Group 5 Pulmonary Hypertension Associated With T-Cell Large Granular Lymphocytic Leukemia: Hemodynamics and Treatment.

Group 5 pulmonary hypertension (PH) encompasses diverse diseases, with a few cases linking it to T-cell large granular lymphocytic (LGL) leukemia. We report a case of a 76-year-old woman, diagnosed with LGL leukemia and concomitant PH, treated with oral triple pulmonary arterial hypertension (PAH) therapy. She initially presented with dyspnea on exertion; evaluation revealed severe precapillary PH. Implementing cyclophosphamide for leukemia along with tadalafil and macitentan for PH led to sustained symptomatic and hemodynamic improvement for over 3 years. At that time, deterioration in PH prompted the addition of selexipag, resulting in sustained clinical improvement for an additional 5 years. This case exemplifies the potential for sustained benefits of PAH therapy in leukemia-associated PH and highlights the need for continued research on the mechanistic relationship between LGL leukemia and PH, with the hope of identifying new management strategies.

Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program.

BACKGROUND: In the Semaglutide Treatment Effect in People with obesity and HFpEF (STEP-HFpEF) program, semaglutide improved heart failure (HF)-related symptoms, physical limitations, and exercise function, and reduced bodyweight in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Whether semaglutide improves functional status, as assessed by NYHA functional class, is unknown. OBJECTIVES: The goal of this study was to examine the effects of semaglutide on change in NYHA functional class over time. We also investigated the effects of semaglutide on HF-related symptoms, physical limitations, and bodyweight and other trial endpoints across baseline NYHA functional class categories. METHODS: This was a prespecified analysis of pooled data from 2 international, double-blind, randomized trials (STEP-HFpEF and STEP-HFpEF type 2 diabetes [STEP-HFpEF DM], comprising the STEP-HFpEF program), which collectively randomized 1,145 participants with obesity-related HFpEF to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. The outcome of interest for this analysis was the change in NYHA functional class (baseline to 52 weeks). We also investigated the effects of semaglutide on the dual primary, confirmatory secondary, and selected exploratory endpoints according to baseline NYHA functional class. RESULTS: More semaglutide-treated than placebo-treated patients had an improvement in NYHA functional class (32.6% vs 21.5%, respectively; OR: 2.20 [95% CI: 1.62-2.99; P < 0.001]) and fewer semaglutide-treated patients experienced deterioration in NYHA functional class (2.09% vs 5.24%, respectively; OR: 0.36 [95% CI: 0.19-0.70; P = 0.003]) at 52 weeks. Semaglutide (vs placebo) improved the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CCS) across NYHA functional class categories; this was especially pronounced in those in NYHA functional classes III/IV (10.5 points [95% CI: 6.6-14.4 points]) vs NYHA functional class II (6.0 points [95% CI: 3.4-8.6 points]) (P interaction = 0.06). By contrast, the degree of reduction in bodyweight was similar with semaglutide vs placebo regardless of baseline NYHA functional class category (NYHA functional class II, -8.4% [95% CI: -9.4% to -7.3%]; NYHA functional classes III/IV, -8.3% [95% CI: -9.9% to -6.8%]; P interaction = 0.96). Semaglutide consistently improved 6-minute walking distance (6MWD), the hierarchical composite endpoint (death, HF events, differences in KCCQ-CSS, and 6MWD changes), and reduced C-reactive protein and N-terminal prohormone of brain natriuretic peptide across NYHA functional class categories (all P interactions = NS). CONCLUSIONS: In patients with obesity-related HFpEF, fewer semaglutide-treated than placebo-treated patients had a deterioration, and more had an improvement, in NYHA functional class at 52 weeks. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced bodyweight and biomarkers of inflammation and congestion in all NYHA functional class categories. Semaglutide-mediated improvements in health status were especially large in patients with NYHA functional classes III/IV. (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure and Obesity; NCT04788511) (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes; NCT04916470).

TAVR-in-TAVR with a balloon-expandable valve for paravalvular leak.

