Annual heart transplant (HT) volumes have increased, as have post-HT outpatient care needs. Data on HT-related emergency department (ED) visits are limited.
A retrospective analysis of 177 450 HT ...patient ED visits from the 2009 to 2018 Nationwide Emergency Department Sample was conducted. HT recipients, primary diagnoses, and comorbidities associated with ED visits were identified via
(
) and
(
) codes. Multivariable logistic regression was used to predict outcomes of hospital admission and death. HT volumes and HT-related ED visits increased from 2009 to 2018. Infection was the most common primary diagnosis (24%), and cardiac primary diagnoses represented 10% of encounters. Hospital admissions occurred in 48% of visits, but overall mortality was low (1.6%). Length of stay was 3.1 days (interquartile range, 1.6-5.9 days), and comorbidity burden was high: 42% had hypertension, 38% had diabetes, and 31% had ≥2 comorbidities. Those aged ≥65 years had significantly higher odds of admission (odds ratio OR, 2.14 95% CI, 1.97-2.33) and death (OR, 2.06 95% CI, 1.61-2.62). Comorbidities increased odds of admission (OR, 1.62 95% CI, 1.51-1.75) but not death. Renal primary diagnosis had the highest risk of admission (OR, 4.1 95% CI, 3.6-4.6), but cardiac primary diagnosis had the highest odds of death (OR, 11.6 95% CI, 9.1-14.8).
HT-related ED visits increased from 2009 to 2018 with high admission rates but low in-hospital mortality, suggesting an opportunity to improve prehospital care. Older patients and those with cardiac primary diagnoses had the highest risk of death. The observed contrast between predictors of admission and mortality signals a need for further study to improve risk stratification and outpatient care strategies.
Aims The aim of this study was to report safety and efficacy of aficamten in patients with non‐obstructive hypertrophic cardiomyopathy (nHCM) over 36 weeks in the ongoing FOREST‐HCM trial. Methods ...and results Patients were started on aficamten 5 mg daily, with doses adjusted in 5‐mg increments (5–20 mg) at ≥2‐week intervals according to site‐read left ventricular ejection fraction (LVEF). Aficamten dose was increased if LVEF ≥55%, maintained if LVEF 50–54%, decreased if LVEF 40–<50%, and temporarily interrupted if LVEF <40%. Safety and efficacy were assessed over 36 weeks. Overall, 34 patients were enrolled (mean age 57.2 ± 15.3 years, 62% female, 41% in New York Heart Association NYHA class III). Over 36 weeks, 82.3% achieved 15–20 mg daily dose and there was a modest reduction in LVEF by −4.3% ± 5.2 from 70% ± 6.1 ( p < 0.0001). At Week 36, NYHA class improved by ≥1 class in 27 (79.4%) patients. Mean Kansas City Cardiomyopathy Questionnaire clinical summary score improved by 13.8 ± 12.5 points relative to baseline. Median (interquartile range) levels of N‐terminal pro‐B‐type natriuretic peptide were significantly improved from baseline (−665.5 pg/ml −1244.0, −232.0; p < 0.0001), while high‐sensitivity cardiac troponin I was unchanged (−2.7 ng/L −11.3, 1.6; p = 0.25). There were no drug discontinuations due to adverse events. LVEF <50% occurred in 2 (5.9%) patients, one following pulmonary vein isolation and one associated with atrial fibrillation. Conclusions Over 36 weeks, aficamten appeared safe and effective in the studied patients with nHCM.
Hypertrophic cardiomyopathy, defined as unexplained left ventricular hypertrophy, has an estimated prevalence of at least 1 in 500 and is among the most common forms of inherited heart disease. The ...pathophysiology of hypertrophic cardiomyopathy is complex and involves the interplay between diastolic dysfunction, myocardial ischemia, systolic anterior motion of the mitral valve resulting in outflow tract obstruction, and arrhythmia. Clinical presentations are heterogeneous and range from asymptomatic to palpitations, dyspnea, exercise intolerance, chest pain, syncope, and sudden death. Here, Owens and Cappola talk about the risk and benefits of exercise of patient with hypertrophic cardiomyopathy.
"Genome-first" approaches, in which genetic sequencing is agnostically linked to associated phenotypes, can enhance our understanding of rare variants' contributions to disease. Loss-of-function ...variants in LMNA cause a range of rare diseases, including cardiomyopathy.
We leveraged exome sequencing from 11,451 unselected individuals in the Penn Medicine Biobank to associate rare variants in LMNA with diverse electronic health record (EHR)-derived phenotypes. We used Rare Exome Variant Ensemble Learner (REVEL) to annotate rare missense variants, clustered predicted deleterious and loss-of-function variants into a "gene burden" (N = 72 individuals), and performed a phenome-wide association study (PheWAS). Major findings were replicated in DiscovEHR.
