Kansas City Research Articles

Gunshot detection technology effect on gun violence in Kansas City, Missouri: A microsynthetic control evaluation

Gunshot detection technology effect on gun violence in Kansas City, Missouri: A microsynthetic control evaluation

Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial

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.

A Pharmacist Medication Titration Program for Patients with Cardiac Sarcoidosis and Systolic Heart Failure: A Retrospective Cohort Study

Background A multidisciplinary approach improves guideline‐directed medical therapy (GDMT) in systolic heart failure (HF), but its efficacy in patients with HF due to cardiac sarcoidosis (CS) is unreported. Methods and Results In a retrospective cohort study, we reviewed 848 patients from our institutional CS clinics, identifying those with a CS diagnosis, HF (LVEF < 50%) at index evaluation, and echocardiograms within 90 days and 11‐36 months. Patients were stratified by participation in a pharmacist‐led medication therapy management (MTM) program for GDMT optimization (MTM vs non‐MTM [NMTM]) without randomization. Demographics, LVEF, GDMT (quantified by Kansas City Medical Optimization [KCMO] score), and immunosuppressive therapy were assessed. Primary outcomes included changes in KCMO score, LVEF, and cardiovascular event‐free survival (unplanned HF hospitalization, LVAD/heart transplant, or death). The final cohort included 111 patients (median age 57 years, 34% female, 64% NYHA Class I‐II); 43 (39%) were MTM and 68 (61%) were NMTM. Mean KCMO score was similar at index evaluation (MTM: 23.2; NMTM: 29.6, p=0.83). At follow‐up (median 16 months), the KCMO score increased significantly in both groups (MTM: 23.2 to 74.8, p<0.001; NMTM: 29.6 to 58.7, p<0.001), but was higher in MTM (p=0.001). Mean LVEF trended towards higher values in MTM (44.4% vs 40.0%, p=0.05). The primary clinical outcome occurred in 1 MTM (2.3%) and 16 NMTM (23.5%) patients, with higher risk in NMTM (HR 11.97 [95%CI 1.58 ‐ 90.54], p=0.002). Conclusions In this retrospective cohort study, a pharmacist‐led MTM program was associated with favorable GDMT optimization and lower risk of adverse cardiovascular outcomes in CS patients with HF.

Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial

AbstractPatients with obesity-related heart failure with preserved ejection fraction (HFpEF) display circulatory volume expansion and pressure overload contributing to cardiovascular–kidney end-organ damage. In the SUMMIT trial, patients with HFpEF and obesity were randomized to the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide (n = 364, 200 women) or placebo (n = 367, 193 women). As reported separately, tirzepatide decreased cardiovascular death or worsening heart failure. Here, in this mechanistic secondary analysis of the SUMMIT trial, tirzepatide treatment at 52 weeks, as compared with placebo, reduced systolic blood pressure (estimated treatment difference (ETD) −5 mmHg, 95% confidence interval (CI) −7 to −3; P < 0.001), decreased estimated blood volume (ETD −0.58 l, 95% CI −0.63 to −0.52; P < 0.001) and reduced C-reactive protein levels (ETD −37.2%, 95% CI −45.7 to −27.3; P < 0.001). These changes were coupled with an increase in estimated glomerular filtration rate (ETD 2.90 ml min−1 1.73 m−2 yr−1, 95% CI 0.94 to 4.86; P = 0.004), a decrease in urine albumin–creatinine ratio (ETD 24 weeks, −25.0%, 95% CI −36 to −13%; P < 0.001; 52 weeks, −15%, 95% CI −28 to 0.1; P = 0.051), a reduction in N-terminal prohormone B-type natriuretic peptide levels (ETD 52 weeks −10.5%, 95% CI −20.7 to 1.0%; P = 0.07) and a reduction in troponin T levels (ETD 52 weeks −10.4%, 95% CI −16.7 to −3.6; P = 0.003). In post hoc exploratory analyses, decreased estimated blood volume with tirzepatide treatment was significantly correlated with decreased blood pressure, reduced microalbuminuria, improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and increased 6-min walk distance. Moreover, decreased C-reactive protein levels were correlated with reduced troponin T levels and improved 6-min walk distance. In conclusion, tirzepatide reduced circulatory volume–pressure overload and systemic inflammation and mitigated cardiovascular–kidney end-organ injury in patients with HFpEF and obesity, providing new insights into the mechanisms of benefit from tirzepatide. ClinicalTrials.gov registration: NCT04847557.

