Faculty Bibliography

BACKGROUND:Electronic health record (EHR) tools can improve prescribing of guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF), but their effectiveness may vary by physician workload. OBJECTIVES/OBJECTIVE:This paper aims to assess whether physician workload modifies the effectiveness of EHR tools for HFrEF. METHODS:This was a prespecified subgroup analysis of the BETTER CARE-HF (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure) cluster-randomized trial, which compared effectiveness of an alert vs message vs usual care on prescribing of mineralocorticoid antagonists (MRAs). The trial included adults with HFrEF seen in cardiology offices who were eligible for and not prescribed MRAs. Visit volume was defined at the cardiologist-level as number of visits per 6-month study period (high = upper tertile vs non-high = remaining). Analysis at the patient-level used likelihood ratio test for interaction with log-binomial models. RESULTS:Among 2,211 patients seen by 174 cardiologists, 932 (42.2%) were seen by high-volume cardiologists (median: 1,853; Q1-Q3: 1,637-2,225 visits/6 mo; and median: 10; Q1-Q3: 9-12 visits/half-day). MRA was prescribed to 5.5% in the high-volume vs 14.8% in the non-high-volume groups in the usual care arm, 10.3% vs 19.6% in the message arm, and 31.2% vs 28.2% in the alert arm, respectively. Visit volume modified treatment effect (P for interaction = 0.02) such that the alert was more effective in the high-volume group (relative risk: 5.16; 95% CI: 2.57-10.4) than the non-high-volume group (relative risk: 1.93; 95% CI: 1.29-2.90). CONCLUSIONS:An EHR-embedded alert increased prescribing by >5-fold among patients seen by high-volume cardiologists. Our findings support use of EHR alerts, especially in busy practice settings. (Building Electronic Tools to Enhance and Reinforce Cardiovascular Recommendations for Heart Failure [BETTER CARE-HF]; NCT05275920).

PURPOSE OF REVIEW/OBJECTIVE:Although rare, the development of mechanical complications following an acute myocardial infarction is associated with a high morbidity and mortality. Here, we review the clinical features, diagnostic strategy, and treatment options for each of the mechanical complications, with a focus on the role of echocardiography. RECENT FINDINGS/RESULTS:The growth of percutaneous structural interventions worldwide has given rise to new non-surgical options for management of mechanical complications. As such, select patients may benefit from a novel use of these established treatment methods. A thorough understanding of the two-dimensional, three-dimensional, color Doppler, and spectral Doppler findings for each mechanical complication is essential in recognizing major causes of hemodynamic decompensation after an acute myocardial infarction. Thereafter, echocardiography can aid in the selection and maintenance of mechanical circulatory support and potentially facilitate the use of a percutaneous intervention.

BACKGROUND:Myocardial infarction and heart failure are major cardiovascular diseases that affect millions of people in the US with the morbidity and mortality being highest among patients who develop cardiogenic shock. Early recognition of cardiogenic shock allows prompt implementation of treatment measures. Our objective is to develop a new dynamic risk score, called CShock, to improve early detection of cardiogenic shock in cardiac intensive care unit (ICU). METHODS:We developed and externally validated a deep learning-based risk stratification tool, called CShock, for patients admitted into the cardiac ICU with acute decompensated heart failure and/or myocardial infarction to predict onset of cardiogenic shock. We prepared a cardiac ICU dataset using MIMIC-III database by annotating with physician adjudicated outcomes. This dataset that consisted of 1500 patients with 204 having cardiogenic/mixed shock was then used to train CShock. The features used to train the model for CShock included patient demographics, cardiac ICU admission diagnoses, routinely measured laboratory values and vital signs, and relevant features manually extracted from echocardiogram and left heart catheterization reports. We externally validated the risk model on the New York University (NYU) Langone Health cardiac ICU database that was also annotated with physician adjudicated outcomes. The external validation cohort consisted of 131 patients with 25 patients experiencing cardiogenic/mixed shock. RESULTS:CShock achieved an area under the receiver operator characteristic curve (AUROC) of 0.821 (95% CI 0.792-0.850). CShock was externally validated in the more contemporary NYU cohort and achieved an AUROC of 0.800 (95% CI 0.717-0.884), demonstrating its generalizability in other cardiac ICUs. Having an elevated heart rate is most predictive of cardiogenic shock development based on Shapley values. The other top ten predictors are having an admission diagnosis of myocardial infarction with ST-segment elevation, having an admission diagnosis of acute decompensated heart failure, Braden Scale, Glasgow Coma Scale, Blood urea nitrogen, Systolic blood pressure, Serum chloride, Serum sodium, and Arterial blood pH. CONCLUSIONS:The novel CShock score has the potential to provide automated detection and early warning for cardiogenic shock and improve the outcomes for the millions of patients who suffer from myocardial infarction and heart failure.

