MUTTON-HF: Rationale and Design of a Study of an Indigenous Food is Medicine Intervention.

Improvements in Health Status Associated with Medication Adjustments in Outpatients with HFrEF: Insights from the CHAMP-HF Registry

BackgroundDiabetes mellitus (DM), chronic kidney disease (CKD), and heart failure (HF) are pathophysiologically linked and increasing in prevalence in Asian populations, but little is known about the interplay of DM and CKD on outcomes in HF. ObjectivesThis study sought to investigate outcomes in patients with heart failure with preserved ejection fraction (HFpEF) vs heart failure with reduced ejection fraction (HFrEF) in relation to the presence of DM and CKD. MethodsUsing the multinational ASIAN-HF registry, we investigated associations between DM only, CKD only, and DM+CKD with: 1) composite of 1-year mortality or HF hospitalization; and 2) Kansas City Cardiomyopathy Questionnaire scores, according to HF subtype. ResultsIn 5,239 patients with HF (74.6% HFrEF, 25.4% HFpEF; mean age 63 years; 29.1% female), 1,107 (21.1%) had DM only, 1,087 (20.7%) had CKD only, and 1,400 (26.7%) had DM+CKD. Compared with patients without DM nor CKD, DM+CKD was associated with 1-year all-cause mortality or HF hospitalization in HFrEF (adjusted HR: 2.07; 95% CI: 1.68-2.55) and HFpEF (HR: 2.37; 95% CI: 1.40-4.02). In HFrEF, DM only and CKD only were associated with 1-year all-cause mortality or HF hospitalization (both HRs: 1.43; 95% CI: 1.14-1.80), while in HFpEF, CKD only (HR: 2.54; 95% CI: 1.46-4.41) but not DM only (HR: 1.01; 95% CI: 0.52-1.95) was associated with increased risk (interaction P < 0.01). Adjusted Kansas City Cardiomyopathy Questionnaire scores were lower in patients with DM+CKD (HFrEF: mean 60.50, SEM 0.77, HFpEF: mean 70.10, SEM 1.06; P < 0.001) than with no DM or CKD (HFrEF: mean 66.00, SEM 0.65; and HFpEF: mean 75.80, SEM 0.99). ConclusionsCombined DM and CKD adversely effected outcomes independently of HF subtype, with CKD a consistent predictor of worse outcomes. Strategies to prevent and treat DM and CKD in HF are urgently required.

Sodium-glucose cotransporter-2 inhibitors are foundational therapy in patients with heart failure with reduced ejection fraction (HFrEF), but underlying mechanisms of benefit are not well defined. We sought to investigate the relationships between sodium-glucose cotransporter-2 inhibitor treatment, changes in metabolic pathways, and outcomes using targeted metabolomics. DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients With HF With Reduced Ejection Fraction) was a placebo-controlled trial of dapagliflozin in HFrEF. We performed targeted mass spectrometry profiling of 63 metabolites (45 acylcarnitines [markers of fatty acid oxidation], 15 amino acids, and 3 conventional metabolites) in plasma samples at randomization and 12 weeks. Using mixed models, we identified principal components analysis-defined metabolite clusters that changed differentially with treatment and examined the relationship between change in metabolite clusters and change in Kansas City Cardiomyopathy Questionnaire scores and NT-proBNP (N-terminal probrain natriuretic peptide). Models were adjusted for relevant clinical covariates and nominal P<0.05 with false discovery rate-adjusted P<0.10 was used to determine statistical significance. Among the 234 DEFINE-HF participants with targeted metabolomic data, the mean age was 62.0±11.1 years, 25% were women, 38% were Black, and mean ejection fraction was 27±8%. Dapagliflozin increased ketone-related and short-chain acylcarnitine as well as medium-chain acylcarnitine principal components analysis-defined metabolite clusters compared with placebo (nominal P=0.01, false discovery rate-adjusted P=0.08 for both clusters). However, ketosis (β-hydroxybutyrate levels >500 μmol/L) was achieved infrequently (3 [2.5%] in dapagliflozin arm versus 1 [0.9%] in placebo arm) and supraphysiologic levels were not observed. Increases in long-chain acylcarnitine, long-chain dicarboxylacylcarnitine, and aromatic amino acid metabolite clusters were associated with decreases in Kansas City Cardiomyopathy Questionnaire scores (ie, worse quality of life) and increases in NT-proBNP levels, without interaction by treatment group. In this study of targeted metabolomics in a placebo-controlled trial of sodium-glucose cotransporter-2 inhibitors in HFrEF, we observed effects of dapagliflozin on key metabolic pathways, supporting a role for altered ketone and fatty acid biology with sodium-glucose cotransporter-2 inhibitors in patients with HFrEF. Only physiologic levels of ketosis were observed. In addition, we identified several metabolic biomarkers associated with adverse HFrEF outcomes. URL: https://www. gov; Unique identifier: NCT02653482.