Finerenone in Women and Men With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial.

Sex is associated with the clinical presentation, outcomes, and response to treatment in patients with heart failure (HF). However, little is known about the safety and efficacy of treatment with finerenone according to sex. To estimate the efficacy and safety of finerenone compared with placebo in both women and men. Prespecified analyses were conducted in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF). The trial was conducted across 653 sites in 37 countries. Participants were adults aged 40 years and older with symptomatic HF and left ventricular ejection fraction (LVEF) of 40% or greater randomized between September 2020 and January 2023. Finerenone (titrated to 20 mg or 40 mg) or placebo. The primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events (unplanned HF hospitalizations or urgent HF visits). A total of 6001 patients were randomized in FINEARTS-HF, of whom 2732 were women (45.5%), with a mean (SD) age of 73.6 (9.1) years. Women had higher rates of any obesity, higher LVEF (54.6 [7.6%] vs 50.9 [7.6] for men), lower mean (SD) estimated glomerular filtration rate than men (59.7 [19.1] vs 64.1 [20.0] for men; P<.001) , worse New York Heart Association functional class, and lower Kansas City Cardiomyopathy Questionnaire-Total Symptom Scores (KCCQ-TSS) (mean [SD] 62.3 [24.0] vs 71.0 [23.1]). The incident rate of the primary outcome was slightly lower in women (15.7; 95% CI, 14.3-17.3) than in men (16.8; 95% CI, 15.4-18.3) per 100 person-years. Compared with placebo, finerenone reduced the risk of the primary end point similarly in women and men: rate ratio 0.78 (95% CI, 0.65-0.95) in women and 0.88 (95% CI, 0.74-1.04) in men (P = .41 for interaction). Consistent effects were observed for the components of the primary outcome and all-cause mortality. The mean increase (improvement) in KCCQ-TSS from baseline to 12 months was greater with finerenone, regardless of sex (P = .73 for interaction). Finerenone had similar tolerability in women and men. In FINEARTS-HF, finerenone reduced the risk of the primary end point similarly in women and men with heart failure with mildly reduced or preserved ejection fraction. Finerenone had similar tolerability in women and men. ClinicalTrials.gov Identifier: NCT04435626.

Interpreting Population Mean Treatment Effects in the Kansas City Cardiomyopathy Questionnaire: A Patient-Level Meta-Analysis.

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a commonly used outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean treatment effects do not necessarily reflect the clinical benefit experienced by individual patients. To evaluate the association between mean KCCQ treatment effects and the proportions of patients experiencing clinically important improvements across a range of clinical trials and heart failure etiologies. A patient-level analysis of 11 randomized clinical trials, including 9977 patients, was performed to examine the association between mean treatment effects and the KCCQ Overall Summary Score (OSS) and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate to large (≥10 points) improvements. There was no target date range, and included studies were those for which patient-level data were available. Validation was performed in 7 additional trials. The data were analyzed between July 1 and September 15, 2023. Proportion of patients experiencing an improvement of 5 or more and 10 or more points in their KCCQ score (with each domain transformed to a range of 0 to 100 points, where higher scores represent better health status). Group mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI], 4.0%-8.1%) in the proportion of patients improving 5 or more points and 5.0% (95% PI, 3.1%-7.0%) in the proportion improving 10 or more points, corresponding to a number needed to treat of 17 (95% PI, 12-25) and 20 (95% PI, 14-33), respectively. Inferences about clinical impacts based on population-level mean treatment effects may be misleading, since even small between-group differences may reflect clinically important treatment benefits for individual patients. Results of this study suggest that clinical trials should explicitly describe the distributions of KCCQ change at the patient level within treatment groups to support the clinical interpretation of their results.

Abstract 4128187: Does Health-related Quality of Life Differ by Race over time in Older Patients with Heart Failure from Before to After Heart Transplantation or Long-term Mechanical Circulatory Support?

