Worsening Heart Failure Research Articles

Outpatient worsening of heart failure and mortality in transthyretin amyloid cardiomyopathy.

Transthyretin cardiomyopathy (ATTR-CM) is characterized by episodes of worsening heart failure (WHF) which can include heart failure (HF) hospitalizations or urgent unplanned visits for administration of intravenous diuretics. WHF characterized by outpatient intensification of oral loop diuretics is common yet its prognostic implications for ATTR-CM patients relative to other WHF events remains unclear. We assessed how WHF characterized by outpatient diuretic intensification (ODI) relates to mortality in this population. This was a retrospective study of ATTR-CM patients presenting to the Columbia University Irving Medical Center. Oral loop diuretic dose was recorded longitudinally. WHF characterized by ODI was defined as a persistent increase in oral loop diuretic dose lasting >1 month. We analysed the all-cause mortality rate after either WHF event (hospitalization or ODI) relative to subjects who had no WHF event. Overall, 303 patients highly treated with tafamidis were included: 152 (50.2%) patients had no WHF events, 35 (11.6%) experienced HF hospitalization, and 145 (47.9%) experienced ODI; 29 (9.6%) patients experienced both WHF events. Patients experiencing ODI had higher rates of subsequent mortality (17.7 per 100 person-years; 95% confidence interval [CI] 13.3-23.7) as did those with a HF hospitalization (29.8 per 100 person-years; 95% CI 17.7-50.3) than patients without WHF events (5.0 per 100 person-years; 95% CI 3.0-8.3) on log-rank test. WHF characterized by ODI was independently associated with mortality in a model adjusting for age, genotype, atrial fibrillation, disease duration, time-varying tafamidis use and National Amyloid Centre (NAC) or Columbia stages. In contemporary patients with ATTR-CM treated with tafamidis, WHF requiring ODI is prognostic of subsequent mortality and is a clinical marker of disease progression.

Effects of Tirzepatide on the Clinical Trajectory of Patients with Heart Failure, a Preserved Ejection Fraction, and Obesity.

Patients with heart failure, a preserved ejection fraction (HFpEF), and obesity have significant disability and suffer frequent exacerbations of heart failure. We hypothesized that tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, would improve a comprehensive suite of clinical endpoints, including measures of health status, functional capacity, quality of life, exercise tolerance, patient well-being, and medication burden in these patients. 731 patients in class II-IV heart failure, ejection fraction ≥50%, and body mass index ≥30 kg/m2 were randomized(double-blind) to tirzepatide(titrated up to 15mg subcutaneously weekly)(n=364) or placebo(n=367), added to background therapy for a median of 104 weeks (Q1=66, Q3=126 weeks). tirzepatide reduced the combined risk of cardiovascular death or worsening heart failure and improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score(KCCQ-CSS). The current expanded analysis included sensitivity analyses of the primary endpoints, 6-minute walk distance(6MWD), EQ-5D-5L health state index, Patient Global Impression of Severity Overall Health(PGIS), NYHA class, use of heart failure medications, and a hierarchical composite based on all-cause death, worsening heart failure, and 52-week changes in KCCQ-CSS and 6MWD. Patients were aged 65.2±10.7, 53.8%(n=393) were female; BMI 38.2±6.7kg/m2, KCCQ-CSS 53.5±18.5, 6MWD 302.8±81.7meters, and 53%(n=388) had a worsening heart failure event in the prior 12 months. Compared with placebo, tirzepatide produced a consistent beneficial effect across all composites of death and worsening heart failure events, analyzed as time-to-first-event (hazard ratios 0.41-0.67). At 52 weeks, tirzepatide increased KCCQ-CSS 6.9 points (95%CI, 3.3, 10.6, P<0.001), 6MWD 18.3 meters (95%CI, 9.9, 26.7, P<0.001) and EQ-5D-5L 0.06 (95%CI, 0.03, 0.09, P<0.001). The tirzepatide group shifted to a more favorable PGIS (proportional odds ratio 1.99 (95%CI, 1.44, 2.76) and NYHA class (proportional odds ratio 2.26 (95%CI, 1.54, 3.31), both P<0.001 and required less heart failure medications (P=0.015). The broad spectrum of effects was reflected in benefits on the hierarchical composite (win ratio 1.63, 95%CI, 1.17, 2.28;P=0.004). Tirzepatide produced a comprehensive, meaningful improvement in heart failure across multiple complementary domains; enhanced health status, quality of life, functional capacity, exercise tolerance and well-being; and reduced symptoms and medication burden in patients with HFpEF and obesity.

