York Heart Association Class III-IV Research Articles

Percutaneous balloon mitral valvuloplasty with shockwave lithotripsy for the treatment of calcific mitral valve stenosis.

Calcific mitral stenosis (calcific MS) presents a challenge for surgical treatment and is a contraindication for most contemporary transcatheter mitral valve replacement devices (TMVR), rendering patients with very limited therapeutic options. This study aims to assess the clinical and hemodynamic follow-up after mitral valve lithotripsy (MVL). All consecutive patients who underwent MVL to treat symptomatic calcific MS at St Michael's Hospital, Toronto, Canada, were included. Patients were deemed unsuitable for mitral surgery or TMVR after heart team assessment. Patients with rheumatic MS or ≥moderate mitral regurgitation (MR) were excluded. The primary endpoint was a reduction in the invasive mitral gradient by ≥50% without significant (≥moderate) MR. Fifteen patients underwent MVL between 2021 and 2023 with a mean age of 74 ± 9 years; 53% were female, with a mean STS score of 10% ± 0.1%. Following MVL, there was a reduction in the invasively measured mean trans-mitral gradient compared to baseline (14 mmHg vs. 6 mmHg; p < 0.05). The primary endpoint was achieved in 8 patients (53%) with no major procedural complications. At follow-up (median 90 days, IQR 58-115 days), 14 (93%) patients reported improved symptoms from New York Heart Association (NYHA) Class III-IV to NYHA Class I-II (p < 0.01) with stable echo-derived mean gradient (7.7 mmHg ± 2 mmHg vs. 8.4 mmHg ± 2.9 mmHg (p = 0.7). In selected patients with symptomatic inoperable calcific MS, MVL was safe and associated with significant short-term clinical and hemodynamic improvement. MVL may represent a new compassionate therapy for this challenging cohort. Further studies are needed to determine the long-term outcomes and help define the role of IVL technology in treating calcific valvular conditions.

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT study).

Liver dysfunction contributes to worse clinical outcomes in heart failure (HF) patients. However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction. Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models. Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP. Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in heart failure with reduced ejection fraction patients in clinical practice.

Clinical Outcomes Following Transcatheter Mitral Valve-in-Valve Replacement Using a Meril Myval Transcatheter Heart Valve

Transcatheter mitral valve-in-valve (TMViV) replacement for degenerated surgically implanted bioprosthetic valves has been described by both transseptal and transapical approaches. The balloon-expandable Myval transcatheter valve (Meril Life Science, Vapi, India) is commonly used for transcatheter valve-in-valve procedures in India. This study aimed to report in-hospital, 30-day, and 1-year outcomes of Myval patients who underwent TMViV in a single tertiary care centre in India. Symptomatic patients with surgical bioprosthetic mitral valve failure with New York Heart Association (NYHA) class III-IV symptoms, despite optimal medical therapy and high or very high risk for redo surgery, were assigned to TMViV following heart team discussions. Data were retrospectively collected and outcomes assessed. Twenty patients were treated, with mean age 64.4 years, 60% were female, and mean Society of Thoracic Surgeons (STS) predicted risk of operative mortality score was 8.1. The failure mechanism was combined stenosis and regurgitation in 60% of patients. Technical success was achieved in 100% of patients. The mean postprocedure and 30-day gradients were 4.6±2.7 and 6.3±2.1, respectively. None of them had significant valvular or paravalvular leaks or left ventricular outflow tract obstruction. All-cause mortality at 1 year was 10%, and all survivors were in New York Heart Association (NYHA) class I or II. TMViV replacement with a Meril Myval can be safely performed with high technical success, and low 30-day and 1-year mortality.

Exploring the association between self-care behaviour, knowledge and cognition in patients with heart failure: a secondary analysis from the HF-Wii study

