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CARS (Cardiac Amyloidosis Registry Study) is a multicenter registry established in 2019 that includes patients with transthyretin (ATTR, wild-type and variant) and light chain (AL) cardiac amyloidosis (CA) evaluated at major amyloidosis centers between 1997 and 2025. CARS aims to describe the natural history of CA with attention to clinical and diagnostic variables at the time of diagnosis, real-world treatment patterns, and associated outcomes of patients in a diverse cohort that is more representative of the at-risk population than that described in CA clinical trials. This article describes the design and methodology of CARS, including procedures for data collection and preliminary results. As of February 2023, 20 centers in the United States enrolled 1415 patients, including 1155 (82%) with ATTR and 260 (18%) with AL CA. Among those with ATTR, wild-type is the most common ATTR (71%), and most of the 305 patients with variant ATTR have the p.V142I mutation (68%). A quarter of the total population identifies as Black. More individuals with AL are female (39%) compared to those with ATTR (13%). CARS will answer crucial clinical questions about CA natural history and permit comparison of different therapeutics not possible through current clinical trials. Future international collaboration will further strengthen the validity of observations of this increasingly recognized condition. [ABSTRACT FROM AUTHOR]

An 11-factor random forest model has been developed among ambulatory heart failure (HF) patients for identifying potential wild-type amyloidogenic TTR cardiomyopathy (wtATTR-CM). The model has not been evaluated in a large sample of patients hospitalized for HF. This study included Medicare beneficiaries aged ≥65 years hospitalized for HF in the Get With The Guidelines-HF® Registry from 2008-2019. Patients with and without a diagnosis of ATTR-CM were compared, as defined by inpatient and outpatient claims data within 6 months pre- or post-index hospitalization. Within a cohort matched 1:1 by age and sex, univariable logistic regression was used to evaluate relationships between ATTR-CM and each of the 11 factors of the established model. Discrimination and calibration of the 11-factor model were assessed. Among 205,545 patients (median age 81 years) hospitalized for HF across 608 hospitals, 627 patients (0.31%) had a diagnosis code for ATTR-CM. Univariable analysis within the 1:1 matched cohort of each of the 11-factors in the ATTR-CM model found pericardial effusion, carpal tunnel syndrome, lumbar spinal stenosis, and elevated serum enzymes (e.g., troponin elevation) to be strongly associated with ATTR-CM. The 11-factor model showed modest discrimination (c-statistic 0.65) and good calibration within the matched cohort. Among US patients hospitalized for HF, the number of patients with ATTR-CM defined by diagnosis codes on an inpatient/outpatient claim within 6 months of admission was low. Most factors within the prior 11-factor model were associated with greater odds of ATTR-CM diagnosis. In this population, the ATTR-CM model demonstrated modest discrimination. [ABSTRACT FROM AUTHOR]

Background: Ventricular arrhythmias (VAs) and electrical storm (ES) are recognized complications following left ventricular assist device (LVAD) implantation; however, their association with long term-outcomes remains poorly understood.Objective: The purpose of this study was to describe the clinical impact of ES in a population of patients undergoing LVAD implantation at a quaternary care center in the United States.Methods: This was an observational retrospective study of patients undergoing LVAD implantation from 2009 to 2020 at Duke University Hospital. The incidence of ES (≥3 sustained VA episodes over a 24-hour period without an identifiable reversible cause) was determined from patient records. Risk factors for ES were identified using multivariable Cox proportional hazards modeling.Results: Among 730 patients undergoing LVAD implant, 78 (10.7%) developed ES at a median of 269 (interquartile range [IQR] 7-766) days following surgery. Twenty-seven patients (34.6%) developed ES within 30 days, while 51 (65.4%) presented with ES at a median 639 (IQR 281-1017) days after implant. Following ES, 41% of patients died within 1 year. Patients who developed ES were more likely to have a history of VAs, ventricular tachycardia ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support around the time of LVAD implant than patients without ES.Conclusion: ES occurs in 1 in 10 patients after LVAD and is associated with higher mortality. Risk factors for ES include a history of VAs, VT ablation, antiarrhythmic drug use, and perioperative mechanical circulatory support. Optimal management of ES surrounding LVAD implant, including escalation of medical therapy, catheter ablation, or adjunctive sympatholytic therapies, remains uncertain. [ABSTRACT FROM AUTHOR]

