NYHA Class III-IV Research Articles

Correlation Between Liver Stiffness and Diastolic Function, Left Ventricular Hypertrophy, and Right Cardiac Function in Patients With Ejection Fraction Preserved Heart Failure.

Objective: Ejection fraction preserved heart failure (HFpEF) is a common clinical syndrome with a high morbidity, accounting for ~50% of all heart failure patients, and a mortality comparable to that of ejection fraction reduced heart failure (HFrEF). The relationship between liver stiffness (LS) and HFpEF remains unclear. The purpose of this study was to explore the correlation between LS and the severity of HFpEF.Methods: We performed a prospective observational study. After accepting liver transient elastography on admission, consecutive 150 hospitalized HFpEF patients were divided into three groups based on their liver elasticity value: first-third quartiles. Left ventricular diastolic function, left ventricular hypertrophy degree, right cardiac function and short-term prognosis (≤1 year) were compared among the three groups, and the correlation between liver elasticity and each indicator was analyzed.Results: The elasticity of the liver was abnormally high in more than two-thirds of cases. The proportion of NYHA class III-IV in the third quartile group was significantly higher than that in the first quartile group (96 vs. 70%, P = 0.013). Significant differences were discovered in the level of lgNT-proBNP between the three groups (2.63 ± 0.65 vs. 2.84 ± 0.44 vs. 3.05 ± 0.71, P = 0.027). In terms of diastolic function and left ventricular hypertrophy, the ventricular septal e′ (5.01 ± 2.69 vs. 6.48 ± 2.29, P = 0.025), lateral wall e′ (6.63 ± 3.50 vs. 8.62 ± 2.73, P = 0.013), mean E/e′ (20.06 ± 7.53 vs. 13.20 ± 6.05, P = 0.001), left atrial volume index (43.53 ± 10.94 vs. 35.78 ± 13.86, P = 0.008), tricuspid regurgitation (TR) peak flow rate (3.16 ± 0.44 vs. 2.75 ± 0.50, P < 0.001), left ventricular mass index (LVMI) in male (163.2 ± 47.6 vs. 131.3 ± 38.0, P = 0.015) and in female (147.4 ± 48.6 vs. 110.6 ± 24.3, P = 0.036) was significantly different between the third quartile and the first quartile. The proportion of patients with diastolic dysfunction in the third quartile was significantly higher than that in the first quartile (70 vs. 36%, P = 0.017). In terms of right cardiac function, right ventricular fractional area change (RVFAC) (30.3 ± 5.4 vs. 36.5 ± 6.8, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (7.7 ± 5.2 vs. 14.8 ± 5.9, P = 0.010), pulmonary systolic pressure (38.0 ± 10.5 vs. 32.4 ± 10.3, P = 0.005), TR peak flow rate (3.16 ± 0.44 vs. 2.75 ± 0.50, P < 0.001), and inferior vena cava diameter (2.53 ± 0.51 vs. 1.98 ± 0.41, P < 0.001) were significantly different between the third quartile and the first quartile. More than half of HFpEF patients were combined with right ventricular dysfunction (RVD). Compared to HFpEF without RVD, HFpEF with RVD had higher male sex (53.6 vs. 30.3%, P < 0.001), higher NYHA class (3.2 ± 0.6 vs. 2.8 ± 0.6, P = 0.010), higher proportion of atrial fibrillation (45.2 vs. 18.2%, P < 0.001), and higher liver elasticity value (7.95 ± 0.60 vs. 7.31 ± 0.84, P = 0.003). In terms of short-term prognosis, the incidence of adverse cardiovascular events was significantly higher in the third quartile than in the first quartile (P = 0.003) and the second quartile (P = 0.008). Multivariate Cox proportional hazard analysis showed that adverse cardiovascular events were independently associated with NYHA class, atrial fibrillation, lgNT-proBNP and liver elasticity value (HR = 1.208, 95% CI 1.115–1.352, P = 0.002).Conclusion: Increase of liver stiffness is common in HFpEF patients. Increased LS in HFpEF patients was significantly associated with worsen left diastolic function, left ventricular hypertrophy, and the right cardiac function. LS in HFpEF patients may be more than the result of right ventricular dysfunction. Male, atrial fibrillation, poorer NYHA class and increased liver elasticity value were significantly associated with HFpEF combined with RVD. Atrial fibrillation, poorer NYHA class, higher NT-proBNP, and increased liver elasticity value were independent predictors of poor short-term prognosis of HFpEF patients.

Abstract 8895: Design of Phase IV, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Trial Evaluating Sodium Zirconium Cyclosilicate for the Management of Hyperkalemia in Patients With Symptomatic Heart Failure With Reduced Ejection Fraction (REALIZE-K Trial)