Introduction: Paravalvular leak (PVL) is a severe complication of transcatheter aortic valve replacement (TAVR) that can lead to poor outcomes. TAVR-in-TAVR is a promising treatment for PVL; however, reports on its safety or efficacy are limited. In this study, we aimed to investigate the clinical outcomes of TAVR-in-TAVR using balloon-expandable prostheses for PVLs after TAVR. Methods: We retrospectively analyzed data from patients who underwent TAVR-in-TAVR using balloon-expandable Sapien prostheses for PVL after an initial TAVR at our institution. The procedural success, in-hospital complications, all-cause mortality, and echocardiographic data for up to 2 years post-surgery were evaluated. Results: In total, 31 patients with a mean age of 81.1 ± 7.9 years and mean Society of Thoracic Surgeons score of 8.8 ± 5.4% were identified. The procedural success rate of TAVR-in-TAVR was 96.8% (30/31). No in-hospital deaths, cardiac tamponade, or conversion to sternotomy occurred. Re-intervention was performed in only one patient (3.2%) during hospitalization. The all-cause mortality rates at 30 days and 2 years were 0% and 16.1%, respectively. A significant reduction in the PVL rate was observed at 30 days compared with that at baseline (p < 0.01). Discussion: Our findings suggest that TAVR-in-TAVR using balloon-expandable prostheses is safe and effective for PVL after TAVR with low complication rates and acceptable long-term outcomes. Further studies with larger sample sizes are needed to confirm our findings.

B-Type Natriuretic Peptide-A Paradox in the Diagnosis of Acute Heart Failure with Preserved Ejection Fraction in Obese Patients.

BACKGROUND AND OBJECTIVES: B-type natriuretic peptide (BNP) represents a clinical tool for the diagnosis and prognostic evaluation of acute and chronic heart failure patients. The purpose of this retrospective study was to evaluate BNP values in obese and non-obese patients with acute heart failure with preserved ejection fraction. MATERIALS AND METHODS: In this study, we enrolled 240 patients who presented to the emergency department complaining of acute shortness of breath and fatigue. The patients were divided into two groups according to their body mass index (BMI) values. The BMI was calculated as weight (kilograms) divided by height (square meters). The BNP testing was carried out in the emergency department. RESULTS: Group I included patients with a BMI of <30 kg/m2 and group II included patients with a BMI of ≥30 kg/m2. The average age of the patients was 60.05 ± 5.02 years. The patients in group II were significantly younger compared with those included in group I. Group II included a higher number of women compared to group I. Group I had fewer patients classified within New York Heart Association (NYHA) functional classes III and IV compared with group II. Echocardiography revealed an ejection fraction of ≥50% in all participants. Lower BNP levels were observed in patients from group II (median = 56, IQR = 53-67) in comparison to group I (median = 108.5, IQR = 106-112) (p < 0.001). CONCLUSIONS: Obesity and heart failure are continuously rising worldwide. In this retrospective study, we have highlighted the necessity to lower the threshold of BNP levels in obese patients with acute heart failure and preserved ejection fraction.

Stem cells treatment in chronic ischemic heart disease: a narrative review.

Chronic ischemic heart disease remains a major cause of morbidity and mortality worldwide. Several trials have been performed to evaluate benefit of stem cells transplantation to restore cardiac function in short- and long-term period after myocardial infarction. This narrative review analyzes 24 clinical trials between 2005 and 2023 comprising 1824 patients with chronic heart disease without heart failure. Percent increase in left ventricular ejection fraction (LVEF) and decrease in New York Heart Association (NYHA) class at 6/12 months after stem cells transplantation are reported. Thirteen trials showed a statistically significant percent LVEF increase between 4% to 19% at 6/12 months after stem cells transplantation (p values from 0.05 to 0.0001). No significant differences in LVEF were observed between patients who underwent intracoronary or intramyocardial transplantation. NYHA class decrease from severe to mild/moderate was demonstrated in 10 trials reporting a significant LVEF increase. Patients transplanted with bone marrow and peripheral blood CD133+ stem cells showed a doubling of percentage LVEF increase in comparison to patients transplanted with CD133- cells. This narrative review reports the conflicting results on this topic. Multicenter randomized clinical trials should be performed to define the efficacy of stem cells transplantation in chronic ischemic heart disease.

Cardiovascular outcomes by time-varying New York Heart Association class among patients with obstructive hypertrophic cardiomyopathy: a retrospective cohort study.

