Cardiovascular-related Hospitalizations Research Articles

TAFAMIDIS FOR TREATMENT OF TRANSTHYRETIN CARDIAC AMYLOIDOSIS: A REAL WORLD EXPERIENCE

Abstract Background A regional network for cardiac amyloidosis (CA) was created in 2019 with the aim of enhancing disease awareness among physicians and favoring appropriate access to innovative diagnostic tools/therapies. The network includes all 14 Cardiology Departments and outpatient clinics from 5 Local Health Units. Therapies for variant (ATTR–v) and wild–type (ATTR–wt) CA have recently become available in Italy. Selected centres with expertise in cardiomyopathies were identified to prescribe new modifying disease drugs. Tafamidis is the first medication approved for the treatment of ATTR–C. The landmark ATTRACT trial showed a reduction in cardiovascular mortality and cardiovascular–related hospitalization in patients treated with tafamidis compared to placebo. From October 2021 tafamidis can be prescribed in Italy according to AIFA criteria (only NYHA I/II patients eligible). The aim of our study is to present the experience of our Network in prescribing tafamidis and to compare the clinical baselibe characteristics of our population and the ATTRACT trial population. Methods Thanks to our network , 189 patients with ATTR–CA were referred to our Center. 58 ATTR patients were treated with tafamidis according to AIFA criteria, while 5 patients with variant–TTR and neuropathy received patisiran iv. The causes of exclusion from tafamidis therapy are shown in figure 1. We prospectively collected all the patientst treated with tafamidis from January 2022 until November 2023. All the data about clinical characteristics, laboratoy findings ECG, echo, bone scintigraphy and concomitant treatment were collected during routin follow–up visits anc compared to those of ATTRACT trial population. Results The main findings of our study are summarized in Table (fig,2) The age of our population was similar to that of the patients enrolled in the ATTR–ACT trial (75,94 ± 11.4 vs. 74,5±7.2, P = 0.21). Of note, our population does not include patients in NYHA class III as the AIFA prescriptive criteria exclude these patients from treatment in Italy. this implies a substantial difference in the distribution of the NYHA class compared to the attract population (p = 0.001). The outcome of our patient was excellent, the drug was well tolerated. Conclusions: Implementing specific clinical network provided excellent results, allowing a precise phenotype/genotype characterization and favoring appropriate access to specific disease–modifying drugs.

Tafamidis 61mg Patient Characteristics and Persistency? A Retrospective Analysis of German Statutory Health Insurance Data (IQVIA™ LRx).

Tafamidis is the first drug approved by the European Commission for the treatment of wild-type or hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. Real-world treatment patterns of tafamidis 61mg in Germany are not well studied in patients with ATTR-CM. This was a non-interventional, retrospective, observational cohort study of adult patients in Germany based on the IQVIA pharmacy claims database (IQVIA™ LRx). Patients included in the analysis were statutory insured and received at least one prescription of tafamidis 61mg between March 1, 2020 and August 31, 2022. Treatment adherence was analyzed using the modified medical possession ratio (mMPR) and proportion of days covered (PDC). Overall, 1565 adult patients received at least one tafamidis prescription in the study period. Their mean age was 78.3years, 82.4% were male, and 23.2% were treated by a cardiologist. Persistency rates for patients treated with tafamidis 61mg were high: 78.0% for 12months and 65.1% for 24months after treatment initiation. Patients also had high adherence rate on filling their prescriptions on time: 94.6% and 90.5% of patients had adherence rates of at least 80%, measured by mMPR and PDC, respectively. In the IQVIA™ LRx database, patients prescribed tafamidis 61mg in Germany displayed high adherence and persistency rates, which suggest good drug tolerability and ease of use.

The Effectiveness of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors on Cardiovascular Outcomes and All-Cause Mortality in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to investigate the impact of early sodium-glucose cotransporter-2 (SGLT2) initiation on long-term cardiovascular outcomes and all-cause mortality among patients with acute coronary syndrome (ACS).For this study, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline. Two researchers independently performed a comprehensive literature search on PubMed, Embase, and the Cochrane Library, spanning from the inception of each database to February 24, 2023, without language limitations. The outcomes examined in this meta-analysis comprised major adverse cardiovascular events (MACE) (as defined by individual studies), all-cause mortality, cardiovascular mortality, stroke (ischemic and hemorrhagic), recurrent ACS, and hospitalization due to heart failure (HF). A total of nine studies were included in this meta-analysis.The pooled analysis of nine studies revealed a significant reduction in the risk of MACE, all-cause mortality, cardiovascular mortality, and cardiovascular-related hospitalizations among patients receiving SGLT2 inhibitors (SGLT2i) compared to those in the control group. Additionally, there was a trend towarda lower risk of recurrent ACS in the SGLT2i group, although this difference did not reach statistical significance. The findings of this study suggest a promising therapeutic effect of SGLT2 inhibitors in this population. Further research, particularly focusing on myocardial infarction (MI) patients, is warranted to validate these results and potentially revolutionize ACS management.