Routine Spironolactone in Acute Myocardial Infarction.

Mineralocorticoid receptor antagonists have been shown to reduce mortality in patients after myocardial infarction with congestive heart failure. Whether routine use of spironolactone is beneficial after myocardial infarction is uncertain. In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients with myocardial infarction who had undergone percutaneous coronary intervention to receive either spironolactone or placebo and either colchicine or placebo. The results of the spironolactone trial are reported here. The two primary outcomes were a composite of death from cardiovascular causes or new or worsening heart failure, evaluated as the total number of events; and a composite of the first occurrence of myocardial infarction, stroke, new or worsening heart failure, or death from cardiovascular causes. Safety was also assessed. We enrolled 7062 patients at 104 centers in 14 countries; 3537 patients were assigned to receive spironolactone and 3525 to receive placebo. At the time of our analyses, the vital status was unknown for 45 patients (0.6%). For the first primary outcome, there were 183 events (1.7 per 100 patient-years) in the spironolactone group as compared with 220 events (2.1 per 100 patient-years) in the placebo group over a median follow-up period of 3 years (hazard ratio adjusted for competing risk of death from noncardiovascular causes, 0.91; 95% confidence interval [CI], 0.69 to 1.21; P = 0.51). With respect to the second primary outcome, an event occurred in 280 of 3537 patients (7.9%) in the spironolactone group and 294 of 3525 patients (8.3%) in the placebo group (hazard ratio adjusted for competing risk, 0.96; 95% CI, 0.81 to 1.13; P = 0.60). Serious adverse events were reported in 255 patients (7.2%) in the spironolactone group and 241 (6.8%) in the placebo group. Among patients with myocardial infarction, spironolactone did not reduce the incidence of death from cardiovascular causes or new or worsening heart failure or the incidence of a composite of death from cardiovascular causes, myocardial infarction, stroke, or new or worsening heart failure. (Funded by the Canadian Institutes of Health Research and others; CLEAR ClinicalTrials.gov number, NCT03048825.).

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 &lt; 0.001), decreased estimated blood volume (ETD −0.58 l, 95% CI −0.63 to −0.52; P &lt; 0.001) and reduced C-reactive protein levels (ETD −37.2%, 95% CI −45.7 to −27.3; P &lt; 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 &lt; 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, Serum Potassium, and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

Treatment with finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), improved outcomes in patients with heart failure with mildly reduced or preserved ejection fraction in FINEARTS-HF, but was associated with increased levels of serum potassium in follow-up. To investigate the frequency and predictors of serum potassium level greater than 5.5 mmol/L and less than 3.5 mmol/L and examine the treatment effect associated with finerenone, relative to placebo, on clinical outcomes based on postrandomization potassium levels. Secondary analysis of the FINEARTS-HF multicenter, randomized clinical trial, performed between September 14, 2020, and January 10, 2023, with a median follow-up of 32 months (final date of follow-up: June 14, 2024). Patients with heart failure and left ventricular ejection fraction greater than or equal to 40%, New York Heart Association class II to IV symptoms, and elevated natriuretic peptides were included. Participants received finerenone or placebo. The primary outcome was a composite of total worsening heart failure events or cardiovascular death. A total of 6001 participants were included (3003 randomized to receive finerenone and 2998 randomized to receive placebo). The increase in serum potassium was greater in the finerenone group than the placebo group at 1 month (median [IQR] difference, 0.19 [0.17-0.21] mmol/L) and 3 months (median [IQR] difference, 0.23 [0.21-0.25] mmol/L), which persisted for the remainder of trial follow-up. Finerenone increased the risks of potassium level increasing to greater than 5.5 mmol/L (hazard ratio [HR], 2.16 [95% CI, 1.83-2.56]; P < .001) and decreased the risks for potassium level decreasing to less than 3.5 mmol/L (HR, 0.46 [95% CI, 0.38-0.56]; P < .001). Both low (< 3.5 mmol/L; HR, 2.49 [95% CI, 1.8-3.43]) and high (>5.5 mmol/L; HR, 1.64 [95% CI, 1.04-2.58]) potassium levels were associated with higher subsequent risks of the primary outcome in both treatment groups. Nevertheless, the risk of the primary outcome was generally lower in patients treated with finerenone compared with placebo, even in those whose potassium level increased to greater than 5.5 mmol/L. In patients with heart failure with mildly reduced or preserved ejection fraction, finerenone resulted in more frequent hyperkalemia and less frequent hypokalemia. However, with protocol-directed surveillance and dose adjustment, clinical benefit associated with finerenone relative to placebo was maintained even in those whose potassium level increased to greater than 5.5 mmol/L. ClinicalTrials.gov Identifier: NCT04435626.

Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.

Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes. In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. The two primary end points were a composite of adjudicated death from cardiovascular causes or a worsening heart-failure event (assessed in a time-to-first-event analysis) and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better quality of life). A total of 364 patients were assigned to the tirzepatide group and 367 to the placebo group; the median duration of follow-up was 104 weeks. Adjudicated death from cardiovascular causes or a worsening heart-failure event occurred in 36 patients (9.9%) in the tirzepatide group and in 56 patients (15.3%) in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.41 to 0.95; P = 0.026). Worsening heart-failure events occurred in 29 patients (8.0%) in the tirzepatide group and in 52 patients (14.2%) in the placebo group (hazard ratio, 0.54; 95% CI, 0.34 to 0.85), and adjudicated death from cardiovascular causes occurred in 8 patients (2.2%) and 5 patients (1.4%), respectively (hazard ratio, 1.58; 95% CI, 0.52 to 4.83). At 52 weeks, the mean (±SD) change in the KCCQ-CSS was 19.5±1.2 in the tirzepatide group as compared with 12.7±1.3 in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events (mainly gastrointestinal) leading to discontinuation of the trial drug occurred in 23 patients (6.3%) in the tirzepatide group and in 5 patients (1.4%) in the placebo group. Treatment with tirzepatide led to a lower risk of a composite of death from cardiovascular causes or worsening heart failure than placebo and improved health status in patients with heart failure with preserved ejection fraction and obesity. (Funded by Eli Lilly; SUMMIT ClinicalTrials.gov number, NCT04847557.).

Right atrial strain measured by 2D speckle-tracking echocardiography is associated with poor cardiac outcomes in patients with heart failure.

Right heart failure (HF) is a poor prognostic factor in patients with HF. The right atrial (RA) function has attracted less attention than the right ventricular (RV) function. The association of RA reservoir strain evaluated by 2D speckle-tracking echocardiography (2DSTE) with clinical outcomes in patients with HF remains unclear. We prospectively enrolled patients with HF admitted to our hospital. We measured the RA, RV, left atrial (LA), and left ventricular (LV) strain using 2DSTE before discharge. The RA reservoir strain (RASr) was measured in the global right atrium. The primary endpoints were cardiac death and worsening of HF requiring rehospitalization or intravenous diuretics. Among 226 patients with HF, 72 primary endpoints were recorded during a median follow-up period of 1081days. Kaplan-Meier analysis showed a higher cardiac event rate in the low RASr group than in the high RASr group (P = 0.0089). Multivariate Cox hazard analysis showed that RASr was independently associated with cardiac events after adjusting for confounding factors [hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.51-0.96; P = 0.0347]. Decreased RASr could be a feasible marker of cardiac events in patients with HF.

Abstract 4118387: Artificial Intelligence-Enhanced Echocardiogram Assessment Helps Distinguish Cardiomyopathy from Beat-to-Beat Variation in Atrial Fibrillation