Background The COMPASS trial showed that rivaroxaban plus aspirin was associated with fewer adverse cardiovascular events, but more major bleeding events, as compared with aspirin alone in patients with chronic vascular disease. The clinical benefit was particularly favorable in high-risk subgroups, who are frequently undertreated because of the fear of severe bleeding events. Purpose Our aim is to evaluate objective effects of anticoagulation strategies with rivaroxaban among patients with stable cardiovascular disease. Methods We considered a population of patients with stable cardiovascular disease (coronary and/or peripheral artery disease) which has had dual antiplatelet therapy (DAPT) for 1 year. Between them we selected 65 patients (52 males and 13 females, mean age 59±7 years) with high risk of ischemic events and low bleeding risk. We used DAPT Score and HAS BLED Score to enroll patients. We stopped them DAPT and starting a dual therapy combining rivaroxaban 2,5 mg twice daily plus aspirin 100 mg. We excluded patients with high bleeding risk and heart failure with less than 35% ejection fraction. At baseline they underwent blood tests, transthoracic echocardiography, six minutes walking test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ) Score, evaluation of carotid– femoral pulse wave velocity (cf-PWV) and ankle brachial index (ABI). We established 3, 6 and 12 months follow-up. Results At 3 months follow-up we evaluated 41 patients (the study is going on) repeating those exams and comparing them with the baseline ones. We observed that 35% of population had reduction of cf-PWV values and in 40% of population ABI increased. 15% of patients had also improvement of more than 100 meters in 6MWT. Particularly, reduction of cf-PWV and improvement of ABI values suggest that rivaroxaban 2,5 mg twice daily may have effects on vascular protection and arterial stiffness through different mechanisms such as improvement of endothelial functionality and fibrinolytic activity at endothelium, anti-inflammatory properties and platelet-dependent thrombin generation. Nevertheless none of the patients experienced subjective clinical improvement and the KCCQ Score was unmodified. This element indicates that patients at 3 months follow-up have imperceptible changes that can be documented only by diagnostic imaging evaluation and not by anamnestic data. Finally, an important evidence was that none of the patients at 3 months follow-up reported major bleeding events. Conclusion Preliminary data suggest that the addiction of rivaroxaban 2,5 mg to aspirin exerts vascular protection and its effects can be primarly documented by evaluation of cf-PWV and ABI. The 6MWT seems to play a minor role at 3 months assessment. The KCCQ may not be useful to fill in at 3 months follow-up because patients seem not to perceive subjective clinical improvement in this phase. If confirmed on a large cohort these results may give rivaroxaban a higher relevance not only for the power but also for the immediacy of its effects. Anyway, we are continuing our check to give our data more statistical significance and to test any role of the other parameters at 6 and 12 months follow-up.

Patient-reported and morbidity-mortality endpoints: can one have the best of both worlds?

BackgroundThe Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF‐15 (growth differentiation factor‐15), galectin‐3, sST2 (soluble suppression of tumorigenesis‐2), hsTnT (high‐sensitivity troponin T), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known.Methods and ResultsWe studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score <75 at year 1 and (2) incident decline in KCCQ score to <75. We used multivariable logistic regression and Cox regression models to evaluate the associations between baseline cardiac biomarkers and cross‐sectional and longitudinal KCCQ scores. Among 2873 participants, GDF‐15 (adjusted odds ratio 1.42 per SD; 99% CI, 1.19–1.68) and galectin‐3 (1.28; 1.12–1.48) were significantly associated with KCCQ scores <75, whereas sST2, hsTnT, and NT‐proBNP were not significantly associated with KCCQ scores <75 after multivariable adjustment. Of the 2132 participants with KCCQ ≥75 at year 1, GDF‐15 (adjusted hazard ratio, 1.36 per SD; 99% CI, 1.12–1.65), hsTnT (1.20; 1.01–1.44), and NT‐proBNP (1.30; 1.08–1.56) were associated with incident decline in KCCQ to <75 after multivariable adjustment, whereas galectin‐3 and sST2 did not have significant associations with KCCQ decline.ConclusionsAmong participants with CKD without clinical HF, GDF‐15, galectin‐3, NT‐proBNP, and hsTnT were associated with low KCCQ either at baseline or during follow‐up. Our findings show that elevations in cardiac biomarkers reflect early symptomatic changes in HF health status in CKD patients.