Introduction: International guideline-recommended therapies for heart failure (HF) with reduced ejection fraction (HFrEF), including mineralocorticoid receptor antagonists (MRA), are underutilized, in part due to concerns of hyperkalemia (HK) especially among those at high risk. The REALIZE-K trial aims to evaluate the efficacy and safety of sodium zirconium cyclosilicate (SZC), a selective potassium (K + ) binder, to enable MRA use in patients with HFrEF at high risk for HK. Methods: REALIZE-K is a prospective, double-blind, placebo (PBO)-controlled randomized withdrawal trial enrolling symptomatic HFrEF (NYHA class II-IV and LVEF ≤40%) patients on guideline-directed medical therapy (but not full-dose MRA) with either HK (serum K + 5.1-5.9 mmol/L) or high risk for HK during MRA titration. All eligible patients enter a 1-month open-label run-in phase, during which patients with hyperkalemia receive SZC to correct HK; all patients undergo protocol-mandated titration of spironolactone (SPL) as tolerated to a target of 50 mg QD with supplemental SZC to maintain normokalemia (serum K + 3.5-5.0 mmol/L; Figure ). All patients tolerating ≥25 mg QD of SPL will be randomly assigned to continued SPL+SZC or SPL+PBO during an 8-month double-blind withdrawal phase. Serial K + monitoring will guide protocol-directed dosing of SZC/PBO and SPL during the randomized period. The primary study endpoint is the occurrence at 8 months of normokalemia on SPL ≥25 mg QD without the need for rescue therapy for severe HK in the SZC vs PBO group. Secondary endpoints include individual components of the primary endpoint and health status assessed by Kansas City Cardiomyopathy Questionnaire Total Symptom Score. Exploratory endpoints include time to first occurrence of the composite of CV death or worsening HF, and change in mean urine albumin-creatinine ratio. Conclusions: REALIZE-K will evaluate the efficacy and safety of SZC, enabling MRA therapy for HFrEF patients at high risk for HK.

Abstract 11037: Procedural Success, Valve Hemodynamics and Outcomes in Patients with Moderate Aortic Stenosis Undergoing Supra-Annular Transcatheter Aortic Valve Replacement

Introduction: Limited evidence supports the hypothesis that early treatment of symptomatic moderate aortic stenosis (AS) may be beneficial. We seek to study procedural success, valve hemodynamics and clinical outcomes in moderate AS patients who underwent transcatheter aortic valve replacement (TAVR) using a supra-annular self-expanding bioprosthesis. Methods: All patients in the STS/ACC/TVT Registry™ with Evolut R, PRO and PRO+ attempted procedures for indication of primary symptomatic (NYHA class II-IV) moderate AS were included. Moderate AS was defined as mean gradient ≥20 and &lt;40 mm Hg, valve area &gt;1.0 and &lt;1.5 cm 2 , and Vmax &gt;3 and &lt;4 m/s. 2.9% of patients had concurrent severe aortic regurgitation at baseline. Valve-in-valve procedures were excluded. Site reported 30-day event rates are reported using Kaplan-Meier analysis. As a quality-of-life metric, KCCQ scores at 30 days and 1 year are compared to baseline scores using paired t-tests. Results: A total of 811 patients (62.1% men, 77.7 ± 8.7 years of age, STS-PROM score 5.3 ± 3.6, baseline LVEF 56.7 ± 13.3 %) were analyzed. The majority of patients underwent elective procedure (n=762, 94.0%) under conscious sedation (n=439, 54.3%) via iliofemoral approach (n=775, 95.6%). Successful device implantation, defined as correct valve positioning, was achieved in 99.3% of patients with low rates of intraprocedural complications (0.4%). Clinical events at 30 days were: all-cause mortality 1.4%, neurological events 2.5%, major bleeding 4.7% and conduction disturbance requiring pacer/ICD 16.1%. Valve hemodynamics improved post procedure compared to baseline (mean gradient 29.8 ± 4.9 to 8.4 ± 4.9 mm Hg, Vmax 3.5 ± 0.2 to 1.9 ± 0.5 m/s), with mean gradient sustained at 1 year (8.6 ± 4.4 mm Hg). Moderate/severe paravalvular regurgitation was present at similar levels at post procedure and 1 year (1.6% and 3.0%). A significant improvement in quality of life was noted from baseline KCCQ score to 30 days (Δ27.5 ± 25.5, 95% CI 25.4 - 29.5, p&lt;0.001) and 1 year (Δ29.1 ± 26.1, 95% CI 26.2 - 32.1, p&lt;0.001). Conclusions: Patients undergoing TAVR with a self-expanding bioprosthesis for symptomatic moderate AS have high procedural success with sustained improvements in valve hemodynamics and quality of life at 30 days and 1 year.

Abstract 13834: The Effect of Dapagliflozin on Serum Uric Acid in Heart Failure With Reduced Ejection Fraction: Insights From DAPA-HF

Introduction: Elevated serum uric acid (sUA) levels are common in patients with heart failure and reduced ejection fraction (HFrEF). sUA, in part, reflects the use of diuretics, and higher sUA is associated with a higher risk of adverse outcomes in HFrEF. We examined the effect of dapagliflozin on sUA, and the efficacy of dapagliflozin according to baseline sUA, in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. Methods: Patients in NYHA class II-IV with a LVEF ≤40%, and elevated plasma NT-proBNP were included in DAPA-HF. Key exclusions included hypotension, systolic BP &lt;95 mmHg, and eGFR &lt;30 ml/min/1.73m 2 . The primary outcome was a composite of worsening HF (hospitalization for HF or an urgent HF visit requiring iv therapy) or CV death. sUA was measured pre-randomization and at 52 weeks. The effect of dapagliflozin on sUA was assessed using a linear regression model adjusted for baseline value. The efficacy of dapagliflozin was assessed using baseline sUA as a continuous variable. Results: Of the 4744 randomized patients, 3119 (65.7%) had sUA measured at baseline, with a mean of 6.10±1.70 (median 5.9, IQR 4.9-7.1) mg/dL. The placebo-corrected change in sUA at 52 weeks was -0.83 mg/dL (95% CI -0.93, -0.74); p&lt;0.001.In adjusted models including diuretic use/dose, higher sUA was associated with an elevated risk of the primary endpoint; hazard ratio 1.09 (1.03-1.14) per 1mg/dL sUA; p=0.0015 Figure, Panel A .The benefit of dapagliflozin, compared with placebo, on the primary endpoint was consistent across the range of sUA studied ( Figure, Panel B ; P interaction=0.77). Conclusions: In DAPA-HF, higher sUA was associated with worse outcomes and dapagliflozin significantly reduced sUA. The efficacy of dapagliflozin on outcomes was consistent across the range of sUA studied.