Background: Minority patients are disproportionately affected by heart failure. Therefore, we aimed to determine the impact of race on health-related quality of life in three groups of older patients (60-80 years) with heart failure who underwent advanced surgical therapies (within race and by surgery group): (1) heart transplantation (HT, with pre-transplant mechanical circulatory support [HT MCS]), (2) HT without pre-transplant MCS (HT Non-MCS), or (3) long-term MCS, if ineligible for HT. Methods: Secondary analyses were conducted using data from the Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support study. From 10/1/15 to 12/31/18, 396 patients with heart failure were recruited at 13 U.S. medical centers, of which 305 patients underwent HT (n=161 [68 HT MCS and 93 HT Non-MCS]) or long-term MCS (n=144) and had data through 1 year follow-up. Analysis included non-inferiority testing (Long-term MCS vs HT MCS; Long-term MCS vs HT Non-MCS). To demonstrate non-inferiority, the surgical strategies by race needed to show a difference of at least 5 percentage points, with a 95% lower confidence boundary and a two-tailed p-value&lt;0.05 in health-related quality of life, using the Kansas City Cardiomyopathy-12 Questionnaire Overall Summary Score at baseline and 3-, 6-, and 12 months. Results: The entire cohort was on average 66.2±4.7 years, 78% male, and 84% White. All three surgical groups experienced improved health-related quality of life from before to 1 year follow-up; with the largest gain through 3-months. Using non-inferiority testing, the long-term MCS minority group did not demonstrate non-inferiority when compared to both the HT MCS minority group and HT Non-MCS minority group confidence limits above the non-inferiority margin of -5 (Figure). Also, the White long-term MCS group did not demonstrate non-inferiority when compared to the White HT MCS and White HT Non-MCS groups. Conclusion: Differences in health-related quality of life among groups based on race were not statistically significant. Per non-inferiority testing, HT is superior to long-term MCS for health-related quality of life, regardless of race.

Abstract 4136785: Interpreting Population Mean Treatment Effects in the Kansas City Cardiomyopathy Questionnaire

Introduction: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a common outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean effects do not necessarily reflect the clinical benefit experienced by patients. Objectives: To evaluate the relationship between mean KCCQ treatment effects in clinical trials and the proportions of patients experiencing clinically important improvements across a range of heart failure etiologies and interventions. Methods: We performed a patient-level meta-analysis of 11 randomized trials (9,977 patients) to examine the relationship between mean KCCQ Overall Summary Score (OSS) treatment effects and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate or larger (≥10 points) improvements. Validation was performed in 7 additional trials. Results: Group mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI] 4.0-8.1) in the proportion of patients improving ≥5 points and 5.0% (95% PI 3.1-7.0) in the proportion improving ≥10 points, corresponding to NNTs of 17 (95% PI 12-25) and 20 (95% PI 14-33), respectively. Similar relationships were observed in the validation studies. Conclusions: Inferences on clinical impact based on population-level mean treatment effects are misleading since even small between group differences may reflect clinically important treatment benefits at the patient level. Clinical trials should explicitly describe the distributions of patient-level KCCQ changes to support clinical interpretation of their results.

Abstract 4124506: Short Physical Performance Battery as a Marker of Severity and Predictor of Clinical Outcomes in Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Background: ATTR-CM has an age dependent prevalence and is a disorder that almost exclusively affects older adults. Objective evaluations of function are critical to assessing and managing ATTR-CM in older adults. The short physical performance battery (SPPB) is a valid measure of functional capacity that predicts morbidity and mortality in older adults but its utility in ATTR-CM remains unknown. Aims/hypothesis: To establish SPPB as a useful marker of disease severity and predictor of outcomes in ATTR-CM. We hypothesized that SPPB scores would correlate with validated markers of ATTR-CM severity and improve clinical prediction. Methods: This is a retrospective analysis of patients referred to the Columbia University Cardiac Amyloid Program. Patients were stratified into low (SPPB 0-6), moderate (7-9), and high (10-12) cohorts based on initial SPPB score and baseline characteristics were compared between groups. Cox proportional hazard models and Kaplan Meier (KM) curves were generated to assess associations with mortality as well as a composite of death and cardiovascular (CV) hospitalization in follow-up. Results: A total of 263 patients, age 78 years (IQR 73, 84), 86% male, 22% with ATTRv (variant) and 78% with ATTRwt (wild type) were studied. SPPB showed no limitation in 59%, mild limitation in 33%, and severe limitation in 8%. Lower SPPB was associated (p &lt;0.05) with older age, prior stroke/TIA, shorter 6-minute walk test, elevated NT-proBNP and HS-troponin, worse quality of life metrics on Kansas City Cardiomyopathy Questionnaire, more advanced NYHA and Mayo stages, and higher Columbia scores. On multivariate regression (adjusted for age, sex, genotype, NYHA), SPPB was independently associated with the composite of mortality and CV hospitalization, with each point increase corresponding to 13% lower incidence of the outcome (HR 0.87, p=0.01). Chair stands score, one of three SPPB subdomains, was independently associated with the composite and mortality. KM curves showed significant association with SPPB and both the composite and mortality (Fig. 1). Conclusions: SPPB score is a marker of ATTR-CM severity, associated with validated biomarkers and staging systems, and independently predicts clinical outcomes.

