Heart Failure With Reduced Ejection Fraction Patients Research Articles

Epstein-Barr Virus Lytic Transcripts Correlate with the Degree of Myocardial Inflammation in Heart Failure Patients

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment.

Evaluation of Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitor Prescribing Patterns in Heart Failure Patients at Hospital Discharge.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) dapagliflozin and empagliflozin are indicated for heart failure with reduced ejection fraction (HFrEF) for cardiovascular death and heart failure hospitalization risk reduction. Due to the recent nature of these data, prescribing of SGLT2is may be suboptimal. Objective: This study sought to assess the prevalence of SGLT2i prescriptions at hospital discharge for HFrEF. Methods: A retrospective chart review was conducted on HFrEF patients discharged from April 1st to December 31st, 2021 from one academic medical center in the United States. The primary objective was to determine the percentage of eligible patients prescribed SGLT2i at discharge and the secondary objective was to characterize covariates impacting prescription. Results: Overall, 115 patients were included. The mean age was 72 ± 14.25 years. The majority were male (73.9%) and Caucasian (74.8%). At discharge, 15.7% of patients were prescribed an SGLT2i, although 94.8% were eligible. Baseline characteristics and concomitant medications did not differ significantly, although the mean number of discharge medications differed significantly between those prescribed an SGLT2i (15.78 ± 6.77) and those not (12.05 ± 5.28) (P = 0.023). Conclusions: SGLT2is are under-prescribed at discharge for HFrEF patients, despite many being eligible. Further studies should be done to elucidate factors that influence the under-prescription of SGLT2is.

A time-dependent analysis of sacubitril/valsartan and gliflozins benefits in patients receiving cardiac resynchronization therapy

Abstract Background While sacubitril/valsartan (ARNi), gliflozins (or SGLT2i) and cardiac resynchronization therapy (CRT) are firmly recognized as cornerstones of therapy for heart failure with reduced ejection fraction (HFrEF), robust evidence validating the long-term efficacy of their combination remains elusive. The few data suggesting a synergistic advantage of these drugs alongside CRT have not rigorously considered their time-varying administration, leading to potential selection bias, since only patients with longer initial survival could commence these treatments. As a result, the literature to date lacks a comprehensive and persuasive demonstration of the additional survival benefits conferred by ARNi and gliflozins over CRT alone in HFrEF. Purpose To evaluate the impact of ARNi and gliflozins on reducing cardiovascular and overall mortality among HFrEF patients undergoing CRT. Methods Patients with heart failure and an ejection fraction ≤ 35%, who were referred for CRT-D implantation from 2015 to 2023, were retrospectively recruited for the study. These patients were grouped into two cohorts: those not receiving drugs (no drugs group) and those treated with ARNi and/or SGLT2i (ARNi/SGLT2i group). Importantly, ARNi and SGLT2i treatments were considered as time-dependent covariates in order to account for patients who initiated or discontinued therapy during follow-up. Results The cohort included 183 ischemic and non-ischemic HFrEF patients (148 male [80.9 %], 113 ischemic [61.7 %], median [IQR] age 73 [65-80] years). 117 (74 %) patients started ARNi (61, 52.1 %), gliflozins (7, 6 %) or both drugs (49, 41.9 %) and were assigned to ARNi/SGLT2i group. During a median follow-up of 5.67 (CI 95 %, 5 – 6.5) years, 63 (34.4 %) patients died, of whom 47 (74.6 %) died of cardiovascular HF-related death. Specifically, 44 (of whom 35 (79 %) due to HF-related death) died in the no drugs group vs 19 (12 (63 %) due to HF-related death) in ARNi/SGLT2i patients. At univariable analysis (Panel A in the Figure), ARNi and/or SGLT2i treatments reduced all-cause (HR 0.59 [0.34-1.02], p = 0.056) and cardiovascular (HR 0.47 [0.24-0.92], p = 0.029) mortality. However, after multivariable adjustment for key covariates (1-year CRT response, age, atrial fibrillation, baseline LVEF, chronic obstructive pulmonary disease, glomerular filtration rate), the survival benefits of ARNi and SGLT2i use diminished, and the only factor strongly associated with reduced mortality risk remained 1-year positive response to CRT (Panel B). Conclusions Despite their recognized therapeutic benefits, ARNi and SGLT2i have not demonstrated additional survival benefit compared to CRT alone in patients with HFrEF. A 1-year positive response to CRT remains the most significant prognostic factor. Further studies with larger sample sizes and extended follow-up periods are needed to confirm this hypothesis, also evaluating whether the timing of introduction of these medications may impact survival.

