Pro B-type Natriuretic Peptide Levels Research Articles

Sex differences in clinical characteristics and long-term outcome in patients with heart failure: data from the KorAHF registry.

Sex differences in the prognosis of heart failure (HF) have yielded inconsistent results, and data from Asian populations are even rare. This study aimed to investigate sex differences in clinical characteristics and long-term prognosis among Korean patients with HF. A total of 5,625 Korean patients hospitalized for acute HF were analyzed using a prospective multi-center registry database. Baseline clinical characteristics and long-term outcomes including HF readmission and death were compared between sexes. Women were older than men and had worse symptoms with higher N-terminal pro B-type natriuretic peptide levels. Women had a significantly higher proportion of HF with preserved ejection fraction (HFpEF). There were no significant differences in in-hospital mortality and rate of guideline-directed medical therapies in men and women. During median follow- up of 3.4 years, cardiovascular death (adjusted hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.07-1.78; p = 0.014), and composite outcomes of death and HF readmission (adjusted HR, 1.13; 95% CI, 1.01-1.27; p = 0.030) were significantly higher in men than women. When evaluating heart failure with reduced ejection fraction (HFrEF) and HFpEF separately, men were an independent risk factor of cardiovascular death in patients with HFrEF. Clinical outcome was not different between sexes in HFpEF. In the Korean multi-center registry, despite having better clinical characteristics, men exhibited a higher risk of all-cause mortality and readmission for HF. The main cause of these disparities was the higher cardiovascular mortality rate observed in men compared to women with HFrEF.

Bicaval TricValve Implantation in Patients With Severe Symptomatic Tricuspid Regurgitation: 1-Year Follow-Up Outcomes

BackgroundSeveral orthotopic transcatheter strategies have been developed to treat severe tricuspid regurgitation (TR); however, many patients are deemed unsuitable. Caval valve implantation with the TricValve system addresses this unmet need. ObjectivesThis study sought to determine the impact of TricValve on systemic congestion and quality of life (QOL) at 1 year. MethodsThe TRICUS (Safety and Efficacy of the TricValve® Transcatheter Bicaval Valves System in the Superior and Inferior Vena Cava in Patients With Severe Tricuspid Regurgitation) and TRICUS EURO studies were prospective, nonblinded, nonrandomized, single-arm trials representing the early-in-man experience of the TricValve system in NYHA functional class III or IV severe TR patients, optimally medicated and ineligible for open heart surgery, with significant caval backflow. The primary endpoint was QOL metrics and functional status. The 1-year results of the combined cohort are described here. ResultsForty-four patients were included. Mean age was 76.2 ± 7.5 years, 81.0% were women, and the TRISCORE (risk score model for isolated tricuspid valve surgery) was 5.3 ± 1.3. Clinical improvement at 1 year was achieved in 42 (95.5%) patients, measured by (at least 1 of) an increase in ≥15 points from baseline in 12-item Kansas City Cardiomyopathy Questionnaire score, improvement to NYHA functional class to I or II, or an increase ≥40 m in the 6-minute walk test. There were 3 (6.8%) deaths at 1-year follow-up (1 cardiovascular), and the heart failure rehospitalization rate was 29.5%. Stent fracture, conduction system disturbances, or clinically significant leaflet thrombosis were not detected. Abolished hepatic vein backflow was achieved and persisted in 63.8% of the patients, contributing towards a reduction in congestive symptoms, N-terminal pro–B-type natriuretic peptide levels (P = 0.032), and diuretic treatment. ConclusionsCaval valve implantation with the TricValve system associated with meaningful 1-year clinical improvements in terms of QOL along with relatively low mortality rates. (TRICUS Study – Safety and Efficacy of the TricValve® Device; NCT03723239)

Effect of Frailty on the Long-Term Prognosis of Elderly Patients with Acute Myocardial Infarction.

To investigate the effect of frailty on the long-term prognosis of elderly patients with acute myocardial infarction (AMI). The data of 238 AMI patients (aged ≥75 years) were retrospectively reviewed. They were divided into two groups according to the Modified Frailty Index (mFI): frailty group (mFI≥0.27, n=143) and non-frailty group (mFI<0.27, n=95). The major adverse cardiovascular and cerebrovascular events (MACEs) and Kaplan-Meier survival curves of the two groups were compared. Multivariate Cox regression analysis was used to identify the risk factors for MACEs. The frailty group showed a significantly older age as well as a higher N-terminal proB-type natriuretic peptide level, Global Registry of Acute Coronary Events score, and CRUSADE bleeding score compared with the non-frailty group (P<0.05). A significantly greater proportion of patients with combined heart failure, atrial fibrillation, comorbidity, and activities of daily living score of <60 was also observed in the frailty group compared with the non-frailty group (P<0.05). At 36 months after AMI, the frailty group vs the non-frailty group showed a significantly poorer survival (log-rank P=0.005), higher incidence of MACEs (50.35 vs 29.47, P=0.001), higher overall mortality rate (20.98% vs 7.37%, P=0.006), higher 30-day mortality rate (13.99% vs 5.26%, P=0.033), higher major bleeding rate (14.69% vs 5.26, P=0.018), and lower repeat revascularization rate (2.10% vs 8.42%, P=0.03). Frailty, type 2 diabetes, and N-terminal proB-type natriuretic peptide ≥1800 pg/mL were independent risk factors for MACEs. Frailty is an independent risk factor affecting the long-term prognosis of elderly patients with AMI.