BACKGROUND:Mitral leaflet elongation is common in hypertrophic cardiomyopathy (HCM), contributes to obstructive physiology, and presents a challenge to dual surgical goals of abolition of outflow gradients and mitral regurgitation. Anterior leaflet shortening, performed as an ancillary surgical procedure during myectomy, is controversial. METHODS:This was a retrospective study of all patients undergoing myectomy from 1/2010 to 3/2020 analyzing survival and echocardiographic results. We compared outcomes of patients treated with myectomy and concomitant mitral leaflet shortening with patients treated with myectomy alone. Over this time technique for mitral shortening evolved from anterior leaflet plication to residual leaflet excision (ReLex). RESULTS:Myectomy was performed on 416 patients age 57.5±13.6 years, 204 (49%) female. Average follow up was 5.4±2.8 years. Survival follow-up was complete in 415. Myectomy without valve replacement was performed in 332 patients, of whom 192 had mitral valve shortening (58%). Mitral leaflet plication was performed in 73, ReLex in 151 and both in 32. Hospital mortality for patients undergoing myectomy was 0.7%. At 8 years, cumulative survival was 95% for both myectomy plus leaflet shortening and myectomy alone groups, with no difference in survival between the two. There was no difference in survival between anterior leaflet plication and ReLex groups. Echocardiography 2.5 years after surgery showed a decrease in resting and provoked gradients, mitral regurgitation and left atrial volume and no difference in key variables between ancillary leaflet shortening and myectomy alone patients. CONCLUSIONS:These results affirm that mitral shortening may be an appropriate surgical judgment for selected patients.

Cardiogenic shock continues to carry a high mortality rate despite contemporary care, with no breakthrough therapies shown to improve survival over the past few decades. It is a time-sensitive condition that commonly results in cardiovascular complications and multisystem organ failure, necessitating multidisciplinary expertise. Managing patients with cardiogenic shock remains challenging even in well-resourced settings, and an important subgroup of patients may require cardiac replacement therapy. As a result, the idea of leveraging the collective cognitive and procedural proficiencies of multiple providers in a collaborative, team-based approach to care (the "shock team") has been advocated by professional societies and implemented at select high-volume clinical centers. A slowly maturing evidence base has suggested that cardiogenic shock teams may improve patient outcomes. Although several registries exist that are beginning to inform care, particularly around therapeutic strategies of pharmacologic and mechanical circulatory support, none of these are currently focused on the shock team approach, multispecialty partnership, education, or process improvement. We propose the creation of a Cardiogenic Shock Team Collaborative-akin to the successful Pulmonary Embolism Response Team Consortium-with a goal to promote sharing of care protocols, education of stakeholders, and discovery of how process and performance may influence patient outcomes, quality, resource consumption, and costs of care.

BACKGROUND:This open-label phase 2 trial evaluated the safety and efficacy of aficamten in patients with non-obstructive hypertrophic cardiomyopathy (nHCM). METHODS:Patients with symptomatic nHCM (left ventricular outflow tract obstruction gradient ≤30 mmHg, left ventricular ejection fraction [LVEF] ≥60%, N-terminal pro-B-type natriuretic peptide [NT-proBNP] >300 pg/mL) received aficamten 5-20 mg once daily (doses adjusted according to echocardiographic LVEF) for 10 weeks. RESULTS:41 patients were enrolled (mean ± SD age 56 ± 16 years; 59% female). At Week 10, 22 (55%) patients experienced an improvement of ≥1 New York Heart Association class; 11 (29%) became asymptomatic. Clinically relevant improvements in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores occurred in 22 (55%) patients. Symptom relief was paralleled by reductions in NT-proBNP (56%; P < 0.001) and high-sensitivity cardiac troponin I (22%; P < 0.005). Modest reductions in LVEF (mean ± SD) of -5.4% ± 10 to 64.6% ± 9.1 were observed. Three (8%) patients had asymptomatic reduction in LVEF <50% (range: 41-48%), all returning to normal after 2 weeks of washout. One patient with prior history of aborted sudden cardiac death experienced a fatal arrhythmia during the study. CONCLUSIONS:Aficamten administration for symptomatic nHCM was generally safe and associated with improvements in heart failure symptoms and cardiac biomarkers. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier: NCT04219826 LAY SUMMARY: Non-obstructive hypertrophic cardiomyopathy (nHCM) is a disease in which the heart muscle becomes abnormally thickened. There are no proven medical therapies. Aficamten is a new cardiac myosin inhibitor designed to target the underlying cause of HCM. REDWOOD-HCM Cohort 4 was the first study exploring the efficacy and safety of aficamten in people with symptoms from nHCM. Most patients reported improved health and functional status. There was also significant decrease in blood levels of biomarkers indicating excessive pressure within the heart and damage to heart muscle cells. These results support a larger placebo-controlled study of aficamten for people with nHCM (ACACIA-HCM).