BackgroundExacerbation of chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) are associated with high health care costs owing to increased emergency room (ER) visits and hospitalizations. Remote patient monitoring (RPM) interventions aim to improve the monitoring of symptoms to detect early deterioration and provide self-management strategies. As a result, RPM aims to reduce health resource utilization. To date, studies have inconsistently reported the benefits of RPM in chronic illnesses. The Smart Program is an RPM intervention that aims to provide clinical benefit to patients and economic benefit to health care payers.ObjectiveThis study aims to economically evaluate the potential benefits of the Smart Program in terms of hospitalizations and ER visits and, thus, associated health care costs from the perspective of the public health care system.MethodsSeventy-four patients diagnosed with COPD or CHF from one hospital site were included in this one-group, pre-post study. The study involved a secondary data analysis of deidentified data collected during the study period – from 3 months before program initiation (baseline), during the program, to 3 months after program completion (follow-up). Descriptive analysis was conducted for the study population characteristics at baseline, the clinical frailty score at baseline and 3-month follow-up, client satisfaction at 3-month follow-up, and number and costs of ER visits and hospitalizations throughout the study period. Furthermore, the cost of the Smart Program over a 3-month period was calculated from the perspective of the potential implementer.ResultsThe baseline characteristics of the study population (N=74) showed that the majority of patients had COPD (50/74, 68%), were female (42/74, 57%), and had an average age of 72 (SD 12) years. Using the Wilcoxon signed-rank test, the number of ER visits and hospitalizations, including their associated costs, were significantly reduced between baseline and 3-month follow-up (P<.001). The intervention showed a potential 68% and 35% reduction in ER visits and hospitalizations, respectively, between the 3-month pre- and 3-month postintervention period. The average cost of ER visits reduced from Can $243 at baseline to Can $67 during the 3-month follow-up, and reduced from Can $3842 to Can $1399 for hospitalizations.ConclusionsIn this study, the number and cost of ER visits and hospitalizations appeared to be markedly reduced for patients with COPD or CHF when comparing data before and after the Smart Program implementation. Recognizing the limitations of the one-group, pre-post study design, RPM requires an upfront investment, but it has the potential to reduce health care costs to the system over time. This study represents another piece of evidence to support the potential value of RPM among patients with COPD or CHF.

Patients with heart failure (HF) often have multiple co-morbidities that contribute to the risk of adverse cardiovascular (CV) and non-CV outcomes. We assessed the relative contribution of cardiac and extra-cardiac disease burden and demographic factors to CV outcomes in HF patients with reduced (HFrEF) or preserved (HFpEF) left ventricular ejection fraction (LVEF). We utilized data from the CHARM trial, which enrolled HF patients across the ejection fraction spectrum. We decomposed the previously validated MAGGIC risk score into cardiac (LVEF, New York Heart Association class, systolic blood pressure, time since HF diagnosis, HF medication use), extra-cardiac (body mass index, creatinine, diabetes mellitus, chronic obstructive pulmonary disease, smoker), and demographic (age, gender) categories, and calculated subscores for each patient representing the burden of each component. Cox proportional hazards models were used to estimate the population attributable risk (PAR) associated with each component to the outcomes of death, CV death, HF, myocardial infarction, and stroke relative to patients with the lowest risk score. PARs for each component were depicted across the spectrum of LVEF. in 2675 chronic HF patients from North America [HFrEF (LVEF ≤40%): n = 1589, HFpEF (LVEF >40%): n = 1086] with data available for calculation of the MAGGIC score, the highest risk of death and CV death was attributed to cardiac burden. This was especially evident in HFrEF patients (PAR: 76% cardiac disease vs. 58% extra-cardiac disease, P < 0.05). Conversely, in HFpEF patients, extra-cardiac burden accounted for a greater proportion of risk for death than cardiac burden (PAR: 15% cardiac disease vs. 49% extra-cardiac disease, P < 0.05). For HF hospitalization, the contribution of both cardiac and extra-cardiac burden was comparable in HFpEF patients (PAR: 42% cardiac disease vs. 53% extra-cardiac disease, P = NS). In addition, demographic burden was especially high in HFpEF patients, with 62% of deaths attributable to demographic characteristics. In North American HF patients enrolled in the CHARM trials, the relative contribution of cardiac and extra-cardiac disease burden to CV outcomes and death differed depending on LVEF. The high risk of events attributable to non-cardiac disease burden may help explain why cardiac disease-modifying medication proven to be efficacious in HFrEF patients has not proven beneficial in HFpEF.