Long-term effects of mavacamten treatment in obstructive hypertrophic cardiomyopathy (HCM): updated cumulative analysis of the EXPLORER cohort of MAVA-long-term extension (LTE) study up to 120 weeks

Abstract Introduction Mavacamten was efficacious and well tolerated in patients (pts) with obstructive HCM over a median follow-up of 62 weeks in a previous interim analysis of the ongoing MAVA-LTE study (NCT03723655) (data cut-off; August 31, 2021). Here, we report an updated cumulative analysis of the EXPLORER cohort of MAVA-LTE up to 120 weeks. Methods Pts who completed EXPLORER-HCM (NCT03470545) could enroll in MAVA-LTE. All pts initiated the study with mavacamten 5 mg/day per protocol; dose adjustments to 2.5, 10, or 15 mg were based on site-read Valsalva left ventricular outflow tract (LVOT) gradient and LV ejection fraction (LVEF). Results In total, 231 pts (median age, 61 years; 39% female) enrolled in the EXPLORER cohort of MAVA-LTE. Median time on study was 101 weeks at data cut-off (May 31, 2022) with variations due to differences in enrollment timing. At data cut-off, 215 pts remained on treatment (total adjusted exposure: 475 pt-years). Mavacamten dosing of pts who reached week 120 (n=80) was: 2.5 mg (27.5%); 5 mg (31.3%); 10 mg (26.3%); 15 mg (12.5%). Between weeks 48–120, 34 of 231 (14.7%) pts underwent dose adjustments. Mavacamten treatment showed sustained improvements in mean [SD] change from baseline to week 120 in LVOT gradients (resting, −35.3 [33.0] mmHg; Valsalva, −47.0 [37.3] mmHg), left atrial volume index (−8.5 [10.3] mL/m2) and E/e’ average (−3.9 [5.0]) (Table). At week 120, 83.5% of pts had a Valsalva LVOT gradient ≤30 mmHg. Mavacamten was associated with sustained reduction from baseline to week 120 in N-terminal pro B-type natriuretic peptide (NT-proBNP) level (Table); 75.9% of pts improved by ≥1 class New York Heart Association class (Figure). Mean (SD) LVEF decreased by 9.1% (7.1) from baseline to week 120 but remained in the normal range. Since the previous interim analysis (data cut-off: August 31, 2021), 1 additional transient reduction in LVEF &amp;lt;50% occurred resulting in temporary treatment interruption (a total of 13 pts [5.6%] experienced LVEF &amp;lt;50% from study initiation). The pt resumed treatment at a lower dose 4 weeks after the event. In total, 74 serious adverse events (SAE) were reported in 47 pts (20.3%), with 18 new SAEs and 13 additional pts (5.6%) with SAEs since the previous interim analysis, including 1 new SAE (atrial fibrillation) considered drug related. No new safety signals were identified. One additional death (leading to a total of 4) occurred, due to intracranial hemorrhage. Like the previous 3 deaths (due to acute myocardial infarction, cardiac arrest, and bacterial endocarditis) the event was considered unrelated to the study drug. Conclusions Long-term mavacamten treatment up to 120 weeks showed sustained improvements in LVOT obstruction, symptoms, and NT-proBNP levels in pts with symptomatic obstructive HCM consistent with the findings of the parent study. Mavacamten treatment continues to be well tolerated with no new safety signals observed.