The LMNA gene burden was significantly associated with primary cardiomyopathy (p = 1.78E-11) and cardiac conduction disorders (p = 5.27E-07). Most patients had not been clinically diagnosed with LMNA cardiomyopathy. We also noted an association with chronic kidney disease (p = 1.13E-06). Regression analyses on echocardiography and serum labs revealed that LMNA variant carriers had dilated cardiomyopathy and primary renal disease.
Pathogenic LMNA variants are an underdiagnosed cause of cardiomyopathy. We also find that LMNA loss of function may be a primary cause of renal disease. Finally, we show the value of aggregating rare, annotated variants into a gene burden and using PheWAS to identify novel ontologies for pleiotropic human genes.
This study sought to determine the extent, time course, and predictors of improvement following cardiac resynchronization therapy (CRT) upgrade among pacing-induced cardiomyopathy (PICM) patients.
...PICM is an important cause of heart failure in patients exposed to frequent right ventricular (RV) pacing. CRT may reverse PICM.
We retrospectively studied 1,279 consecutive patients undergoing CRT procedures between 2003 and 2016. Patients undergoing CRT upgrade from a dual-chamber or single-chamber ventricular pacemaker for PICM were included. PICM was defined as decrease of ≥10% in left ventricular ejection fraction (LVEF), resulting in LVEF <50% among patients experiencing ≥20% RV pacing without an alternative cause of cardiomyopathy. Severe PICM was defined as pre-upgrade LVEF ≤35%. Clinical, electrocardiographic, and echocardiographic characteristics associated with both the extent of LVEF recovery and with post-upgrade LVEF of >35% among those with severe PICM were identified.
Of 69 PICM patients, LVEF improved from 29.3% to 45.3% over a median 7.0 months. Of 54 patients with severe PICM, 39 (72.2%) improved to LVEF >35% over a median 7.0 months. Most improvement occurred within the first 3 months, although improvement continued over the remainder of the first year. In linear regression, narrower native QRS was associated with greater LVEF improvement following CRT upgrade (+2.00% per 10-ms decrease; p = 0.05).
CRT is highly efficacious in reversing PICM, with 72% of severe PICM patients achieving LVEF >35% and most of the improvement occurring within 1 year. These data support initial upgrade to a CRT pacemaker with consideration of further upgrade to CRT defibrillator after 1 year if LVEF remains ≤35%.
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The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the ...prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children.
Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. LVSD was defined as left ventricular ejection fraction <50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models.
We studied 1010 patients diagnosed with HCM during childhood (<18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age <12 years at HCM diagnosis (hazard ratio HR, 1.72 CI, 1.13-2.62), male sex (HR, 3.1 CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 CI, 1.08-4.4), previous septal reduction therapy (HR, 2.34 CI, 1.42-3.9), and lower initial left ventricular ejection fraction (HR, 1.53 CI, 1.38-1.69 per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 CI, 1.41-4.78) and patients with a left ventricular ejection fraction <35% (HR, 3.76 2.16-6.52).
Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care.
The diagnostic history in the years leading up to the definitive diagnosis of patients with obstructive hypertrophic cardiomyopathy (HCM) has not been studied.
Patients with a delay in the definitive ...diagnosis of obstructive HCM from January 2009 to March 2019 were identified in the US IBM MarketScan Commercial and Medicare Supplemental Databases if they had an alternative diagnosis indicating a misdiagnosis during the 24 months before the definitive obstructive HCM diagnosis. Resource use and costs associated with the delay were estimated during the same period.
Of 3,888 eligible patients with obstructive HCM, 59.5% had a delay in definitive diagnosis. Patients received a mean of 4.0 misdiagnoses before the definitive obstructive HCM diagnosis, most of which were other cardiovascular conditions. Consequently, 15.7% of patients may have received inappropriate treatment. Approximately 78.4% of patients visited a cardiologist (mean 4.7 visits) before the definitive obstructive HCM diagnosis. Additionally, 26.8% and 32.1% of patients had an inpatient and emergency room visit, respectively. Annualized healthcare costs associated with the delay were $4,379 per patient.
The current study used administrative claims data for a commercially insured population. Therefore, the results may not be generalizable to other populations (e.g. those insured by Medicare or Medicaid and the uninsured). Like other database studies, the current study may have suffered from miscoding or undercoding, which may have caused misclassification of patients. Owing to insufficient data, the study could not evaluate all potential consequences of a delay in definitive diagnosis.
Most patients with obstructive HCM had a delay of ≤ 2 years before receiving the definitive diagnosis. The diagnostic journey involved multiple potential misdiagnoses, predominantly cardiovascular, as well as a substantial clinical and economic burden on patients and the healthcare system.
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