Abstract Background Self-care is vital for patients with heart failure and is influenced by different factors, Knowledge and the ability to reflect on behaviors is important to make decisions on self-care. Cognition may also be an important factor in relation to both knowledge and self-care. It has been found that cognitive impairment in patients with heart failure is common, with a reported prevalence of 20–80%. Aim To explore association between self-care behaviour, knowledge and cognition in patients with heart failure. Methods This is a secondary analysis of the baseline measures from the HF-Wii study with data from 605 patients, mean age 70 ± 12, 29% female, 30 % in New York Heart Association Class III-IV. Data on self-care was collected with European Self-care Behaviour Scale (EHFScBS) (possible range 0-100). Knowledge was collected with the Dutch HF Knowledge Scale (possible range 0-15 points). Cognition was assessed Montreal Cognitive Assessment (MoCA). Knowledge was dichotomised into low vs. high knowledge (cut off 13) and cognition into mild, moderate or severe cognitive problems vs. no or light cognitive problems. Results The total score on the EHFScBS was 64.6 ± 21.0 with 41% (N=245) of the patients performing good self-care (score &amp;gt; 70). The mean score on the Dutch HF Knowledge Scale was 12.3 ± 1.9 and 308 patients had high knowledge (score &amp;gt; 13). The majority of the patients (61%; N=371) had mild cognitive problems and 195 (32%) had no or light cognitive problems with a mean MOCA score of 24.4 ± 3.8. Self-care was significantly correlated to total knowledge (r = .23; p &amp;lt; .001), but it was not correlated to cognition. Furthermore, there was a positive correlation between total knowledge and cognition (r = .43; p &amp;lt;.001). Out of the 308 patients with high level of knowledge (&amp;gt;13), 130 had mild, moderate or severe cognitive problems. The other 178 patients with high knowledge had no or only light cognitive problems. Patients with high knowledge had a significantly higher score on the self-care behavior scale, independently of their cognitive function. In a multivariable logistic regression analysis, higher age [odds ratio (OR) 1.03; 95% confidence interval (CI) 1.02-1.06), better quality of life (OR .95; 95% CI .90 - .99) and higher levels of knowledge (OR 1.25; OR 1.13 – 1.38) were independently related to self-care. Conclusion HF knowledge and cognition are related in patients with heart failure, but only knowledge, not cognition, was independently related to self-care.

Prognostic implications of angiopoietin-2 in heart failure and the influence of empagliflozin: the EMPEROR program

Abstract Background Heart failure (HF) development and progression is associated with endothelial dysfunction, oxidative stress, and inflammation. The mechanisms involved in endothelial repair in HF are not fully understood. Emerging evidence suggests that angiopoietin-2 (Angpt2), a vascular destabilizing factor, may be related to outcome in HF. Aim To assess the association between Angpt2 and clinical outcomes in a pooled analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials, and to evaluate if the response to empagliflozin therapy in HF is modulated by Angpt2 levels. Methods and results Angpt2 levels (ng/ml) were measured in serum samples from 1131 EMPEROR study participants by using Roche Cobas Elecsys assay, within biomarker research agreement between Boehringer Ingelheim and Roche Diagnostics International Ltd, at baseline, week 12 and week 52. Patients were divided into tertiles of baseline Angpt2 levels (&amp;lt;2.58 ng/mL; ≥2.58 ng/mL &amp;lt;4.71 ng/mL and ≥4.71 ng/mL). Patients in the highest tertile were more frequently white people, had a higher prevalence of New York Heart Association class III-IV symptoms, HF hospitalization within 12 months, obesity, diabetes, atrial fibrillation, elevated natriuretic peptides, worse renal function, and lower prevalence of coronary disease, compared to the lowest tertile (p&amp;lt;0.05 for all). Higher tertile at baseline was associated with increased risk for adverse HF and kidney events (Table 1). Empagliflozin treatment was associated with reduction of the serum Angpt2 versus placebo at week 12 (adjusted gMean 0.872 [0.828-0.917], p&amp;lt;0.0001) but not at week 52 (adjusted gMean ratio 0.946, [0.879-1.019], p=0.145). Empagliflozin significantly reduced the risk of hospitalization for HF and cardiovascular death particularly for patients with highest baseline Angpt2 levels (lowest tertile HR 1.21 [0.63-2.31]; middle tertile HR 0.65 [0.37-1.16]; highest tertile HR 0.64 [0.42-0.97], P-trend=0.139). Conclusion Higher Angpt2 levels at baseline were associated with more advanced HF and worse prognosis. Treatment with empagliflozin was associated with reduction of Angpt2 level at week 12. The benefit of empagliflozin on major HF events was consistent across baseline Angpt2 levels.Table 1

Palliative care assessment and outcomes in patients admitted for heart failure in an Australian quaternary healthcare service

