Rare Variant Genetics and Dilated Cardiomyopathy Severity: The DCM Precision Medicine Study.

BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Effectiveness of the Family Heart Talk Communication Tool in Improving Family Member Screening for Dilated Cardiomyopathy: Results of a Randomized Trial.

BACKGROUND: Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive. METHODS: The DCM Precision Medicine Study developed Family Heart Talk, a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive the day after proband enrollment and not enrolled on the same day as the proband. RESULTS: Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08-∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P=0.90). CONCLUSIONS: Family Heart Talk, a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of these patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Genetic Architecture of Dilated Cardiomyopathy in Individuals of African and European Ancestry.

Importance: Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. Objective: To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. Design: Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. Exposure: Presence of DCM. Main Outcomes and Measures: Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). Results: A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, -0.09 [95% CI, -0.14 to -0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, -0.06 [95% CI, -0.11 to -0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, -0.07 [95% CI, -0.22 to 0.09]) due to a larger number of non-TTN non-predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P < .001). Conclusion and Relevance: Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets.

Whither digitalis? What we can still learn from cardiotonic steroids about heart failure and hypertension.

Cloning of the "Na+ pump" (Na+,K+-ATPase or NKA) and identification of a circulating ligand, endogenous ouabain (EO), a cardiotonic steroid (CTS), triggered seminal discoveries regarding EO and its NKA receptor in cardiovascular function and the pathophysiology of heart failure (HF) and hypertension. Cardiotonic digitalis preparations were a preferred treatment for HF for two centuries, but digoxin was only marginally effective in a large clinical trial (1997). This led to diminished digoxin use. Missing from the trial, however, was any consideration that endogenous CTS might influence digitalis' efficacy. Digoxin, at therapeutic concentrations, acutely inhibits NKA but, remarkably, antagonizes ouabain's action. Prolonged treatment with ouabain, but not digoxin, causes hypertension in rodents; in this model, digoxin lowers blood pressure (BP). Furthermore, NKA-bound ouabain and digoxin modulate different protein kinase signaling pathways and have disparate long-term cardiovascular effects. Reports of "brain ouabain" led to the elucidation of a new, slow neuromodulatory pathway in the brain; locally generated EO and the α2 NKA isoform help regulate sympathetic drive to the heart and vasculature. The roles of EO and α2 NKA have been studied by EO assay, ouabain-resistant mutation of α2 NKA, and immunoneutralization of EO with ouabain-binding Fab fragments. The NKA α2 CTS binding site and its endogenous ligand are required for BP elevation in many common hypertension models and full expression of cardiac remodeling and dysfunction following pressure overload or myocardial infarction. Understanding how endogenous CTS impact hypertension and HF pathophysiology and therapy should foster reconsideration of digoxin's therapeutic utility.

Prevalence and Cumulative Risk of Familial Idiopathic Dilated Cardiomyopathy.

Importance: Idiopathic dilated cardiomyopathy (DCM) aggregates in families, and early detection in at-risk family members can provide opportunity to initiate treatment prior to late-phase disease. Most studies have included only White patients, yet Black patients with DCM have higher risk of heart failure-related hospitalization and death. Objective: To estimate the prevalence of familial DCM among DCM probands and the age-specific cumulative risk of DCM in first-degree relatives across race and ethnicity groups. Design, Setting, and Participants: A family-based, cross-sectional study conducted by a multisite consortium of 25 US heart failure programs. Participants included patients with DCM (probands), defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes, and their first-degree relatives. Enrollment commenced June 7, 2016; proband and family member enrollment concluded March 15, 2020, and April 1, 2021, respectively. Exposures: The presence of DCM in a proband. Main Outcomes and Measures: Familial DCM defined by DCM in at least 1 first-degree relative; expanded familial DCM defined by the presence of DCM or either left ventricular enlargement or left ventricular systolic dysfunction without known cause in at least 1 first-degree relative. Results: The study enrolled 1220 probands (median age, 52.8 years [IQR, 42.4-61.8]; 43.8% female; 43.1% Black and 8.3% Hispanic) and screened 1693 first-degree relatives for DCM. A median of 28% (IQR, 0%-60%) of living first-degree relatives were screened per family. The crude prevalence of familial DCM among probands was 11.6% overall. The model-based estimate of the prevalence of familial DCM among probands at a typical US advanced heart failure program if all living first-degree relatives were screened was 29.7% (95% CI, 23.5% to 36.0%) overall. The estimated prevalence of familial DCM was higher in Black probands than in White probands (difference, 11.3% [95% CI, 1.9% to 20.8%]) but did not differ significantly between Hispanic probands and non-Hispanic probands (difference, -1.4% [95% CI, -15.9% to 13.1%]). The estimated prevalence of expanded familial DCM was 56.9% (95% CI, 50.8% to 63.0%) overall. Based on age-specific disease status at enrollment, estimated cumulative risks in first-degree relatives at a typical US advanced heart failure program reached 19% (95% CI, 13% to 24%) by age 80 years for DCM and 33% (95% CI, 27% to 40%) for expanded DCM inclusive of partial phenotypes. The DCM hazard was higher in first-degree relatives of non-Hispanic Black probands than non-Hispanic White probands (hazard ratio, 1.89 [95% CI, 1.26 to 2.83]). Conclusions and Relevance: In a US cross-sectional study, there was substantial estimated prevalence of familial DCM among probands and modeled cumulative risk of DCM among their first-degree relatives. Trial Registration: ClinicalTrials.gov Identifier: NCT03037632.