Background: Atrial fibrillation (AF) can be associated with reductions in left ventricular ejection fraction (LVEF) that improve upon conversion of AF to sinus rhythm. Such LVEF changes during AF may be due to LVEF measurement error from beat-to-beat variations related to AF itself. More precise artificial intelligence (AI)-enhanced LVEF assessment could help distinguish between such LVEF “pseudo-reduction” during AF and true cardiomyopathy, thus potentially preventing unnecessary downstream workup and treatment. Methods: Using a transthoracic echocardiogram database at a large academic medical center, we identified all patients whose LVEF fell below 50% while in AF who had subsequent LVEF recovery to over 50% within 90 days after converting from AF to sinus rhythm. For echocardiograms in AF, we compared the clinically assessed LVEF with AI-enhanced LVEF assessment by EchoNet-Dynamic, a validated deep learning algorithm. Results: In our cohort of 84 patients, the mean age was 74 years old, 36.9% were female, and 26.2% non-White. The mean LVEF recovery was 19.3% (95% CI 17.1-21.5%) after converting from AF to sinus rhythm with a mean duration of 27.4 days between the AF and sinus rhythm echocardiograms (Figure 1). For AF echocardiograms, the LVEF when reassessed by deep learning was 8.4% (6.3-10.5%) higher than the original clinical read, resulting in 30.3% of patients being reclassified as no longer having a reduced LVEF less than 50% while in AF. Among these patients with LVEF reductions during AF, 27.4% and 19.0% were given a new or worsened heart failure with reduced ejection fraction (HFrEF) diagnosis, 15.5% underwent ischemic testing, and 17.9% were started on new HFrEF medications. Discussion: LVEF reductions during AF can lead to new HFrEF diagnosis, workup, and treatment. However, such LVEF reductions may be temporary and partially explained by undermeasurement of LVEF during AF. AI-enhanced LVEF assessment may help reduce such measurement errors during AF and thereby prevent overdiagnosis of HFrEF. Further research is needed to understand the clinical significance of true but temporary LVEF reductions during AF.

Abstract 4138662: Mineralocorticoid receptor antagonist in patients with acute myocardial infarction: An updated systematic review and meta-analysis of randomized trials

Background: While mineralocorticoid antagonists (MRA) reduce mortality in patients developing heart failure post myocardial infarction (MI), it is unclear whether they are beneficial in an unselected post-MI population. Aims: Using a systematic review and meta-analysis, we aim to determine the effect of MRA treatment versus no MRA treatment on all-cause mortality in unselected post-MI patients from randomized data, simultaneously with the presentation of the largest randomized controlled trial on the topic, the CLEAR SYNERGY trial. Methods/Approach: We completed a systematic review of all randomized controlled trials comparing MRA treatment to no MRA treatment in post-MI patients. We will perform our primary analysis using fixed effects with the Peto odds ratio method and use random effects as a sensitivity analysis. The primary outcome will be all-cause mortality, and secondary outcomes will include cardiovascular mortality, new or worsening heart failure, recurrent myocardial infarction and stroke. Results/Data: Our systematic review of Pubmed, Embase, and CENTRAL from inception until April 30, 2024, yielded 456 records. A total of 11,199 participants from 11 randomized clinical trials will be included in addition to the late-breaking CLEAR SYNERGY trial. The CLEAR SYNERGY trial is a 2 x 2 factorial randomized controlled trial of low-dose colchicine 0.5mg daily versus placebo and spironolactone 25mg daily versus placebo in 7,062 post-MI patients who were within 72h of the index percutaneous coronary intervention. The results of the spironolactone factorial will be presented in the fall of 2024 with an expected median follow-up of 3.5 years. As the investigators of the CLEAR SYNERGY trial, we will combine our data with the other 11 trials for a total of 12 trials and 18,261 participants. Conclusions: CLEAR SYNERGY is the largest randomized controlled trial with the longest follow-up of spironolactone in the post-MI population. Our meta-analysis will provide updated effect estimates of post-MI MRA treatment, leveraging the late-breaking CLEAR SYNERGY data to reflect the totality of the evidence.

Abstract 4134273: Low 5-hydroxytryptamine levels are associated with adverse outcomes in patients with heart failure with preserved ejection fraction

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome and its pathophysiology is not fully understood. A monoamine, 5-hydroxytryptamine (5-HT), is involved in diverse biological functions and suggested to play a role in cardiovascular diseases. However, the clinical relevance of 5-HT in HFpEF remains unclear. Aims: This study aimed to elucidate the clinical significance and prognostic value of 5- HT in patients with HFpEF. Methods: We conducted a prospective study involving 240 consecutive hospitalized patients with HFpEF (mean age 72 years, 52% male). We measured circulating blood 5-HT levels using the enzyme-linked immunosorbent assay method. Clinical and outcome data were collected. Results: Correlation analysis revealed that 5-HT levels were negatively correlated with blood B-type natriuretic peptide concentration and tricuspid regurgitation pressure gradient. When patients were stratified into two groups based on the median 5-HT levels (90.5 ng/mL), Kaplan-Meier analysis showed that HFpEF patients with low blood 5-HT levels had lower event-free survival rates from the composite event of cardiac death and worsening heart failure over a median follow-up period of 725 days (Figure). In a multivariable Cox proportional hazard model adjusting for confounding variables, low levels of 5-HT were independently associated with increased risks of the composite of cardiac events (hazard ratio, 3.25; P &lt; 0.01). Conclusion: Low 5-HT levels are associated with adverse outcomes in patients with HFpEF and 5-HT may serve as a useful biomarker for predicting prognosis in such patients.

