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Key Points: Question: Is the antisense oligonucleotide eplontersen associated with changes in serum transthyretin concentration and improvement in neuropathy symptoms among adults with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy? Findings: In this open-label study that enrolled 168 patients (144 assigned to subcutaneous eplontersen) and included 60 historical placebo patients, the eplontersen treatment group demonstrated changes from baseline to week 65/66 consistent with significantly lower serum transthyretin concentration (−81.7% vs −11.2%), less neuropathy impairment, and better quality of life compared with the historical placebo group. Meaning: Among adults with ATTRv polyneuropathy, the eplontersen treatment group had lower serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. 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 This open-label, single-group, phase 3 trial evaluates eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in adults with hereditary amyloid transthyretin (ATTRv) polyneuropathy at 40 sites in 15 countries, compared with historical controls. [ABSTRACT FROM AUTHOR]

A study was conducted to evaluated the association between length of stay and short-term outcomes among Medicare older patients hospitalized for heart failure. Results indicated that with a reduced length of hospital stay 30-day mortality decreased; however, posthospital readmission and mortality risk increased.

Cross-sectional analyses of data from Medicare administrative claims for all fee-for-service beneficiaries hospitalized between 2004 and 2006 in acute care hospitals in US was conducted to determine the association between hospital volume threshold and the death rate for patients hospitalized for acute myocardial infarction, heart failure, or pneumonia. Admission to higher-volume hospitals was found to be associated with a reduction in mortality for acute myocardial infarction, heart failure, and pneumonia, but volume threshold above which an increased condition-specific hospital was not significantly associated with reduced mortality.

A study was conducted to evaluate the low-dose ionizing radiation exposure that occurs after medical imaging procedures. Results indicate that such procedures lead to high cumulative effective doses of radiation.

The study attempts to evaluate the hospital 30-day risk-standardized mortality rates (RSMRs) for those patients that have been discharged with acute myocardial infarction (AMI). The results indicate that there was a significant decrease in hospital mortality rate for patients with AMI.

A study was conducted to evaluate whether patients receiving an implantable cardioverter-defibrillator (ICD) from nonelectrophysiologists had more negative outcomes as compared to implants done by electrophysiologists who were certified for the procedure. Results indicated that implants done by nonelectrophysiologists had a higher risk of procedural complications.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2005.03.009 Byline: Tobias T. Lee, Jersey Chen, David J. Cohen, Lana Tsao Abstract: The association between low blood pressure and prognosis in the general population has been controversial, with some reports suggesting an increased mortality for patients with the lowest blood pressures. Whereas many standard heart failure therapies decrease blood pressure, the relationship between mortality and blood pressure in patients with heart failure has not been previously evaluated. Author Affiliation: Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA Article History: Received 6 October 2004; Accepted 1 March 2005

Aims: Heart failure (HF) substantially limits the ability of patients to engage in physical activities. A detailed understanding of how patients experience these limitations is required to develop valid and sensitive measures for use in clinical research. This qualitative study was designed to provide a thorough description of how HF patients experience physical activity limitations in their daily lives. Methods and results: Semi‐structured interviews were conducted with 40 HF patients. Interview transcripts were coded with the aim of identifying key aspects of physical activity. Patients were divided between HF with preserved ejection fraction (n = 21, 52.5%) and HF with reduced ejection fraction (n = 19, 47.5%); the majority of patients were New York Heart Association Class II (n = 22, 52.5%) or Class III (n = 16, 40.0%). Relevant physical activity themes, including mobility and broader daily function areas, were identified. The most frequently reported mobility limitations involved difficulty walking (up a steep incline, up steps, and long distances), limited walking speed, difficulty standing for long periods of time, and difficulty carrying and lifting objects. These limitations were principally related to three HF symptoms: dyspnoea, tiredness/fatigue, and peripheral oedema. Patients adapted to their symptoms and related mobility limitations in several ways, including taking rests during an activity, doing an activity more slowly, and avoiding/refraining from an activity altogether. The broader daily function areas most commonly impacted by the mobility limitations were housework, exercising or playing sports, and going shopping. Conclusions: Heart failure patients report numerous physical activity limitations. These specific mobility and daily function areas can be measured using clinical outcome assessments (e.g. patient‐reported outcomes and performance outcomes) in clinical trials and observational research. Accelerometry can be used to contribute to a holistic picture of patient functioning by passively collecting this type of data. [ABSTRACT FROM AUTHOR]

Byline: Harlan M. Krumholz, Jersey Chen, Jaime E. Murillo, David J. Cohen, Martha J. Radford Abstract: Although cost estimates for acute myocardial infarction are necessary for decisions about allocating scarce resources, there is a relative paucity of studies that estimate these costs across the entire spectrum of hospitals in actual clinical practice. This study sought to determine the correlates of in-hospital costs for acute myocardial infarction in patients 65 years of age and older. In the Cooperative Cardiovascular Project pilot, medical records were abstracted for acute myocardial infarction hospitalizations in Connecticut from June 1, 1992, through May 20, 1993. In-hospital costs were calculated by multiplying charges from cost centers by the Medicare ratio of cost-to-charge. Among the 2628 patients in the study sample, the total mean in-hospital cost was $14,772, and the median in-hospital cost was $10,409 (twenty-fifth to seventy-fifth percentile, $6960 to $17,225). The largest proportion of the costs were concentrated in room costs (43% of the total). Although several demographic and clinical characteristics were significantly associated with cost, they accounted for only 7% of the variation. In-hospital procedures and adverse outcomes accounted for 53% of the variation. (Am Heart J 1998;135:523-31.) Author Affiliation: New Haven, Middletown, and Farmington, Conn., and Boston, Mass Article History: Received 27 February 1997; Accepted 18 August 1997 Article Note: (footnote) [star] From the aSection of Cardiovascular Medicine, bDepartment of Medicine, the Section of Chronic Disease Epidemiology, cDepartment of Epidemiology and Public Health, and the Yale-New Haven Hospital Center for Outcomes Research and Evaluation, Yale School of Medicine, New Haven, the dConnecticut Peer Review Organization, Middletown, eCardiology Division, Department of Medicine, University of Connecticut Medical School, Farmington, Conn., and the fDivision of Cardiovascular Medicine, Department of Medicine, Beth Israel Hospital, Boston, Mass., [star][star] Supported in part by the Patrick and Catherine Weldon Donaghue Medical Research Foundation., a Reprint requests: Harlan M. Krumholz, MD, Yale University School of Medicine, 333 Cedar St., P.O. Box 208025, New Haven, CT 06520-8025, E-mail: harlan.krumholz@yale.edu, aa The analyses upon which this publication is based were performed under Contract Number 500-96-P549, entitled 'Utilization and Quality Control Peer Review Organization for the State of Connecticut,' sponsored by the Health Care Financing Administration, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The author assumes full responsibility for the accuracy and completeness of the ideas presented. This article is a direct result of the Health Care Quality Improvement Program initiated by the Health Care Financing Administration, which has encouraged identification of quality improvement projects derived from analysis of patterns of care, and therefore required no special funding on the part of this Contractor. Ideas and contributions to the author concerning experience in engaging with issues presented are welcomed., acents 0002-8703/98/$5.00 + 0 4/1/86011