Abstract 13569: A Composite Score Summarizing Use And Dosing Of Evidence-based Medical Therapies In Heart Failure: Application To The DAPA-HF Trial

Introduction: The Heart Failure Collaboratory consortium (HFC) has developed a score to quantify background guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF). One potential use of this score is to test the incremental value of new therapies. We evaluated the effect of dapagliflozin according to a modified HFC score in the DAPA-HF trial. Methods: The key inclusion criteria in DAPA-HF were: 1) NYHA class II-IV, 2) LVEF ≤40%, and 3) elevated plasma NT-proBNP and 4) eGFR ≥30 ml/min/1.73m2. The primary outcome was a composite of a first episode of worsening HF (hospitalization for HF or an urgent HF visit requiring iv therapy) or cardiovascular death. The HFC score is calculated based on the use of GDMT and dose of GDMT. The modified HFC score used here also accounted for race (Black/non-Black) and ECG rhythm/rate with a maximum possible score of 100 (percent) for any patient (Panel A). Results: Among the 4744 patients (mean age 66 years; 23% women) randomized, an ACEi/ARB was used in 84%, beta-blocker 96%, MRA 71%, ARNI 11%, ivabradine 4.8%, and hydralazine 4.3%. During a median follow-up of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and 502 of 2371 patients (21.2%) in the placebo group (HR, 0.74; 95%CI 0.65 to 0.85; P&lt;0.001). The benefit of dapagliflozin on the primary outcome was consistent across the range of baseline treatment score (Panel B). Examination of the effect of dapagliflozin on the primary outcome by score tertile (T1 ≤40, T2 41-60 and T3 &gt;60) gave HRs for the effect of dapagliflozin, compared with placebo, of 0.75 (0.61-0.93), 0.77 (0.61-0.98), and 0.71 (0.55-0.90), respectively (P-interaction 0.87). Conclusions: A composite score for GDMT of the type developed by the HFC can be easily calculated in clinical trials and used to evaluate the incremental effect of new therapies.

Closing the Digitalis Divide: Back to the Basics of Randomized Controlled Trials.

Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a series of meta-analyses linking digoxin treatment and mortality have contributed to a narrower application of this medication for the management of heart failure (HF) and atrial fibrillation (AF). Given the conflicting data from the earlier RCTs and more recent meta-analyses, there is a growing polarization among providers for and against the use of digoxin in managing these conditions. To help close this divide, we provide a perspective on the literature with special attention to the quality of both older and more recent studies on this subject. The data from the highest quality studies we have, RCTs, suggest that digoxin use in patients with HF and/or AF is associated with improvement in several areas of outcomes including functional capacity, symptom management, reduced hospitalizations, fewer deaths due to HF, and treatment of refractory chronic heart failure with rEF, and may even have overall mortality benefit when serum digoxin concentrations are within therapeutic range. These effects are more pronounced in patients with EF < 25% and NYHA Class II-IV and at highest risk for hospitalization. As the risk of confounding factors was minimized by the study design, the likelihood that positive outcomes were identified with digoxin use increased. Clinicians and researchers need further adequately designed and powered RCTs exploring the connection between digoxin therapy and mortality, hospitalizations, and symptom management.

Selection Criteria for Heart Transplantation in Patients with End-Stage Heart Failure

Today, heart transplantation remains the gold standard of treatment for patients with end-stage heart failure (HF). As the number of donors is limited and the risk of intervention is quite high, the key to achieving optimal outcomes and reducing the incidence of complications is the proper selection of patients who meet clearly defined criteria for inclusion in the waiting list for heart transplantation. This review presents the latest knowledge on indications and contraindications for inclusion recipients in the waiting list for heart transplantation, including the latest clinical guidelines of The International Society for Heart and Lung Transplantation (ISHLT) published in 2016.&#x0D; Thus, the absolute indications are dependence on intravenous inotropic and mechanical circulatory support; inoperable heart diseases or a history of volume reducing operations; refractory angina or life-threatening refractory arrhythmias despite maximal drug therapy and/or surgical correction; reduction of maximum oxygen consumption up to &lt;12-14 ml/kg/min when performing the maximum cardiopulmonary exercise test. While including patients in the waiting list for heart transplantation, it should be noted that the low left ventricular ejection fraction &lt;30%, a history of documented NYHA class III-IV HF, low maximum oxygen consumption as the only criterion of terminal HF and poor prognosis for annual survival in HF calculated on prognostic scales are not sufficient indications. Absolute contraindications include a systemic disease with a life expectancy of less than 2 years and irreversible pulmonary hypertension.&#x0D; The current procedure for the distribution of recipients by urgency status for heart transplantation is presented according to the updated recommendations of the United Network for Organ Sharing (UNOS) published in 2018 which consists of 6 degrees, compared with the 1999 edition which contained 3 degrees.