Real-World Effectiveness of High-Dose Tafamidis on Neurologic Disease Progression in Mixed-Phenotype Variant Transthyretin Amyloid Cardiomyopathy.

Transthyretin amyloidosis (ATTR) is a progressive, heterogeneous rare disease manifesting as ATTR polyneuropathy (ATTR-PN), ATTR cardiomyopathy (ATTR-CM), or a mixed phenotype. Tafamidis meglumine (20mg po qd) is approved in some markets to delay neurologic progression in ATTR-PN, while high-dose tafamidis (80/61mg po qd) is approved worldwide to reduce cardiovascular mortality and cardiovascular-related hospitalization in ATTR-CM. The objective of this study was to assess the real-world benefit of high-dose tafamidis for delaying neurologic progression in patients with mixed-phenotype variant ATTR-CM (ATTRv-CM). This exploratory, retrospective, observational cohort study evaluated anonymized electronic medical records and included adult patients with mixed-phenotype ATTRv-CM treated with high-dose tafamidis for at least 6months. Neurologic assessments included the Medical Research Council (MRC) Scale for Muscle Strength, Neuropathy Impairment Score (NIS) muscle weakness subscale, and Polyneuropathy Disability (PND) instrument. Modified body mass index (mBMI) was also assessed. Patients (N = 10) started tafamidis treatment an average of 3.8months after diagnosis, with an average treatment duration of 20.8months. Seven of 10 patients demonstrated normal muscle strength on the MRC scale throughout the study, and 9 of 10 patients had no decline in muscle strength during the post-treatment period. The NIS muscle weakness subscale score was ≤ 60 for all patients in the study at all time points, suggesting normal function to mild impairment. Six of 10 patients had no change in walking capacity as measured by the PND instrument at pre- and post-assessments, while one-third of patients had a decrease in PND stage (signaling improvement) from pre- to post-assessment. mBMI remained relatively stable throughout the study. This is the first real-world study to demonstrate the potential value of high-dose tafamidis for delaying neurologic disease progression in patients with mixed-phenotype ATTRv-CM. The findings underscore the importance of multidisciplinary assessment for patients with ATTR amyloidosis. ClinicalTrials.gov: NCT05139680.

Intravenous iron therapy for patients with iron deficiency and heart failure: a systematic review and meta-analysis of randomized controlled trials

Introduction Heart failure (HF) presents a significant health challenge, with intravenous (IV) iron therapy considered a potential treatment avenue. Method We assessed IV iron therapy’s efficacy in HF patients with concurrent iron deficiency versus standard of care. Primary outcomes included the composite of HF hospitalizations or cardiovascular-related mortality, HF hospitalizations, and all-cause, HF, and cardiovascular mortality rates. Secondary measures encompassed improvements in New York Heart Association functional classification, quality of life, 6-minute walk test, left ventricular ejection fraction, and adverse events. We used a random-effects model to compute relative risk (RR) or mean difference (MD) with 95% confidence intervals (CIs). Results Based on an analysis of 14 randomized controlled trials involving 6614 patients, IV iron therapy significantly reduced composite outcome (RR: 0.84, 95% CI: 0.73, 0.96; P = 0.01) and HF hospitalizations (RR: 0.74, 95% CI: 0.61, 0.89; P = 0.002) compared to standard of care. Mortality rates showed no significant difference. IV iron therapy improved New York Heart Association functional classification, quality of life, and 6-minute walk test, with no major impact on left ventricular ejection fraction. Adverse events remained stable. Conclusions IV iron therapy holds promise for diminishing HF hospitalizations and enhancing quality of life and 6-minute walk test in HF patients. Yet, its effect on all-cause or cardiovascular mortalities appears limited.

Association of soluble ST2 Level with 6-month Mortality and/or Recurrent Cardiovascular-Related Hospitalization in Pulmonary Embolism.