BACKGROUND:Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management. METHODS AND RESULTS/RESULTS:=0.49), with no significant sex-by-treatment-group interactions. CONCLUSIONS:Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk-adjusted outcomes to men in the ISCHEMIA trial. REGISTRATION/BACKGROUND:URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.

BACKGROUND:Cardiometabolic risk factors diabetes, obesity, and hypertension are highly prevalent and contribute to increased cardiovascular disease (CVD). Endothelial dysfunction precedes CVD development. The current study aimed to investigate the EC transcriptome among individuals with varying degree of cardiometabolic risk. METHODS:Adult participants without CVD and various degrees of cardiometabolic risk factor burden (hypertension, diabetes, obesity) were included. Participants underwent brachial vein EC harvesting followed by RNA sequencing. To evaluate the association between cardiometabolic comorbidity burden and outcome transcripts we performed linear regression with multivariable models, adjusting for age, sex, and race/ethnicity. RESULTS:A total of 18 individuals were included in the present analysis (mean age 47 ± 14, 44% female, and 61% White adults). Endothelial cell RNA sequencing revealed 588 differentially expressed transcripts (p-adj <0.05) with excellent discrimination in unsupervised hierarchical clustering analysis. Gene ontology enrichment analysis revealed upregulated pathways associated with T-cell activation (NES = 2.22, p<0.001), leukocyte differentiation (NES= 2.16, p<0.001), leukocyte migration (NES= 2.12, p<0.001), regulation of cell-cell adhesion (NES= 1.91, p=0.006). Downregulated pathways of interest included endothelial cell proliferation (NES= -1.68, p=0.03) and response to interleukin-1 (NES= -1.61, p=0.04). Upregulated genes included VCAM1, CEACAM1, ADAM 17, and CD99L2, all with a log-2-fold change >3 and p-adj <0.05. These genes demonstrated a graded increase in mean normalized counts with increasing number of risk factors. CONCLUSIONS:We demonstrate a proinflammatory and pro-adhesive EC transcriptome associated with increased cardiometabolic risk factor burden offering insight into a potential mechanism linking these risk factors with the development of CVD.

INTRODUCTION/UNASSIGNED:Hypertension affects approximately 50 % of patients with hypertrophic cardiomyopathy (HCM) but clinical course in adults with co-occurring HCM and hypertension is underexplored. Management may be challenging as routine anti-hypertensive medications may worsen obstructive HCM, the most common HCM phenotype. In this scoping review, we sought to synthesize the available literature related to clinical course and outcomes in adults with both conditions and to highlight knowledge gaps to inform future research directions. METHODS/UNASSIGNED:We searched 5 electronic databases (PubMed, CINAHL, Scopus, Embase, Web of Science) to identify peer-reviewed articles, 2011-2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (PRISMA-ScR) guideline. RESULTS/UNASSIGNED:Eleven articles met eligibility. Adults with both conditions were older and had higher rates of obesity and diabetes than adults with HCM alone. Results related to functional class and arrhythmia were equivocal in cross-sectional studies. Only 1 article investigated changes in medical therapy among adults with both conditions. Hypertension was a predictor of worse functional class, but was not associated with all-cause mortality, heart failure-related mortality, or sudden-death. No data was found that related to common hypertension-related outcomes, including renal disease progression, nor patient-reported outcomes, including quality of life. CONCLUSIONS/UNASSIGNED:Our results highlight areas for future research to improve understanding of co-occurring HCM and hypertension. These include a need for tailored approaches to medical management to optimize outcomes, evaluation of symptom burden and quality of life, and investigation of hypertension-related outcomes, like renal disease and ischemic stroke, to inform cardiovascular risk mitigation strategies.