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Background: Patients with heart failure, a preserved ejection fraction (HFpEF), and obesity have significant disability and suffer frequent exacerbations of heart failure. We hypothesized that tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, would improve a comprehensive suite of clinical endpoints, including measures of health status, functional capacity, quality of life, exercise tolerance, patient well-being, and medication burden in these patients.

Methods: 731 patients in class II-IV heart failure, ejection fraction ≥50%, and body mass index ≥30 kg/m² were randomized(double-blind) to tirzepatide(titrated up to 15mg subcutaneously weekly)(n=364) or placebo(n=367), added to background therapy for a median of 104 weeks (Q1=66, Q3=126 weeks).

Primary endpoints: tirzepatide reduced the combined risk of cardiovascular death or worsening heart failure and improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score(KCCQ-CSS). The current expanded analysis included sensitivity analyses of the primary endpoints, 6-minute walk distance(6MWD), EQ-5D-5L health state index, Patient Global Impression of Severity Overall Health(PGIS), NYHA class, use of heart failure medications, and a hierarchical composite based on all-cause death, worsening heart failure, and 52-week changes in KCCQ-CSS and 6MWD.

Results: Patients were aged 65.2±10.7, 53.8%(n=393) were female; BMI 38.2±6.7kg/m², KCCQ-CSS 53.5±18.5, 6MWD 302.8±81.7meters, and 53%(n=388) had a worsening heart failure event in the prior 12 months. Compared with placebo, tirzepatide produced a consistent beneficial effect across all composites of death and worsening heart failure events, analyzed as time-to-first-event (hazard ratios 0.41-0.67). At 52 weeks, tirzepatide increased KCCQ-CSS 6.9 points (95%CI, 3.3, 10.6, P<0.001), 6MWD 18.3 meters (95%CI, 9.9, 26.7, P<0.001) and EQ-5D-5L 0.06 (95%CI, 0.03, 0.09, P<0.001). The tirzepatide group shifted to a more favorable PGIS (proportional odds ratio 1.99 (95%CI, 1.44, 2.76) and NYHA class (proportional odds ratio 2.26 (95%CI, 1.54, 3.31), both P<0.001 and required less heart failure medications (P=0.015). The broad spectrum of effects was reflected in benefits on the hierarchical composite (win ratio 1.63, 95%CI, 1.17, 2.28;P=0.004).

Conclusions: Tirzepatide produced a comprehensive, meaningful improvement in heart failure across multiple complementary domains; enhanced health status, quality of life, functional capacity, exercise tolerance and well-being; and reduced symptoms and medication burden in patients with HFpEF and obesity.

Background: In the phase 3 randomized controlled study, ATTRibute-CM, acoramidis, a transthyretin (TTR) stabilizer, demonstrated significant efficacy on the primary endpoint. Participants with transthyretin amyloid cardiomyopathy (ATTR-CM) who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE.

Methods: Participants who previously received acoramidis through Month 30 (M30) in ATTRibute-CM continued to receive it (continuous acoramidis), and those who received placebo through M30 were switched to acoramidis (placebo to acoramidis). Participants who received concomitant tafamidis in ATTRibute-CM were required to discontinue it to be eligible to enroll in the OLE. Clinical efficacy outcomes analyzed through Month 42 (M42) included time to event for all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH), ACM alone, first CVH alone, ACM or recurrent CVH, change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), serum TTR, and the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS). Safety outcomes were analyzed through M42.

Results: Overall, 438 of 632 participants in ATTRibute-CM completed treatment and 389 enrolled in the ongoing OLE (263 continuous acoramidis, 126 placebo to acoramidis). The hazard ratio (HR) (95% CI) for ACM or first CVH was 0.57 (0.46, 0.72) at M42 based on a stratified Cox proportional hazards model (P-value < 0.0001) favoring continuous acoramidis. Similar analyses were performed on ACM alone and first CVH alone, with HRs (95% CI) of 0.64 (0.47, 0.88) and 0.53 (0.41, 0.69), respectively, at M42. Treatment effects for NT-proBNP and 6MWD also favored continuous acoramidis. Upon initiation of open-label acoramidis in the placebo-to-acoramidis arm there was a prompt increase in serum TTR. Quality of life assessed by KCCQ-OS was well preserved in continuous acoramidis participants compared with the placebo to acoramidis participants. No new clinically important safety issues were identified in this long-term evaluation.