Abstract Background/Introduction Heart failure (HF) has high mortality and healthcare utilisation, and despite patients having similar palliative care needs to cancer patients(1), they are much less likely to have their PC needs assessed and managed (2-3). Expert consensus guidelines from cardiology and palliative care groups recommend early integration of a palliative approach in addition to usual care, but the complex and unpredictable trajectory of HF, lack of referral criteria and misunderstandings about PC are potential barriers that affect specialist PC referrals. Given the issues surrounding integration of PC in HF patients, we sought to understand the use of PC by patients with HF at our institution. Purpose To characterise the pattern and predictors of referrals of HF patients to the inpatient PC service in an Australian quaternary health service. Methods A single-centre retrospective cohort study was performed using electronic medical record data in consecutive patients admitted for HF at a quaternary health service in Australia, over a 12 month period from July 2019 to June 2020. All adults ≥ 18 years of age and admitted for HF were identified using the Diagnostic Related Group (DRG) admission code for ‘Heart Failure and Shock’. Results The 502 patients admitted for HF were elderly (median age 82 years, IQR 15) and 50% were male. Functional status was poor, with 29% unable to care for themselves and 56% requiring some level of assistance. General medicine was the major admitting unit with 67% (n=338 of 502) of patients, and the cardiology and advanced heart failure units admitted 12% (n=59) and 5% (n=26) of patients, respectively. Conversely, the main treating team in the ambulatory setting was cardiology in 51% (n=253). HF patients had high mortality rate at 32% during the median follow up time of 27 months (interquartile range 8 months). Seven percent (n=37 of 502) were referred to inpatient specialist PC, and often in the terminal phase. High dependency (defined as Australian-modified Karnofsky Performance Status 10-40) (62% vs 28%, p&amp;lt;0.01) and New York Heart Association class III-IV symptoms (86% vs 42%, p&amp;lt;0.01) were associated with referral, but one or more previous admission for HF in the last 12 months was not (35% vs. 28%, p=0.35). In all HF patients, symptoms were poorly assessed and discussion about prognosis occurred in 10% despite the high mortality. Referral to inpatient PC resulted in more prescribing of symptom medications on discharge (41% vs 2%, p&amp;lt;0.01) and referral to community PC (46% vs 1%, p&amp;lt;0.01). Conclusion Referral to inpatient specialist PC in hospitalised HF patients is low relative to the morbidity and mortality in these patients. In addition, treating teams do not routinely assess symptoms or discuss disease trajectory. More work is needed to ensure that HF patients’ PC needs are integrated into care as recommended by expert consensus.Table 1

Transfemoral tricuspid valve replacement and one-year outcomes: the TRISCEND study.

For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes. The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year. Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure. In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490.

Hedinger Syndrome-Lessons Learnt: A Single-Center Experience.

Hedinger syndrome (HS) or carcinoid heart disease (CD) is a rare and challenging manifestation of malignant neuroendocrine tumours (NETs) involving the heart. We aimed to report our experience with surgical strategies and midterm results in HS patients. Eleven patients (58 ± 11 (range 41 to 79 years); 5 females) with HS who underwent cardiac surgery in our department between 07/2005 and 05/2023 were analysed. All patients showed a New York Heart Association (NYHA) class III-IV and in all the tricuspid valve (TV) was involved. Four patients received a TV replacement, and three TV reconstruction. Recently, to preserve the geometry and function of the compromised right ventricle (RV), we have applied the TV "bio-prosthesis in native-valve" implantation technique with the preservation of the valve apparatus (tricuspid valve implantation: TVI) in four cases. Concomitant procedures included pulmonary valve replacement in four, pulmonary implantation in one, and aortic valve replacement in three cases. To treat RV failure, we adapted a combined TandemHeart®-CytoSorb® haemoperfusion strategy in Patient #10 and venoarterial extracorporeal membrane oxygenation (V-A ECMO) support avoidance, after experiencing an ECMO-induced carcinoid-storm-related death in Patient #8. Mortality at 30 days was 18% (2/11). The median follow up was 2 ± 2.1 years (range 1 month to 6 years) with an overall mortality during the follow-up period of 72.7% (8/11). HS surgery, despite being a high-risk procedure, can efficiently prolong survival, and represents a safe and feasible procedure. However, patient selection seems to be crucial. Further follow up and larger cohorts are needed.