The association of soluble suppression of tumorigenesis-2 (sST2) levels with prognosis in pulmonary embolism (PE) is unknown. This study aimed to investigate the relationship between sST2 levels in patients with acute PE and 6-month mortality and recurrent hospitalizations. This prospective study included 100 patients with acute PE. Patients were classified into two groups according to 6-month mortality and the presence of recurrent Cardiovascular-Related hospitalizations. Two groups were compared. A p-value of 0.05 was considered statistically significant. Soluble ST2 levels were significantly higher in the group with mortality and recurrent hospitalizations. (138.6 ng/mL (56.7-236.8) vs. 38 ng/mL (26.3-75.4); p<0.001) The best cut-off threshold for sST2 levels in the prediction of a composite outcome of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization was found to be >89.9 with a specificity of 90.6% and a sensitivity of 65.2%, according to the receiver operating characteristic curve (area under the curve = 0.798; 95% CI, 0.705-0.891; p <0.0001). After adjusting for confounding factors that were either statistically significant in the univariate analysis or for the variables correlated with the sST2 levels, sST2 level (OR = 1.019, 95% CI: 1.009-1.028, p 0.001) and C-reactive protein (CRP ) (OR = 1.010, 95% CI: 1.001-1.021, p = 0.046) continued to be significant predictors of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in the multiple logistic regression model via backward stepwise method. Soluble ST2 level seems to be a biomarker to predict 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in patients with acute PE.

Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy

BackgroundTransthyretin amyloid cardiomyopathy is characterized by the deposition of misfolded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo.MethodsIn this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein–Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire–Overall Summary, and the serum TTR level.ResultsA total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0%). The overall incidence of adverse events was similar in the acoramidis group and the placebo group (98.1% and 97.6%, respectively); serious adverse events were reported in 54.6% and 64.9% of the patients.ConclusionsIn patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.)

Direct oral anticoagulant use in hospitalized patients with atrial fibrillation across body mass index categories: design and rationale for a retrospective cohort study.

Atrial fibrillation (AF) and obesity are common conditions globally; yet, there remains suboptimal pharmacological management contributing to high rates of hospitalization in patients with AF. The altered pathophysiology of both obese and underweight individuals may influence the pharmacology of medications, including those used to manage AF. This, in turn, increases the risk of adverse events and impacts patient risk for stroke and rehospitalization. Despite the well-established complications of obesity, research investigating the relationship between obesity and AF is scant. The primary aim of this study is to describe cardiovascular-related hospitalization in AF patients according to BMI categories. A secondary aim is to describe anticoagulant and antiarrhythmic prescribing practice patterns in patients with AF, according to the BMI category. A retrospective, exploratory descriptive observational cohort study, using routinely collected electronic medical record data from five public hospitals within a single health district, with a population dominantly that is culturally and linguistically diverse, and has a low socioeconomic status. Data extraction will include a 24-month period (January 2017 to December 2018) with a 12-month follow-up. All adult (⩾18 years) patients at discharge diagnosed with AF, prescribed any oral anticoagulant and/or oral rate/rhythm control agent, will be eligible for inclusion. Ethics approval from the health district and the University of Wollongong has been granted. Findings will seek to demonstrate associations between management strategies and patient outcomes, as well as describe patterns of acute care management from prescribers. These data will be used to inform and generate hypotheses for large-scale studies examining the impact of body weight on anticoagulation prescribing at national and global scales.

Intensive Versus Traditional Cardiac Rehabilitation: Mortality and Cardiovascular Outcomes in a 2016-2020 Retrospective Medicare Cohort.

Traditional cardiac rehabilitation (CR) improves cardiovascular outcomes and reduces mortality, but less is known about the relative benefit of intensive CR (ICR) which incorporates greater lifestyle education through 72 sessions (versus 36 in CR). Our objective was to determine whether ICR is associated with a mortality and cardiovascular benefit compared with CR. Retrospective cohort study of Medicare Fee-For-Service beneficiaries in a 100% sample, claims data set. Qualifying events were captured from May 1, 2016 to December 31, 2019 and ICR/CR utilization captured from May 1, 2016 to December 31, 2020. Among patients attending at least 1 day of either CR or ICR, Cox proportional hazards models using a 1 to 5 propensity score match were used to compare utilization and the association of ICR versus CR participation with (1) all-cause mortality and (2) cardiovascular-related hospitalizations or nonfatal cardiac events. Dose-response was assessed by the number of days attended. From 2016 to 2019, 1 277 358 unique patients met at least one qualifying indication for ICR/CR from 2016 to 2019. Of these, 262 579 (20.6%) and 4452 (0.4%) attended at least one session of CR or ICR, respectively (mean [SD] age, 73.2 [7.8] years; 32.3% female). In the matched sample, including 26 659 total patients (median, 2.4-year follow-up), ICR was associated with 12% lower all-cause mortality (multivariable adjusted hazard ratio, 0.88 [95% CI, 0.78-0.99]; P=0.036) compared with CR but no significant difference for cardiovascular-related hospitalization or nonfatal cardiac events. The mortality benefit was seen for both ICR and CR per day strata, with each modality demonstrating a clear dose-response benefit. ICR is associated with lower mortality than traditional CR among Medicare beneficiaries but no difference in cardiovascular-related hospitalization or nonfatal cardiac events. Moreover, ICR and CR demonstrate a dose-response relationship for mortality. Additional studies are needed to confirm these observations and to better understand the mechanisms by which ICR may lead to a reduction in mortality.