Atrial arrhythmias commonly occur in patients with cardiac amyloidosis (CA), but there is limited data on safety or efficacy of cardioversion (DCCV) for management of these rhythms in CA. We identified 25 patients with CA (20 with transthyretin (TTR) and 5 with light-chain (AL) amyloidosis) at Duke University who underwent DCCV for atrial arrhythmias and documented procedural success, complications, and long-term morbidity and mortality. While DCCV successfully restored sinus rhythm in 96% of patients, 36% of patients experienced immediate procedural complications (primarily bradycardia and hypotension), 80% had recurrence of atrial arrhythmias at 1 year, and 52% died at 3 years, highlighting short-term safety concerns, long-term inefficacy, and poor prognosis associated with symptomatic atrial arrhythmias requiring DCCV in CA. [ABSTRACT FROM AUTHOR]

Objectives This study was performed to determine whether a 4-tiered classification of left ventricular hypertrophy (LVH) defines subgroups in the general population that are at variable risks of adverse cardiovascular (CV) outcomes. Background We recently proposed a 4-tiered classification of LVH where eccentric LVH is subdivided into “indeterminate hypertrophy” and “dilated hypertrophy” and concentric LVH into “thick hypertrophy” and “both thick and dilated hypertrophy,” based on the presence of increased left ventricular (LV) end-diastolic volume. Methods Participants from the Dallas Heart study who underwent cardiac magnetic resonance and did not have LV dysfunction or a history of heart failure (HF) (n = 2,458) were followed for a median of 9 years for the primary outcome of HF or CV death. Multivariable Cox proportional hazards models were used to adjust for age, sex, African-American race, hypertension, diabetes, and history of CV disease. Results In the cohort, 70% had no LVH, 404 (16%) had indeterminate hypertrophy, 30 (1%) had dilated hypertrophy, 289 (12%) had thick hypertrophy, and 7 (0.2%) had both thick and dilated hypertrophy. The cumulative incidence of HF or CV death was 2% with no LVH, 1.7% with indeterminate, 16.7% with dilated, 11.1% with thick, and 42.9% with both thick and dilated hypertrophy (log-rank p < 0.0001). Compared with participants without LVH, those with dilated (hazard ratio [HR]: 7.3; 95% confidence interval [CI]: 2.8 to 18.8), thick (HR: 2.4; 95% CI: 1.4 to 4.0), and both thick and dilated (HR: 5.8; 95% CI: 1.7 to 19.5) hypertrophy remained at increased risk for HF or CV death after multivariable adjustment, whereas the group with indeterminate hypertrophy was not (HR: 0.9; 95% CI: 0.4 to 2.2). Conclusions In the general population, the 4-tiered classification system for LVH stratified LVH into subgroups with differential risk of adverse CV outcomes. [ABSTRACT FROM AUTHOR]

Increased myocardial stiffness (MS) is an important hallmark of cardiac amyloidosis (CA) caused by myocardial amyloid deposition. Standard echocardiography metrics assess MS indirectly via downstream effects of cardiac stiffening. The ultrasound elastography methods acoustic radiation force impulse (ARFI) and natural shear wave (NSW) imaging assess MS more directly. This study compared MS in 12 healthy volunteers and 13 patients with confirmed CA using ARFI and NSW imaging. Parasternal long-axis acquisitions of the interventricular septum were obtained using a modified Acuson Sequoia scanner and a 5V1 transducer. ARFI-induced displacements were measured through the cardiac cycle, and ratios of diastolic-over-systolic displacement were calculated. NSW speeds from aortic valve closure were extracted from echocardiography-tracked displacement data. ARFI stiffness ratios were significantly lower in CA patients than controls (mean ± standard deviation: 1.47 ± 0.27 vs. 2.10 ± 0.47, p < 0.001), and NSW speeds were significantly higher in CA patients than controls (5.58 ± 1.10 m/s vs. 3.79 ± 1.10 m/s, p < 0.001). A linear combination of the two metrics exhibited greater diagnostic potential than either metric alone (area under the curve = 0.97 vs. 0.89 and 0.88). MS was measured to be significantly higher in CA patients using both ARFI and NSW imaging. Together, these methods have potential utility to aid in clinical diagnosis of diastolic dysfunction and infiltrative cardiomyopathies. [ABSTRACT FROM AUTHOR]