RIP1/RIP3-MLKL signaling pathway correlates with occurrence, progression and prognosis of chronic heart failure

To detect plasma levels of receptor-interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL) in patients with chronic heart failure and explore the expression pattern of programmed necrosis signaling pathway RIP1/RIP3-MLKL in the progression of heart failure. The patients with chronic heart failure (NYHA class Ⅱ-Ⅳ) admitted in our hospital between February, 2020 and March, 2021 were prospectively enrolled in this study, with 21 healthy volunteers as the control group. The enrolled patients included 20 with grade Ⅱ, 33 with grade Ⅲ, and 43 with grade Ⅳ cardiac function. Fasting venous blood was collected from all the participants for detecting plasma levels of RIP1, RIP3, and MLKL and protein expressions of RIP1/RIP3-MLKL pathway using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The patients with grade Ⅳ cardiac function were followed up for 5 months to evaluate the clinical prognostic indicators. Compared with the healthy volunteers, the patients with grade Ⅱ, Ⅲ and Ⅳ cardiac function had significantly increased plasma levels of RIP1, RIP3, and MLKL (P < 0.01), and their levels were significantly higher in grade Ⅲ/Ⅳ patients than in those with grade Ⅱ cardiac function (P < 0.01); the plasma levels of RIP1 and MLKL were significantly higher in grade Ⅳ patients than in grade Ⅲ patients (P < 0.05). The results of Western blotting also showed increased expressions of the proteins in the RIP1/RIP3-MLKL pathway in patients with heart failure. Pearson correlation analysis suggested that in patients with heart failure, the expression levels of RIP1, RIP3, and MLKL were positively correlated with SCR, AST, LVEDD and NT-proBNP (P < 0.05). Follow-up study of the patients with grade Ⅳ cardiac function showed that higher expression levels of RIP1/RIP3-MLKL were associated with a poorer prognosis of the patients. The expressions of RIP1, RIP3 and MLKL are significantly upregulated in patients with heart failure in positive correlation with the severity of the disease condition, and the activation of the RIP1/RIP3-MLKL signaling pathway may contribute to the occurrence, development and prognosis of chronic heart failure.

Transcatheter Aortic Valve Replacement for Severe Symptomatic Aortic Stenosis in Rheumatic Heart Disease: A Systematic Review.

Transcatheter aortic valve replacement (TAVR) is well-established for severe symptomatic aortic stenosis (AS), but its use in rheumatic heart disease (RHD) has been limited. We systematically review the use of TAVR for severe symptomatic AS in RHD. Pubmed, Embase, and Scopus were searched for TAVR for symptomatic severe AS and proven or suspected RHD. Procedure characteristics, efficacy, and safety endpoints were collected and all definitions were based on the Valve Academic Research Consortium-2 (VARC-2) criteria. We included 3 case series and 12 case reports, with a total of 43 patients. Mean age was 76 years, 75% were female, and 85% had NYHA class III-IV symptoms. Follow up ranged from 1 to 29 months. Patients were moderate to high risk, with Society of Thoracic Surgery score ranging from 6.1% to 17.6%. The approach was transfemoral in 30 (83%) cases. Procedural success occurred in 37 (86%) patients. Of the 7 patients with periprocedural complications, 4 had valve dislodgement, 1 deployment failure, 1 unplanned cardiopulmonary bypass, and 1 moderate aortic regurgitation. Paravalvular leak was reported in 5 (11.6%) patients. Only 1 patient had heart block requiring pacemaker. Among 13 studies (23 patients), 30-day mortality was 0%. One case series with 19 patients had a 30-day, 1-year, 2-year, and 5-year mortality of 5%, 11%, 31%, and 48%, respectively. TAVR appears feasible for selected patients with rheumatic severe AS, albeit our results indicate a 14% incidence of device failure. Future randomized clinical trials may clarify the role of TAVR in this group.

Prognostic value of left atrial function in patients with severe primary mitral regurgitation undergoing mitral valve repair

Abstract Background Timing of mitral valve surgery for primary mitral regurgitation (MR) remains challenging. Since MR has a significant hemodynamic impact on the left atrium (LA), assessment of LA function may have prognostic value in these patients which is incremental to LA volume and left ventricular (LV) remodeling parameters. Purpose This study sought to investigate whether preoperative assessment of LA reservoir strain (LASr) by speckle tracking echocardiography is associated with long-term outcome in patients undergoing mitral valve repair for severe primary MR. Methods Echocardiography was performed prior to mitral valve surgery in 566 patients (age 64±12 years, 66% men) with severe primary MR. Complete clinical information was collected and the endpoint was all-cause mortality after operation. The study population was divided based on a cut-off value of LASr (22%) derived from a spline curve analysis (hazard ratio for all-cause mortality &amp;gt;1). Results Patients with LASr ≤22% (n=277) were significantly older, had more impaired renal function and were more symptomatic (NYHA functional class III to IV) compared to patients with LASr &amp;gt;22% (n=289). In terms of echocardiographic data, patients with LASr ≤22% had significantly lower LV ejection fraction and LV global longitudinal strain (LV-GLS) and significantly higher systolic pulmonary artery pressures and LA volume index compared with patients with LASr &amp;gt;22%. During a median follow-up of 95 (56 – 147) months, 129 patients (22.8%) died. Patients with LASr ≤22% experienced significantly higher mortality rates compared to patients with LASr &amp;gt;22% (log rank chi-square 35.1; p&amp;lt;0.001) (Figure). On multivariable analysis, age (hazard ratio (HR): 1.06; 95% confidence interval (CI): 1.03 to 1.09; p&amp;lt;0.001), LV-GLS (HR: 1.08; 95% CI: 1.02 to 1.15; p=0.014) and LASr (HR: 0.96; 95% CI: 0.93 to 0.99; p=0.014) were independently associated with all-cause mortality. The addition of LASr to a clinical model (including: age, coronary artery disease, estimated glomerular filtration rate, NYHA class III-IV, atrial fibrillation, LV end-diastolic volume index, LV ejection fraction, LV-GLS, LA volume index and systolic pulmonary artery pressure) showed a significant increase in the chi-square value (chi-square differences = 6.9; p=0.011), demonstrating the incremental prognostic value of LASr in patients with primary MR. Conclusions Preoperative LASr is independently associated with all-cause mortality in patients undergoing mitral valve repair for primary MR, has incremental prognostic value over LA volume and LVEF and might therefore be helpful to guide surgical timing. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Jan Stassen has received an ESC training grant (Appehab724.011364741) Association of LASr and outcome