Association of Remote Patient Monitoring with Mortality and Healthcare Utilization in Hypertensive Patients: a Medicare Claims–Based Study

BackgroundHypertension management is complex in older adults. Recent advances in remote patient monitoring (RPM) have warranted evaluation of RPM use and patient outcomes.ObjectiveTo study associations of RPM use with mortality and healthcare utilization measures of hospitalizations, emergency department (ED) utilization, and outpatient visits.DesignA retrospective cohort study.PatientsMedicare beneficiaries aged ≥65 years with an outpatient hypertension diagnosis between July 2018 and September 2020. The first date of RPM use with a corresponding hypertension diagnosis was recorded (index date). RPM non-users were documented from those with an outpatient hypertension diagnosis; a random visit was selected as the index date. Six months prior continuous enrollment was required.Main MeasuresOutcomes studied within 180 days of index date included (i) all-cause mortality, (ii) any hospitalization, (iii) cardiovascular-related hospitalization, (iv) non-cardiovascular-related hospitalization, (v) any ED, (vi) cardiovascular-related ED, (vii) non-cardiovascular-related ED, (viii) any outpatient, (ix) cardiovascular-related outpatient, and (x) non-cardiovascular-related outpatient. Patient demographics and clinical variables were collected from baseline and index date. Propensity score matching (1:4) and Cox regression were performed. Hazard ratios (HR) and 95% confidence intervals (CI) are reported.Key ResultsThe matched sample had 16,339 and 63,333 users and non-users, respectively. Cumulative incidences of mortality outcome were 2.9% (RPM) and 4.3% (non-RPM), with a HR (95% CI) of 0.66 (0.60–0.74). RPM users had lower hazards of any [0.78 (0.75–0.82)], cardiovascular-related [0.79 (0.73–0.87)], and non-cardiovascular-related [0.79 (0.75–0.83)] hospitalizations. No significant association was observed between RPM use and the three ED measures. RPM users had higher hazards of any [1.10 (1.08–1.11)] and cardiovascular-related outpatient visits [2.17 (2.13–2.19)], while a slightly lower hazard of non-cardiovascular-related outpatient visits [0.94 (0.93–0.96)].ConclusionsRPM use was associated with substantial reductions in hazards of mortality and hospitalization outcomes with an increase in cardiovascular-related outpatient visits.

Cost Analysis of Remote Cardiac Rehabilitation Compared With Facility-Based Cardiac Rehabilitation for Coronary Artery Disease

Remote cardiac rehabilitation (RCR) represents a promising, noninferior alternative to facility-based cardiac rehabilitation (FBCR). The comparable cost of RCR in US populations has yet to be extensively studied. The purpose of this prospective, patient-selected study of traditional FBCR versus a third-party asynchronous RCR platform was to assess whether RCR can be administered at a comparable cost and clinical efficacy to FBCR. Adult insured patients were eligible for enrollment after an admission for a coronary heart disease event. Patients selected either FBCR or Movn RCR, a 12-week telehealth intervention using an app-based platform and internet-capable medical devices. Clinical demographics, intervention adherence, cost-effectiveness, and hospitalizations at 1-year after enrollment were assessed from the Highmark claims database after propensity matching between groups. A total of 260 patients were included and 171 of those eligible (65.8%) received at least 1 cardiac rehabilitation session and half of the patients chose Movn RCR. The propensity matching produced a sample of 41 matched pairs. Movn RCR led to a faster enrollment and higher completion rates (80% vs 50%). The total medical costs were similar between Movn RCR and FBCR, although tended toward cost savings with Movn RCR ($10,574/patient). The cost of cardiac rehabilitation was lower in those enrolled in Movn RCR ($1,377/patient, p=0.002). The all-cause and cardiovascular-related hospitalizations or emergency department visits in the year after enrollment in both groups were similar. In conclusion, this pragmatic study of patients after a coronary heart disease event led to equivalent total medical costs and lower intervention costs for an asynchronous RCR platform than traditional FBCR while maintaining similar clinically important outcomes.