Abstract 4147610: Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Background: Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant inherited condition with limited management options, primarily focusing on symptom improvement through beta blockers. A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM. One limitation of all these RCTs, for obvious reasons, is the small sample size, which poses a challenge in its actual clinical significance. Aims: To analyze the efficacy and safety of novel selective cardiac myosin inhibitors in symptomatic HOCM patients Methods: We included 4 RCTs, comparing the efficacy and safety of selective cardiac myosin inhibitors and placebo groups. These studies were selected through a detailed search of the MEDLINE, COCHRANE, and PUBMED databases. We compared various common primary and secondary endpoints between both the groups: changes in exercise tolerance, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). The results were reported as Odds Ratios (OR) with 95% confidence intervals (CI), using a random effects model. Results: The outcomes from 704 HOCM patients, which consisted of 361 patients who received a myosin inhibitor and 343 who received a placebo were analyzed. The primary endpoint in all the studies was improvement in exercise tolerance [measured as 1.5 mL/kg per min or greater increase in peak oxygen consumption (pVO2)], which was not statistically significant in our study (OR: 1.75, 95% CI: 0.89-3.43, p:0.1). There was a statistically significant improvement in ≥1 NYHA functional Class (OR: 3.9, 95% CI:2.49-6.12 p&lt;0.05). There was no significant change seen in KCCQ-CSS (OR: 1.26, 95% CI: 0.75-2.12, p:0.3) and1 or more Serious Adverse Events (OR: 0.75, 95% CI: 0.42-1.32, p:0.3). (Figures A-D) Conclusion: Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed.

Abstract 4135480: Effect of Time Since Heart Failure Diagnosis or Hospitalization on the Cost-effectiveness of Dapagliflozin in Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction

Background: Previous studies have shown dapagliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), to be a cost-effective treatment option for patients with heart failure (HF) with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF) in multiple European settings. Research question: Is the cost-effectiveness of dapagliflozin treatment in HFpEF/HFmrEF modified by either the time since HFpEF/HFmrEF diagnosis or the time since the last hospitalization for heart failure (HHF) event? Methods: A Markov cohort transition model was built for the UK setting, informed by patient-level data from the randomized, placebo-controlled DELIVER trial. The patient population was subset according to categories of time since last HHF event (including no prior HHF) and time since HF diagnosis (further subset to those with no prior HHF). For each subgroup, disease evolution was characterized by transitions among health states defined by quartiles of the Kansas City Cardiomyopathy Questionnaire Total Symptom Scale. The risk of fatal (cardiovascular and non-cardiovascular) and non-fatal events of worsening HF were modelled, adjusting for baseline characteristics and time-updating health state. Incremental costs and quality-adjusted life-years (QALYs) were calculated for each subgroup to yield incremental cost-effectiveness ratios (ICERs). Results: The lowest ICERs were observed for subgroups with the shortest time from HF diagnosis (with and without prior HHF) or last HHF event (Figure 1). Across all subgroups, the calculated ICERs were below the UK willingness-to-pay (WTP) threshold of £20,000/QALY gained. Conclusions: In patients with HFpEF/HFmrEF, the cost-effectiveness of dapagliflozin improved (via lower ICERs) in the subgroups corresponding to earliest disease (least time since an HHF event or HF diagnosis) compared with groups of later disease and potentially delayed treatment initiation. These findings suggest early optimization of HF therapy with implementation of guideline-directed medical therapy, including SGLT2is, may improve economic value.

Abstract 4129729: Relationship Between Inflammatory Biomarkers and Quality of Life in Black Adults Living with Heart Failure: A Pilot Study