Eligibility for omecamtiv mecarbil in a real-world heart failure population: Data from the Swedish Heart Failure Registry.

We assessed eligibility for omecamtiv mecarbil (OM) in a real-world cohort with heart failure with reduced ejection fraction (HFrEF) according to the selection criteria of the GALACTIC-HF trial (trial scenario) and selected trial´s criteria more likely to impact real-world use (pragmatic scenario). We included 31,015 patients with HFrEF lasting ≥3 months and registered in the Swedish HF registry between 2000-2021. Trial eligibility was calculated by applying all the GALACTIC-HF selection criteria. The pragmatic scenario considered only the New York Heart Association class, history of worsening HF, N-terminal pro-B-type natriuretic peptides (NT-proBNP), blood pressure and renal failure criteria defined as in the trial. Eligibility for OM in chronic HFrEF was 21% and 36% in the trial and pragmatic scenarios, respectively. Eligibility was higher in those with EF<30% (trial: 27%, pragmatic: 44%), in-patients (trial:30%, pragmatic:57%), severe HF (trial: 35%, pragmatic: 60%), NYHA class III-IV (trial: 26%, pragmatic: 45%), and NT-proBNP≥5,000pg/mL (trial: 30%, pragmatic: 51%). The criteria that most limited eligibility were history of a recent worsening HF event (60% eligible in chronic HFrEF), elevated NT-proBNP (82% eligible), and deviating blood pressure (82% eligible). Overall, eligible patients were characterized by more severe HF and higher CV event-rates in both scenarios, and higher comorbidity burden in the pragmatic scenario. Approximately 21% of real-world chronic HFrEF patients would be eligible for OM according to the GALACTIC-HF selection criteria, and 36% according to the criteria more likely to affect OM use in clinical practice. Criteria in both scenarios identified a patient-group with severe HF and high CV event-rates.

Effects of different sodium–glucose cotransporter 2 inhibitors in heart failure with reduced or preserved ejection fraction: a network meta-analysis

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.

INDEPENDENT EFFECT OF SGLT2I ON DIASTOLIC FUNCTION IN HFREF POPULATION

Abstract Background Scientific literature reinforces the role of diastolic dysfunction in patients with heart failure with reduced ejection fraction (HFrEF) as an independent prognostic indicator of all–cause mortality. In this context, E/e’ ratio plays a central role in diastolic dysfunction assessments and diagnosis. Despite the introduction of several novel medical therapies for HFrEF that led to improvement in mortality and HF hospitalization, the effect of the combined treatment with Sacubitril/Valsartan (SV) and Sodium Glucose Transporter 2 inhibitors (SGLT2i) on E/e’ ratio has not been addressed yet. Aim We aimed to evaluate the effect of SV alone vs SV+SGLT2i on E/e’ ratio in a real–life population of HFrEF outpatients. Methods This is an observational monocentric study including patients treated with either SV alone or with SV+SGLT2i from 2018 to 2023. E/e’ ratio was measured at baseline, at 6 and 12 months. Results 178 HFrEF patients (mean age 69 years±11, left ventricular ejection fraction (LVEF) 31±6%) in optimal medical therapy were enrolled. 121 of them received SV and 58 received SV+SGLT2i. Baseline E/e’ ratio was similar in the two groups (median value 11,2 [IQR 8;16] in SV group and 10,9 [IQR 8;16] in SV+SGLT2i group, p=0.45). At follow up, only SV+SGLT2i group showed a significative decrease in E/e’ ratio after therapy initiation while SV group showed a E/e’ ratio similar to baseline (E/e’ ratio median value 8,5 [IQR 7;12] vs 11,8 [IQR 8;15] respectively, p=0.035). Moreover, after 12 months most patients receiving SV+SGLT2i didn‘t required diuretic administration compared to those treated with only SV (43% vs 16% respectively; p=0,0002). Conclusions Among patients with HFrEF, treatment with SGLT2i+SV was associated with a significative reduction of E/e’ ratio and of diuretic administration. This result might suggest a favorable independent effect of SGLT2i on diastolic function and myocytes relaxation and might provide new evidence on the positive results observed on hard endpoints.