The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been psychometrically evaluated in multiple heart failure (HF) populations, but the comparability of its psychometric properties between men and women is unknown. Data from 3 clinical trials (1 in stable HF with preserved ejection fraction, 1 each in stable and acute HF with reduced ejection fraction) and 1 prospective cohort study (stable HF with reduced ejection fraction), incorporating 6773 men and 3612 women with HF, were used to compare the construct validity, internal and test-retest reliability, ability to detect change, predict mortality and hospitalizations and minimally important differences between the 2 sexes. Interactions of the KCCQ overall summary and subdomain scores by sex were independently examined. The KCCQ-Overall Summary score correlated well with New York Heart Association functional class in both sexes across patients with stable (correlation coefficient: -0.40 in men versus -0.49 in women) and acute (-0.37 in men versus -0.34 in women) HF. All KCCQ subdomains demonstrated concordant relationships with relevant comparison standards with no significant interactions by sex in 19 of 21 of these construct validity analyses. All KCCQ scores were equally predictive and other psychometric evaluations showed similar results by sex: test-retest reliability (intraclass correlation coefficient 0.94 in men versus 0.92 in women), responsive to change (standardized response mean 1.01 in both sexes), as were the minimally important differences and internal reliability. The psychometric properties of the KCCQ, in terms of validity, prognosis, reliability, and sensitivity to change, are comparable in men and women with HF with preserved ejection fraction and HF with reduced ejection fraction.

Introduction: Heart failure (HF) represents a major global health burden characterized by significant morbidity, mortality, and healthcare expenditure. While established therapies exist for HF with reduced ejection fraction (HFrEF), effective treatments for HF with preserved ejection fraction (HFpEF) have been elusive. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially developed as anti-hyperglycemic agents, have emerged as a transformative therapeutic class for HF. This systematic review synthesizes the evidence from landmark clinical trials on the efficacy and safety of SGLT2 inhibitors in improving HF outcomes. Methods: A systematic search of major electronic databases PubMed, Google Scholar, Semanthic Scholar, Springer, Wiley Online Library was conducted to identify large-scale, randomized, double-blind, placebo-controlled trials evaluating SGLT2 inhibitors in patients with HF or those at high risk for HF. Key efficacy outcomes included the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF), its individual components, all-cause mortality, total HHF, renal outcomes, and changes in quality of life. The methodological quality of included trials was assessed using the Cochrane Risk of Bias tool. Results: Sixteen landmark clinical trials and two major meta-analyses were included, encompassing a diverse population of patients with and without type 2 diabetes (T2DM) across the full spectrum of left ventricular ejection fraction (LVEF). The evidence demonstrates a consistent and robust class effect. SGLT2 inhibitors significantly reduce the primary composite outcome of CV death or HHF by approximately 20-25% across all HF phenotypes. This benefit is predominantly driven by a substantial reduction in the risk of first and total HHF, observed in HFrEF (Hazard Ratio ~), HFpEF (HR ~), and in patients with recent worsening HF. A significant reduction in CV death and all-cause mortality was established in patients with HFrEF, with large meta-analyses suggesting a modest mortality benefit across the broader HF population. Furthermore, SGLT2 inhibitors consistently demonstrated profound nephroprotective effects and led to clinically meaningful improvements in patient-reported symptoms and quality of life. The safety profile was generally favorable and consistent across trials. Discussion: The consistent benefits observed across a wide range of patient populations, irrespective of baseline LVEF or diabetes status, have fundamentally altered the HF treatment paradigm. The pleiotropic mechanisms of SGLT2 inhibitors, including hemodynamic, metabolic, and direct myocardial effects, likely contribute to these favorable outcomes. Conclusion: SGLT2 inhibitors have unequivocally been established as a foundational pillar of guideline-directed medical therapy for HF. They significantly reduce the burden of HF hospitalizations, slow the progression of concomitant kidney disease, improve quality of life, and, in HFrEF, reduce mortality.