Abstract 4129974: Increased Expression of Histone Deacetylases-2 and -6 in Left Ventricular Myocardium of Dogs with Chronic Heart Failure

Background: Histone deacetylases (HDACs) -2 and -6 are localized in the nucleus and cytoplasm of cells and have been implicated in the development of left ventricular (LV) hypertrophy, cardiac interstitial fibrosis, inflammation and worsening of LV systolic and diastolic function thus contributing to progressive worsening of heart failure (HF) with reduced ejection fraction (HFrEF) as well as HF with preserved ejection fraction (HFpEF). There is considerable interest in the application of small molecules that inhibit the activity of HDAC proteins in HF in the hope of fostering clinical benefit. Purpose: In the present study we examined the expression of HDAC-2 and -6 in LV tissue from normal (NL) dogs and dogs with chronic HF (LVEF &lt;35%) produced by multiple sequential intracoronary microembolizations. Methods: Studies were performed in LV tissue from 7 NL dogs and 7 HF dogs. HDAC-2 and -6 protein levels were determined by Western blotting in the lysate of homogenate and 9000g supernatant (cytosolic) fractions prepared from powder of approximately 200 mg frozen LV tissue. After determining the protein by Lowry method, approximately 30 μg homogenate and 15 μg supernatant for HDAC-2 and 8 μg protein for both homogenate and supernatant for HDAC-6 were separated on 4%-20% SDS-PAGE and transferred on PVDF membrane. Band intensities were quantified in densitometric units (du). All data were normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results: HDAC-2 proteins levels normalized to GAPDH were higher in the cytosol (0.59 ± 0.10 vs. 0.17 ± 0.04, p&lt;0.05 vs. NL) and homogenate (0.75 ± 0.12 vs. 0.55 ± 0.10, not statistically significant) of LV tissue of dogs with HF compared to NL dogs. HDAC-6 protein levels were higher in the homogenate (2.54 ± 0.36 vs. 0.57 ± 0.19, p&lt;0.05 vs. NL) and the cytosol (0.96 ± 0.15 vs. 0.78 ± 0.13, not statistically significant) of LV tissue of dogs with HF compared to NL dogs. Conclusions: These findings indicate upregulation of protein levels of HDAC-2 and -6 isoforms in LV myocardium of dogs with chronic HF. These abnormalities are likely to contribute to worsening HF. Selective inhibition of HDAC-2 and -6 represents a potential therapeutic approach for the treatment of both HFrEF and HFpEF.

Abstract 4125606: Systolic Blood Pressure During Sleep Determined by Pulse Transit Time Predicts Worsening Heart Failure in Patients with Heart Failure

Introduction: Intensive blood pressure (BP) lowering therapy is associated with lower rates of major adverse cardiac and cerebrovascular events in the general population. On the other hand, lower daytime systolic BP (SBP) is associated with higher mortality in patients with heart failure (HF). However, prognostic impact of SBP during sleep was unclear in patients with HF. Methods and Results: We measured continuous SBP during sleep non-invasively by pulse transit time in 379 patients with HF (median age 71, male 53.6%). Beat-to-beat SBP was calculated based on pulse transit time, which was defined as the travel time from the R-wave of electrocardiogram to the pulse wave at the finger detected by plethysmography. Mean values of SBP during sleep were used in the present study. The primary endpoint was hospitalization for worsening HF. The patients were divided into three groups based on the tertiles of SBP during sleep: High SBP group (median SBP 138 mmHg, n = 127), Middle SBP group (median SBP 117 mmHg, n = 127), and Low SBP group (median SBP 100 mmHg, n = 125). The Low SBP group showed the youngest age (High, Middle, and Low groups; 73, 73, 68 years, P &lt; 0.001). Levels of B-type natriuretic peptide (207.7, 216.7, and 407.2 pg/mL, P = 0.039) and estimated glomerular filtration rate (52.6, 54.0, and 57.1 mL/min/1.73 m 2 , P = 0.041) were the highest in the Low SBP group. During the follow-up period of median 1,083 days after SBP measurement, 66 patients experienced hospitalization for worsening HF. Kaplan-Meier analysis revealed that primary endpoint occurred most frequently in the Low SBP group ( Figure ). Multivariable Cox proportional hazard analysis showed that the lowest SBP tertile was associated with the primary endpoint compared to the highest SBP tertile (hazard ratio 2.546, 95% confidence interval 1.257–5.158, P = 0.009). Conclusion: Low SBP during sleep was associated with hospitalization for HF in patients with HF.