Echocardiography-based risk score predicts cardiovascular outcomes in ischemic heart failure patients with reduced ejection fraction

Abstract Background Ischemic heart disease (IHD) is the most common cause of heart failure (HF) and serves as an important prognostic factor across the whole HF spectrum. Prognostic assessment is important for optimal patient care, and a number of prediction models or prognostic scores have been developed in the past years for risk stratification of HF patients. Purpose Present study aimed to develop a comprehensive echocardiography-based score algorism for risk assessment of ischemic heart failure (IHF) patients with reduced left ventricular ejection fraction (&amp;lt;50%). Methods This study included 1355 IHF patients with ejection fraction &amp;lt;50%, the median clinical follow-up was 25 months. Multivariable Cox hazard models were used to assess the associations between echocardiography variables [including 13 standard parameters and global longitudinal strain (GLS)] and major adverse outcomes [including all-cause mortality, cardiovascular (CV) death, and CV related hospitalization]. Results Rates of all-cause mortality, CV mortality, and combined CV events including death and hospitalization, were 29.2%, 18.2%, 41.1%, respectively. Right ventricular mid-cavity diameter (RVD)&amp;gt;38mm, mitral annular plane systolic excursion (MAPSE)&amp;lt;8mm, tricuspid annular plane systolic excursion (TAPSE)&amp;lt;12mm, transmitral early flow velocity to mitral annular velocity ratio (E/E´)&amp;gt;14.5, systolic pulmonary artery pressure (sPAP)&amp;gt;38mmHg, and absolute GLS&amp;lt;8% were identified as independent echocardiographic indexes for worse clinical outcome in the multivariable Cox models. An echocardiography-based risk score (Echo Risk Score, ranged from 0 to 6 points) was established based on these markers and patients were classified into 3 risk groups: a score of 0 to 1 as low-risk, 2 to 3 as intermediate-risk, and 4-6 as high-risk. After adjustment for all clinical covariates, high-risk patients faced 2 to 3-fold increased risk of all-cause mortality (HR 2.42, 95% CI 1.81-3.24), CV mortality (HR 2.75, 95% CI 1.88-4.02), and combined CV events (HR 1.84, 95% CI 1.43-2.36) compared with low-risk patients. Incremental predicting efficacy was evidenced after the addition of Echo Risk Score either to the model including clinical risk factors or to the model including clinical risk factors and N-terminal prohormone of brain natriuretic peptide (all P&amp;lt;0.001, Figure 1). Conclusions This new echocardiography-based risk score is significantly and independently associated with all-cause mortality and CV mortality or hospitalization in ischemic heart failure patients with reduced ejection fraction. Future studies are warranted to validate the predicting efficacy of this echocardiography-based risk score in ischemic heart failure patients with reduced ejection fraction.Figure 1

Tafamidis Efficacy Among Octogenarian Patients in the Phase 3 ATTR-ACT and Ongoing Long-Term Extension Study

BackgroundTafamidis was approved to treat patients with transthyretin amyloid cardiomyopathy (ATTR-CM) on the basis of findings from the phase 3 Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). ObjectivesThis study was a post hoc analysis exploring tafamidis efficacy in octogenarian patients. MethodsAnalysis of patients aged <80 and ≥80 years in ATTR-ACT and its ongoing open-label long-term extension (LTE) study, where all patients receive tafamidis. ResultsAfter 30 months in ATTR-ACT, least squares (LS) mean change from baseline in 6-minute walk test (6MWT) distance, N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration, and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score were smaller (all P < 0.05) in patients aged ≥80 years treated with tafamidis (n = 51) vs placebo (n = 37). At the LTE study interim analysis, patients aged ≥80 years treated continuously with tafamidis had a smaller decline in KCCQ-OS score (P < 0.05) and trended toward longer median survival (45 vs 27 months; all-cause mortality HR: 0.6828 [95% CI: 0.4048-1.1517]; P = 0.1526) than those initially treated with placebo in ATTR-ACT. Similar efficacy was observed in patients aged <80 years in ATTR-ACT, including smaller LS mean change from baseline in 6MWT distance, NT-proBNP concentration, and KCCQ-OS score, and lower rate of cardiovascular-related hospitalizations with tafamidis (n = 125) vs placebo (n = 140). In the LTE study, patients aged <80 years treated continuously with tafamidis had a longer median survival (80 vs 41 months; HR = 0.4513 [95% CI: 0.3176-0.6413]; P < 0.0001) and a smaller decline in KCCQ-OS score than those initially treated with placebo. ConclusionsThe findings demonstrate tafamidis efficacy for patients with ATTR-CM both in those aged <80 and those aged ≥80 years. (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial [ATTR-ACT]; NCT01994889/Long-term Safety of Tafamidis in Subjects With Transthyretin Cardiomyopathy; NCT02791230)