Effects of sacubitril/valsartan on atrial function and structure as treatment response indicators in patients with heart failure with reduced ejection fraction: an observational prospective study

Abstract Funding Acknowledgements Type of funding sources: None. Background Sacubitril/valsartan (Sac/Val) has been shown to improve mortality and reduce hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF), also through reverse cardiac remodeling. However, temporal changes of functional and structural left atrial parameters, including speckle tracking (ST) analysis, have not been comprehensively characterized yet. Purpose This prospective study sought to: (1) evaluate the impact of Sac/Val on echo parameters, focusing on left atrial function and structure metrics, at two timepoints, 6 and 12 months, after treatment initiation; (2) assess the predictive role of these factors on Sac/Val response at 12 months, including LVEF and biomarker outcomes. Methods From January 2020 to September 2021, HFrEF patients from Policlinico Universitario Agostino Gemelli IRCSS outpatient HF service with indication to Sac/Val treatment were prospectively enrolled; subjects with history of atrial fibrillation and more than moderate mitral regurgitation were excluded. Echocardiographic evaluation was performed before Sac/Val, at 6 and 12 months after treatment initiation. Patients with improvement in left ventricular ejection fraction (LVEF) ≥ 35% and with N-terminal pro-b-type natriuretic peptide (NT pro-BNP) reduction below 1000 pg/mL were considered responders. Results Sixty-six patients (50 males, 16 females) with an age of 64 ± 12 years were finally enrolled, of which 41% were affected by chronic ischemic heart disease. At enrollment, 19 subjects were in New York Heart Association class III-IV, median NT-proBNP was 3063.00 pg/mL and mean LVEF was 30.3±7.7%. LA-EF was 27.8±12.8%, while Left Atrio-ventricular coupling index (LACi) was 0,30±0,12. At ST echocardiography, LV GLS was -8,2±3,0% and LA reservoir strain (LARS) 11,60%. All structural and functional LA parameters significantly improved at T1 and T2: at T2, LARS was 22,51%, LA-EF 37,4±15,8% and LACi 0,28±0,12 (respectively p &amp;lt;0,001, p = 0,05, p = 0,018 compared to baseline). No differences were detected according to dysfunction etiology. Improvements were larger among patients who achieved the pre-specified outcome. LA reservoir strain was the best predictor of positive changes in LVEF and NT-proBNP. Conclusions Precise characterization of LA structural and functional parameters, including ST analysis, may help identifying patients experiencing the highest benefit from Sac/Val, therefore guiding treatment in the HFrEF population.

Left atrial remodeling and right ventricular-pulmonary arterial coupling after MitraClip implantation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Transcatheter edge-to-edge mitral valve repair (TEER) with the MitraClip system has emerged as a therapeutic alternative to surgical solutions in high risk patients with severe mitral regurgitation (MR). MR is characterized by left ventricular volume overload, which leads to left ventricular dilatation. Furthermore, MR is a common cause of pulmonary hypertension. Right ventricular (RV) intrinsic contractility and its response to afterload is referred to as RV-pulmonary arterial (PA) coupling. Effect of TEER in patients with MR on left atrial (LA) function and RV-PA coupling is less investigated. Purpose The aim of our study was to assess clinical characteristics of patients undergoing MitraClip implantation including LA function and RV-PA coupling. Methods Eighty-eight consecutive patients with chronic severe MR were enrolled in the single-center observational study (mean age 71.5±7.9 years, male 54.5%, ischemic cardiomyopathy 54.5%). Primary MR (PMR) was present in 22.7%, secondary MR (SMR) in 73.9 % and mixed (MxMR) etiology in 3.4%. Conventional and advanced echocardiography examination was performed using speckle tracking echocardiography before TEER and at 6 month post-TEER follow-up. Left atrial maximal (LAV max) and minimal (LAV min) volumes were measured indexed for body surface area. Furthermore, we analysed left atrial functional parameters, such as reservoir strain, conduit strain and contraction strain. Results The technical success of MitraClip implantation was 95,5%. Mortality rate at 6 month follow-up time was 10.8% (1/88 PMR, 7/88 SMR, 1/88 MxMR). Severe residual MR developed during follow-up in 4.2% and New York Heart Association class III-IV functional status was concluded in 6.8% at 6 month post-TEER. Significant decrease in left ventricular end-diastolic median diameter (mm) was observed at follow-up compared to pre-TEER: 57.5 (IQR: 51.25 – 63.75) vs 60.5 (IQR: 52.5 – 66.75), respectively, p = 0.01. Similarly, the median value of pulmonary artery systolic pressure (PASP) substantially decreased (mmHg) after TEER: 42 (IQR: 32 – 52) vs 49.5 (IQR: 41 – 57), respectively, p = 0.003. Tricuspid annulus systolic excursion/PASP median value, representing RV-PA coupling, improved remarkably: 0.45 (IQR: 0.31 – 0.69) vs 0.38 (IQR: 0.29 – 0.52), respectively, p = 0.02. Compared to pre-TEER, median LA volumes and strain parameters did not change significantly at 6 month post-TEER: reservoir strain (%) 12.88 (IQR: 8.18–18.78) vs 11.74 (IQR: 7.48–20.36), p = 0.41; LAV max (ml) 48.70 (IQR: 39.81–62.29) vs 48.17 (IQR: 42.08–58.7), p = 0.31; LAV min (ml) 34.33 (IQR: 24.5–46.32) vs 33.89 (IQR: 26.02–44.53), p = 0.69. Conclusions The function of the enlarged LA was severely reduced, which did not change after MitraClip implantation in our population. However, positive left ventricular remodeling and improvement in RV-PA coupling was observed 6 month after MitraClip procedure.