Intentional weight loss in overweight and obese patients with heart failure: A systematic review.

Approximately 30-49% of heart failure (HF) patients are living with obesity. The recommended body mass index (BMI) for the general population is 18.5-24.9 kg/m2. The obesity paradox suggests that HF patients with obesity (HFpwO) have a better prognosis compared to normal BMI. Guideline recommendations on ideal BMI for HFpwO are limited. This systematic review aims to examine the evidence base for intentional weight loss in HFpwO on the following parameters: mortality, hospitalization, symptoms, quality of life (QOL), effects on left ventricular ejection fraction (LVEF) and adverse events. A total of 22 studies were identified: lifestyle intervention (n = 9), pharmacotherapy (n = 3), bariatric surgery (n = 10). Mortality and hospitalization, symptoms, QOL, and LVEF were reported in 8, 15 and 14 studies, respectively. All studies had moderate to high risk of bias except one randomized controlled trial (RCT) which evaluated semaglutide in HF with preserved ejection fraction (HFpEF) patients. Semaglutide resulted in weight loss with improvement in QOL. Lifestyle intervention led to weight loss, minimal adverse events, and improvement in symptoms in both HF with reduced ejection fraction (HFrEF) and HFpEF patients. In six observational studies, bariatric surgery in HFrEF patients achieved weight loss and improvement in LVEF safely in most patients but some patients developed worsening HF perioperatively. There is a need for high-quality adequately powered RCTs on intentional weight loss in HFpwO with survival and hospitalization outcomes. All forms of weight loss intervention studied in this review were likely to result in significant weight loss, improved symptoms and QOL. Careful monitoring is required due to an increase in certain adverse events.

Correlations between soluble ST2 concentration and the nutritional status in patients with heart failure with reduced ejection fraction - cross-sectional study.

Heart failure (HF) is a global problem that stimulates research on markers associated with the diagnosis and course of the disease. Soluble suppression of tumorigenicity-2 (sST2) is a receptor for interleukin-33 and is associated with increased mortality rates in HF patients. Malnutrition in HF is also connected with inflammation and is associated with worse prognosis. The present study aimed to evaluate the relationship between sST2 concentration and the nutritional status of patients with HF with reduced ejection fraction (HFrEF). 138 patients with HFrEF were enrolled in this cross-sectional study. Nutritional status was assessed using Geriatric Nutritional Risk Index (GNRI) and Controlling Nutritional Status (CONUT). The mean age was 53.6 ± 10.8 years. In the group with sST2 > 32.9 ng/mL, the GNRI score was higher and the associated risk of malnutrition was more common (29% vs. 12%; p = 0.011). Coherently in the group with sST2 > 32.9 ng/mL the median CONUT score was worse (2 [IQR 1-3] vs. 1 [IQR 0-2]; p = 0.0016) and the risk of malnutrition defined by this tool was also more prevalent (p = 0.0079). This relationship was independent of the concentration of natriuretic peptides, age and sex. According to available research, this research is the first study showing that sST2 concentration is related with nutritional status in HFrEF patients. sST2 may help to evaluate the necessity for nutritional intervention in HFrEF patients.