Abstract 4144512: Impact of Nutritional Status on Transcatheter Edge-to-Edge Repair Outcomes in Mitral Regurgitation: Insights from a National Database Analysis

Introduction: Transcatheter edge-to-edge repair of the mitral valve with the MitraClip has offered a less invasive percutaneous alternative to surgical repair in select candidates with mitral regurgitation. Various factors impact the outcomes of MitraClip. We investigated the impact of nutritional status on the outcomes of MitraClip. Methods: Utilizing the nationwide inpatient sample data for years from January 1, 2016, and December 31, 2021, patients who underwent MitraClip were identified. They were categorized based on obesity and protein energy malnutrition (PEM). Statistical significance was assigned at p&lt;05. Results: Out of the 8115 patients undergoing MitraClip, 2215 had PEM, and 5900 had obesity—table 1. Patients in the PEM group were older, with a higher prevalence of comorbidities, including anemia, pneumonia, liver disease, and fluid and electrolyte disorders, compared to the obese group. Conversely, the obesity group had a higher prevalence of hypertension, diabetes, and hypertension with complications. Our analysis revealed that PEM subgroups had significantly higher in-hospital mortality, cardiogenic shock, mechanical circulatory support (MCS) requirement, post-procedural worsening heart failure, spontaneous cardiac arrest, and major adverse cardiovascular and cerebrovascular events (MACCE). After adjusting for potential confounders, PEM remained an independent predictor of increased odds of death, cardiac arrest, ECMO, MCS, and MACCE compared to obesity. The propensity score matching analysis confirmed that PEM was associated with significantly higher rates of in-hospital mortality, cardiac arrest, and MACCE compared to obesity. (Figure 1) Conclusion: Our results reveal that PEM is associated with significantly worse outcomes in patients undergoing MitraClip procedures compared to obesity. These findings are consistent across multivariate and propensity score matching analyses.

Abstract 4112944: A diagnostic challenge overcome with persistent clinical suspicion in a case of cardiac AL amyloidosis

Case: A 62-year old male with a history of chronic kidney disease and paroxysmal atrial fibrillation presented with several months of fatigue, a progressive decline in functional status (NYHA IIIb-IV), weight loss, and intermittent lower extremity swelling. Blood pressure was 92/72 mmHg on presentation, and heart rate was 90 bpm. Physical examination revealed a jugular venous pressure of 12-14 cm H2O and 2+ bilateral lower extremity edema with mild wheezing. Methods/workup: Laboratories are shown in Table 1 and were notable for a serum free light chain ratio of 0.14. Transthoracic echocardiogram (figure 1) revealed a left ventricular (LV) ejection fraction of 33% with increased LV wall thickness and severe bi-atrial enlargement. Bone marrow biopsy revealed 2% lambda restricted plasma cells without evidence of amyloid deposits; metastatic bone survey was negative. A fat pad biopsy and endomyocardial biopsy stained negative for amyloid with Congo red. Cardiac MRI showed diffuse, circumferential subendocardial late gadolinium enhancement, most compatible with cardiac amyloidosis (figure 2). The patient also had a chest CT scan that demonstrated a few patchy nodular pulmonary infiltrates. Given his extensive negative workup, he was referred to pulmonary and endobronchial biopsy was positive for amyloid on Congo red staining (figure 3). Biopsy tissue typing revealed Lambda subtype AL amyloidosis. Management: The patient was started on Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone by Hematology. Unfortunately, about a month after his diagnosis, he developed worsening heart failure despite treatment. He was admitted to an outside hospital with refractory cardiogenic shock and passed away during that admission. Discussion: The diagnosis of AL amyloidosis requires a high index of suspicion for prompt diagnosis and treatment. We present a case in which cardiac amyloidosis was suspected based on the patient’s clinical picture and cardiac imaging; however, multiple initial biopsies were negative. An expedited, multimodal and interdisciplinary diagnostic assessment is imperative as prognosis with chemotherapy is highly dependent on extent of AL disease, patient functional status, and presence of cardiac compromise. Elevated natriuretic peptides, troponins, autonomic dysfunction, and hypotension are negative prognostic features.