Introduction: Heart failure (HF) impacts quality of life considerably, with inflammatory biomarkers potentially playing a significant role in this relationship. The purpose of this study is to examine the relationship between NYHA Class, inflammatory biomarkers, and quality of life in Black adults living with HF. Methods: Black adults living with HF (N=41) were enrolled in this study. NYHA Class was extracted from the medical record. Health-related quality of life was measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 23-item questionnaire that quantifies physical function, symptoms, social function, and health-related quality of life in HF. Scores are transformed to a range of 0-100, with higher scores reflecting better health status. One-way ANOVA and correlation analyses were used to assess associations between NYHA class, inflammatory biomarkers (XO activity, IL-1β, IL-15, and CCL-19), and KCCQ scores. Results: Participants were 57±11 years of age and 66% female, with mean LVEF 33±14%. NYHA Class ranged from I (20%) to IV (12%), with the majority of participants in Class II (34%) and III (22%). Mean KCCQ Clinical Summary Score was 85± 21. NYHA Class I had significantly lower scores on the KCCQ Clinical Summary Score compared to Class III and IV (p &lt; .001, η 2 = 0.54), KCCQ Physical Limitation compared to Class II, III, and IV (p &lt; .001, η 2 = 0.53), and KCCQ Symptom Frequency compared to Class IV (p = .001, η 2 = 0.39). The KCCQ Clinical Summary Score was negatively associated with XO activity (r = -0.440, p = .046), IL-1β (r = -0.407, p = .043), IL-15 (r = -0.427, p = .033), and CCL-19 (r = -0.559, p = .004). Similar negative associations were observed for the KCCQ subscales. Conclusion: The negative association between XO activity and health-related quality of life (KCCQ) in individuals with HF highlights the potential impact of oxidative stress on these patients' subjective well-being and functional status. Understanding this relationship could underscore the importance of mitigating oxidative stress pathways to improve the overall quality of life and symptom burden experienced by individuals with HF. The KCCQ and subscales were also negatively associated with markers of inflammation, highlighting the potential impact of systemic inflammatory processes on subjective well-being and functional status in persons with HF. Targeting inflammatory pathways may improve quality of life and mitigate the burden of symptoms in HF.

Efficacy of Intravenous Ferric Carboxymaltose in Heart Failure Patients with Iron Deficiency Anemia: A Meta-analysis of 6271 Patients.

Iron deficiency is prevalent among heart failure patients and is associated with worse clinical outcomes, including decreased quality of life and functional capacity. This condition often results in a higher incidence of hospitalization and mortality. Iron supplementation, particularly with intravenous ferric carboxymaltose (FCM), has shown potential benefits as an adjunct therapy in heart failure management. This study aims to evaluate the efficacy of FCM in the treatment of patients with heart failure and iron deficiency anemia, with a focus on its impact on mortality and hospitalization rates. A comprehensive search was conducted in PubMed, Web of Science, and Scopus databases from their inception until 1st December 2023. Meta-analysis was performed using RevMan 5.4, employing a random-model effect. The results were reported as risk ratios (RRs), standard mean differences (SMDs), and 95 % confidence intervals (CIs). The meta-analysis included 13 studies with a total of 6271 patients. Ferric carboxymaltose administration resulted in a significant improvement in the 6-minute walk distance (SMD: 1.45; 95 % CI: 0.55, 2.36; p = 0.002), quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) (SMD: 1.49; 95 % CI: 0.87, 2.11; p < 0.00001), the rate of first hospitalization for heart failure or cardiovascular death (RR: 0.91; 95 % CI: 0.84, 0.98; p = 0.02). However, FCM did not show a significant impact on the risk of cardiovascular death (RR: 0.90; 95 % CI: 0.77, 1.05; p = 0.17), the need for intervention due to worsening heart failure (RR: 0.41; 95 % CI: 0.04, 4.51; p = 0.47), or all-cause mortality rates (RR: 0.89; 95 % CI: 0.69, 1.16; p = 0.28). While FCM treatment in patients with heart failure and iron deficiency anemia significantly improves functional capacity and quality of life, it has no notable effect on mortality rates or the likelihood of hospitalization. These findings highlight the need for further research to explore comprehensive treatment strategies that address both the symptomatic and survival aspects of heart failure management in this patient population.

Stem cell therapy for non-ischemic dilated cardiomyopathy: a systematic review and meta-analysis