Contemporary guideline-directed medical therapy in de novo, chronic, and worsening heart failure patients: First data from the TITRATE-HF study.

Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management.

Reduced congestion and improved response to a fluid/sodium challenge in chronic heart failure patients after initiation of sacubitril/valsartan: The NATRIUM-HF study.

The effects of initiating sacubitril/valsartan in patients with stable heart failure with reduced ejection fraction (HFrEF) on response to fluid and sodium expansion are unknown. We have explored changes in natriuresis, diuresis, and congestion in response to the administration of intravenous fluid/sodium load in patients with HFrEF before as compared to after the initiation of sacubitril/valsartan. At baseline (before sacubitril/valsartan initiation) and 2 and 3 months after the initiation, patients underwent an evaluation that consisted of three phases of 3 h: the rest phase (0-3 h), the load phase (3-6 h) in which 1 L of intravenous Ringer solution was administered, and the diuretic phase (6-9 h) at the beginning of which furosemide was administered. Overall, 216 patients completed the study. In comparison to baseline values, at 2 and 3 months after sacubitril/valsartan initiation, patients' diuresis and natriuresis in response to Ringer administration significantly increased (mean difference: 38.8 [17.38] ml, p = 0.0040, and 9.6 [2.02] mmol, p < 0.0001, respectively). Symptoms and signs of congestion after the fluid/sodium challenge were significantly decreased at months 2 and 3 compared to baseline. Compared to baseline, there was also an increment of natriuresis after furosemide administration on sacubitril/valsartan (9.8 [5.13] mmol, p = 0.0167). There was a significant decrease in body weight in subsequent visits when compared to baseline values (-0.50 [-12.7, 7.4] kg at 2 months, and -0.75 [-15.9, 7.5] kg at 3 months; both p < 0.0001). The initiation of sacubitril/valsartan in HFrEF patients was associated with improvements in natriuresis, diuresis, and weight loss and better clinical adaptation to potentially decongestive stressors.

Contemporary outpatient management of patients with worsening heart failure with reduced ejection fraction: Clinical outcome results from the CHART-HF study

BackgroundBased on available data from randomized clinical trials, patients with heart failure with reduced ejection fraction (HFrEF) and worsening HF events (WHFE) have substantial disease burden and poor outcomes. WHFE clinical outcome data in non-clinical trial patients, more representative of the US clinical practice, has not been demonstrated. Methods and resultsCHART-HF collected data from two complementary, non-clinical trial cohort with HFrEF (LVEF <45 %): 1) 1,000 patients from an integrated delivery network and 2) 458 patients from a nationwide physician panel. CHART-HF included patients with WHFE between 2017 and 2019 followed by an index outpatient cardiology visit ≤6 months, and patients without WHFE in a given year between 2017 and 2019, with the last outpatient cardiology visit in the same year as the index visit. Compared to patients without WHFE (after covariate adjustment, all p < 0.05), patients with WHFE had a greater risk of HF-related hospitalization (hazard ratio [HR]: 1.53–2.40) and next WHFE event (HR: 1.67–2.41) following index visits in both cohorts. ConclusionHFrEF patients with recent WHFE consistently had worse clinical outcomes in these non-clinical trial cohorts. Despite advances in therapies, unmet need to improve clinical outcomes in HFrEF patients with WHFE remains.