Application of Machine Learning Algorithms to Predict New-Onset Postoperative Atrial Fibrillation and Identify Risk Factors Following Isolated Valve Surgery.

New-onset postoperative atrial fibrillation (POAF) is the most common complication after valvular surgery, but its etiology and risk factors are incompletely understood. This study investigates the benefits of machine learning methods in risk prediction and in identifying relative perioperative variables for POAF after valve surgery. This retrospective study involved 847 patients, who underwent isolated valve surgery from January 2018 to September 2021 in our institution. We used machine learning algorithms to predict new-onset postoperative atrial fibrillation and to select relatively important variables from a set of 123 preoperative characteristics and intraoperative information. The support vector machine (SVM) model demonstrated the best area under the receiver operating characteristic (AUC) value of 0.786, followed by logistic regression (AUC = 0.745) and the Complement Naive Bayes (CNB) model (AUC = 0.672). Left atrium diameter, age, estimated glomerular filtration rate (eGFR), duration of cardiopulmonary bypass, New York Heart Association (NYHA) class III-IV, and preoperative hemoglobin were high-ranked variables. Risk models based on machine learning algorithms may be superior to traditional models, which were primarily based on logistic algorithms to predict the occurrence of POAF after valve surgery. Further prospective multicenter studies are needed to confirm the performance of SVM in predicting POAF.

Survival and Independent Predictors of Mortality Following Coronary Artery Bypass Graft Surgery in a Single-Unit Practice in the United Kingdom Over 20 Years

The types of graft conduits and surgical techniques may impact the long-term outcomes of patients after coronary artery bypass graft (CABG) revascularization. This study observed a long-term survival rate following CABG surgery over 20 years in the United Kingdom. A total of 2979 isolated CABG patients were studied from 1999 to 2020, and postoperative data were obtained from the hospital-recorded mortality by the data quality team of the information department. Postdischarge survival was estimated using the Kaplan-Meier method, and statistical significance was obtained with log-rank tests and the Gehan-Breslow test, and the Holm-Sidak method was used for multiple pairwise comparisons. The study observed male predominance (80%), and the median age was statistically significant (P <0.001) among the groups, 66 years (interquartile range 58-73) and 72 years (interquartile range 66-78) in survivor and non-survivor groups, respectively. In the Holm-Sidak method analysis, the best survival rate (mean 18.7 years) was observed in the total arterial group with significantly decreased survival for the mixed arterial and venous group (mean 16.12 years) and only the vein group (10.44 years). The Cox regression model observed that the New York Heart Association (NYHA) class III-IV (HR 1.57), chest re-exploration (HR 2.14), preoperative dialysis (HR 3.13), and redo surgery (HR 3.04) were potential predictors of the postoperative mortality (P ≤0.05). In our series over 20 years, albeit off-pump and on-pump CABG observed similar survival rates, the total arterial myocardial revascularization population has significantly better long-term survival benefits.

Nationwide Temporal Trends in Clinical Characteristics and Treatment of Dilated Cardiomyopathy From 2003 to 2013 in Japan - A Report From Clinical Personal Records.

