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Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis., Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy., Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013-November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group., Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60)., Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, -22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, -4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights., Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen and -11.2% with placebo (difference, -70.4% [95% CI, -75.2% to -65.7%]; P < .001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P < .001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P < .001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group., Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo., Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10.

Context: Whether decreases in the length of stay during the past decade for patients with heart failure (HF) may be associated with changes in outcomes is unknown., Objective: To describe the temporal changes in length of stay, discharge disposition, and short-term outcomes among older patients hospitalized for HF., Design, Setting, and Participants: An observational study of 6,955,461 Medicare fee-for-service hospitalizations for HF between 1993 and 2006, with a 30-day follow-up., Main Outcome Measures: Length of hospital stay, in-patient and 30-day mortality, and 30-day readmission rates., Results: Between 1993 and 2006, mean length of stay decreased from 8.81 days (95% confidence interval [CI], 8.79-8.83 days) to 6.33 days (95% CI, 6.32-6.34 days). In-hospital mortality decreased from 8.5% (95% CI, 8.4%-8.6%) in 1993 to 4.3% (95% CI, 4.2%-4.4%) in 2006, whereas 30-day mortality decreased from 12.8% (95% CI, 12.8%-12.9%) to 10.7% (95% CI, 10.7%-10.8%). Discharges to home or under home care service decreased from 74.0% to 66.9% and discharges to skilled nursing facilities increased from 13.0% to 19.9%. Thirty-day readmission rates increased from 17.2% (95% CI, 17.1%-17.3%) to 20.1% (95% CI, 20.0%-20.2%; all P < .001). Consistent with the unadjusted analyses, the 2005-2006 risk-adjusted 30-day mortality risk ratio was 0.92 (95% CI, 0.91-0.93) compared with 1993-1994, and the 30-day readmission risk ratio was 1.11 (95% CI, 1.10-1.11)., Conclusion: For patients admitted with HF during the past 14 years, reductions in length of stay and in-hospital mortality, less marked reductions in 30-day mortality, and changes in discharge disposition accompanied by increases in 30-day readmission rates were observed.

Context: Allowing nonelectrophysiologists to perform implantable cardioverter-defibrillator (ICD) procedures is controversial. However, it is not known whether outcomes of ICD implantation vary by physician specialty., Objective: To determine the association of implanting physician certification with outcomes following ICD implantation., Design, Setting, and Patients: Retrospective cohort study using cases submitted to the ICD Registry performed between January 2006 and June 2007. Patients were grouped by the certification status of the implanting physician into mutually exclusive categories: electrophysiologists, nonelectrophysiologist cardiologists, thoracic surgeons, and other specialists. Hierarchical logistic regression models were developed to determine the independent association of physician certification with outcomes., Main Outcome Measures: In-hospital procedural complication rates and the proportion of patients meeting criteria for a defibrillator with cardiac resynchronization therapy (CRT-D) who received that device., Results: Of 111,293 ICD implantations included in the analysis, 78,857 (70.9%) were performed by electrophysiologists, 24,399 (21.9%) by nonelectrophysiologist cardiologists, 1862 (1.7%) by thoracic surgeons, and 6175 (5.5%) by other specialists. Compared with patients whose ICD was implanted by electrophysiologists, patients whose ICD was implanted by either nonelectrophysiologist cardiologists or thoracic surgeons were at increased risk of complications in both unadjusted (electrophysiologists, 3.5% [2743/78,857]; nonelectrophysiologist cardiologists, 4.0% [970/24,399]; thoracic surgeons, 5.8% [108/1862]; P < .001) and adjusted analyses (relative risk [RR] for nonelectrophysiologist cardiologists, 1.11 [95% confidence interval {CI}, 1.01-1.21]; RR for thoracic surgeons, 1.44 [95% CI, 1.15-1.79]). Among 35,841 patients who met criteria for CRT-D, those whose ICD was implanted by physicians other than electrophysiologists were significantly less likely to receive a CRT-D device compared with patients whose ICD was implanted by an electrophysiologist in both unadjusted (electrophysiologists, 83.1% [21 303/25,635]; nonelectrophysiologist cardiologists, 75.8% [5950/7849]; thoracic surgeons, 57.8% [269/465]; other specialists, 74.8% [1416/1892]; P < .001) and adjusted analyses (RR for nonelectrophysiologist cardiologists, 0.93 [95% CI, 0.91-0.95]; RR for thoracic surgeons, 0.81 [95% CI, 0.74-0.88]; RR for other specialists, 0.97 [95% CI, 0.94-0.99])., Conclusions: In this registry, nonelectrophysiologists implanted 29% of ICDs. Overall, implantations by a nonelectrophysiologist were associated with a higher risk of procedural complications and lower likelihood of receiving a CRT-D device when indicated compared with patients whose ICD was implanted by an electrophysiologist.