AIMS: Assess the relationship between New York Heart Association (NYHA) functional class and cardiovascular (CV) outcomes in obstructive hypertrophic cardiomyopathy (HCM). MATERIALS AND METHODS: This retrospective cohort study used the Optum Market Clarity database with linked claims and electronic health records. Adults (aged ≥18 years) with obstructive HCM and ≥1 NYHA class assessment after first HCM diagnosis were eligible (selection period: 2007-2021). Thirteen outcomes were assessed following the index date (first documented NYHA class assessment after first HCM diagnosis in the study period): all-cause mortality; first occurrences of all-cause hospitalization; CV-related hospitalization; primary ischemic stroke or transient ischemic attack (TIA); myocardial infarction (MI); deep vein thrombosis (DVT) or pulmonary embolism (PE); and major adverse CV event (MACE); as well as first incident events of atrial fibrillation or flutter; primary ischemic stroke or TIA; heart failure; acute MI; DVT/PE; and a composite endpoint of pacemaker and cardiac resynchronization therapy. Their associations with the index NYHA class were described using the Kaplan-Meier method (mortality) or cumulative incidence functions (other outcomes). Hazard ratios between NYHA class over time and outcomes were evaluated using time-varying Cox models, adjusting for age at first observed HCM diagnosis, sex, and race. RESULTS: Among 4,631 eligible patients, the mean age was 59 years at the first observed HCM diagnosis (female, 47%; White, 77%). The risks of all outcomes increased with worse (higher) index NYHA class and worsening NYHA class over time. Deterioration in the NYHA class from the index date was associated with increased risks of outcomes. LIMITATIONS: The study population may not be representative of all patients with obstructive HCM in the real world. Documented NYHA classes may not fully reflect the longitudinal variation of NYHA class for each patient. CONCLUSIONS: Worsening NYHA class was associated with increased risks of all-cause mortality and CV outcomes in obstructive HCM.

The New York Heart Association (NYHA) class is a simple way for doctors to measure how bad a patient's heart failure is by how it affects a person's ability to do everyday activities. It is a 4-point scale from 1, indicating no limitations on activity and no shortness of breath, to 4, at which patients have symptoms even at rest and any activity leaves people struggling to catch their breath. NYHA class is also used to assess patients with obstructive hypertrophic cardiomyopathy (HCM), a disease that causes thickening of the heart muscle. While doctors know that as obstructive HCM becomes worse, patients are at greater risk of having to go to the hospital, getting other conditions (like atrial fibrillation or heart failure), having to have more treatments (like surgery), or even death, doctors and researchers do not know how much risk the patient has and how it changes as the disease changes over time. Although there have been some smaller studies that have estimated this risk, we studied a large, national database and found that patients with worse (higher) NYHA class over time had an increased risk of dying, having to go to the hospital for heart-related care, and developing other heart-related conditions. This finding suggests that it is important for doctors to follow up patients with obstructive HCM carefully and to adjust treatments in order to help patients to stay at lower NYHA classes to improve long-term outcomes.

Predictors of Outcomes After Coronary Artery Bypass Grafting: The Effect of Concomitant Mitral Repair.