Little is known about nationwide temporal trends in the clinical characteristics and treatment of dilated cardiomyopathy (DCM) in Japan.Methods and Results: We collected data regarding demographics, echocardiography, and treatment of DCM between 2003 to 2013 from Clinical Personal Records, a national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Among the 40,794 DCM patients screened, 27,702 with left ventricular ejection fraction (LVEF) <50% and age ≥18 years were enrolled in this study and divided into 3 groups according to registration year: Group 1, 2003-2005 (10,006 patients); Group 2, 2006-2010 (11,252 patients); and Group 3, 2011-2013 (6,444 patients). Over time, there were decreases in age at registration (mean [±SD] 58.6±13.0 vs. 56.8±13.8 vs. 56.2±13.8 years; P<0.001) and LVEF (33.5±10.0% vs. 31.1±9.9% vs. 29.2± 9.7%; P<0.001), and an increase in patients with New York Heart Association Class III-IV (28.2% vs. 35.2% vs. 41.0%; P<0.001). The use of β-blockers (59.1% vs. 79.3% vs. 87.8%; P<0.001) and mineralocorticoid receptor antagonists (30.6% vs. 35.8% vs. 39.7%; P<0.001) increased over time. In multivariate analysis, male sex, systolic blood pressure, chronic kidney disease, hemoglobin, and registration year were positively associated, whereas age and LVEF were negatively associated, with β-blocker prescription. Although the clinical characteristics of DCM changed, the implementation of optimal medical therapy for DCM increased from 2003 to 2013 in Japan.

Abstract P177: Circulating Ketone Bodies and Mortality in Heart Failure: A Community Cohort Study

Background: Heart failure (HF) is associated with metabolic alterations, including ketogenesis. However, determinants of ketogenesis and risk of mortality in HF is not defined. Total ketone bodies (KB) include β-hydroxybutyrate, acetoacetate, and acetone and can be measured in plasma by nuclear magnetic resonance (NMR). The aim of this study is to determine the relationship between KB and clinical characteristics in a community HF cohort and to assess the association between KB and all-cause mortality. Methods: A population-based cohort of 1,389 HF patients was prospectively enrolled between 2003 and 2012. Plasma KB was measured by LP4 NMR LipoProfile ® assay/test on the Vantera® NMR analyzer platform. A conditional inference tree method (ctree R Package) was used to determine optimal KB group cut points. Associations between clinical characteristics and KB were measured with Wilcoxon rank sum test and Pearson’s Chi-squared test. Kaplan-Meier method estimated survival. Cox regression analyses were used to estimate associations between KB concentrations and mortality. Results: Among the 1,382 HF patients with KB measurements, the median age was 78 years (IQR 68-84) and 52% were men. Median KB was 180 μM (IQR 134-308). Patients were divided into two groups with lower KB (≤471.5 μM) and higher KB (&gt;471.5 μM). Patients with higher KB (N=210) had lower BMI, higher BNP, and were more likely to be in the New York Heart Association class III-IV; however, these patients were less likely to have hyperlipidemia, coronary disease, or diabetes mellitus (P &lt; 0.05). Age, sex, creatinine, ejection fraction, or Meta-Analysis Global Group in Chronic HF (MAGGIC) score did not differ by KB group. Higher KB was associated with worse survival (figure). After adjustment for the MAGGIC score, higher KB was associated with increased risk of mortality (HR 1.3; 95% CI, 1.08-1.48). Conclusions: In this community HF cohort, higher KB was associated with increased mortality, independent of the MAGGIC score.

The interaction of forced expiratory volume in 1 s and N-terminal pro-B-type natriuretic peptide with outcomes after transcatheter aortic valve replacement.

Low forced expiratory volume in 1 s (FEV1) and elevated N-terminal pro-B-type natriuretic peptide (NT-Pro-BNP) have been individually associated with poor outcomes after transcatheter aortic valve replacement (TAVR). We hypothesized a combination of the 2 would provide prognostic indication after TAVR. We categorized 871 patients who received TAVR from 2008 to 2018 into 4 groups according to baseline FEV1 (<60% or ≥60% predicted) and NT-Pro-BNP (<1601 or ≥1601 pg/ml): group A (n = 312, high FEV1, low NT-Pro-BNP), group B (n = 275, high FEV1, high NT-Pro-BNP), group C (n = 123 low FEV1, low NT-Pro-BNP) and group D (n = 161, low FEV1, high NT-Pro-BNP). The primary end point was survival at 1 and 5 years. Patients in group A had more severe aortic stenosis and achieved the best long-term survival at 1 [93% (95% CI: 90-96)] and 5 [45.3% (95% CI: 35.4-58)] years. Low FEV1 and high NT-Pro-BNP (group D) patients had more severe symptoms, higher Society of Thoracic Surgeons predicted risk of operative mortality, lower ejection fraction and aortic valve gradient at baseline. Patients in group D had the worst survival at 1 [76% (95% CI: 69-83)] and 5 years [13.1% (95% CI: 7-25)], hazard ratio compared to group A: 2.29 (95% CI: 1.6-3.2, P < 0.001) with 25.7% of patients in New York Heart Association class III-IV. Patients in groups B and C had intermediate outcomes. The combination of FEV1 and NT-Pro-BNP stratifies patients into 4 groups with distinct risk profiles and clinical outcomes. Patients with low FEV1 and high NT-Pro-BNP have increased comorbidities, poor functional outcomes and decreased long-term survival after TAVR.