BackgroundStem cell therapy is the transplantation of human cells to aid the healing of damaged or wounded tissues and cells. Only a few small-scale trials have been conducted to investigate stem cell therapy for non-ischemic dilated cardiomyopathy (DCM). We aimed to perform a systematic review and meta-analysis to assess the efficacy and safety of stem cell therapy for DCM.MethodsA comprehensive search of the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, and ProQuest was conducted from their inception to June 30, 2024, to access randomized controlled trials (RCTs) that were centered on stem cell therapy for DCM. The primary outcome was left ventricular ejection fraction (LVEF), and the secondary outcomes included left ventricular end-diastolic dimension (LVEDD), left ventricular end-diastolic volume (LVEDV), 6-min walk test (6MWT), NYHA functional classification, quality of life (QoL) such as Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro-brain natriuretic peptide (NT-proBNP), and VO2 peak. Moreover, major adverse cardiovascular events (MACEs) were also recorded. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of the included RCTs, and the certainty of the evidence was assessed using the GRADE method. Sensitivity analysis was taken into consideration to determine the stability of the results. This review was registered with PROSPERO (CRD42024568912).ResultsEleven RCTs involving 637 participants were included in the quantitative analysis. The results indicated that there was a significant increase in mean LVEF (MD = 4.84, 95% CI 3.25–6.42, P < 0.00001) and considerable decrease in LVEDV (MD = − 29.51, 95% CI − 58.07 to − 0.95, P = 0.04) and NT-proBNP (MD = − 737.55, 95% CI − 904.28 to − 570.82, P < 0.00001) in DCM patients treated with stem cell therapy compared with controls. Stem cell therapy was also related to the improvement in functional capacity, as evaluated by 6MWT (MD = 44.32, 95% CI 34.70 − 53.94, P < 0.00001) and NYHA functional classification (MD = − 0.63, 95% CI − 0.96 to − 0.30, P = 0.0002). It also had positive effects on improving QoL, including significantly decreasing MLHFQ score (MD = − 16.60, 95% CI − 26.57 to − 6.63, P = 0.001) and increasing the KCCQ score (MD = 14.76, 95% CI 7.76 − 21.76, P < 0.0001). No significant differences were observed in LVEDD, VO2 peak, and MACEs between the two groups. The GRADE analysis revealed that the evidence was graded from low to moderate. Sensitivity analysis of the results suggested that the results were stable.ConclusionThe systematic review and meta-analysis indicates that stem cell therapy may be an effective and safe approach to improve cardiac function and quality of life in DCM patients. Nevertheless, given the limitations of existing studies, larger well-designed RCTs are required to confirm and support our findings.

Loss of quality of life and increased societal costs in patients with hypertrophic cardiomyopathy: the AFFECT-HCM study.

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease. The impact of HCM on quality of life (QoL) and societal costs remains poorly understood. This prospective multi-centre burden of disease study estimated QoL and societal costs of genotyped HCM patients and genotype-positive phenotype-negative (G+/P-) subjects. Participants were categorized into three groups based on genotype and phenotype: 1) G+/P- (left ventricular (LV) wall thickness <13 mm), 2) non-obstructive HCM (nHCM, LV outflow tract (LVOT) gradient <30 mmHg), and 3) obstructive HCM (oHCM, LVOT gradient ≥30 mmHg). We assessed QoL with EQ-5D-5L and Kansas City Cardiomyopathy Questionnaires (KCCQ). Societal costs were measured using medical consumption (iMCQ) and productivity cost (iPCQ) questionnaires. We performed subanalyses within three age groups: <40, 40-59, and ≥60 years. From three Dutch hospitals, 506 subjects were enrolled (84 G+/P-, 313 nHCM, 109 oHCM; median age 59 years, 39% female). HCM (both nHCM and oHCM) patients reported reduced QoL vs G+/P- subjects (KCCQ: 88 vs 98, EQ-5D-5L: 0.88 vs 0.96; both p<0.001). oHCM patients reported lower KCCQ scores than nHCM patients (83 vs 89, p=0.036). Societal costs were significantly higher in HCM patients (€19,035/year vs €7,385/year) compared to G+/P- controls, mainly explained by higher healthcare costs and productivity losses. Being symptomatic and of younger age (<60 years) particularly led to decreased QoL and increased costs. HCM is associated with decreased QoL and increased societal costs, especially in younger and symptomatic patients. oHCM patients were more frequently symptomatic than nHCM patients. This study highlights the substantial disease burden of HCM and can aid in assessing new therapy cost-effectiveness for HCM in the future.

Exercise Training in Patients With Hypertrophic Cardiomyopathy Without Left Ventricular Outflow Tract Obstruction: A Randomized Clinical Trial.

Patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction commonly experience reduced exercise capacity. Physical training improves exercise capacity in these patients, but whether the underlying effects of exercise are a result of central hemodynamic or peripheral improvement is unclear. This study assessed whether exercise training reduces left ventricular filling pressure measured during exercise in patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction. Between March 2019 and June 2022, patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction were randomly assigned (1:1) to a 12-week (3 h/wk) supervised, moderate-intensity exercise training program or continued usual activity. The primary outcome was the change in invasively measured pulmonary capillary wedge pressure during mild exercise (25 W) from baseline to week 12. Pressure tracings were analyzed offline by a blinded investigator. Secondary outcomes included changes in peak oxygen consumption, cardiac index, quality of life, echocardiographic indices of diastolic function, and natriuretic peptides. Of 59 patients randomized (mean age, 58.1±12.2 years; 27% women), 51 (86%) completed all follow-up assessments. At week 12, the change in 25-W pulmonary capillary wedge pressure was -2.8±6.8 mm Hg in the exercise group, compared with +1.2±4.9 mm Hg in the usual-activity group (between-group difference, 4.0 mm Hg [95% CI, 0.7-7.3]; P=0.018). Peak oxygen consumption improved by +1.8±2.0 mL/kg/min in the exercise group versus -0.3±3.1 mL/kg/min in the usual-activity group (P=0.005). Exercise training improved the ventilatory efficiency (VE/VCO2) slope compared with usual activity (between-group difference, 2.0 [95% CI, 0.6-3.5]; P=0.006). Peak cardiac index improved by +0.38±1.38 L/min/m2 in exercise versus -0.85±1.20 L/min/m2 in the usual-activity group (P=0.002). Change in overall Kansas City Cardiomyopathy Questionnaire score was similar between groups. However, the change in physical limitation scores (+8.4±12.0 points in exercise versus +0.7±6.8 points in usual-activity group; P=0.034) and quality-of-life scores (+8.7±18.0 points in exercise versus 0.7±4.0 points in usual-activity group; P=0.01) differed significantly. There were no significant changes in diastolic function assessed by echocardiography or in natriuretic peptides. In patients with hypertrophic cardiomyopathy without left ventricular outflow tract obstruction, a 12-week moderate-intensity exercise training program resulted in reduced left ventricular filling pressures at mild exertion and improved exercise performance. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03537183.

Meta-analysis of the efficacy and impact on cardiac function of sodium-glucose cotransporter 2 inhibitor Empagliflozin in heart failure patients.

Currently, there is no comprehensive systematic review available to comprehensively assess the efficacy and safety of Empagliflozin and other sodium-glucose cotransporter 2 inhibitors in the treatment of heart failure (HF). This study employed a meta-analysis approach to systematically evaluate the therapeutic effects of Empagliflozin in HF patients and its impact on cardiac function. The keywords including "heart failure," "HF," "cardiac failure," "cardiac disease," "Empagliflozin," and "sodium-glucose cotransporter 2 inhibitors" were utilized to search for relevant clinical studies on Empagliflozin in the treatment of HF in various databases, such as China National Knowledge Infrastructure, Wanfang, VIP Chinese Medical Journal Database, PubMed, MEDLINE, Embase, Cochrane Library, Springer, and Science Direct. The studies included patients with HF who received drug treatment. Data on baseline characteristics and posttreatment outcomes, including HF hospitalization (HHF), cardiovascular mortality, all-cause mortality, estimated glomerular filtration rate changes, Kansas City Cardiomyopathy Questionnaire quality of life (QoL) scores, N-terminal pro-B-type natriuretic peptide, left ventricular ejection fraction, hematocrit, and other relevant indicators were collected. Meta-analysis was conducted using RevMan5.3 to analyze the extracted data. A total of 15 studies were included in the final analysis, comprising 36,917 patients with HF. Among them, 18,486 patients were in Empagliflozin group, and 18,431 patients were in control (Ctrl) group. The results of the meta-analysis demonstrated that, relative to Ctrl group, Empagliflozin group showed a substantially lower HHF rate, a substantial improvement in estimated glomerular filtration rate changes, a reduced cardiovascular mortality rate, a higher Kansas City Cardiomyopathy Questionnaire QoL score, increased hematocrit values, reduced N-terminal pro-B-type natriuretic peptide changes, and enhanced left ventricular ejection fraction changes. These findings suggest that remarkable improvements in various outcomes compared to the Ctrl group. The sodium-glucose cotransporter 2 inhibitor Empagliflozin markedly reduces the HHF rate and cardiovascular mortality in HF patients. It also improves patients' QoL, enhances renal function, and increases cardiac function while reducing both, the preload and afterload.