Eisenmenger syndrome: is it the same entity in adulthood and pediatric age?

Abstract Introduction Eisenmenger syndrome is the final clinical stage of different congenital heart diseases (CHD) associated with pulmonary arterial hypertension (PAH). Children born in recent years with CHD have benefited from advances in pediatric cardiac surgery that have modified their evolution compared to adults with the same pathologies. Purpose Our objective was to define and compare the characteristics and prognosis of the adult and pediatric population with Eisenmenger Syndrome. Methods REHAP and REHIPED are Spanish, voluntary, multicenter registries that include patients with PAH associated with CHD. REHAP started in 2007 and includes patients over 18 years of age. Patients diagnosed with PAH after this time were prospectively included, until 2020. Patients who were followed in the participating centres and diagnosed after January 1998 were retrospectively included in the registry. REHIPED started in 2009 and collects patients between 2 months and 18 years of age. Patients diagnosed with PAH after this time were prospectively included, until 2020. Patients who were followed and diagnosed after January 1998 were retrospectively included. The baseline characteristics, hemodynamic profile, treatment, and 10-year survival of the REHAP patients were compared to those included in the REHIPED. Results Eisenmenger syndrome is the main clinical group in adults (56% of patients with PAH associated with CHD enlisted in REHAP), 371 patients were included. On the other hand, Eisenmenger syndrome is the least frequent clinical group in childhood (21% of patients with PAH associated with CHD enlisted in REHIPED), 32 patients were included. Among adults, simple defects were significatively more common, whereas complex defects were more frequent in children (p 0.004). Half of the patients were in NYHA class III-IV, with no difference between groups. Adults presented greater hemodynamic severity, with higher mean pulmonary arterial pressure and greater pulmonary vascular resistance index. There were no differences in treatment: neither in first line therapy nor in the percentage of patients who received prostanoids at any time during follow up. The usage of prostanoids was very low in both groups. Two-thirds of the patients who died or underwent transplantation did so without taking prostanoids at any time. The 10-years survival analysis showed no significative difference between groups. Conclusions The prevalence of Eisenmenger syndrome is clearly lower in the pediatric population with CHD compared to the adult population. However, once Eisenmenger syndrome has developed, even though adults present greater hemodynamic severity, the clinical characteristics and the prognosis are similar in both groups. The usage of prostanoids is low in adulthood and in childhood, even in those with more severe forms of the disease. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Ferrer, MSD, Janssen, GSK Table 1Figure 1

Gender differences in reverse cardiac remodeling following initiation of sacubitril/valsartan in heart failure with reduced ejection fraction: real world experience

Abstract Background Gender related differences in physiology and pharamocokinetics have long been appreciated; however, the clinical relevance of these differences are unclear (1). Sacubitril/Valsartan has become established as a guideline directed therapy for the treatment of heart failure with reduced ejection therapy (HFref) and NYHA class II-IV symptoms. Interestingly; recent secondary analysis of key trials such as PARAGON-HF and PARADIGM, have highlighted possible differential gender specific benefits from Sacubitril/Valsartan therapy (2). We therefore sought to evaluate if there were gender specific effects of Sacubitril/Valsartan on both quantitative and qualitative measures of heart failure outcomes. Methods We performed a retrospective data interrogation of all patients commenced on Sacubitril/valsartan therapy in the SHSCT between 2016 and 2019. Data was extracted using electronic care records. Local ethical approval was granted. The primary endpoint were change in LVEF% on echocardiography and improvement in QOL (defined as NYHA score) at one year following initiation of Sacubitril/Valsartan. Differences in means between baseline and one year were assessed using a paired student's t-test. Interaction of gender on respective outcomes was assessed using a two way ANOVA. Significance defined as p&amp;lt;0.05. Data expressed as mean ± SD. Analysis performed using SPSS™. Results A total of 422 patients were included (mean age 69.1±12.1 years; 66% male). The predominant NYHA class' were II (n=298, 67.7%) and III (n=118, 26.8%). Aetiology and comorbidities were similar across male and females. In both groups, there was a statistically significant improvement in LVEF% at one year following initiation of Sacubitril/Valsartan (female; 27.1±8.6 to 34.6±9.5, n=40 p&amp;lt;0.01) (male; 27.4±7.5% to 32.6±9.3%, n=91, p&amp;lt;0.01). There was a statistically significant interaction between gender and degree of reverse cardiac remodeling defined as LVEF% on echocardiography following initiation of Sacubitril/Valsartan (F[2,52]=8.280, p=0.04, partial n2=0.27) (Figure 1). Similarly, there was a significant improvement in NYHA scores in both groups (male; 2.2±0.5 to 2.02±0.6, n=331, p&amp;lt;0.05) (female; 2.29±0.6 to 2.07±0.5, n=91, p&amp;lt;0.05) (Figure 2). However; there was no statistically significant interaction between gender and NYHA score following initiation of Sacubitril/Valsartan (F[2,52]=0.133, P=0.716, partial n2≤0.0). Conclusion Sacubitril/Valsartan produced significant improvement in reverse cardiac remodelling and QOL measures in both groups. Notably, had a stronger effect of reverse cardiac remodelling in women – suggesting possible gender specific differential benefits. Funding Acknowledgement Type of funding sources: None.