Abstract 15363: Equivalent Total Medical Costs Between Remote Cardiac Rehabilitation and Facility-Based Cardiac Rehabilitation

Purpose: Remote cardiac rehabilitation (RCR) represents a promising, non-inferior alternative to facility-based cardiac rehabilitation (FBCR). The comparable cost of RCR in US populations has not been previously studied. The purpose of this prospective, patient-selected study of traditional FBCR vs. a 3 rd party RCR platform was to assess whether RCR can be administered at comparable cost and clinical efficacy to FBCR. Methods: Adult insured patients were eligible for enrollment following an admission for a coronary event. Patients selected either FBCR or Movn RCR, a 12-week telehealth intervention using an app-based platform and internet-capable medical devices. Clinical demographics, intervention adherence, cost-effectiveness, and hospitalizations at 1-year post-enrollment were assessed from the Highmark claims database following propensity matching between groups. Results: A total of 260 patients were included, and 171 (65.8%) of those eligible received at least one cardiac rehab session, half of those choosing Movn RCR. Propensity matching produced a sample of 41 matched pairs between FBCR and RCR groups. Movn RCR led to quicker program initiation and higher completion rates (80% vs. 50%). Total medical costs were similar between Movn RCR and FBCR, though tended toward cost savings with Movn RCR ($10,574/patient). Cost of cardiac rehabilitation was lower in those enrolled in Movn RCR ($1377/patient, p=0.002). All-cause and cardiovascular-related hospitalizations or ED visits in the year following enrollment in both groups were similar. Conclusions: This pragmatic study of patients after a coronary event led to equivalent total medical costs and lower intervention costs for an RCR platform when compared to traditional FBCR while maintaining similar clinically important outcomes.

Abstract 16556: Tafamidis: A Game Changer in Transthyretin Cardiomyopathy? A Systematic Review of Efficacy and Safety

Introduction: FDA approval of tafamidis as a treatment for Transthyretin cardiomyopathy (ATTR-CM) was preceded by demonstrating clinical efficacy and safety based on double-blind trials that showed reduction in mortality, and cardiovascular-related hospitalization. We conducted a systematic review to assess the safety and efficacy using present literature. Methods: 7 studies were included in this meta-analysis from PubMed and Embase comparing tafamidis treatment to no tafamidis for ATTR-CM. Mantel-Haenszel method was used to calculate pooled log odds-ratio (OR) for binary outcomes and Hedges’ g using inverse-variance method for continuous outcomes. Results: Tafamidis was associated with decreased odds of mortality (OR 0.55, 95% CI 0.42-0.73, I2=41%, p&lt;0.0001) and reduced CHF exacerbations (OR 0.71, 95% CI 0.51-0.99, I2= 0%, p= 0.04). While, CHR related hospitalizations (OR 0.35, 95% CI 0.07-1.67, I2= 87%, p= 0.19), atrial arrythmias (OR 0.98, 95% CI 0.67-1.42, I2= 0%, p= 0.9), change in left ventricular ejection fraction (OR 0.78, 95% CI -0.32-1.87, I2= 91%, p= 0.16), left ventricular end-diastolic diameter (OR -0.12, 95% CI -0.41-0.18, I2= 0%, p= 0.4), interventricular septal thickness from baseline (OR -0.26, 95% CI 0.56-0.04, I2= 0%, p= 0.08) were not statistically different for tafamidis compared to no tafamidis for ATTR-CM. Conclusion: Tafamidis treatment in ATTR-CM is associated with reduced all-cause mortality and CHF exacerbation. These observations are consistent with the ATTRACT trial supporting the efficacy of tafamidis in the treatment of ATTR-CM.