Machine learning insights into regional dynamics and prevalence of COVID-19 variants in US health and human services regions

BackgroundThe COVID-19 pandemic arising from the emergence of SARS-CoV-2 in late 2019 has led to global devastation with millions of lives lost by January 2024. Despite the WHO’s declaration of the end of the global health emergency in May 2023, the virus persists, propelled by mutations. Variants continue to challenge vaccination efforts, underscoring the necessity for ongoing vigilance. This study aimed at contributing to a more data-driven approach to pandemic management by employing random forest regression to analyze regional variant prevalence.MethodsThis study utilized data from various sources including National COVID Cohort Collaborative database, Bureau of Transportation Statistics, World Weather Online, EPA, and US Census. Key variables include pollution, weather, travel patterns, and demographics. Preprocessing steps involved merging and normalization of datasets. Training data spanned from January 2021 to February 2023. The Random Forest (RF) Regressor was chosen for its accuracy in modeling. To prevent data leakage, time series splits were employed. Model performance was evaluated using metrics such as MSE and R-squared.ResultsThe Alpha variant was predominant in the Southeast, with less than 80% share even at its peak. Delta surged initially in Kansas City and maintained dominance there for over 5 months. Omicron subvariant BA.5 spread nationwide, becoming predominant across all Health and Human Services regions simultaneously, with New York seeing the earliest and fastest decline in its share. Variant XBB.1.5 concentrated more in the Northeast, but limited data hindered full analysis. Using RF Regressor, key features affecting spread patterns were identified, with high predictive accuracy. Each variant showed specific environmental correlations; for instance, Alpha with air quality index, Delta with ozone density, BA.5 with UV index, and XBB.1.5 with land area and income. Correlation analysis further highlighted variant-specific associations.ConclusionsThis research provides a comprehensive analysis of the regional distribution of COVID-19 variants, offering critical insights for devising targeted public health strategies. By utilizing machine learning, the study uncovers the complex factors contributing to variant spread and reveals how specific factors contribute to variant prevalence, offering insights crucial for pandemic management.

Phase 3 Open-Label Study Evaluating the Efficacy and Safety of Mavacamten in Japanese Adults With Obstructive Hypertrophic Cardiomyopathy - The HORIZON-HCM Study.

Mavacamten, a cardiac myosin inhibitor, significantly improved symptoms and cardiac function vs. placebo in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in EXPLORER-HCM. However, the efficacy and safety profiles of mavacamten in Japanese patients are unclear. HORIZON-HCM is a Phase 3 single-arm study in Japanese patients with symptomatic obstructive HCM. The mavacamten starting dose was 2.5 mg; individualized dose titration occurred in Weeks 6-20 based on Valsalva left ventricular outflow tract (LVOT) gradient and resting left ventricular ejection fraction (LVEF). Overall, 38 patients were treated; 36 completed the 30-week primary treatment analysis period. Clinically significant improvements in postexercise LVOT gradient were observed after 30 weeks of treatment (mean change from baseline -60.7 mmHg). Improvements in N-terminal pro B-type natriuretic peptide, New York Heart Association class, and Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score were observed over 30 weeks, and mean LVEF was ≥74% at all visits. Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 63.2% and 7.9% of patients, respectively; none resulted in treatment discontinuation. One patient experienced a transient asymptomatic reduction in LVEF to <50%. No deaths occurred during the study. In Japanese patients with obstructive HCM, mavacamten was associated with similar improvements in LVOT gradients, cardiac biomarkers, and symptoms to those observed in EXPLORER-HCM. Treatment was well tolerated with no new safety concerns.

Symptom prevalence in patients with advanced heart failure and its association with quality of life and activities of daily living.

Quality of life (QOL) and functional status are two key outcomes for patients with advanced heart failure (HF). We examined the association of eleven symptoms with QOL and functional status impairment in patients with advanced HF. This was a retrospective analysis of baseline data from a multi-center, cluster-randomized controlled trial (NCT01459744) which enrolled patients with an implanted cardioverter-defibrillator and advanced HF at high-risk for mortality. Study instruments included the Condensed Memorial Symptom Assessment Scale, the Kansas City Cardiomyopathy Questionnaire QOL subscale, and the number of activities of daily living (ADL) patients had difficulties with. The study included 413 subjects. In generalized linear models which were adjusted for baseline characteristics, the total number of symptoms was significantly associated with worse QOL, as was the presence of each individual symptom, except constipation. Lack of energy demonstrated the strongest negative association with QOL. Similarly, the total number of symptoms was associated with a higher number of ADL difficulties (i.e., worse functional status). The presence of pain, lack of energy and drowsiness was individually associated with more ADL difficulties. Among patients with advanced HF, a higher number of symptoms and specific individual symptoms were associated with worse QOL and functional status.