Conclusions: Early initiation and continuous use of acoramidis in the ATTRibute-CM study through M42 of the ongoing OLE study was associated with sustained clinical benefits in a contemporary ATTR-CM cohort, with no clinically important safety issues newly identified.

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128.

Methods: A double-blind randomized placebo-controlled multicenter trial at 19 sites in the United States included symptomatic obstructive HCM patients referred for SRT (enrollment July 2020 through October 2021). The group initially randomized to mavacamten continued the drug for 128 weeks and the placebo to mavacamten group from week 16 to 128 (112-week exposure). Dose titrations were performed using echocardiographic left ventricular outflow tract gradient and left ventricular ejection fraction measurements. The principal end point was proportion of patients proceeding with SRT or remaining guideline-eligible at week 128.

Results: At week 128, 17 of 108 (15.7%) patients in the total study sample met the composite end point (7 underwent SRT, 1 was SRT-eligible, and 9 SRT-status unevaluable). Additionally, 87 of 108 (80.5%) patients demonstrated ≥1 New York Heart Association class improvement by week 128, and 52 of 108 (48.1%) demonstrated ≥2, with a sustained reduction in resting and Valsalva left ventricular outflow tract gradients of 38.2 mm Hg and 59.4 mm Hg, respectively. Ninety-five of 108 (88%) patients transitioned to commercial mavacamten. Overall, 15 of 108 (13.8%) patients (5.41 per 100 patient-years) had an left ventricular ejection fraction <50% (2 with left ventricular ejection fraction ≤30%; 1 death). Of these, 12 of 15 (80%) continued treatment. New-onset atrial fibrillation occurred in 11 (10.2%) patients (4.55 per 100 patient-years).

Conclusions: In severely symptomatic obstructive HCM patients, sustained freedom from SRT was observed at 128 weeks, with nearly 90% patients remaining on long-term mavacamten.

Background: The ability to predict recovery of left ventricular ejection fraction (LVEF) in response to guideline-directed therapy among patients with nonischemic cardiomyopathy is desired. We sought to determine whether left ventricular endocardial unipolar voltage measured during invasive electroanatomic mapping could be used to predict LVEF recovery among those with recent-onset nonischemic cardiomyopathy.

Methods: We analyzed the left ventricular voltage maps of patients included in the eMAP trial (Electrogram-Guided Myocardial Advanced Phenotyping; NCT03293381), a prospective, nonrandomized, interventional trial conducted at 2 institutions between 2017 and 2020. Patients had recent-onset nonischemic cardiomyopathy defined by LVEF ≤45% and development of symptoms or signs of heart failure within the past 6 months. Detailed voltage maps of the left ventricular endocardium were generated using the CARTO electroanatomic mapping system. Abnormal unipolar amplitude was defined as <8.27 mV. The primary end point was recovery of LVEF (Recovery) defined by a 1-year LVEF ≥50% or ≥45% with ≥10% increase from baseline.

Results: Of the 29 enrolled patients (median age, 49 years [25th percentile, 39; 75th percentile, 59], 8 females [27.6%]), LVEF recovered in 13 (44.8%) by 1-year follow-up. The percentage of total endocardial surface area with unipolar voltage abnormality (AUA) was significantly lower among Recovery patients than No Recovery patients (18.2% [6.4, 22.4] versus 80.0% [29.5, 90.9]; P=0.004). Percent AUA was associated with lower likelihood of Recovery (odds ratio, 0.64 per 10% increase in AUA; 95% CI, 0.47-0.88; P=0.006). A 28% cutoff value for percent AUA was 92% sensitive and 75% specific with an area under the receiver operating characteristic curve of 0.81 (95% CI, 0.63-0.99; P=0.001) for predicting recovery versus no recovery. The majority of patients (12 of 13; 92.3%) with a percent AUA >28% did not recover.

Conclusions: Left ventricular unipolar voltage abnormality is a potent predictor of LVEF recovery among patients recently diagnosed with nonischemic cardiomyopathy. Detailed left ventricular unipolar voltage mapping could therefore be used as a valuable prognostic tool in guiding treatment decisions.