This systematic review evaluates the effectiveness of the Kansas City Cardiomyopathy Questionnaire (KCCQ) in assessing quality of life improvements among patients with heart failure (HF) undergoing various forms of exercise training rehabilitation, including telemedicine and in-person modalities, across all stages of HF, irrespective of ejection fraction (EF) and clinical status. The aim was to collate evidence from studies employing the KCCQ as a measure of quality of life (QoL). A comprehensive search strategy was implemented across PubMed, Scopus, and Embase databases, adhering to the PRISMA guidelines, including literature up until October 2023. Inclusion criteria encompassed studies on patients diagnosed with HF undergoing exercise training rehabilitation assessed by KCCQ. Nine articles met the inclusion criteria, involving a total of 3905 patients from various global locations and conducted between 2012 and 2022. Results indicated significant heterogeneity in exercise interventions and patient characteristics. Notably, high-intensity interval training (HIIT) showed a marked improvement in KCCQ scores (from 68.0 to 80.0) compared to moderate continuous training (MCT) and control groups, underscoring its potential for enhancing QoL. Additionally, a significant improvement in the 6-min walking test (6MWT) outcomes was observed, with an average increase of 106 m (95% CI: 60, 152) in one study, reflecting physical capacity enhancements. However, the difference in KCCQ scores between intervention and control groups was not statistically significant in several studies. In conclusion, the KCCQ's effectiveness is highlighted by its ability to detect clinically meaningful improvements in QoL across diverse exercise modalities, including HIIT and MCT, tailored to the specific needs of HF populations. The consistent correlation between KCCQ score improvements and enhanced physical outcomes, such as the 6MWT, supports its reliability in capturing the nuanced benefits of exercise interventions on patient well-being.

BackgroundThis systematic review and meta-analysis aimed to explore the effects of different sodium–glucose cotransporter-2 inhibitors (SGLT2i) on prognosis and cardiac structural remodeling in patients with heart failure (HF).MethodsRelevant studies published up to 20 March 2024 were retrieved from PubMed, EMBASE, Web of Science, and Cochrane Library CNKI, China Biomedical Literature Service, VIP, and WanFang databases. We included randomized controlled trials of different SGLT2i and pooled the prognosis data of patients with HF. We compared the efficacy of different SGLT2i in patients with HF and conducted a sub-analysis based on left ventricular ejection fraction (LVEF).ResultsWe identified 77 randomized controlled trials involving 43,561 patients. The results showed that SGLT2i significantly enhanced outcomes in HF, including a composite of hospitalizations for HF and cardiovascular death, individual hospitalizations for HF, Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, left atrial volume index (LAVi), and LVEF among all HF patients (P &amp;lt; 0.05) compared to a placebo. Sotagliflozin was superior to empagliflozin [RR = 0.88, CI (0.79–0.97)] and dapagliflozin [RR = 0.86, CI (0.77–0.96)] in reducing hospitalizations for HF and CV death. Dapagliflozin significantly reduced hospitalizations [RR = 0.51, CI (0.33–0.80)], CV death [RR = 0.73, CI (0.54–0.97)], and all-cause mortality [RR = 0.69, CI (0.48–0.99)] in patients with HF with reduced ejection fraction (HFrEF). SGLT2i also plays a significant role in improving cardiac remodeling and quality of life (LVMi, LVEDV, KCQQ) (P &amp;lt; 0.05). Among patients with HF with preserved ejection fraction (HFpEF), SGLT2i significantly improved cardiac function in HFpEF patients (P &amp;lt; 0.05). In addition, canagliflozin [RR = 0.09, CI (0.01–0.86)] demonstrated greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF patients.ConclusionOur systematic review showed that SGLT2i generally enhances the prognosis of patients with HF. Sotagliflozin demonstrated superiority over empagliflozin and dapagliflozin in a composite of hospitalization for HF and CV death in the overall HF patients. Canagliflozin exhibited greater safety compared to sotagliflozin in a composite of urinary and reproductive infections of HFpEF. Overall, the efficacy of SGLT2i was greater in HFrEF patients than in HFpEF patients.

Background: Prior studies have posited poor patient adherence to remote patient monitoring as the reason for observed lack of benefits. Introduction: The purpose of this study was to examine the relationship between average adherence to the daily use of home telehealth (HT) and emergency room (ER) visits in Veterans with heart failure. Materials and Methods: This was a retrospective study using administrative data of Veterans with heart failure enrolled in Veterans Affairs (VA) HT Program in the first half of 2014. Zero-inflated negative binomial regression was used to determine which predictors affect the probability of having an ER visit and the number of ER visits. Results: The final sample size was 3,449 with most being white and male. There were fewer ER visits after HT enrollment (mean ± standard deviation of 1.85 ± 2.8) compared with the year before (2.2 ± 3.4). Patient adherence was not significantly associated with ER visits. Age and being from a racial minority group (not white or black) and belonging to a large HT program were associated with having an ER visit. Being in poorer health was associated with higher expected count of ER visits. Discussion: Subgroups of patients (e.g., with depression, sicker, or from a racial minority group) may benefit from added interventions to decrease ER use. Conclusions: This study found that adherence was not associated with ER visits. Reasons other than adherence should be considered when looking at ER use in patients with heart failure enrolled in remote patient monitoring programs.

Treatment of Diabetes in People with Heart Failure

Rate-adaptive pacing in right-sided heart failure with tricuspid regurgitation: A prospective pilot study.