Background Ischemic mitral regurgitation (IMR) or functional MR intensity with or without repair increases the risk of coronary artery bypass grafting (CABG), and if the contaminant is undertaken, it doubles the risk of the surgery. This study aimed to characterize patients with concomitant CABG and mitral valve repair (MVR) and assess the surgical and long-term outcomes. Methods We conducted a cohort study from 2014 to 2020 on 364 patients who underwent CABG. A total of 364 patients were enrolled and divided into two groups. Group I (n= 349) included patients with isolated CABG, and Group II included patients who underwent CABG with concomitant mitral valve repair (MVR) (n= 15). Results Regarding preoperative presentation, most patients were male: 289 (79.40%), hypertensive 306 (84.07%), diabetic 281 (77.20%), dyslipidemic 246 (67.58%), presenting with NYHA classes III-IV: 200 (54.95%), and upon angiography, found to have the three-vessel disease: 265 (73%). Regarding their age mean± SD and Log EuroSCORE median (Q1-Q3), they had a mean age of 60.94± 10.60 years and a median score of 1.87 (1.13-3.19). The most prevalent postoperative complications were low cardiac output 75 (20.66%), acute kidney injury (AKI) 63 (17.45%), respiratory complications 55 (15.32%), and atrial fibrillation (AF) 55 (15.15%). Regarding long-term outcomes, most patients reported class I NYHA 271 (83.13%) and an echocardiographic decrease in MR severity. Patients with a CABG + MVR were significantly younger (53.93± 15.02 vs. 61.24± 10.29 years; P= 0.009), had a lower ejection fraction (33.6 [25-50] vs. 50 [43-55] %; p= 0.032), and had a higher prevalence of LV dilation (32 [9.17%]). EuroSCORE was significantly higher in patients with mitral repair (3.59 [1.54-8.63] vs. 1.78 (1.13-3.11); P= 0.022). The mortality percentage was higher with MVR but did not attain statistical significance. Intraoperative CPB and ischemic durations were longer in the CABG + MVR group. Furthermore, neurological complications were higher in patients with mitral repair (4 (28.57%) vs. 30 (8.65%), P= 0.012). The study's follow-up duration median was 24 (9-36) months. The composite endpoint occurred more frequently in older patients (HR: 1.05 [95% CI: 1.02-1.09]; 0.001), patients with low ejection fraction (HR: 0.96 [95% CI: 0.93-0.99]; P= 0.006) and in patients with preoperative myocardial infarction (MI) (HR: 2.3 [95%: 1.14- 4.68]; P= 0.021). Conclusion Most IMR patients benefited from CABG and CABG + MVR, as evident by NYHA class and echocardiographic follow-up. CABG + MVR had a higher Log EuroSCORE risk with increased intraoperative cardiopulmonary bypass (CPB) and ischemic durations, which may have played a role in increasing the incidence of postoperative neurological complications. On follow-up, no differences were reported between the two groups. However, age, ejection fraction, and a history of preoperative MI were identified as factors affecting the composite endpoint.

Improved mid-term stability of MR reduction with an increased number of clips after percutaneous mitral valve repair in functional MR.

Background: Percutaneous mitral valve repair (PMVR) has evolved to be a standard procedure in suitable patients with mitral regurgitation (MR) not accessible for open surgery. Here, we analyzed the influence of the number and positioning of the clips implanted during the procedure on MR reduction analyzing also sub-collectives of functional and degenerative MR (DMR). Results: We included 410 patients with severe MR undergoing PMVR using the MitraClip® System. MR and reduction of MR were analyzed by TEE at the beginning and at the end of the PMVR procedure. To specify the clip localization, we sub-divided segment 2 into 3 sub-segments using the segmental classification of the mitral valve. Results: We found an enhanced reduction of MR predominantly in DMR patients who received more than one clip. Implantation of only one clip led to a higher MR reduction in patients with functional MR (FMR) in comparison to patients with DMR. No significant differences concerning pressure gradients could be observed in degenerative MR patients regardless of the number of clips implanted. A deterioration of half a grade of the achieved MR reduction was observed 6 months post-PMVR independent of the number of implanted clips with a better stability in FMR patients, who got 3 clips compared to patients with only one clip. Conclusions: In patients with FMR, after 6 months the reduction of MR was more stable with an increased number of implanted clips, which suggests that this specific patient collective may benefit from a higher number of clips.

Simultaneous total occlusion of the 3 major coronary arteries in a patient with inferior ST-segment elevation myocardial infarction complicated by cardiogenic shock and sinus bradycardia.

Simultaneous occlusion of more than one coronary artery is uncommon and associated with poor prognosis. We reported a particular case of a 62-year-old patient, who presented with an inferior ST-segment elevation myocardial infarction with right ventricular involvement complicated by cardiogenic shock, sinus bradycardia, and an extensive echocardiographic ischemia with severe left ventricular systolic dysfunction. Coronary angiography revealed occlusion of 3 major coronary arteries. Primary percutaneous coronary intervention of the right coronary artery was performed with hemodynamic recovery, chest pain, and ST-segment resolution. Treatment for heart failure with reduced ejection fraction was initiated, with a good outcome.