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

Codeveloped by the American Heart Association and the American Red Cross, these guidelines represent the first comprehensive update of first aid treatment recommendations since 2010. Incorporating the results of structured evidence reviews from the International Liaison Committee on Resuscitation, these guidelines cover first aid treatment for critical and common medical, traumatic, environmental, and toxicological conditions. This update emphasizes the continuous evolution of evidence evaluation and the necessity of adapting educational strategies to local needs and diverse community demographics. Existing guidelines remain relevant unless specifically updated in this publication. Key topics that are new, are substantially revised, or have significant new literature include opioid overdose, bleeding control, open chest wounds, spinal motion restriction, hypothermia, frostbite, presyncope, anaphylaxis, snakebite, oxygen administration, and the use of pulse oximetry in first aid, with the inclusion of pediatric-specific guidance as warranted.

Background: Many studies have explored whether individual plasma protein biomarkers improve cardiovascular disease risk prediction. We sought to investigate the use of a plasma proteomics-based approach in predicting different cardiovascular outcomes.

Methods: Among 51 859 UK Biobank participants (mean age, 56.7 years; 45.5% male) without cardiovascular disease and with proteomics measurements, we examined the primary composite outcome of fatal and nonfatal coronary heart disease, stroke, or heart failure (major adverse cardiovascular events), as well as additional secondary cardiovascular outcomes. An exposome-wide association study was conducted using relative protein concentrations, adjusted for a range of classic, demographic, and lifestyle risk factors. A prediction model using only age, sex, and protein markers (protein model) was developed using a least absolute shrinkage and selection operator-regularized approach (derivation: 80% of cohort) and validated using split-sample testing (20% of cohort). Their performance was assessed by comparing calibration, net reclassification index, and c statistic with the PREVENT (Predicting Risk of CVD Events) risk score.

Results: Over a median 13.6 years of follow-up, 4857 participants experienced first major adverse cardiovascular events. After adjustment, the proteins most strongly associated with major adverse cardiovascular events included NT-proBNP (N-terminal pro B-type natriuretic peptide; hazard ratio [HR], 1.68 per SD increase), proADM (pro-adrenomedullin; HR, 1.60), GDF-15 (growth differentiation factor-15; HR, 1.47), WFDC2 (WAP four-disulfide core domain protein 2; HR, 1.46), and IGFBP4 (insulin-like growth factor-binding protein 4; HR, 1.41). In total, 222 separate proteins were predictors of all outcomes of interest in the protein model, and 86 were selected for the primary outcome specifically. In the validation cohort, compared with the PREVENT risk factor model, the protein model improved calibration, net reclassification (net reclassification index +0.09), and c statistic for major adverse cardiovascular events (+0.051). The protein model also improved the prediction of other outcomes, including ASCVD (c statistic +0.035), myocardial infarction (+0.023), stroke (+0.024), aortic stenosis (+0.015), heart failure (+0.060), abdominal aortic aneurysm (+0.024), and dementia (+0.068).

Conclusions: Measurement of targeted protein biomarkers produced superior prediction of aggregated and disaggregated cardiovascular events. This study represents an important proof of concept for the application of targeted proteomics in predicting a range of cardiovascular outcomes.

Kawasaki disease (KD), an acute self-limited febrile illness that primarily affects children <5 years old, is the leading cause of acquired heart disease in developed countries, with the potential of leading to coronary artery dilation and coronary artery aneurysms in 25% of untreated patients. This update summarizes relevant clinical data published since the 2017 American Heart Association scientific statement on KD related to diagnosis, cardiac imaging in acute KD treatment, and long-term management. Criteria defining North American patients at high risk for developing coronary artery aneurysms who may benefit from more intensive initial treatment have been published. Advances in cardiovascular imaging have improved the ability to identify coronary artery stenosis in patients with KD, yet knowledge gaps remain regarding optimal frequency of serial imaging and the best imaging modality to identify those at risk for inducible myocardial ischemia. Recent data have advanced the understanding of safety and dosing for several anti-inflammatory therapies in KD. New anticoagulation medication, myocardial infarction management, transition of health care for patients with KD, and future directions in research are discussed.