Preventive catheter ablation for ventricular arrhythmias in patients with end-stage heart failure referred for heart transplantation evaluation: Rationale for and design of the CASTLE-VT trial.

Timely referrals for transplantation and left ventricular assist device (LVAD) play a key role in favourable outcomes in patients with advanced heart failure (HF). Cardiovascular mortality, driven by sudden cardiac death, is the main reason for dying while waiting for heart transplantation (HTx). The purpose of the Preventive Catheter Ablation for ventricular arrhythmiaS in patients with end-sTage heart faiLure rEferred for heart transplantation eValuaTion (CASTLE-VT) trial is to test the hypothesis that prophylactic catheter ablation of arrhythmogenic ventricular scar tissue will reduce mortality, need for LVAD implantation, and urgent HTx in patients with end-stage HF related to ischaemic cardiomyopathy (ICM). CASTLE-VT is a randomized evaluation of prophylactic ablative treatment of arrhythmogenic ventricular scar in patients referred for HTx evaluation and diagnosed with ICM. Ablation will be performed with the use of a substrate-based approach in which the myocardial scar is mapped and ablated while the heart remains predominantly in sinus rhythm. The primary endpoint is the composite of all-cause mortality, worsening of HF requiring prioritized transplantation or LVAD implantation. The main secondary study endpoints are all-cause mortality, cardiovascular mortality, incidence of implantable cardioverter-defibrillator (ICD) therapy, hospitalizations, quality of life, time to first ICD therapy, number of device-detected ventricular tachycardia/ventricular fibrillation episodes, left ventricular function, and exercise tolerance. CASTLE-VT will randomize 160 patients with a follow-up period of 2 years. CASTLE-VT will determine whether prophylactic catheter ablation of arrhythmogenic ventricular scar tissue reduces mortality in patients with end-stage HF who are referred for HTx evaluation.

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.

Acute myocarditis in a paediatric patient with pre-existing dilated cardiomyopathy following SARS-COV-2 infection: a journey from decompensation to heart transplantation.

A 10-year-old child with stabilised idiopathic dilated cardiomyopathy was admitted to the hospital with sudden worsening of heart failure. Further analysis showed increased NT-proBNP and positive for COVID-19. Myocarditis secondary to COVID-19 was assumed. Recurrent hospitalizations with inotropic support were required due to the progressive worsening of cardiac function. Seven months after SARS-CoV-2 myocarditis, she underwent heart transplantation.

Outpatient Worsening Heart Failure in Patients with Transthyretin Amyloidosis with Cardiomyopathy in the HELIOS-B Trial.

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a fatal disease, caused by misfolded transthyretin depositing as amyloid fibrils in the heart. Because disease progression is common, practical and sensitive methods are needed to monitor patients and optimize treatment decisions. Outpatient worsening heart failure (HF) (oral loop diuretic intensification or initiation) is simple to assess and has been shown to be prognostic of mortality in patients with ATTR-CM. We aimed to assess the clinical and prognostic significance of and the effect of vutrisiran treatment on outpatient worsening HF in patients with ATTR-CM from the HELIOS-B trial. Associations between outpatient worsening HF and a composite of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent HF visits), all-cause mortality, and other disease progression-related endpoints were evaluated. The impact of vutrisiran over 36 months on outpatient worsening HF and an expanded composite of all-cause mortality, recurrent CV events, and outpatient worsening HF was also assessed. Overall, 321 patients (49.1%) had ≥1 outpatient worsening HF, 245 (37.5%) had ≥1 CV event(s), and 120 (18.3%) died; 237 patients (36.2%) had no events. Patients with outpatient worsening HF had an increased risk of all-cause mortality and CV events (hazard ratio [HR]: 2.58; 95% confidence interval [CI]: 2.04-3.27) and all-cause mortality (HR: 2.45; 95% CI: 1.70-3.52), as well as a greater deterioration in 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and a greater increase in N-terminal prohormone of B-type natriuretic peptide. In recurrent event analyses over the double-blind period, vutrisiran versus placebo reduced the rate of outpatient worsening HF (relative rate ratio: 0.66; 95% CI: 0.56-0.78). Vutrisiran also reduced the risk of the composite of all-cause mortality, CV events, and outpatient worsening HF versus placebo (HR: 0.69; 95% CI: 0.57-0.83). Outpatient worsening HF was frequent in patients with ATTR-CM in HELIOS-B, and was associated with increased mortality, and reduced by vutrisiran.