Background: Monogenic diseases are individually rare but collectively common, and are likely underdiagnosed.Objectives: The purpose of this study was to estimate the prevalence of monogenic cardiovascular diseases (MCVDs) and potentially missed diagnoses in a cardiovascular cohort.Methods: Exomes from 8,574 individuals referred for cardiac catheterization were analyzed. Pathogenic/likely pathogenic (P/LP) variants associated with MCVD (cardiomyopathies, arrhythmias, connective tissue disorders, and familial hypercholesterolemia were identified. Electronic health records (EHRs) were reviewed for individuals harboring P/LP variants who were predicted to develop disease (G+). G+ individuals who did not have a documented relevant diagnosis were classified into groups of whether they may represent missed diagnoses (unknown, unlikely, possible, probable, or definite) based on relevant diagnostic criteria/features for that disease.Results: In total, 159 P/LP variants were identified; 2,361 individuals harbored at least 1 P/LP variant, of whom 389 G+ individuals (4.5% of total cohort) were predicted to have at least 1 MCVD. EHR review of 342 G+ individuals predicted to have 1 MCVD with sufficient EHR data revealed that 52 had been given the relevant clinical diagnosis. The remaining 290 individuals were classified as potentially having an MCVD as follows: 193 unlikely (66.6%), 50 possible (17.2%), 30 probable (10.3%), and 17 definite (5.9%). Grouping possible, probable, definite, and known diagnoses, 149 were considered to have an MCVD. Novel MCVD pathogenic variants were identified in 16 individuals.Conclusions: Overall, 149 individuals (1.7% of cohort) had MCVDs, but only 35% were diagnosed. These patients represents a "missed opportunity," which could be addressed by greater use of genetic testing of patients seen by cardiologists. [ABSTRACT FROM AUTHOR]

Background: Circulating high-density lipoprotein particle (HDL-P) subfractions impact atherogenesis, inflammation, and endothelial function, all of which are implicated in the pathobiology of heart failure (HF).Objectives: The authors sought to identify key differences in plasma HDL-P subfractions between patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) to determine their prognostic utility.Methods: Patients with HFrEF (n = 782), HFpEF (n = 1,004), and no HF (n = 4,742) were identified in the CATHGEN (Catheterization Genetics) biorepository of sequential patients undergoing cardiac catheterization. Nuclear magnetic resonance-based lipoprotein profiling was performed on frozen fasting plasma obtained at catheterization. The authors used multivariable analysis of covariance to compare high-density lipoprotein particle (HDL-P) subfractions across groups, and Cox proportional hazards modeling to determine associations between HDL-P subfractions and time to death or major adverse cardiac events.Results: Mean HDL-P size was greater in HFrEF than HFpEF, both of which were greater than in no HF (all 2-way p < 0.0001). By contrast, concentrations of small HDL-P and total HDL-P were lesser in HFrEF than HFpEF, which were both lesser than no HF (all 2-way p ≤ 0.0002). In both HFrEF and HFpEF, total HDL-P and small HDL-P were inversely associated with time to adverse events. These findings persisted after adjustment for 14 clinical covariates (including high-density lipoprotein cholesterol content, coronary artery disease, and the inflammatory biomarker GlycA), and in sensitivity analyses featuring alternate left ventricular ejection fraction definitions, or stricter inclusion criteria with diastolic dysfunction or left ventricular end-diastolic pressure thresholds.Conclusions: In the largest analysis of HDL-P subfractions in HF to date, derangements in HDL-P subfractions were identified that were more severe in HFrEF than HFpEF and were independently associated with adverse outcomes. These data may help refine risk assessment and provide new insights into the complex interaction of HDL and HF pathophysiology. [ABSTRACT FROM AUTHOR]