EFFECT OF DAPAGLIFLOZIN ON CARDIOVASCULAR OUTCOMES IN HFREF PATIENTS: IMPACT OF DIABETES MELLITUS TYPE 2 STATUS

Dapagliflozin has shown promise in the treatment of heart failure with reduced ejection fraction (HFrEF), but its effects in patients with and without diabetes remain unclear. Objective: This study aimed to assess the effects of dapagliflozin in HFrEF patients, both with and without diabetes. Methods: From January to July 2023, a six-month case-control study was conducted in the cardiology department of a Tertiary Care Hospital in Peshawar, Pakistan. All patients received an additional dose of dapagliflozin (10 mg) alongside their usual treatment plans. The primary outcome was a composite of heart failure exacerbation or cardiovascular death. Data analysis was performed using SPSS version 22. Results: Patients with diabetes mellitus type 2 (DMT2) exhibited a higher rate of cardiovascular death (22%) and hospitalization for heart failure (14.4%) compared to those without diabetes. The hospitalisation rate for heart failure was also higher in the DMT2 group (12.21%) than in the non-diabetic group (8.6%). Over the trial period, cardiovascular death occurred in 12.44% of patients with DMT2 compared to 7.30% in those without DMT2. Patients with diabetes experienced a significantly higher number of first and recurrent hospitalizations for heart failure and cardiovascular death compared to those without diabetes (32.45% vs. 19.20%, p=0.021). Conclusion: Dapagliflozin therapy in HFrEF patients demonstrated varying effects between those with and without diabetes. The study underscores the importance of personalised management strategies considering comorbid medical conditions. Despite dapagliflozin treatment, patients with both heart failure and diabetes continued to experience cardiovascular complications, highlighting the need for individualised treatment plans that account for a patient's complete medical profile.

Pulmonary Function Abnormalities in Heart Failure Subtypes: Impact of Upper Body Adiposity

Study objective: Heart failure (HF) syndrome is associated with pulmonary system abnormalities that have a direct impact on mortality. Heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are distinct subtypes of HF with different pathophysiologies, clinical presentations, and treatment approaches. Obesity is highly prevalent in HFpEF and significantly contributes to its development. Importantly, obesity and high abdominal adiposity can have significant effects on pulmonary function. Therefore, HFpEF patients may have more pronounced pulmonary function impairment than HFrEF patients in part due to higher prevalence of upper body adiposity. Hypothesis: We hypothesized that lung volumes would be lower in patients with HFpEF compared to those with HFrEF and CTL. Further, we hypothesized that higher upper body adiposity (measured as trunk fat by dual-energy X-ray absorptiometry) would be associated with lower lung volumes in patients with HFpEF. Methods: HFpEF patients (n=26), HFrEF patients (n=26) and CTL (n=36) performed pulmonary function tests according to ATS/ERS guidelines. Total lung capacity (TLC), residual volume (RV), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) were measured and absolute and % predicted values are reported. Dual-energy X-ray absorptiometry scans quantified % trunk fat. Absolute lung volumes were compared across groups using ANCOVA with age as a covariate and % predicted lung volumes were compared using one-way ANOVA. Results: HFpEF patients were older than HFrEF patients and CTL (HFpEF: 71±9 vs. HFrEF: 65±9 vs. CTL: 63±11 yrs, both p&lt;0.05) while no differences were present among groups for sex, height, or BMI (all, p&gt;0.05). HFpEF patients had higher % trunk fat than CTL (p&lt;0.01), while no differences were present between HFrEF and HFpEF or CTL (p&gt;0.05) (HFpEF: 46±11 vs. HFrEF: 42±8 vs. CTL: 38±11%). HFpEF patients had lower FVC (HFpEF: 3.0±0.7 vs. HFrEF: 3.7±1.0 vs. CTL: 3.8±0.8 L), FEV1 (HFpEF: 2.3±0.5 vs. HFrEF: 2.8±0.8 vs. CTL: 2.9±0.6 L), TLC (HFpEF: 5.5±1.3 vs. HFrEF: 6.3±1.4 vs. CTL: 6.4±1.1 L), and % predicted TLC than CTL (all, p&lt;0.05). HFpEF and HFrEF patients had lower % predicted FVC and % predicted FEV1 than CTL (p&lt;0.05). All other pulmonary function parameters were not different among groups (p&gt;0.05). There was a negative relationship between % trunk fat and TLC for HFpEF patients (r= -0.51, p&lt;0.05). There were negative relationships between % trunk fat and FVC for CTL (r= -0.37) and HFpEF patients (r= -0.50) (both, p&lt;0.05), with statistically different y-intercepts (p&lt;0.01). There were no other significant relationships (all, p&gt;0.05). Conclusion: These findings demonstrate that patients with HF have smaller lung volumes than CTL. Further, our findings suggest that upper body adiposity may be an important contributing factor to these pulmonary system abnormalities in HFpEF. None. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cost-Utility Analysis of Vericiguat in Heart Failure with Reduced Ejection Fraction After Worsening Heart Failure Events in China.