Changes in standard of care (SOC) medication during long-term mavacamten treatment for obstructive hypertrophic cardiomyopathy (HCM): results from the EXPLORER cohort of MAVA-Long-Term Extension (LTE)

Abstract Introduction Mavacamten is efficacious and well tolerated in patients with obstructive HCM in the ongoing MAVA-LTE study (NCT03723655) as shown in previous interim analyses. Here, we present exploratory data from the EXPLORER cohort of MAVA-LTE investigating the effect of changes in SOC treatment on the efficacy and safety of mavacamten. Methods Patients who completed EXPLORER-HCM (NCT03470545) could enroll in MAVA-LTE and comprised the EXPLORER cohort. All patients in the EXPLORER cohort received mavacamten. Patients could receive beta blockers or nondihydropyridine calcium channel blockers (verapamil/diltiazem) as SOC treatment. After 24 weeks on study, SOC treatment could be adjusted. A cumulative interim analysis (data cut-off: May 31, 2022) was performed on patients who: received no SOC, discontinued SOC, had any reduction in SOC and had ≥50% reduction in SOC from baseline to data cut-off. Results In total, 231 patients (mean age, 60 years; 39% female) comprised the EXPLORER-LTE cohort (median time on study: 101 weeks at data cut-off). At baseline, 176 patients (76.2%) received beta blockers and 38 (16.5%) received nondihydropyridine calcium channel blockers. At data cut-off, 12 (5.2%) patients had received no SOC treatment from baseline, 11 (4.8%) patients had discontinued SOC, 27 (11.7%) patients had any dose reduction in SOC, 18 (7.8%) patients had a ≥50% reduction in SOC and 14 (6.1%) patients had an increase in SOC. In the no SOC subgroup, mavacamten treatment was associated with improvements from baseline to last visit in resting and Valsalva left ventricular outflow tract (LVOT) gradients, left atrial volume index (LAVI), and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels (Table 1). Improvements in these parameters were also observed in the SOC discontinuation and SOC dose reduction subgroups (Table 1). In the SOC discontinuation subgroup, improvements in resting and Valsalva LVOT gradients, LAVI, and NT-proBNP levels from baseline were maintained after SOC discontinuation (Table 1). SOC medications were discontinued or reduced over a mean (range) period of 63 (9–96) and 62 (3–133) weeks, respectively. At data cut-off, left ventricular ejection fraction remained within the normal range for all patients regardless of the SOC subgroup. Patients who reduced SOC medication had small increases in heart rate (within normal range) from baseline to last visit (Table 2). Overall, blood pressure remained stable across subgroups throughout the observation period (Table 2). No patients experienced worsening of NYHA class from baseline to last visit or from withdrawal to last visit. Conclusions Beneficial and sustained effects on LVOT obstruction, NT-proBNP levels and symptoms in patients with symptomatic obstructive HCM were observed with long-term mavacamten treatment alone or after SOC discontinuation or dose reduction.

Effects of dapagliflozin in heart failure with preserved ejection fraction and chronic obstructive pulmonary disease: an analysis of the DELIVER trial

Abstract Introduction Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure (HF) with preserved ejection fraction (HFpEF) and associated with worse outcomes. Purpose We investigated the relationship between COPD status and outcomes, and the efficacy of dapagliflozin, compared with placebo, according to COPD status in patients with heart failure (HF) with preserved ejection fraction (HFpEF) randomized in DELIVER. Methods A total of 6,263 patients with HF with New York Heart Association functional class II-IV, left ventricular ejection fraction &amp;gt;40%, evidence of structural heart disease, and elevated N-terminal pro–B-type natriuretic peptide levels were randomized to dapagliflozin or placebo. Clinical outcomes and the effect of dapagliflozin, according to COPD status at baseline, were examined. The primary outcome was a composite of cardiovascular death or worsening HF. Results Of the 6,261 patients with data on baseline COPD, 692 (11.1%) had a history of COPD. Compared with patients without COPD, those with COPD were older, more often men and current smokers, and they had a higher BMI, but lower systolic blood pressure. Patients with COPD also had a longer duration of HF, a higher rate of prior HF hospitalization, higher NT-proBNP, and worse NYHA functional class and KCCQ-TSS. The risk of the primary endpoint was higher in patients with COPD compared with those without COPD (adjusted HR: 1.29 (95% CI: 1.09-1.52). The benefit of dapagliflozin on the primary outcome was consistent irrespective of COPD status: no COPD, HR: 0.82 (95% CI: 0.72-0.93); COPD, HR: 0.84 (95% CI: 0.63-1.12) (Pinteraction = 0.92). Consistent effects were observed for HF hospitalization, cardiovascular death, and all-cause mortality (Table). Dapagliflozin, as compared with placebo, increased (improved) the KCCQ-TSS from baseline to 8 months to a similar extent in patients with and without COPD (Pinteraction = 0.75) (Table). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of COPD status. Conclusions COPD is common in patients with HFpEF and associated with worse outcomes. Dapagliflozin reduced the risk of worsening HF or cardiovascular death, and improved symptoms, similarly in patients with and without COPD. In addition, dapagliflozin was safe and well-tolerated, irrespective of COPD status.