Clinical characteristics and medical therapy in randomized clinical trial eligible-and-enrolled vs. eligible-but-not enrolled patients with ischaemic heart failure

Abstract Introduction Clinical trial applicability to routine clinical practice is a fundamental consideration. Little is known about eligibility and enrolment in ischaemic heart failure (iHF) trials. Aim To compare clinical characteristics and medical therapy between subjects eligible-and-enrolled vs eligible-but-not-enrolled in iHF interventional randomized controlled trials (RCT). Material and methods Using our detailed database of consecutive hospitalizations, iHF patients clinical characteristics and medical treatment were compared for 4 following periods: P1 (6 months of RCT#1 recruitment), P2 (6 months after the RCT#1), P3 (6 months of RCT#2 recruitment), P4 (6 months after RCT#2). RCT#1 and RCT#2 had similar criteria that involved 18–80 years old, NYHA Class II-IV inclusion and LVEF ≤40% (inclusion), and tumor/neoplasm history, recent (≤3 months) or planned major surgery, heart transplant waiting list (exclusion). Eligibility and enrolment, and reasons for non-eligibility and non-enrolment, were evaluated along baseline clinical characteristics and medical treatment. Results Data of 5,436 patients were reviewed. Eligibility rate was similar between the periods evaluated (P1–56.45%, P2–43.14%, P3–58.49%, P4–50.25%). One in 2 (50.62%) ineligible patients had a single-only reason for ineligibility (recent [≤3 months] or recommended cardiac surgery/cardiovascular intervention outside the trial 16.3%, age&amp;gt;80 years 14.6%, Fig. 1 and Fig. 2). 13.2% of eligible patients were not enrolled due to lack of consent. Eligible-and-enrolled patients did not differ in baseline clinical characteristics such as sex, age, diabetes, and the clinical stage of heart failure against the eligible-but-not-enrolled patients. However, the eligible-and-enrolled had lower left ventricle ejection fraction (echocardiography; 31.2% vs. 33.9%, p=0.0393) and higher end-diastolic volume (197.8ml vs 160.4ml, p&amp;lt;0.0001). There were no differences in ACE/ARB inhibitor, B-blocker, diuretic (thiazide, loop, K+ sparing), sacubitril/valsartan and statin therapy between the groups. Eligible patients characteristics were not different between the recruitment (P1, P3) and non-recruitment periods (P2, P4). Conclusion Enrolment rate was high. Ineligibility resulted mainly from recent or recommended cardiovascular intervention outside RCT. Medical treatment was similar between eligible-and-enrolled and eligible-but-not-enrolled patients. Age (when within the inclusion criteria), gender and time frame were not factors of bias. However, the trial-enrolled patients had more severe left ventricle impairment. This argues, for iHF RCTs, against the routinely assumed lower-risk patient enrolment bias as signalled in other trial types and populations. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): John Paul II Hospital, Krakow, Poland Figure 1Figure 2

Prognostic impact of uric acid in patients with acute decompensated heart failure

To evaluate the prognostic impact of serum uric acid (SUA) on clinical outcomes in patients with acute decompensated heart failure, as well as identify the correlation between hyperuricemia and renal function and diuretic resistance in these patients. The study included 175 patients (125 men and 50 women) with NYHA class IIIV acute decompensated heart failure. Median age was 64 (5675) years. The Information regarding the survival was obtained 3 years after the admission by telephone calls. 57 patients reached the end point (death from all causes); therefore, all patients were divided into groups: "alive", "dead". The SUA levels did not differ in the groups. The only significant difference in the studied parameters was the estimated glomerular filtration rate (eGFR), which was significantly higher in the "alive" group [70.5 (52.894) and 56 (4079), respectively; p=0.006]. A moderate negative correlation was found between SUA levels and eGFR in the correlation analysis (r=-0.313, p0.001). A comparative analysis showed, that SUA level on admission was significantly higher in patients who subsequently received increased doses of diuretics than in patients with a satisfactory response to standard doses of diuretics [567.8 (479.6791.9) and 512 (422.4619.4), respectively; p=0.011]. Also, higher eGFR level on admission was observed in patients from the normal SUA level group than in patients from the hyperuricemia group [94 (74.5101.5) and 63 (48.881.3), respectively; p=0.002]. We found no significant differences in the uric acid level in patients who reached the end point and those who did not reach it during the three-year follow-up. However, the found correlation between uric acid levels and diuretic resistance calls for further research.

