patients. Predicting which COVID-19 patients will develop progressive disease that will require hospitalization has important implications for clinical trials that target outpatients. Enrollment of patients at low risk for progression of disease and hospitalization would likely not result in such therapy demonstrating efficacy. There are efforts to use artificial intelligence to integrate digital data from smartwatch applications or digital monitoring systems and biological data to enable identification of the high risk COVID-19 patient. The ultimate goal of precision medicine using such modern technology is to recognize individual differences to improve health for all., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the frequency and outcomes of patients requiring renal replacement therapy (RRT) early after left ventricular assist device (LVAD) implantation., Patients and Methods: We examined use of in-hospital RRT and outcomes in consecutive adults who underwent continuous-flow LVAD implantation from February 15, 2007, through August 8, 2017. Logistic regression was used to examine predictors of RRT. The associations of RRT with outcomes were examined using Cox proportional hazards regression., Results: Of 354 patients who underwent LVAD implantation, 54 (15%) required in-hospital RRT. Patients receiving RRT had higher preoperative Charlson Comorbidity Index values (median, 5 vs 4; P=.03), Model for End-Stage Liver Disease scores (mean, 19.0 vs 14.5; P<.001), right atrial pressure (mean, 19.1 vs 13.4 mm Hg; P<.001), and estimated 24-hour urine protein levels (median, 357 vs 174 mg; P<.001) and lower preoperative estimated glomerular filtration rate (eGFR) (median, 43 vs 57 mL/min; P<.001) and measured GFR using 125 I-iothalamate clearance (median, 33 vs 51 mL/min; P=.001) than those who did not require RRT. Approximately 40% of patients with eGFR less than 45 mL/min/1.73 m 2 and 24-hour urine protein level greater than 400 mg required RRT vs 6% with eGFR greater than45 mL/min/1.73 m 2 and without significant proteinuria. Lower preoperative eGFR, higher estimated 24-hour urine protein level, higher right atrial pressure, and longer cardiopulmonary bypass time were independent predictors of RRT after LVAD implantation. Of patients requiring in-hospital RRT, 18 (33%) had renal recovery, 18 (33%) required outpatient hemodialysis, and 18 (33%) died before hospital discharge. After median (Q1, Q3) follow-up of 24.3 (8.9, 49.6) months, RRT was associated with increased risk of death (adjusted hazard ratio [HR], 2.86; 95% CI, 1.90-4.33; P<.001) and gastrointestinal bleeding (adjusted HR, 4.47; 95% CI, 2.57-7.75; P<.001)., Conclusion: In-hospital RRT is associated with poor prognosis after LVAD. A detailed preoperative assessment of renal function before LVAD may be helpful in risk stratification and patient selection., (Published by Elsevier Inc.)

Objective: To investigate differences in invasive hemodynamic parameters and outcomes in patients with and without heart failure (HF) symptoms after left ventricular assist device (LVAD) implantation., Patients and Methods: We performed a single-center retrospective analysis of 51 symptomatic patients and 50 patients with resolved HF symptoms who underwent right-sided heart catheterization (RHC) after LVAD implantation from March 1, 2007, through June 30, 2016. Patient characteristics and outcomes including all-cause mortality and right ventricular (RV) failure were compared between groups., Results: Fifty-one patients had development of HF symptoms after LVAD implantation and underwent RHC a mean ± SD of 243.7±288 days postoperatively. Fifty asymptomatic LVAD recipients underwent routine RHC 278.6±205 days after implantation. Compared with patients who had resolved HF symptoms, symptomatic patients were older, more likely to be male, and more likely to have ischemic cardiomyopathy. Symptomatic patients had higher right atrial pressure (P<.001), mean pulmonary arterial pressure (P<.001), and pulmonary capillary wedge pressure (P<.001). Improvements in right atrial pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure before and after LVAD implantation were less remarkable in symptomatic patients. The frequency of RV dysfunction was significantly higher among symptomatic patients than patients with resolved HF symptoms (P=.001). Symptomatic patients displayed significantly higher risk of all-cause mortality (hazard ratio, 3.0; 95% CI, 1.3-6.5; P=.007) and RV failure (hazard ratio, 6.2; 95% CI, 1.3-29.7; P=.02) independent of other predictors of outcome., Conclusion: Patients with recurrent HF symptoms after LVAD implantation display more profound hemodynamic derangements, greater burden of RV failure, and increased rates of all-cause mortality compared with LVAD recipients with resolved HF symptoms., (Copyright © 2018 Mayo Foundation for Medical Education and Research. All rights reserved.)

Myocarditis is a polymorphic disease characterized by great variability in clinical presentation and evolution. Patients presenting with severe left ventricular dysfunction and life-threatening arrhythmias represent a demanding challenge for the clinician. Modern techniques of cardiovascular imaging and the exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have provided valuable insight into the pathophysiology of this disease, and several clinical registries have unraveled the disease's long-term evolution and prognosis. However, uncertainties persist in crucial practical issues in the management of patients. This article critically reviews current information for evidence-based management, offering a rational and practical approach to patients with myocarditis. For this review, we searched the PubMed and MEDLINE databases for articles published from January 1, 1980, through December 31, 2015, using the following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial biopsy. Articles were selected for inclusion if they represented primary data or were review articles published in high-impact journals. In particular, a risk-oriented approach is proposed. The different patterns of presentation of myocarditis are classified as low-, intermediate-, and high-risk syndromes according to the most recent evidence on prognosis, clinical findings, and both invasive and noninvasive testing, and appropriate management strategies are proposed for each risk class., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Heart failure (HF) is an important public health problem, and strategies are needed to improve outcomes and decrease health care resource utilization and costs. Its prevalence has increased as the population ages, and HF continues to be associated with a high mortality rate and frequent need for hospitalization. The total cost of care for patients with HF was $30.7 billion in 2012, and it is estimated to more than double to $69.8 billion by 2030. Given this reality, there has been recent investigation into ways of identifying and preventing HF in patients at risk (stage A HF) and those with cardiac structural and functional abnormalities but no clinical HF symptoms (stage B). For patients who have symptoms of HF (stage C), there has been important research into the most effective ways to decongest patients hospitalized with acute decompensated HF and prevent future hospital readmissions. Successful strategies to treat patients with HF and preserved ejection fraction, which has increased in prevalence, continue to be sought. We are in the midst of a rapid evolution in our ability to care for patients with end-stage HF (stage D) because of the introduction of and improvements in mechanical circulatory support. Left ventricular assist devices used as destination therapy offer an important therapeutic option to patients who do not qualify for heart transplant because of advanced age or excessive comorbidity. This review provides a thorough update on contemporary strategies in the diagnosis and management of HF by stage (A to D) that have emerged during the past several years., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)