Mavacamten for Obstructive Hypertrophic Cardiomyopathy With or Without Hypertension: Post-Hoc Analysis of the EXPLORER-HCM Trial

BackgroundHypertension (HTN) is common in patients with hypertrophic cardiomyopathy (HCM), but its effect on the treatment of left ventricular outflow tract (LVOT) obstruction is undefined. Although elevated systolic blood pressure (SBP) may impact dynamic LVOT gradients, its response to cardiac myosin inhibition is unknown. ObjectivesIn a post hoc exploratory analysis of the EXPLORER-HCM trial (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy), the authors examined the characteristics of patients with obstructive HCM and HTN and the associations between HTN, SBP, and the response to mavacamten treatment of LVOT obstruction. MethodsPatients were stratified by baseline history of HTN and mean SBP during 30-week treatment with mavacamten or placebo. The study estimated treatment differences and evaluated HTN and SBP groups by treatment interaction. Analysis of covariance was used to model changes in continuous endpoints, and a generalized linear model was used for binary endpoints. ResultsHTN was present in 119 of 251 patients (47.4%), including 60 receiving mavacamten and 59 receiving placebo. Patients with HTN vs no HTN were older (63.4 vs 54.0 years; P < 0.001), had higher SBP (134 ± 15.1 mm Hg vs 123 ± 13.8 mm Hg; P < 0.001), more comorbidities, and lower peak oxygen consumption (19 ± 3 vs 20 ± 4 mL/kg/min; P = 0.021). Patients with HTN had similar NYHA functional class (NYHA functional class II, 72% vs 73%), Valsalva LVOT gradients (72 ± 34 mm Hg vs 74 ± 30 mm Hg), Kansas City Cardiomyopathy Questionnaire–Clinical Summary Scores (70.6 ± 18.8 vs 68.9 ± 23.1), and NT pro–B-type natriuretic peptide levels (geometric mean 632 ± 129 pg/mL vs 745 ± 130 pg/mL). Mavacamten-treated patients had improvement in all primary, secondary, and exploratory endpoints regardless of HTN status or mean SBP. ConclusionsThe clinical benefits of mavacamten in symptomatic, obstructive HCM were similar in patients with and without HTN, despite differences in baseline characteristics. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [EXPLORER-HCM]; NCT03470545)

The relationship between serum pro-B type natriuretic peptide level and bone mineral density in peritoneal dialysis patients.

We aimed to evaluate the relationship between serum N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and lumbar bone mineral density (BMD) in peritoneal dialysis (PD) patients. Fasting blood samples were obtained from 46 PD patients. BMD was measured by dual-energy X-ray absorptiometry of the lumbar vertebrae (L1-L4). Circulating serum NT-pro-BNP levels were measured using commercial kits compatible with the Roche Cobas e 601 immunoassay device. Forty-six patients were included in our study. Increased age, low body mass index (BMI), and high-serum NT-pro-BNP are significantly associated with decreased BMD. The results show a statistically positive correlation between lumbar T-score values and BMI (r = 0.456; P = .001), while lumbar T-score values and PTH (rho = -0.336; P = .022) and log-NT-pro-BNP. There is a statistically negative correlation between BNP (rho = -0.355; P = .015). The lumbar T-score value decreases by 0.800 units when log-NT-pro-BNP increases by 1 unit and increases by 0.323 units when BMI increases by 1 unit. The established model is statistically significant (F = 6.190; P < .001). Our study in PD patients showed that serum NT-pro-BNP level was negatively correlated and BMI was positively correlated with lumbar BMD.

Predictors and prognostic implications of hospital-acquired pneumonia in patients admitted for acute heart failure.

Data on predictors and prognosis of hospital acquired pneumonia (HAP) in patients admitted for acute heart failure (AHF) to intensive care units (ICU) are scarce. Better knowledge of these factors may inform management strategies. This study aimed to assess the incidence and predictors of HAP and its impact on management and outcomes in patients hospitalised for AHF in the ICU. this was a retrospective single-centre observational study. Patient-level and outcome data were collected from an anonymized registry-based dataset. Primary outcome was in-hospital all-cause mortality and secondary outcomes included length of stay (LOS), requirement for inotropic/ventilatory support, and prescription patterns of heart failure (HF) drug classes at discharge. Of 638 patients with AHF (mean age, 71.6 ± 12.7 years, 61.9% male), HAP occurred in 137 (21.5%). In multivariable analysis, HAP was predicted by de novo AHF, higher NT proB-type natriuretic peptide levels, pleural effusion on chest x-ray, mitral regurgitation, and a history of stroke, diabetes, and chronic kidney disease. Patients with HAP had a longer LOS, and a greater likelihood of requiring inotropes (adjusted odds ratio, OR, 2.31, 95% confidence interval, CI, 2.16-2.81; p < 0.001) or ventilatory support (adjusted OR 2.11, 95%CI, 1.76-2.79, p < 0.001). After adjusting for age, sex and clinical covariates, all-cause in-hospital mortality was significantly higher in patients with HAP (hazard ratio, 2.10; 95%CI, 1.71-2.84; p < 0.001). Patients recovering from HAP were less likely to receive HF medications at discharge. HAP is frequent in AHF patients in the ICU setting and more prevalent in individuals with de novo AHF, mitral regurgitation, higher burden of comorbidities, and more severe congestion. HAP confers a greater risk of complications and in-hospital mortality, and a lower likelihood of receiving evidence-based HF medications at discharge.