Background The oral vasopressin-2 receptor antagonist tolvaptan causes aquaresis in patients with volume overload, potentially facilitating decongestion and improving the clinical course of patients with acute heart failure (AHF). Objectives The TACTICS-HF (Targeting Acute Congestion with Tolvaptan in Congestive Heart Failure) study was conducted to address the acute use of tolvaptan to improve congestion in AHF. Methods The TACTICS-HF study randomized patients (n = 257) within 24 h of AHF presentation in a prospective, double blind, placebo-controlled trial. Patients were eligible regardless of ejection fraction, and were randomized to either 30 mg of tolvaptan or placebo given at 0, 24, and 48 h, with a fixed-dose furosemide regimen as background therapy. The primary endpoint was the proportion of patients considered responders at 24 h. Secondary endpoints included symptom improvement, changes in renal function, and clinical events. Results Dyspnea relief by Likert scale was similar between groups at 8 h (25% moderately or markedly improved with tolvaptan vs. 28% placebo; p = 0.59) and at 24 h (50% tolvaptan vs. 47% placebo; p = 0.80). Need for rescue therapy was also similar at 24 h (21% tolvaptan, 18% placebo; p = 0.57). The proportion defined as responders at 24 h (primary study endpoint) was 16% for tolvaptan and 20% for placebo (p = 0.32). Tolvaptan resulted in greater weight loss and net fluid loss compared with placebo, but tolvaptan-treated patients were more likely to experience worsening renal function during treatment. There were no differences in in-hospital or post-discharge clinical outcomes. Conclusions In patients hospitalized with AHF, dyspnea, and congestion, the addition of tolvaptan to a standardized furosemide regimen did not improve the number of responders at 24 h, despite greater weight loss and fluid loss. (Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure [TACTICS-HF]; NCT01644331 ) [ABSTRACT FROM AUTHOR]

Abstract: Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n =25 per group) after RP. AT consisted of five walking sessions per week at 55–100% of peak oxygen uptake (VO 2peak) for 30–60min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow–mediated dilation (FMD), VO 2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤21) decreased by 20% in the AT group and by 24% in the UC group (difference: p =0.406). There were no significant between-group differences in any erectile function subscale (p >0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs. In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP. Trial registration: Clinicaltrials.gov identifier NCT00620932. [Copyright &y& Elsevier]

Background: The oral vasopressin-2 receptor antagonist tolvaptan causes aquaresis in patients with volume overload, potentially facilitating decongestion and improving the clinical course of patients with acute heart failure (AHF).Objectives: The TACTICS-HF (Targeting Acute Congestion with Tolvaptan in Congestive Heart Failure) study was conducted to address the acute use of tolvaptan to improve congestion in AHF.Methods: The TACTICS-HF study randomized patients (n = 257) within 24 h of AHF presentation in a prospective, double blind, placebo-controlled trial. Patients were eligible regardless of ejection fraction, and were randomized to either 30 mg of tolvaptan or placebo given at 0, 24, and 48 h, with a fixed-dose furosemide regimen as background therapy. The primary endpoint was the proportion of patients considered responders at 24 h. Secondary endpoints included symptom improvement, changes in renal function, and clinical events.Results: Dyspnea relief by Likert scale was similar between groups at 8 h (25% moderately or markedly improved with tolvaptan vs. 28% placebo; p = 0.59) and at 24 h (50% tolvaptan vs. 47% placebo; p = 0.80). Need for rescue therapy was also similar at 24 h (21% tolvaptan, 18% placebo; p = 0.57). The proportion defined as responders at 24 h (primary study endpoint) was 16% for tolvaptan and 20% for placebo (p = 0.32). Tolvaptan resulted in greater weight loss and net fluid loss compared with placebo, but tolvaptan-treated patients were more likely to experience worsening renal function during treatment. There were no differences in in-hospital or post-discharge clinical outcomes.Conclusions: In patients hospitalized with AHF, dyspnea, and congestion, the addition of tolvaptan to a standardized furosemide regimen did not improve the number of responders at 24 h, despite greater weight loss and fluid loss. (Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure [TACTICS-HF]; NCT01644331). [ABSTRACT FROM AUTHOR]