Gender-Related Differences in Patients with Acute Heart Failure: Observation from the Journey Heart Failure-Turkish Population Study.

Gender-related clinical variations in patients with acute heart failure have been described in previous studies. However, there is still a lack of research on gender differences in patients hospitalized for acute heart failure in Türkiye. The aim of this study is to compare the clinical features, in-hospital approaches, and outcomes of male and female patients hospitalized for acute heart failure. Differences in clinical characteristics, medication prescription, hospital management, and outcomes between males and females with acute heart failure were investigated from the Journey Heart Failure-Turkish Population study. Nine hundred eighteen patients (57.2%) were men and 688 (42.8%) were women. Women were older than men (70.48 ± 13.20 years vs. 65.87 ± 12.82 years; P <.001). The frequency of comorbidities such as hypertension (72.7% vs. 62.4%, P <.001), diabetes (46.5% vs. 38.5%, P = .001), atrial fibrillation (46.5% vs. 33.4%, P <.001), New York Heart Association class III-IV symptoms (80.6% vs. 71.2%, P =.001), and dyspnea in the rest (73.8% vs. 68.3%, P =.044) were more common in women on admission. Male patients were more frequently hospitalized with reduced left ventricular ejection fraction (51.0% vs. 72.4%, P <.001). In-hospital mortality was higher among female patients (9.3% vs. 6.4%, P =.022). Higher New York Heart Association class, lower estimated glomerular filtration rate, higher N-terminal pro-B type natriuretic peptide on admission, and mechanical ventilation usage were the independent parameters of in-hospital mortality, whereas the female gender was not. Our study clearly demonstrated the diversity in presentation, management, and in-hospital outcomes of acute heart failure between male and female patients. Although left ventricular systolic functions were better in female patients, in-hospital mortality was higher. Recognizing these differences in the management of heart failure in different sexes will serve better results in clinical practice.

Phase 2 Study of Oral Decitabine/Cedazuridine in Combination with Magrolimab for Previously Untreated Subjects with Intermediate to Very High-Risk Myelodysplastic Syndromes (MDS)

Rationale Hypomethylating agents (HMAs) are approved for higher risk MDS (azacitidine, decitabine, oral decitabine/cedazuridine US package insert). Parenteral therapy (subcutaneous or intravenous) is required 5-7 days each month, often resulting in hospital or clinic visits on a chronic basis and represents a substantial burden for this primarily elderly population and their caregivers. Not surprisingly, patients with higher risk MDS are often not started and/or have low compliance with parenteral HMAs, with patients preferring oral medications (Zeidan et al., CLML 2022). Magrolimab has demonstrated encouraging preliminary data in the higher-risk MDS population in combination with azacitidine and is currently being evaluated in a randomized Phase 3 study (ENHANCE, NCT04313881), comparing the efficacy and safety of magrolimab plus azacitidine with that of azacitidine plus placebo in previously untreated patients with higher-risk MDS. This phase 2 study examines the possibility of using an oral HMA (oral decitabine/cedazuridine) in combination with magrolimab which may provide the benefits without the burden of significant parenteral therapy (4-6 additional clinic days each month). Study Design ASTX727-10 is a phase 2, international, single-arm, open-label study investigating the safety and efficacy of combination oral decitabine/cedazuridine and magrolimab treatment in intermediate to very high-risk MDS, based on the MDS International Prognostic Scoring System - Revised (IPSS-R). Secondary objectives include evaluating the pharmacokinetic profiles of oral decitabine/cedazuridine and magrolimab, other clinical efficacy of the combination, and safety and efficacy in prespecified subgroups (e.g. IPSS-Molecular, p53 mutant status). To be eligible, subjects with ECOG Performance Status ≤2 must have previously untreated MDS per WHO 2016 classification with < 20% bone marrow blasts and be willing to undergo red blood cell transfusions to achieve a hemoglobin >9 gm/dl at the start of study treatment. Subjects must also be willing to undergo blood transfusions as per the parameters of the protocol and as clinically necessary. Key exclusion criteria include significant medical issues (including uncontrolled diabetes and New York Heart Association Class III-IV heart failure), creatinine clearance < 50 ml/min, immediate eligibility for hematopoietic stem cell transplant, secondary MDS, or MDS / (myeloproliferative neoplasm) overlap syndromes. As part of the study, tolerability of the combination regimen will be confirmed in the first 6-18 subjects. Dose and/or dosing decreases identified during this dose limiting toxicity assessment will be applied to the entire study. Approximately 100 subjects will be enrolled. Anticipated study opening is November 2022.