Use of Outpatient Intravenous Calcitropes for Heart Failure in the United States.

BACKGROUND: Outpatient calcitrope infusions-that is, the cardiac inotropes milrinone and dobutamine-are often used for bridge to transplantation and palliation in advanced heart failure, but few data exist about the real-world use of these agents. METHODS AND RESULTS: We used the Symphony Integrated DataVerse of commercial, managed Medicare, and Medicaid insurance claims of approximately 280 million people (2012-2020) to determine the incidence and characteristics of ambulatory calcitrope use. Demographics were calculated, including geographic densities at the metropolitan statistical area level. A population projection normalized for age, sex, and location was extrapolated to the total US population. Ambulatory dispensing of milrinone was found in 10,533 outpatients, 1867 in 2019. Ambulatory dobutamine use was found in 4967 outpatients, 836 in 2019. The 2019 total US projection was 3411 for milrinone and 1281 for dobutamine. The mean age was 62 years for milrinone and 68 for dobutamine. Males represented 70% of use. There were differences between drugs in geographic distribution, with more milrinone use in the Northeast and South and more dobutamine use in the Midwest. Duration of use was 4.6 ± 7.2 months for milrinone and 1.8 ± 4.0 months for dobutamine. Of the patients receiving milrinone, 30.6% subsequently underwent cardiac transplantation or left ventricular assist device placement, whereas 10% receiving dobutamine went on to advanced therapies. Less than 0.5% of patients received calcitropes while enrolled in hospice care. CONCLUSIONS: More than 4000 patients receive outpatient infusion of calcitropes annually in the outpatient setting. Men are much more likely to receive these medications. A minority of the use is as a bridge to advanced therapies. Geographic variability in use suggests better evidence and consistent guidelines may be helpful.

Renal Dysfunction and Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) constitute a high-risk phenotype with significant morbidity and mortality and poor prognosis. Multiple proinflammatory comorbid conditions influence the pathogenesis of HFpEF and CKD. Renal dysfunction in HFpEF is a consequence of the complex interplay between hemodynamic factors, systemic congestion, inflammation, endothelial dysfunction, and neurohormonal mechanisms. In contrast to heart failure with reduced ejection fraction, there is a dearth of effective targeted therapies for HFpEF. Tailoring study design toward the different phenotypes and delving into their pathophysiology may be fruitful in development of effective phenotype-specific targeted pharmaceutical therapies.

Impact of Mental Stress and Anger on Indices of Diastolic Function in Patients With Heart Failure.

BACKGROUND: Under controlled conditions, mental stress can provoke decrements in ventricular function, yet little is known about the effect of mental stress on diastolic function in patients with heart failure (HF). METHODS AND RESULTS: Twenty-four patients with HF with ischemic cardiomyopathy and reduced ejection fraction (n = 23 men; mean left ventricular [LV] ejection fraction 27 ± 9%; n = 13 with baseline elevated E/e') completed daily assessment of perceived stress, anger, and negative emotion for 7 days, followed by a laboratory mental stress protocol. Two-dimensional Doppler echocardiography was performed at rest and during sequential anger recall and mental arithmetic tasks to assess indices of diastolic function (E, e', and E/e'). Fourteen patients (63.6%) experienced stress-induced increases in E/e', with an average baseline to stress change of 6.5 ± 9.3, driven primarily by decreases in early LV relaxation (e'). Age-adjusted linear regression revealed an association between 7-day anger and baseline E/e'; patients reporting greater anger in the week before mental stress exhibited higher resting LV diastolic pressure. CONCLUSIONS: In patients with HF with reduced ejection fraction, mental stress can provoke acute worsening of LV diastolic pressure, and recent anger is associated with worse resting LV diastolic pressure. In patients vulnerable to these effects, repeated stress exposures or experiences of anger may have implications for long-term outcomes.