Prognostic Efficacy of Complete Blood Count Indices for Assessing the Presence and the Progression of Myxomatous Mitral Valve Disease in Dogs.

This study investigated the complete blood count (CBC) indices, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in dogs with myxomatous mitral valve disease (MMVD) and analyzed their correlation with conventional biomarkers, as well as the effect of CBC indices on survival time in dogs with MMVD. Medical records of 75 healthy controls and 249 dogs with MMVD from March 2015 to October 2022 were analyzed. The NLR, MLR, and PLR were calculated by dividing the absolute counts of the CBC parameters. Dogs with MMVD had significantly higher NLR, MLR, and PLR than healthy dogs (all p < 0.0001), especially those in the symptomatic MMVD group with pulmonary edema (p < 0.0001, p = 0.0002, and p = 0.0387, respectively). The NLR and MLR were significantly correlated with N-terminal pro-B type natriuretic peptide levels (both p < 0.0001). The CBC indices showed potential as biomarkers for detecting the presence of MMVD (all p < 0.0001) and severity of MMVD (p < 0.0001, p < 0.0001, and p = 0.006, respectively) using receiver operating characteristic curve analysis. The negative effects of increased NLR, MLR, and PLR on survival were confirmed using Kaplan-Meier curve analysis. In conclusion, NLR, MLR, and PLR could be cost-effective and readily available potential diagnostic and prognostic biomarkers for MMVD in dogs.

First study demonstrating speckle tracking echocardiography has prognostic value in patients with idiopathic inflammatory myopathies.

To measure left ventricular (LV) global longitudinal strain (GLS) using speckle tracking echocardiography in idiopathic inflammatory myopathy (IIM) patients and to determine whether the LV GLS predicts outcomes in those patients. Prospective study consisted of a cross-sectional phase with 61 IIM patients and 32 individuals without IIM and longitudinal phase, in which patients were divided into two subgroups: 26 with reduced LV GLS and 35 with normal LV GLS; patients were followed for a mean of 25months, and the occurrence of cardiovascular events and criteria for IIM activity were compared. The mean LV GLS (18.5 ± 2.9% vs. 21.6 ± 2.5%; p < 0.001) and right ventricle free wall strain (21.9 ± 6.1% vs. 27.5 ± 4.7%; p < 0.001) were lower in patients than in controls. The mean N-terminal pro B-type natriuretic peptide level was higher in patients than in controls. There were no differences regarding other cardiac involvement. Anti-Jo1 antibody was associated with general electrocardiographic abnormality and LV diastolic dysfunction. The subgroup with reduced GLS progressed with higher mean creatine phosphokinase, myositis disease activity assessment visual analogue scales, the physician's and patient's visual analogue scales, the health assessment questionnaire, and a higher proportion of relapses than the subgroup with normal GLS. There was no difference between the subgroups regarding cardiovascular events. The LV GLS appears to be useful for evaluating patients with IIM. Abnormal values are associated with more frequent relapses and increased disease activity during follow-up.

Association among β2-adrenergic receptor autoantibodies and proximal left anterior descending artery lesions in patients with initial ST-segment elevation myocardial infarction.

β2 -adrenergic receptor autoantibody (β2 -AA) are widely present in patients with many different types of cardiovascular diseases. Proximal left anterior descending (LAD) artery lesions are associated with adverse prognostic events in patients with ST-segment elevation myocardial infarction (STEMI). β2 -AA is associated with the presence of proximal LAD lesions in patients with STEMI. A cohort of 153 patients with STEMI who underwent primary percutaneous coronary intervention (PPCI) was enrolled in the study. Baseline characteristics were compared between the proximal LAD group (n = 62) and the nonproximal LAD group (n = 91). Admission serum of patients was collected to detect the level of β2 -AA. Data for echocardiogram within 24 hours after PPCI and at the 6-month follow-up were recorded. The optical density values and positive rates of β2 -AA in the proximal LAD group were higher than those in the nonproximal LAD group (p < 0.05). β2 -AA positively correlated with high sensitivity C-reactive protein and peak N-terminal pro-B type natriuretic peptide levels in the proximal LAD group, but those were not relevant in the nonproximal LAD group. Multivariate logistic regression analysis revealed that high β2 -AA levels was independently associated with the presence of proximal LAD lesions in patients with STEMI. Furthermore, a receiver operating characteristic curve was used to show the efficiency of β2 -AA levels to detect proximal LAD lesions, and the AUC of the β2-AA OD value was 0.658 (95% confidence interval 0.568-0.749; p = 0.001). The STEMI patients with high β2 -AA levels had a greater possibility having proximal LAD lesions.