Vericiguat is a new medication to demonstrate clinical efficacy in heart failure with reduced ejection fraction (HFrEF) after worsening heart failure (WHF) events, but its cost-utility was unknown. We aimed to assess the cost-utility of combining the application of vericiguat with standard treatment in HFrEF patients who had WHF events. A multistate Markov model was implemented to mimic the economic results of HFrEF patients who had WHF events in China after receiving vericiguat or placebo. An analysis of cost-utility was conducted; most parameters were set according to the published studies and related databases. All the utilities and costs were decreased at a rate of 5% annually. The incremental cost-effectiveness ratios (ICERs) were the primary outcome measure. We also conducted sensitivity analyses. Over a 20 year lifetime horizon, additional use of vericiguat led to an elevated cost from US$9725.03 to US$20,660.76 at the current vericiguat costs. This was related to increased quality-adjusted life years (QALYs) from 2.50 to 2.66, along with an ICER of US$65,057.24 per QALY, which was over the willingness-to-pay (WTP) threshold of US$36,096.30 per QALY. If the vericiguat costs were discounted at 80%, it contributed to an ICER of US$12,226.77 per QALY. Additional use of vericiguat for patients with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) of ≤ 5314 pg per ml produced an ICER of US$23,688.46 per QALY. The outcomes of the one-way sensitivity analysis showed the risk of death from cardiovascular disease in both groups was variable with the highest sensitivity. The probabilistic sensitivity analysis showed that 41.6% of the mimicked population receiving vericiguat combined with standard therapy was cost-effective at the WTP threshold of US$36,096.30 per QALY. From the perspective of Chinese public healthcare system, the combined use of vericiguat and standard treatment in patients with HFrEF following WHF events did not generate advantages in cost-utility in China but was a cost-effective therapeutic strategy for those who with plasma NT-proBNP of ≤ 5314 pg per ml.

The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure.

Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into HF pathophysiology. We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters, as well as with elevated left atrial pressure (LAP), in HFrEF patients, to provide insights into underlying mechanisms. In 173 HFrEF patients, we performed six-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7(IQR:2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular (left ventricular ejection fraction[LVEF], global longitudinal strain[GLS]), and left atrial function (left atrial reservoir strain[LASr]) and elevated LAP(E/e' ratio >15), and used gene enrichment analyses to identify underlying pathophysiological processes. We found 723, 249, 792 and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr and E/e' ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix (ECM). Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: Cystatin-D, Fibulin-5 and HSP40. Circulating proteins show varying associations with different echocardiographic parameters in HFrEF patients. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

Effect of sacubutril/valsartan on Tp-e, QT, QTc, Tp-e/QTc parameters in heart failure with reduced ejection fraction