Abstract 13338: Intravenous Iron for Patients With Iron Deficiency and Acute or Chronic Heart Failure, a Meta Analysis

Iron deficiency is very common in heart failure (HF), both with preserved and reduced ejection fraction (HFp/rEF); and has significant impact on both symptoms and prognosis. This review highlights the effect of use of intravenous iron (IVI) therapy in patients with HFrEF Several databases were searched to identify RCTs that investigate the efficacy and safety of IVI therapy in patients with acute or chronic HF. A meta-analysis was performed using RevMan using random effect model. We used the odds ratio (OR) and mean difference (MD) for dichotomous and continuous outcomes, respectively presented with the corresponding 95% confidence interval (CI). A total of 18 studies were included with 3,436 patients with mean age of 68 years old. There was no statistically significant difference between IVI and placebo in terms of cardiovascular death or all-cause hospital admission. However, IVI was associated with statistically significant lower risk for hospitalization for any cardiovascular disorder and all cause death with OR 0.42 [95% CI 0.28, 0.64, p&lt;0.0001] and 0.61 [95% CI 0.39, 0.96, p=0.03], respectively. Additionally, there was statistically significant variation in serum ferritin and serum transferrin from baseline favoring intravenous iron with MD -189.62 [95%CI -236.55, -142.69, p=0.01], and -7.65 [95% CI -13.43, -1.87, p=0.009], respectively. Furthermore, IVI was associated with a significant improvement in HF patients’ functional status, evaluated by both Kansas City Cardiomyopathy Questionnaire (KCCQ), and changes from baseline in left ventricular ejection fraction (LVEF) with MD -7.14 [95% CI -10.52, -3.76, p&lt;0.0001], and 3.76 [95% CI 2.32, 5.21, p&lt;0.00001], respectively. Our meta-analysis demonstrated the capability of IVI to improve clinically meaningful outcomes as HF-related cardiovascular-related hospitalization as well as functional status; however, intravenous iron showed no difference in term of mortality.

Clonal Hematopoiesis in Clinical and Experimental Heart Failure With Preserved Ejection Fraction.

Clonal hematopoiesis (CH), which results from an array of nonmalignant driver gene mutations, can lead to altered immune cell function and chronic disease, and has been associated with worse outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the role of CH in the prognosis of HF with preserved ejection fraction (HFpEF) has been understudied. This study aimed to characterize CH in patients with HFpEF and elucidate its causal role in a murine model. Using a panel of 20 candidate CH driver genes and a variant allele fraction cutoff of 0.5%, ultradeep error-corrected sequencing identified CH in a cohort of 81 patients with HFpEF (mean age, 71±6 years; ejection fraction, 63±5%) and 36 controls without a diagnosis of HFpEF (mean age, 74±7 years; ejection fraction, 61.5±8%). CH was also evaluated in a replication cohort of 59 individuals with HFpEF. Compared with controls, there was an enrichment of TET2-mediated CH in the HFpEF patient cohort (12% versus 0%, respectively; P=0.02). In the HFpEF cohort, patients with CH exhibited exacerbated diastolic dysfunction in terms of E/e' (14.9 versus 11.7, respectively; P=0.0096) and E/A (1.69 versus 0.89, respectively; P=0.0206) compared with those without CH. The association of CH with exacerbated diastolic dysfunction was corroborated in a validation cohort of individuals with HFpEF. In accordance, patients with HFpEF, an age ≥70 years, and CH exhibited worse prognosis in terms of 5-year cardiovascular-related hospitalization rate (hazard ratio, 5.06; P=0.042) compared with patients with HFpEF and an age ≥70 years without CH. To investigate the causal role of CH in HFpEF, nonconditioned mice underwent adoptive transfer with Tet2-wild-type or Tet2-deficient bone marrow and were subsequently subjected to a high-fat diet/L-NAME (Nω-nitro-l-arginine methyl ester) combination treatment to induce features of HFpEF. This model of Tet2-CH exacerbated cardiac hypertrophy by heart weight/tibia length and cardiomyocyte size, diastolic dysfunction by E/e' and left ventricular end-diastolic pressure, and cardiac fibrosis compared with the Tet2-wild-type condition. CH is associated with worse heart function and prognosis in patients with HFpEF, and a murine experimental model of Tet2-mediated CH displays greater features of HFpEF.

Effect of Furosemide Versus Torsemide on Hospitalizations and Mortality in Patients With Heart Failure: A Meta-Analysis of Randomized Controlled Trials