Management of Sleep Disordered Breathing in Patients with Heart Failure.

PURPOSE OF REVIEW: This paper reviews treatment options for sleep disordered breathing (SDB) in patients with heart failure. We sought to identify therapies for SDB with the best evidence for long-term use in patients with heart failure and to minimize uncertainties in clinical practice by examining frequently discussed questions: what is the role of continuous positive airway pressure (CPAP) in patients with heart failure? Is adaptive servo-ventilation (ASV) safe in patients with heart failure? To what extent is SDB a modifiable risk factor? RECENT FINDINGS: Consistent evidence has demonstrated that the development of SDB in patients with heart failure is a poor prognostic indicator and a risk factor for cardiovascular mortality. However, despite numerous available interventions for obstructive sleep apnea and central sleep apnea, it remains unclear what effect these therapies have on patients with heart failure. To date, all major randomized clinical trials have failed to demonstrate a survival benefit with SDB therapy and one major study investigating the use of adaptive servo-ventilation demonstrated harm. Significant questions persist regarding the management of SDB in patients with heart failure. Until appropriately powered trials identify a treatment modality that increases cardiovascular survival in patients with SDB and heart failure, a patient's heart failure management should remain the priority of medical care.

Observation of Patients Transitioned to an Oral Loop Diuretic Before Discharge and Risk of Readmission for Acute Decompensated Heart Failure.

BACKGROUND: Heart failure (HF) is associated with high 30-day readmission rates and places significant financial burden on the health care system. The aim of this study was to determine if the duration of observation on an oral loop diuretic before discharge is associated with a reduction in 30-day HF readmission in patients with acute decompensated HF (ADHF). METHODS AND RESULTS: This was a retrospective study of adult patients admitted for ADHF at a large academic medical center. A total of 123 patients were included. Baseline characteristics were similar between groups. The primary outcome of 30-day HF readmission occurred in 11 of 61 patients (18%) observed on an oral loop diuretic for <24 hours and in 2 of 62 patients (3.2%) observed on an oral loop diuretic for ≥24 hours (P = .023). Readmissions for 60- and 90-day HF were also significantly lower in patients observed for ≥24 hours (P = .014 and P = .049, respectively). Associations became stronger after multivariate analysis (P < .001). Observation for <24 hours and previous admission within 30 days were independent predictors of 30-day HF readmission (P = .03). CONCLUSIONS: Observation of patients on an oral loop diuretic for <24 hours was associated with significantly higher 30-day HF readmission. Therefore, observation on an oral loop diuretic for ≥24 hours before discharge in patients presenting with ADHF should be strongly considered.

Depression and human immunodeficiency virus infection are risk factors for incident heart failure among veterans: Veterans Aging Cohort Study.

BACKGROUND: Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF. METHODS AND RESULTS: Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99). CONCLUSIONS: Our study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.

Nesiritide, renal function, and associated outcomes during hospitalization for acute decompensated heart failure: results from the Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure (ASCEND-HF).

BACKGROUND: Contradictory results have been reported on the effects of nesiritide on renal function in patients with acute decompensated heart failure. We studied the effects of nesiritide on renal function during hospitalization for acute decompensated heart failure and associated outcomes. METHODS AND RESULTS: A total of 7141 patients were randomized to receive either nesiritide or placebo and creatinine was recorded in 5702 patients at baseline, after infusion, discharge, peak/nadir levels until day 30. Worsening renal function was defined as an increase of serum creatinine >0.3 mg/dL and a change of ≥25%. Median (25(th)-75(th) percentile) baseline creatinine was 1.2 (1.0-1.6) mg/dL and median baseline blood urea nitrogen was 25 (18-39) mmol/L. Changes in both serum creatinine and blood urea nitrogen were similar in nesiritide-treated and placebo-treated patients (P=0.20 and P=0.41) from baseline to discharge. In a multivariable model, independent predictors of change from randomization to hospital discharge in serum creatinine were a lower baseline blood urea nitrogen, higher systolic blood pressure, lower diastolic blood pressure, previous weight gain, and lower baseline potassium (all P<0.0001). The frequency of worsening renal function during hospitalization was similar in the nesiritide and placebo group (14.1% and 12.8%, respectively; odds ratio with nesiritide 1.12; confidence interval, 0.95-1.32; P=0.19) and was not associated with death alone and death or rehospitalization at 30 days. However, baseline, discharge, and change in creatinine were associated with death alone and death or rehospitalization for heart failure (all tests, P<0.0001). CONCLUSIONS: Nesiritide did not affect renal function in patients with acute decompensated heart failure. Baseline, discharge, and change in renal function were associated with 30-day mortality or rehospitalization for heart failure.