Age, Sex, and Outcomes in Heart Failure With Reduced EF: Insights From the VICTORIA Trial

BackgroundAge and sex influence treatment and outcomes in patients with heart failure (HF). ObjectivesThe authors examined the associations of age and sex with clinical characteristics, background therapies, outcomes, and response to vericiguat in this post hoc analysis of 5,050 VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) patients with HF and reduced ejection fraction; 1,568 (31%) were ≥75 years of age, of whom 445 (24%) were women. MethodsClinical characteristics were compared across age (<65, 65 to <75, and ≥75 years) and sex. The treatment effect of vericiguat was estimated by age and sex on the primary composite outcome (time to first HF hospitalization or cardiovascular death) using Cox proportional hazards regression. ResultsCompared with younger patients, those ≥75 years of age had more class III and IV symptoms, higher N-terminal pro–B-type natriuretic peptide levels, and worse kidney function but had the lowest use of triple therapy. No sex differences in triple therapy existed by age, but achieving target doses of triple therapy was less likely in older patients. Men ≥75 years of age were more than twice as likely to receive defibrillators and 65% more likely to undergo cardiac resynchronization than women. The primary composite outcome was nominally lower in women than men across all age groups. Vericiguat dosing did not differ between sexes in each age group, and its beneficial effect on the primary endpoint was not modified by age (continuous age, Pinteraction = 0.169; categorical age, Pinteraction = 0.189); and sex (3-way interaction; P = 0.847). ConclusionsAlthough elderly women received less intense background HF therapy than men, their prognosis was nominally better. The benefit of vericiguat was independent of age and sex. (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction [HFrEF] [MK-1242-001] [VICTORIA]; NCT02861534)

Overview of Long-Term Outcome in Adults with Systemic Right Ventricle and Transposition of the Great Arteries: A Review.

The population of patients with a systemic right ventricle (sRV) in biventricular circulation includes those who have undergone an atrial switch operation for destro-transposition of the great arteries (d-TGA) and those with congenitally corrected transposition of the great arteries (ccTGA). Despite the life expectancy of these patients is significantly increased, the long-term prognosis remains suboptimal due to late complications such as heart failure, arrhythmias, and premature death. These patients, therefore, need a close follow-up to early identify predictive factors of adverse outcomes and to implement all preventive therapeutic strategies. This review analyzes the late complications of adult patients with an sRV and TGA and clarifies which are risk factors for adverse prognosis and which are the therapeutic strategies that improve the long-term outcomes. For prognostic purposes, it is necessary to monitor sRV size and function, the tricuspid valve regurgitation, the functional class, the occurrence of syncope, the QRS duration, N-terminal pro B-type natriuretic peptide levels, and the development of arrhythmias. Furthermore, pregnancy should be discouraged in women with risk factors. Tricuspid valve replacement/repair, biventricular pacing, and implantable cardioverter defibrillator are the most important therapeutic strategies that have been shown, when used correctly, to improve long-term outcomes.

Carcinoid Heart Disease Management: A Multi-Disciplinary Collaboration.

Carcinoid heart disease (CaHD) is an important complication among patients with metastatic neuroendocrine tumors and carcinoid syndrome (CS). CS patients (25%-65%) eventually develop CaHD; these patients face a significantly increased risk of morbidity and mortality. Guidance papers (eg, clinical practice guidelines, consensus guidelines, and expert statements) have been established by major organizations across the disciplines of cardiology and oncology; however, these recommendations are not routinely implemented. The aim of this article is to encourage the integration of current recommendations from national societies into clinical practice. Early screening upon recognition of CS and prior to the development of CaHD symptoms is paramount, as no existing therapies are approved to reverse the fibrotic damage to the heart once it occurs. Valvular replacement is the only definitive treatment for CaHD once it has developed. When patients are noted to have urinary 5-hydroxyindoleacetic acid (5-HIAA) levels ≥300 µmol/24 h and/or serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels >260 pg/mL, echocardiography is recommended. Systemic approaches to control tumor growth and hormonal secretion include somatostatin analogs (SSAs), followed by options including peptide receptor radiotherapy (PRRT), everolimus and liver embolization. Telotristat is the primary choice for control of diarrhea refractory to SSA. Diuretics are the mainstay of heart failure symptom management for patients who develop CaHD. Considerations for future research are discussed, including the ongoing TELEHEART (TELotristat Ethyl in a HEART biomarker study) trial involving telotristat and not yet activated CHARRT (Carcinoid Heart disease And peptide Receptor Radiotargetted Therapy) study involving PRRT with lutetium 177 (177Lu) dotatate.