Loop diuretics are essential in the treatment of patients with heart failure (HF) who develop congestion. Furosemide is the most commonly used diuretic; however, some randomized controlled trials (RCTs) have shown varying results associated with torsemide and furosemide in terms of hospitalizations and mortality. We performed an updated meta-analysis of currently available RCTs comparing furosemide and torsemide to see if there is any difference in clinical outcomes in patients treated with these loop diuretics. PubMed, MEDLINE, Cochrane, and Embase databases were searched for RCTs comparing the outcomes in patients with HF treated with furosemide versus torsemide. The primary end points included all-cause mortality, all-cause hospitalizations, cardiovascular-related hospitalizations, and HF-related hospitalizations. A random-effects meta-analysis was performed to estimate the risk ratio (RR) with a 95% confidence interval (CI). A total of 10 RCTs with 4,127 patients (2,088 in the furosemide group and 2,039 in the torsemide group) were included in this analysis. A total of 56% of the patients were men and the mean age was 68years. No significant difference was noted in all-cause mortality between the furosemide and torsemide groups (RR 1.02, 95% CI 0.91 to 1.15, p=0.70); however, patients treated with furosemide compared with torsemide had higher risks of cardiovascular hospitalizations (RR 1.36, 95% CI 1.13 to 1.65, p=0.001), HF-related hospitalizations (RR 1.65, 95% CI 1.21 to 2.24, p=0.001), and all-cause hospitalizations (RR 1.06, 95% CI 1.01 to 1.11, p=0.02). In conclusion, patients with HF treated with torsemide have a reduced risk of hospitalizations compared with those treated with furosemide, without any difference in mortality. These data indicate that torsemide may be a better choice to treat patients with HF.

Primary and secondary prevention in hypercholesterolemia: differences relevant to patient care in the PROCYON trial

Cardiovascular disease accounts for one third of deaths in Germany. Elevated levels of low-density lipoprotein cholesterol (LDL-C) are considered a major risk factor. Lowering LDL-C levels is therefore an integral part of the prevention of cardiovascular events. The aim of this work is to identify potential differences between primary prevention (PP) and secondary prevention (SP) by means of a post-hoc comparison of cross-sectional data from the PROCYON survey. Medical history, concomitant diseases, adherence, and disease awareness in relation to hypercholesterolemia were queried. 5,494 patients had participated in the survey (PP: 3,798; SP: 1,696). Comparison of the results showed a numerically higher proportion of women (PP 70.7% vs. SP 42.5%) as well as more frequent comorbidities such as hypertension (PP 45.6% vs. SP 61.0%), obesity (PP 20.9% vs. SP 27.4%), and type 2 diabetes mellitus (PP 14.1% vs. SP 23.8%). In primary prevention, hypercholesterolemia was most often diagnosed during screening (PP 74.6%), and in secondary prevention, the diagnosis was most often made during cardiovascular-related hospitalization (SP 58.0%). A cardiologist was consulted by 16.3% (PP) and 54.0% (SP) of patients, respectively. At least semiannual LDL-C checks (PP 46.8% vs. SP 77.9%) and drug intervention (PP 43.0% vs. SP 87.0%) were more frequent in the secondary prevention group. In addition, differences in the implementation of lifestyle changes, improvement of LDL-C levels, adjustment of therapy as well as adherence, treatment satisfaction and patient knowledge were observed. The comparison of primary and secondary prevention from the PROCYON survey shows overall better utilization of treatment options and higher intensity of care in the secondary prevention group. However, there is still great potential for improvement in both groups to ensure efficient prevention of cardiovascular events.

The effect of Remote Monitor vs Standard of Care therapy on outcome A systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Project no. RRF-2.3.1-21-2022-00004 (MILAB) has been implemented with the support provided by the European Union. Background Remote monitoring (RM) in heart failure (HF) patients with cardiac implantable electronic devices (CIED) is a reliable approach to strictly following the device-specific and heart failure-related parameters. Despite a few positive outcome data, results are incomprehensive. Aims We aimed to assess the benefit of continuous RM vs. standard of care (SoC) in the reduction of all-cause mortality, heart failure hospitalization (HF), and cardiovascular-related hospitalization (CV), and inappropriate therapy. Methods A systematic review and meta-analysis of randomized controlled trials (RCT) testing RM vs. SoC for the management of HF patients were performed. Endpoints were all-cause mortality, CV- and HF hospitalizations and inappropriate therapy. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated. CENTRAL, EMBASE and MEDLINE were searched up to 21th of December 2021. Only randomized controlled studies were included. Results Fourteen RCTs that enrolled a total of 8370 patients were identified to evaluate all-cause mortality, resulting in an OR 0.88 (95% CI 0.75 to 1.03). When CV - and HF hospitalizations were assessed, there were no differences between the RM group and SoC group, and the OR was 0.93 (95% CI 0.82 to 1.05) and 0.95 (95% CI 0.75 to 1.19), respectively.Moreover RM did not have an effect on the rate of inappropriate therapy, OR was 0.73. (95% CI 0.30 to 1.81). Conclusions RM proved to be non-inferior in reducing all-cause mortality, CV- and HF hospitalization and rate of inappropriate therapy when compared to standard of care despite of the heterogeneous study cohorts and unstandardized alert actions.