Comparative efficacy of medication and cardiac resynchronization therapy in patients with heart failure with reduced ejection fraction

Aim. To compare the effectiveness of standard conservative therapy for heart failure (HF) with the inclusion of sacubitril/valsartan combination and device therapy.Material and methods. The study included 64 patients from 38 to 73 years old (45 men and 19 women; mean age, 59,5±0,9 years) hospitalized in Baku (Azerbaijan) hospital due to NYHA class II-IV HF. The patients were divided into the experimental (group 1) and control (group 2) groups. The experimental group included 33 patients who took sacubitril/valsartan twice a day in combination with other drugs for standard HF therapy. The control group included 31 patients after cardiac resynchronization therapy. We compared clinical and hemodynamic parameters (including 6-minute walk test and echocardiography data) before and 6 months after treatment, as well as blood concentration of brain natriuretic peptide (BNP). In addition, Kaplan-Meier survival curves were analyzed.Results. As a result of 6-month therapy, clinical condition of patients in both groups was improved. In the experimental group, some parameters were significantly better than in the control one. So, the differences regarded distance in 6-minute walk test (pu=0,002), changes in HF class (pu=0,017), LV ESD (pu=0,006), LV EDD (pu=0,001) and blood BNP concentrations (pu&lt;0,001).Conclusion. The use of sacubitril/valsartan combination as part of standard HF therapy was accompanied by a significant improvement in the clinical, hemodynamic and biochemical parameters of patients with HF compared with device therapy.

Clinical impact of mitral regurgitation in aortic valve stenosis: Insight from effective regurgitant orifice area.

Mechanisms leading to heart failure (HF) symptoms in aortic valve stenosis (AS) are contentious. We examined the impact of secondary mitral regurgitation (MR) on the symptomatic status in patients with AS. Outpatients performing echocardiography with any degree of AS, without organic mitral valve disease, mitral valve intervention, or aortic insufficiency were enrolled. MR was quantitatively defined through mitral effective regurgitant orifice area (EROA) using the proximal isovelocity surface area method. Patients were divided into two groups (New York Heart Association [NYHA] class I-II vs. NYHA class III-IV). Five hundred and eighty-four patients were enrolled (484 NYHA I-II, 100 NYHA III-IV). More symptomatic patients had smaller aortic valve area (AVA), lower left ventricular ejection fraction (LVEF) and stroke volume, higher E/E', and LV global afterload. MR was present in 178 (30%) patients and EROA was<.20 cm2 in 158 (89%). NYHA III-IV patients showed higher prevalence of MR (78% vs 21%, P<0.0001) and larger EROA (.13±.08 cm2 vs .09±.07 cm2 , P<0.0001). An association between EROA and symptoms was present in the total cohort and in subgroups with preserved LVEF, AVA ≥ 1 and<1 cm2 , EE' 8-14 and ≥14 (P<0.05 for all). EROA was associated with severe symptoms after adjustment for LVEF, E/E', and AVA in the overall population (OR 1.10 [1.06-1.15]; P<0.0001) and in the 516 patients with preserved LVEF (OR 1.13 [1.08-1.19]; P<0.0001). In patients with AS, greater EROA values are associated with HF symptoms, even though MR degree is far from the threshold of MR severity. Therefore, even a mild MR represents a supportive marker of HF symptoms presence.

Prevalence and effect of cardiac cachexia in advanced heart failure patients living in northern ireland

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Northern Ireland Chest Heart and Stroke Background/Introduction: Cardiac cachexia (CC) is a multifactorial wasting syndrome, resulting in significant weight loss and reduction in muscle mass. This is reflected in a detrimental effect on the patients’ physical condition, quality of life and increases the patient’s risk of premature death. Nonetheless, cardiac cachexia remains frequently unrecognised in clinical practice and therefore understudied. Purpose To determine the prevalence and effect of cardiac cachexia in 200 patients with advanced heart failure (NYHA class III-IV) living in Northern Ireland. Methods A mixed methods cross sectional study of patients recruited from a regional heart failure centre. A total of 200 patients with NYHA class III-IV heart failure were consented, enrolled and detailed data collected from their records. Anthropometric measures were taken (i.e. measures of lean muscle mass and fat tissue) and each individual completed three validated questionnaires - EQ-5D-5L (quality of life), FACIT-Fatigue and FAACT (various wellbeing subscales). Results This population was predominately male (65.5%), with an average age of 74.4 years. Of the 200 NYHA class III-IV patients recruited, 30 were identified as cachectic (15%) Physically, cachectic patients were approximately 25 kg lighter than non-cachectic patients (p &amp;lt; 0.01) with an average BMI of 21.8 ± 4.4. The cachectic group showed significant reductions in mid-upper arm circumference (p &amp;lt; 0.01), skinfold thickness (p &amp;lt; 0.01) and upper arm fat area (p &amp;lt; 0.01), in comparison to the non-cachectic group. Measures of muscle mass were reduced, for example upper arm muscle circumference and area (p &amp;lt; 0.01), as well as grip strength (p &amp;lt; 0.01 for both right and left hands). Quality of life results from the EQ-5D-5L [see figure part b)] indicated an overall reduction for the cachectic group (p = 0.047). Of the EQ-5D-5L subscales, mobility and ‘usual activities’ were significantly reduced (p = 0.02 and p &amp;lt; 0.01 respectively), highlighting a significant change in the daily routine and ability of these patients. The FACIT-Fatigue questionnaire showed cachectic patients to be significantly more fatigued (p &amp;lt; 0.01) [see figure part a)], whilst the FAACT demonstrated reduced physical wellbeing (p = 0.02) and greater issues with diet and appetite (p &amp;lt; 0.01). Conclusions This is the first prevalence study of cardiac cachexia within Northern Ireland. The 15% prevalence rate shows that the syndrome is relatively common in the advanced heart failure population. Cardiac Cachexia has severe physical consequences, attributed to an individual’s weight loss in both fat and muscle tissue. Such changes may explain the subsequent decrease in mobility and the ability of these patients to conduct their ‘usual activities’. Increased fatigue, reduced physical wellbeing and issues with diet and appetite only intensify these dire physical effects. It is hoped that these results will highlight the impact of this syndrome and promote targeted interventions.