Effect of Dapagliflozin on Total Heart Failure Events in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction

In the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial, dapagliflozin reduced the risk of time to first worsening heart failure (HF) event or cardiovascular death in patients with HF with mildly reduced or preserved ejection fraction (EF). To evaluate the effect of dapagliflozin on total (ie, first and recurrent) HF events and cardiovascular death in this population. In this prespecified analysis of the DELIVER trial, the proportional rates approach of Lin, Wei, Yang, and Ying (LWYY) and a joint frailty model were used to examine the effect of dapagliflozin on total HF events and cardiovascular death. Several subgroups were examined to test for heterogeneity in the effect of dapagliflozin, including left ventricular EF. Participants were enrolled from August 2018 to December 2020, and data were analyzed from August to October 2022. Dapagliflozin, 10 mg, once daily or matching placebo. The outcome was total episodes of worsening HF (hospitalization for HF or urgent HF visit requiring intravenous HF therapies) and cardiovascular death. Of 6263 included patients, 2747 (43.9%) were women, and the mean (SD) age was 71.7 (9.6) years. There were 1057 HF events and cardiovascular deaths in the placebo group compared with 815 in the dapagliflozin group. Patients with more HF events had features of more severe HF, such as higher N-terminal pro-B-type natriuretic peptide level, worse kidney function, more prior HF hospitalizations, and longer duration of HF, although EF was similar to those with no HF events. In the LWYY model, the rate ratio for total HF events and cardiovascular death for dapagliflozin compared with placebo was 0.77 (95% CI, 0.67-0.89; P < .001) compared with a hazard ratio of 0.82 (95% CI, 0.73-0.92; P < .001) in a traditional time to first event analysis. In the joint frailty model, the rate ratio was 0.72 (95% CI, 0.65-0.81; P < .001) for total HF events and 0.87 (95% CI, 0.72-1.05; P = .14) for cardiovascular death. The results were similar for total HF hospitalizations (without urgent HF visits) and cardiovascular death and in all subgroups, including those defined by EF. In the DELIVER trial, dapagliflozin reduced the rate of total HF events (first and subsequent HF hospitalizations and urgent HF visits) and cardiovascular death regardless of patient characteristics, including EF. ClinicalTrials.gov Identifier: NCT03619213.

Association of Right Ventricular Myocardial Blood Flow With Pulmonary Pressures and Outcome in Cardiac Amyloidosis

BackgroundCardiac amyloidosis (CA) is a restrictive and infiltrative cardiomyopathy, characterized by increased biventricular filling pressures and low output. Symptoms are predominantly of right heart origin. The role of right ventricular (RV) myocardial blood flow (MBF) in CA has not been studied. ObjectivesThis study aimed to first associate RV MBF measured by using positron emission tomography (PET) with reference standards of RV pressures and then to explore its prognostic value in CA. MethodsCardiac PET was performed at rest in 52 patients with CA and 9 healthy control subjects. MBF was quantified from the right and left ventricles by using 11C-acetate, 15O-water, or both (n = 25). RV pressure was measured invasively or by echocardiography. Associations between biventricular MBF toward symptoms, RV function, and outcome (death or acute heart failure) were studied in patients with CA. ResultsMBF of the right ventricle (MBFRV) and the ratio of MBFRV and MBF of the left ventricle (MBFRV/LV) for the 2 tracers were significantly correlated (r > 0.92). MBFRV was directly correlated with RV systolic pressures with both tracers (P ≤ 0.005). MBFLV was inversely correlated with wall thickness (P < 0.0001). MBFRV/LV was significantly associated with N-terminal pro–B-type natriuretic peptide levels, NYHA functional class, RV pressures, and RV systolic function (all; P < 0.001). Twenty-six cardiac events (25 deaths) occurred during follow-up (median 44 months). MBFRV/LV higher than 56% was associated with a diagnosis of pulmonary hypertension (AUC: 0.96 [95% CI: 0.91-1.00]; P < 0.0001); and predicted outcome with HR: 9.0 (95% CI: 4.2-14.5), P < 0.0001). ConclusionsMeasurements of MBFRV using PET are feasible, as confirmed with 2 different tracers. Imbalance between RV and LV myocardial perfusion is associated with increased RV load and adverse events in cardiac amyloidosis.