Trajectory of health-related quality of life during and after hospitalisation due to worsening of heart failure.

This study aimed to examine the trajectory in health-related quality of life (HRQoL) during and after hospitalisation for worsening of heart failure (HF) in Malaysia. 200 patients with heart failure and reduced ejection fraction (HFrEF) admitted into two hospitals in Malaysia due to worsening of HF were surveyed using the EQ-5D-5L questionnaire. The primary outcomes were utility values at admission, discharge and 1-month post-discharge (1MPD). Secondary outcomes included the visual analogue scores (VAS) and the proportion of patients reporting each EQ-5D-5L dimension levels. Missing data were imputed using multiple imputation, and generalised linear mixed models were fitted. At admission, the unadjusted mean utility values and VAS scores for HFrEF patients in Malaysia were as low as 0.150 ± 0.393 and 38.2 ± 20.8, respectively. After a median hospital stay of 4 days, there was a significant improvement in utility values and VAS scores by 0.510 (95% CI: 0.455-0.564) and 28.8 (95% CI: 25.5-32.1), respectively. The utility value and VAS score at 1-month post-discharge were not significantly different from discharge. The proportion of HFrEF patients reporting problems and severe problems in mobility, self-care, usual activities, and anxiety/depression, pain/discomfort reduced at varying degree from admission to discharge and 1MPD. HF is a progressive condition with substantial variation in HRQoL during the disease trajectory. During hospitalisation due to worsening of HF, HFrEF population has unfavourable HRQoL. Rapid and significant HRQoL improvement was observed at discharge, which sustained over one month. The study findings can inform future cost-effectiveness analyses and policies.

Clinical and financial implications of inpatient and outpatient management strategies for worsening heart failure

Abstract Introduction Hospitalizations for worsening heart failure (HF) represent an enormous public health and financial burden. Accordingly, select centers have developed outpatient worsening HF (WHF) management strategies focused on care in emergency departments (ED), observation units, or intravenous (IV) diuretic clinics. However, broad use of these outpatient strategies and the associated outcomes and healthcare costs remain unclear. Methods Among US Medicare beneficiaries age ≥65 years hospitalized for HF in the Get With The Guidelines Heart Failure registry 2010-2018, we identified patients with a post-discharge non-fatal WHF event. Patients were divided into 4 mutually exclusive groups defined by type of first post-discharge WHF event (HF hospitalization, ED visit with ED discharge, observation unit stay, and outpatient clinic visit with IV diuretics). Following each type of WHF event, mortality, home-time (days alive and out of any healthcare institution), and healthcare costs were compared over the subsequent 12-months. Costs of the initial WHF management strategy were also assessed. Results Among 181,827 patients hospitalized for HF, during the 12-months post-discharge, 83,971 (46.2%) survived with no WHF event, 36,697 (20.2%) died prior to a WHF event, and 61,159 (33.6%) had a WHF event. Of patients with a WHF event, 48,612 were managed with HF hospitalization (79.5%), 8,139 (13.3%) with an ED visit, 1,767 (2.9%) with an observation unit stay, and 2,641 (4.3%) with an outpatient IV diuretic visit. Compared with HF hospitalization, patients with WHF managed in the ED, observation unit, or IV diuretic clinic experienced lower subsequent mortality (Figure 1). Mean 12-month home-time was lowest following HF hospitalization (207 ± 144 days), intermediate following ED (238 ±136 days) and outpatient IV diuretic visits (252 ±128 days), and highest following observation unit stays (277 ± 125 days). For the initial WHF event, median (25th, 75th) total per-patient costs were highest for HF hospitalization and lowest for outpatient IV diuretic visits (Figure 2). Over the 12-months following the WHF event, median total per-patient costs were highest following outpatient IV diuretic visits, intermediate following HF hospitalization and ED stays, and lowest following observation unit stays. Conclusions In a nationwide analysis of older US adults, 1 in 5 episodes of recurrent WHF were exclusively managed as an outpatient within the ED, observation unit, or IV diuretic clinic. High rates of death and substantial reductions in home-time occurred following WHF regardless of inpatient or outpatient management, but were worse following HF hospitalization. Outpatient IV diuretic administration was the least expensive initial management strategy, but was associated with the highest per-patient costs over the subsequent 12 months.