Appetite is an important factor for dietary intake in patients with heart failure - a comparison study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden, the Swedish Heart and Lung Foundation. Background Loss of appetite and suboptimal dietary intake is common in heart failure, which can result in malnutrition. Malnutrition is associated with poor prognosis and needs to be identified and treated. Despite this, few studies have investigated whether appetite and dietary intake may be intertwined. Purpose To compare dietary intake between heart failure patents with poor and good appetite. Methods A cross-sectional observational study design was used, and patients were recruited from three outpatient heart failure clinics in Sweden. The sample included 186 patients with confirmed heart failure with NYHA class II-IV (Mdn = NYHA class II). The mean age was 70 (SD = 11) years and 119 were male 69%. Dietary intake was assessed by a 3-day self-recorded food diary, including two weekdays and one week-end-day. Components including energy intake, macronutrients, fiber, minerals, vitamins, and water were collected, entered, and calculated by a dietician using the software Dietist XP. Appetite was self-reported using the Council on Nutritional Appetite Questionnaire (CNAQ). The total score ranges between 8-40, low scores indicate poor appetite. Mann-Whitney U test was used to investigate differences in dietary intake between patients with poor appetite (CNAQ ≤ 28) and good appetite (CNAQ &amp;gt; 28). The eta2 (Z2/N-1) was used to estimate the effect size. Results Patients with poor appetite (n = 71, 38%) reported significantly lower intake (p &amp;lt; 0.05) of calories, protein, fat, fiber, vitamin B6 and B12, thiamin, riboflavin, niacin, folate, phosphor, potassium, sodium, magnesium, iron, zinc, selenium and water compared to those with good appetite (n = 115, 62%). The effect size was small (eta2 = 0.02-0.09). Conclusions This study shows that poor appetite contributes to a significant lower intake of essential nutrients compared to patients with good appetite. Health care professionals should assess appetite routinely during heart failure follow-up since poor appetite may contribute to inadequate dietary intake with risk for malnutrition. Future longitudinal studies are required to increase the knowledge whether assessment of appetite can be used to determine malnutrition in heart failure.

Impact of the COVID-19 Pandemic on the Management of Acute Myocardial Infarction.

AimThe coronavirus (COVID-19) outbreak in 2019 has negatively impacted the care of patients with other life-threatening diseases, including acute myocardial infarction (AMI). However, there is little published information concerning the depth of the impact on the clinical management and outcome following AMI.MethodsWe enrolled patients with AMI who received urgent primary percutaneous coronary intervention at the Beijing Tiantan Hospital (Beijing, China) between December 1, 2019 and April 10, 2020. Patients were divided into 2 cohorts, the pre-COVID-19 group (from December 1, 2019 to January 31, 2020) and during-COVID-19 group (from February 1, 2020 to April 10, 2020) for analysis. The door-to-balloon (D to B) time, total hospitalization stay (days) and coronary care unit (CCU) hospitalization days were calculated. New York Heart Association heart functional class (NYHA class), re-hospitalization and death ratio in patients were assessed between the two cohorts.ResultsA total of 148 AMI patients were enrolled in this study comprising 53 patients pre-COVID-19 group and 95 patients during-COVID-19 group. Patients with AMI during-COVID-19 group had longer symptom onset to hospital time (4.5 [2.0–9.3] vs 3.0 [2.0–5.0] hours, p = 0.013) and D to B time (96 [74–119] vs 67 [52–81] minutes, p <0.001); the D to B time shortened during the study period. The two cohorts did not have significantly different number of hospitalization days, re-hospitalization rates, peak cTnI, BNP or death rates. For the one-year follow-up, the patients in the during-COVID-19 group were classified as NYHA class III–IV more frequently (9 [9.7%] vs 0 [0%], p=0.004).ConclusionThe COVID-19 pandemic significantly affected one measure of critical care of patients with AMI, NYHA classification, which may have resulted in increased medical expenses.

Usefulness of High-Sensitivity Cardiac Troponin T to Predict Long-Term Outcome in Patients with Hypertrophic Cardiomyopathy

Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity in confirmative data. We performed a prospective, prespecified 5-year follow-up cohort study of 135 HC patients who participated in a national multicenter project and underwent clinical evaluation, MRI (cine, LGE and T2-weighted imaging) and biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide of Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up was systematically performed for the primary endpoint: a composite of sudden cardiac death, heart failure related death, stroke-related death, heart failure hospitalization, hospitalization for stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, and progression to NYHA class III-IV. Elevated hs-cTnT was present in 33 of 135 (24%) HC patients. During a median follow-up of 5.0 years (IQR: 4.9-5.1) 18 patients reached the primary endpoint. Using Cox regression analysis, elevated hs-cTnT was univariately associated with the primary endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, previous non-sustained VT, reduced LV ejection fraction (<50%) and CICP were associated with the primary endpoint. In multivariable analysis, elevated hs-cTnT remained independently associated with outcome (aHR: 4.7 (95%CI: 1.8-12.6, p=0.002). In conclusion, this 5-year follow-up study is the first to prospectively confirm the association of elevated hs-cTnT and adverse outcomes. In addition to established clinical variables, cTn seems the biomarker of interest to further improve risk prediction in HC, which should be evaluated in larger prospective registries.