Ethical Challenges and Implications of Deactivating Mechanical Circulatory Support for Patients With Preserved Cognitive Function.

Ethical Challenges and Implications of Deactivating Mechanical Circulatory Support for Patients With Preserved Cognitive Function.

Delays in Door-to-Diuretic Time and 1-Year Mortality Among Patients With Heart Failure.

Achieving prompt euvolemic state in heart failure (HF) is associated with reduced mortality. Time-sensitive metrics such as door-to-diuretic time , or the time between presentation and administration of intravenous diuretics, may be an important facilitator of achieving a faster euvolemic state and reducing mortality. The aim of this study was to investigate whether reduced door-to-diuretic time was associated with lower odds of death among hospitalized patients with HF. A retrospective chart review of patients with HF admitted to a medical center was performed between 2020 and 2021. Inclusion criteria were an International Classification of Diseases, 10th Revision code for HF with positive Framingham Criteria and the use of intravenous bolus furosemide. Exclusion criteria included ventricular assist devices, dialysis, and ultrafiltration therapy. Data collected from the medical records included demographics, echocardiography, staff notes, and medications. The end point was 1-year all-cause mortality. Descriptive statistics, t tests or median test, and multivariate logistic regression were used to describe the sample, evaluate group differences, and determine odds of mortality, respectively. Among 160 charts from patients with HF (age, 70 ± 14.4 years; 52%, n = 83, male; 53%, n = 85, ischemic cardiomyopathy; 83%, n = 134, New York Heart Association classes III-IV), 30% (n = 48) died within 1 year. The median diuretic dose was 40 mg (interquartile range, 20 mg), with a median time of administration of 247 minutes (4.12 hours) (interquartile range, 294 minutes to 4.9 hours). After covariate adjustment, prolonged door-to-diuretic time more than doubled (2.22; 95% confidence interval, 1.03-4.8; P = .04) the odds of 1-year mortality. On the basis of this sample of charts from older highly symptomatic patients with HF, delayed door-to-diuretic time was associated with significantly greater odds of 1-year all-cause mortality.

Factors associated with health-related quality of life in heart failure in 23 000 patients from 40 countries: results of the G-CHF research programme.

To examine clinical and social correlates of health-related quality of life (HRQL) in patients with heart failure (HF) from high- (HIC), upper middle- (UMIC), lower middle- (LMIC) and low-income (LIC) countries. Between 2017 and 2020, 23 292 patients with HF (32% inpatients, 61% men) from 40 countries were enrolled in the Global Congestive Heart Failure study. HRQL was recorded at baseline using the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12. In a cross-sectional analysis, we compared age- and sex-adjusted mean KCCQ-12 summary scores (SS: 0-100, higher=better) between patients from different country income levels. We used multivariable linear regression examining correlations (estimated coefficients) of KCCQ-12-SS with sociodemographic, comorbidity, treatment and symptom covariates. The adjusted model (37 covariates) was informed by univariable findings, clinical importance and backward selection. Mean age was 63 years and 40% of patients were in New York Heart Association (NYHA) class III-IV. Average HRQL was 55 SD 27. It was 62.5 (95% confidence interval [CI] 62.0-63.1) in HIC, 56.8 (56.1-57.4) in UMIC, 48.6 (48.0-49.3) in LMIC, and 38.5 (37.3-39.7) in LICs (p < 0.0001). Strong correlates (estimated coefficient [95% CI]) of KCCQ-12-SS were NYHA class III versus class I/II (-12.1 [-12.8 to -11.4] and class IV versus class I/II (-16.5 [-17.7 to -15.3]), effort dyspnoea (-9.5 [-10.2 to -8.8]) and living in LIC versus HIC (-5.8 [-7.1 to -4.4]). Symptoms explained most of the KCCQ-12-SS variability (partial R2 =0.32 of total adjusted R2 =0.51), followed by sociodemographic factors (R2 =0.12). Results were consistent in populations across income levels. The most important correlates of HRQL in HF patients relate to HF symptom severity, irrespective of country income level.