Clinical trial design in contemporary device studies in heart failure: is there a gold standard?

The assessment of the efficacy and safety of implantable cardiac devices used for the management of heart failure is complicated by procedural challenges. We present an overview of the advantages and disadvantages of different clinical trial designs, and discuss investigator and patient blinding. We conclude that blinding is optimal, but methodologically difficult. Until rules for and assessment of blinding are developed or surrogate measures are considered to be acceptable from a regulatory standpoint, an open-label design with objective end points is an unavoidable default standard.

The effect of a randomized trial of home telemonitoring on medical costs, 30-day readmissions, mortality, and health-related quality of life in a cohort of community-dwelling heart failure patients.

BACKGROUND: Telemonitoring has been advocated as a way of decreasing costs and improving outcomes, but no study has looked at true Medicare payments and 30-day readmission rates in a randomized group of well treated patients. OBJECTIVE: The aim of this work was to analyze Medicare claims data to identify effects of home telemonitoring on medical costs, 30-day rehospitalization, mortality, and health-related quality of life. METHODS: A total of 204 subjects were randomized to usual-care and monitored groups and evaluated with the SF-36 and Minnesota Living With Heart Failure Questionnaire (MLHF). Hospitalizations, Medicare payments, and mortality were also assessed. Monitored subjects transmitted weight, blood pressure, and heart rate, which were monitored by an experienced heart failure nurse practitioner. RESULTS: Subjects were followed for 802 ± 430 days; 75 subjects in the usual-care group (316 hospitalizations) and 81 in the monitored group (327 hospitalizations) were hospitalized at least once (P = .51). There were no differences in Medicare payments for inpatient or emergency department visits, and length of stay was not different between groups. There was no difference in 30-day readmissions (P = .627) or mortality (P = .575). Scores for SF-36 and MLHF improved (P < .001) over time, but there were no differences between groups. The percentage of patients readmitted within 30 days was lower with telemonitoring for the 1st year, but this did not persist. CONCLUSIONS: Telemonitoring did not result in lower total costs, decreased hospitalizations, improved symptoms, or improved mortality. A decrease in 30-day readmission rates for the 1st year did not result in decreased total cost or better outcomes.

Trastuzumab-induced cardiomyopathy: incidence and associated risk factors in an inner-city population.

BACKGROUND: Although it is known that trastuzumab causes cardiotoxicity, its extent and reversibility are still in question. Earlier studies have not evaluated consecutive patients with reproducible nuclear ventriculography. OBJECTIVE: We sought to evaluate the baseline characteristics which predispose patients to increased risk of trastuzumab cardiotoxicity and to determine the natural history of the cardiotoxicity. METHODS AND RESULTS: Left ventricular ejection fraction (LVEF) was measured in 76 women aged 36-73 years who had been treated with trastuzumab at the University of Maryland Greenebaum Cancer Center. LVEF was determined at baseline and then 3, 6, 9, and 12 months after treatment initiation. Cardiotoxicity was defined as ≥ 16% decrease in LVEF or ≥ 10% decrease in LVEF to <50%. There were no differences in comorbidities, earlier treatment, or demographics between patients with and without trastuzumab-induced cardiomyopathy except that African Americans were more likely to develop decreased LVEF (P < .05). Twenty-one patients (28%) met criteria for cardiotoxicity. Four of those patients were continued on trastuzumab and 17 patients had therapy withheld at some point. Only 1 patient developed symptomatic heart failure requiring inpatient hospitalization. LVEF improved in most patients regardless of whether or not trastuzumab was continued. CONCLUSIONS: Decreased LVEF while undergoing trastuzumab therapy occurs frequently and is usually reversible. African Americans had a higher risk of developing decreased LVEF. These findings raise clinically important questions as to whether it is necessary to discontinue trastuzumab for asymptomatic decrease in LVEF and whether African Americans are more predisposed to a decrease in LVEF while receiving trastuzumab. Further studies carefully assessing LVEF should address these hypotheses.

Importance and management of chronic sleep apnoea in cardiology.

Sleep apnoea is a common, yet underestimated, chronic disorder with a major impact on morbidity and mortality in the general population. It is quickly becoming recognized as an independent risk factor for cardiovascular impairment. Hypertension, coronary artery disease, diabetes, cardiovascular rhythm and conduction abnormalities, cerebrovascular disease, and heart failure have all been linked to this syndrome. This review will explore the critical connection between sleep apnoea and chronic cardiovascular diseases while highlighting established and emerging diagnostic and treatment strategies.