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension

BackgroundPulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, the disease-associated morbidity and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension.MethodsWe conducted a multicenter, double-blind, phase 3 trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was the change from baseline at week 24 in the 6-minute walk distance. Nine secondary end points, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro–B-type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension–Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms, and Cognitive/Emotional Impacts domain scores; all were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit.ResultsA total of 163 patients were assigned to receive sotatercept and 160 to receive placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, −0.3 to 3.5) in the placebo group. The Hodges–Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P<0.001). The first eight secondary end points were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive/Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure.ConclusionsIn patients with pulmonary arterial hypertension who were receiving stable background therapy, sotatercept resulted in a greater improvement in exercise capacity (as assessed by the 6-minute walk test) than placebo. (Funded by Acceleron Pharma, a subsidiary of MSD; STELLAR ClinicalTrials.gov number, NCT04576988.)

Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial

BackgroundPatients with heart failure with preserved ejection fraction (HFpEF) frequently develop atrial fibrillation (AF). There are no randomized trials examining the effects of AF ablation on HFpEF outcomes. ObjectivesThe aim of this study is to compare the effects of AF ablation vs usual medical therapy on markers of HFpEF severity, including exercise hemodynamics, natriuretic peptide levels, and patient symptoms. MethodsPatients with concomitant AF and HFpEF underwent exercise right heart catheterization and cardiopulmonary exercise testing. HFpEF was confirmed with pulmonary capillary wedge pressure (PCWP) of 15 mm Hg at rest or ≥25 mm Hg on exercise. Patients were randomized to AF ablation vs medical therapy, with investigations repeated at 6 months. The primary outcome was change in peak exercise PCWP on follow-up. ResultsA total of 31 patients (mean age: 66.1 years; 51.6% females, 80.6% persistent AF) were randomized to AF ablation (n = 16) vs medical therapy (n = 15). Baseline characteristics were comparable across both groups. At 6 months, ablation reduced the primary outcome of peak PCWP from baseline (30.4 ± 4.2 to 25.4 ± 4.5 mm Hg; P < 0.01). Improvements were also seen in peak relative VO2 (20.2 ± 5.9 to 23.1 ± 7.2 mL/kg/min; P < 0.01), N-terminal pro–B-type natriuretic peptide levels (794 ± 698 to 141 ± 60 ng/L; P = 0.04), and MLHF (Minnesota Living with Heart Failure) score (51 ± −21.9 to 16.6 ± 17.5; P < 0.01). No differences were detected in the medical arm. Following ablation, 50% no longer met exercise right heart catheterization–based criteria for HFpEF vs 7% in the medical arm (P = 0.02). ConclusionsAF ablation improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with concomitant AF and HFpEF.

Prevalence and significance of relative apical sparing in aortic stenosis: insights from an echo and cardiovascular magnetic resonance study of patients referred for surgical aortic valve replacement.

This study aims to assess the prevalence of relative apical sparing pattern (RASP) in patients with severe symptomatic aortic stenosis (AS), referred for surgical aortic valve replacement (AVR), to evaluate its significance, possible relation to amyloid deposition, and persistence after surgery. Prospective study of 150 consecutive patients [age 73 (interquartile range: 68-77), 51% women], with severe symptomatic AS referred to surgical AVR. All patients underwent cardiac magnetic resonance (CMR) before surgery. RASP was defined by [average apical longitudinal strain (LS)/(average basal LS + average mid LS)] > 1 by echocardiography. AVR was performed in 119 (79.3%) patients. Both Congo red and sodium sulphate-Alcian blue (SAB) stain were used to exclude amyloid on septal myocardial biopsy. LV remodelling and tissue characterization parameters were compared in patients with and without RASP. Deformation pattern was re-assessed at 3-6 months after AVR.RASP was present in 23 patients (15.3%). There was no suspicion of amyloid at pre-operative CMR [native T1 value 1053 ms (1025-1076 ms); extracellular volume (ECV) 28% (25-30%)]. None of the patients had amyloid deposition at histopathology. Patients with RASP had significantly higher pre-operative LV mass and increased septal wall thickness. They also had higher N-terminal pro b-type natriuretic peptide (NT-proBNP) levels [1564 (766-3318) vs. 548 (221-1440) pg/mL, P = 0.010], lower LV ejection fraction (53.7 ± 10.5 vs. 60.5 ± 10.2%, P = 0.005), and higher absolute late gadolinium enhancement (LGE) mass [9.7 (5.4-14.1) vs. 4.8 (1.9-8.6) g, P = 0.016] at CMR. Follow-up evaluation after AVR revealed RASP disappearance in all except two of the patients. RASP is not specific of cardiac amyloidosis. It may also be found in severe symptomatic AS without amyloidosis, reflecting advanced LV disease, being mostly reversible after surgery.