Purpose: The purpose of this study is to evaluate ventricular repolarization before, at the first month, and sixth month after Sacubutril/Valsartan, an angiotensin receptor neprilysin inhibitor (ARNI) treatment in heart failure patients with reduced ejection fraction (HFrEF).&#x0D; Materials and Methods: We included 49 patients with HFrEF who switched to ARNI therapy. The 12-lead electrocardiography (ECG) was evaluated before ARNI therapy and also during the first and sixth months of the therapy. We evaluated demographic, clinical, and laboratory parameters, as well as medications and ECG data, including heart rate. Additionally, we examined QT, QTc, Tp-e, Tp-e calculated (Tp-ec), Tp-ec/QTc, Tp-e/QT, and Tp-e/QTc.&#x0D; Results: After receiving ARNI treatment, ventricular repolarization indices were significantly reduced in the first and sixth months compared to before treatment. Specifically, the QTc values decreased from 457.6 ms to 443.8 ms, and the Tp-e/QT ratio decreased from 0.21±0.03 to 0.19±0.03. Additionally, the QTc values decreased from 457.6 ms to 444.9 ms, and the Tp-e/QT ratio decreased from 0.21±0.03 to 0.18±0.03. However, when the first and sixth months under ARNI treatment were compared, no significant difference was found (QTc: 443.8 ms vs. 444.9 ms, Tp-e/QT: 0.19±0.03 vs. 0.18±0.003).&#x0D; Conclusion: ARNI treatment in HFrEF positively affected QTc, Tp-e, and Tp-ec intervals and Tp-e/QT, Tp-e/QTc, and Tp-ec/QTc ratios, which are indicators of ventricular repolarization. Moreover, this effect started in the first month and continued in the sixth month.

Effects of levothyroxine in subclinical hypothyroidism and heart failure with reduced ejection fraction: An open-label randomized trial

We report a randomized, multicenter, open-label trial (ClinicalTrials.gov: NCT03096613) to investigate the clinical benefits of levothyroxine (L-T4) administration in subclinical hypothyroidism (SCH) patients with heart failure with reduced ejection fraction (HFrEF). Overall, 117 patients were enrolled and received L-T4 plus standard HFrEF treatment (experimental group, N= 57) or standard HFrEF therapy alone (control group, N= 60). The change of 6-min walk test distance in the experimental group was significantly higher than that in the control group at 24weeks (70.08± 85.76m vs. 27.73± 82.00 m, mean difference [95% confidence interval (CI)] 46.90 [12.90, 80.90], p<0.001). Improvements in New York Heart Association (NYHA) classification (p= 0.033) and thyroid function were significant. Adverse event incidence was similar between groups (risk ratio [95% CI]: 0.942 1.053 (0.424, 2.616); p= 0.628). L-T4 addition to HFrEF treatment improved activity tolerance, NYHA class, and thyroid function within 6months, suggesting its potential for combined therapy in HFrEF patients with SCH. Future double-blind, placebo-controlled trials should be performed to confirm these results.

Assessing the diversity and determinants of health-related quality of life measures in patients with acute heart failure.

Heart failure with reduced ejection fraction (HFrEF) significantly impacts health-related quality of life (HR-QoL). Existing HR-QoL questionnaires can show inconsistencies, potentially misrepresenting patient self-reports. This study examines the variation in HR-QoL measurement tools for HFrEF patients, identifying related determinants. We retrospectively analysed 134 hospitalized patients with acute decompensated HFrEF at a Taiwanese tertiary centre's Heart Failure Post-Acute-Care (HF-PAC) programme. Participants completed the EuroQol-5 dimension (EQ-5D) questionnaire, the EQ-5D visual analogue scale (VAS), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Utility values were obtained from the EQ-5D questionnaire. Demographic features were depicted using descriptive statistics, while multivariate regression was used to ascertain relationships between HR-QoL measurements and determinants. Average scores for EQ-5D, MLHFQ, EQ-5D utility, and VAS were 6.1±1.6, 21.8±21.3, 81.7±27.0, and 59.5±14.6, respectively. Significant correlations were observed among the three tools. The New York Heart Association functional class showed a notable association with all tool scores. Other associations encompassed EQ-5D with coronary artery disease, mineralocorticoid receptor antagonists, and the 6min walk test; EQ-5D VAS with chronic kidney disease; and MLHFQ with age. This study illuminates the variance in HR-QoL measurement tools for Taiwanese HFrEF patients. Using a range of these tools is beneficial in unveiling diverse determinants and approaching comprehensive patient-centred care. However, for a more precise HR-QoL assessment in Taiwanese HFrEF patients, recalibrating the EQ-5D-derived utility scores might be necessary, emphasizing the importance of patient-specific considerations within the HF-PAC programme.