Implications of Atrial Fibrillation for Guideline-Directed Therapy in Patients With Heart Failure: JACC State-of-the-Art Review.

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular conditions that frequently coexist. Among patients with HF, more than one-half also have AF. Both are associated with significant morbidity and mortality. Moreover, the prevalence of each is increasing globally, and this trend is expected to continue owing to an aging population and increased life expectancy. Diagnosis of AF in a patient with HF is associated with greater symptom burden, more frequent hospitalizations, and a worse prognosis. Guideline-directed medical therapy (GDMT) for HF can affect the incidence of AF. Once present, AF can influence the efficacy of some components of GDMT for HF. In this review, we discuss the effect of GDMT for HF across the spectrum of ejection fraction on prevention of AF as well as the benefit of GDMT in patients with vs without AF.

A Retrospective Cohort Study of the Association of Inpatient Amlodipine Dose With Renal Complication Rates and Hospital Length of Stay.

Background Correct hospital medication reconciliation is important for continuity of care, but optimal home antihypertensive medication ordering has not been adequately studied. Since excessive hospital blood pressure control is associated with adverse renal and cardiovascular outcomes, we assessed the association of inpatient doses of amlodipine (10mg vs. 5mg) with length of stay and renal failure and fluid and electrolyte disorders (RF/FED). Methods In this retrospective cohort study, clinical and demographic data on patients not initially admitted to the ICU between 2008 and 2019 were extracted from the Medical Information Mart for Intensive Care (MIMIC-IV). Multivariable logistic regression was used to assess the association between amlodipine dose during the first 24 hours of admission and RF/FED. Multivariable linear regression was used to assess the association between amlodipine dose and length of stay when controlling for RF/FED or maximum blood urea nitrogen (BUN) concentration and other confounders. Results There were 5,932 patients included in this study, and 3,038 of whom received 10mg of amlodipine. A 10mg dose of amlodipine was associated with an increased likelihood of RF/FED (OR: 1.248, 95% CI (1.104, 1.412), p<0.001). It was also associated with a longer length of stay (coef.: 0.338, 95% CI (0.067, 0.609), p=0.015). This was not significant when controlling for RF/FED (dose coef.: 0.197, 95% CI (-0.070, 0.464), p=0.147) or maximum BUN (dose coef.: 0.082, 95% CI (-0.147, 0.312), p=0.482). Interpretation Higher amlodipine dose was associated with longer length of stay, and this is likely mediated by RF/FED. Randomized trials are needed to determine which home blood pressure medications should be ordered in the hospital.

Knowledge of Genome Sequencing and Trust in Medical Researchers Among Patients of Different Racial and Ethnic Groups With Idiopathic Dilated Cardiomyopathy.

Importance: Cardiovascular disease contributes outsized mortality in patients from underrepresented racial and ethnic groups. Understanding levels of trust in medical researchers and knowledge of genome sequencing may help identify barriers to research participation and develop strategies to educate patients about the role of genetics in cardiovascular disease. Objective: To assess racial and ethnic differences in trust in medical researchers and genome-sequencing knowledge among patients with idiopathic dilated cardiomyopathy and determine the association between trust in medical researchers and genome-sequencing knowledge. Design, Setting, and Participants: This cross-sectional study conducted by a consortium of 25 US heart failure programs included patients with idiopathic dilated cardiomyopathy defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes. Enrollment occurred from June 7, 2016, to March 15, 2020. Main Outcomes and Measures: Percent distributions, means, and associations of genome-sequencing knowledge scores and research trust scores for Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White participants (hereafter referred to as White). Results: Among 1121 participants, mean (SD) age was 51.6 (13.6) years with 41.4% Black, 8.5% Hispanic, and 43.4% female. After accounting for site effects, the level of genome-sequencing knowledge was lower in Hispanic and Black participants compared with White participants (mean score difference, -2.6; 95% CI, -3.9 to -1.2 and mean score difference, -2.9; 95% CI, -3.6 to -2.2, respectively). The level of trust in researchers was lowest in Black participants (mean score, 27.7), followed by Hispanic participants (mean score, 29.4) and White participants (mean score, 33.9). Racial and ethnic differences remained after adjusting for education, age at enrollment, duration of dilated cardiomyopathy, and health status. A higher level of trust was associated with a higher level of genome-sequencing knowledge within different racial and ethnic groups. Conclusions and Relevance: In this cross-sectional study, large racial and ethnic differences in levels of genome-sequencing knowledge and trust in medical researchers were observed among patients with dilated cardiomyopathy. Findings from this study can inform future studies that aim to enhance the uptake of genomic knowledge and level of trust in medical researchers.