O163: CABG versus PCI in Heart Failure with Reduced Ejection Fraction Patients: A Systematic Review &amp; Meta-analysis Stratified by Left Ventricular Ejection Fraction

Abstract Background Comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with heart failure with reduced ejection fraction (HFrEF) remains controversial within the literature. The current meta-analysis aimed to compare CABG and PCI in HFrEF patients regarding mortality and long-term survival, repeat revascularization, new postoperative myocardial infarction (MI) and stroke, stratified by the degree of LVEF reduction. Methods In a systematic review, a comprehensive literature search was conducted on multiple electronic databases using strict search terms. Twenty studies met the set inclusion/exclusion criteria. Meta-analysis of extracted data was conducted using the R-studio and STATA software. Furthermore, the aforementioned study endpoints were stratified by the degree of left ventricular ejection fraction (LVEF) reduction into severe (&amp;lt;35%), moderate (&amp;lt;40%) and mild (&amp;lt;50%). Results Data from 25,031 HFrEF patients was analysed, out of which 12,957 (52%) underwent CABG and 12,074 (48%) received PCI. Long-term survival was significantly higher in the severe (&amp;lt;35%) and mildly (&amp;lt;50%) reduced LVEF groups, with no significant different found in the moderately (&amp;lt;40%) reduced LVEF cohort. However, all 3 groups significantly favoured CABG in terms of need for revascularization, but no difference in stroke incidence was found. As for postoperative MI, this followed the same trend as survival. No evidence of significant heterogeneity or publication bias was found. Conclusion CABG yields more favourable results than PCI in HFrEF patients. Further stratifying the clinical outcomes measured by the degree of LVEF reduction sheds light on the importance of risk stratification of patients to optimise results.

Heart rate score in remote monitoring: An additional tool for predicting outcomes in heart failure with reduced ejection fraction.

Heart rate score (HRS) ≥ 70% has been associated with arrhythmic events and mortality but these studies were not specific for heart failure (HF) patients. We hypothesized that HRS ≥ 70% obtained from remote monitoring (RM) is associated with HF hospitalizations and arrhythmic events in HF with reduced ejection fraction (HFrEF). HRS was calculated from RM in patients with HFrEF and ICD or CRT-D. Two groups were defined: HRS ≥ 70% (G1, n=55) and HRS<70% (G2, n=48) RESULTS: A total of 103 patients were included (64.4±13.04 years, 69.9% male, mean left ventricular ejection fraction (LVEF) 33.62±11.97% and FUP 61.7±38.87 months). The device was CRT-D in 59.2% and ICD in 40.8% and the majority (90.3%) had the device implanted in primary prevention. G1 patients were more frequently male (p=.017) and had more coronary disease (p=.035). HRS ≥70% was an independent predictor for unplanned HF hospitalizations (OR: 1.905 (95% CI: 1.328-3.649), p<.001)). The indication for device implantation (primary vs. secondary prevention), type of device, NYHA class, age, gender and LVEF were not independent predictors of the outcome. VF (4.9±20.0 G1 vs. 1.1±5.47 G2, p=.046) and VT episodes were more prevalent in G1 (3.1±8.93 G1 vs. 0.3±1.59 G2, p=.026), as well as appropriate device shocks (4.3±12.06 G1 vs. 0.3±1.49 G2, p=.023). There was no difference in inappropriate shocks or mortality outcomes between groups. HRS ≥70% obtained from RM was an independent predictor of HF hospitalizations and was associated with arrhythmic events with VT and VF episodes and appropriate device shocks in HFrEF patients.