Panagiotis Simitsis

Summary: Studies of cardiovascular (CV) events after chimeric antigen receptor T‐cell (CAR‐T) therapy have mostly focused on patients with lymphoma. We evaluated the incidence, timing and prognostic significance of in‐hospital and post‐discharge CV events in patients with multiple myeloma (MM) receiving CAR‐T therapy. We conducted a retrospective analysis of MM patients treated with CAR‐T between 2018 and 2024. CV events (heart failure, arrhythmias, myocardial infarction and stroke) and all‐cause mortality were assessed separately during hospitalization and post‐discharge. Time‐dependent Cox regression was used to evaluate associations with mortality. Among 256 patients, 11.7% ( n = 30) experienced in‐hospital CV events, most commonly atrial arrhythmias (5.5%) and new left ventricular (LV) dysfunction (3.9%), with a median onset of 8 (Q1, Q3: 5, 11) days. Ninety percent of those with LV dysfunction recovered function. Independent predictors of in‐hospital CV events included age >65, prior atrial fibrillation, antiplatelet use, cytokine release syndrome grade ≥2 and higher immune effector cell‐associated neurotoxicity syndrome grade. Post‐discharge CV events were less common (7.8%), occurring at a median of 13 (Q1, Q3: 7, 22) months. Only post‐discharge CV events were associated with higher post‐discharge all‐cause mortality. There were no in‐hospital CV deaths and one post‐discharge CV death. In this large MM CAR‐T cohort, in‐hospital CV events were relatively uncommon, reversible and not linked to mortality. In contrast, post‐discharge CV events, while rare, predicted worse survival.

As the prevalence of heart failure (HF) continues to rise, prompt diagnosis and management of various medical conditions, which may lead to HF exacerbation and result in poor patient outcomes, are of paramount importance. Infection has been identified as a common, though under-recognized, precipitating factor of acute heart failure (AHF), which can cause rapid development or deterioration of HF signs and symptoms. Available evidence indicates that infection-related hospitalizations of patients with AHF are associated with higher mortality, protracted length of stay, and increased readmission rates. Understanding the intricate interaction of both clinical entities may provide further therapeutic strategies to prevent the occurrence of cardiac complications and improve prognosis of patients with AHF triggered by infection. The purpose of this review is to investigate the incidence of infection as a causative factor in AHF, explore its prognostic implications, elucidate the underlying pathophysiological mechanisms, and highlight the basic principles of the initial diagnostic and therapeutic interventions in the emergency department.

Background/Aim: Arterial stiffness is involved in the clinical course of atherogenesis. We have previously shown that PBR, a marker of glycocalyx integrity is predictor of cardiovascular events in patients without established cardiovascular disease. The purpose of this study was to investigate whether altered arterial properties of the vessels confers predictively and additively to estimation of cardiovascular risk. Methods: Pulse wave velocity carotid-femoral (PWVc-f), the gold standard method to assess arterial stiffness, was measured non-invasively by Complior device. Increased PWV(c-f), especially above 10 m/s, indicates increased arterial stiffness. We measured baseline PWV(c-f) in 600 apparently healthy subjects (47.61±13.84 years old, 50.1% males), without established cardiovascular disease. We prospectively monitored the occurrence of major cardiovascular events (MACE-death, myocardial infarction, stroke and heart failure hospitalization) during a 6-year follow-up period using electronic records and clinic visits. Results: Fifty-seven MACEs were documented during follow-up. In univariate analysis, subjects with increased PWV were found to exert greater risk for MACEs (hazard ratio (HR): 1.09, 95% CI: 1.02–1.17, p=0.01). In all subjects, PWV predicted higher risk for MACEs in a model including PBR, sex, age, hyperlipidemia, diabetes, hypertension, current smoking, family history of coronary artery disease and treatment with ACEi/ARBs or lipid lowering agents (HR: 1.12; 95% CI: 1.04–1.17, p=0.029,net reclassification improvement (NRI): 23%; C-statistic: from 0.644 to 0.697). However, only in participants older than 50 years old, PWV was an independent and additive predictor of outcome when added in a model including PBR, SCORE, those risk factors not included in SCORE (diabetes, family history of CAD) and medication (HR: 1.09; 95% CI: 1.02–1.13, NRI: 23.8%, C-statistic increase from 0.703 to 0.762, p<0.01). Conclusion: Arterial stiffness is an independent and additive predictor to endothelial glycocalyx and SCORE for adverse outcome at 6 years follow-up in individuals over 50 years old. Funding Acknowledgement: Type of funding sources: None.

OBJECTIVES: The objective of this study was to compare rates of redo surgery for the Medtronic Mosaic 305 A Porcine Prosthesis and the Carpentier-Edwards Perimount Pericardial Aortic Bioprosthesis 2900. METHODS: This was a single-centre retrospective observational study. We included all 1018 patients who underwent aortic valve replacement with a Mosaic (n = 216) or Perimount (n = 809) bioprosthesis between October 2000 and August 2008. The total follow-up was 1508 patient-years for the Mosaic valve and 5813 for the Perimount valve. The maximal follow-up and interquartile range were 14.8 and 7.0 years for the Mosaic valve and 15.1 and 5.6 years for the Perimount valve, respectively. A propensity score-weighted version of the Cox model, Kaplan-Meier analysis and multivariate regression model was used. RESULTS: Despite no statistical difference in the number of non-structural valve deterioration cases between valves, redo surgery occurred earlier in 10 (4.6%) Mosaic than for 17 (2.1%) Perimount valves (P = 0.02) and was required for structural valve deterioration in 5 (2.3%) Mosaic valves when compared with 7 (0.9%; P = 0.04) Perimount valves. Four of 5 Mosaic failures occurred before 5 years, whereas all Perimount failures occurred after 5 years. Redo surgery for non-structural valve deterioration occurred in 3 patients with Mosaic valves (1.4%) and no patients with Perimount valves. Surgery for the remaining patients with Perimount valves was due to infection or aortic disease. CONCLUSIONS: Early redo surgery for structural valve degeneration was uncommon but occurred earlier for the Mosaic porcine than the Perimount bovine pericardial replacement aortic valve.

Mineralocorticoid receptor antagonists (MRAs) constitute a beneficial therapy in chronic heart failure, but their use in the acute heart failure (AHF) setting remains rather unexplored. To assess the effect of MRAs administered during hospitalization on in-hospital outcomes of patients with AHF, we performed a post-hoc analysis of the Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF). Patients of the original study cohort (n = 4953) were categorized according to in-hospital MRA treatment status as MRA-treated (n = 1439) and untreated (n = 3514) subjects. Nearest-neighbor propensity score with 1:1 matching yielded a subsample of pairs of MRA-treated and MRA-untreated patients (n = 1003 in each treatment group) that were balanced in an extensive list of baseline characteristics. In-hospital mortality between MRA-treated and untreated patients were assessed by Cox regression analysis before and after adjustment for known prognostic factors and other concomitantly administered intravenous and oral HF specific therapies. In the matched cohort, in-hospital mortality was 4.2 vs 10.8% in MRA-treated vs untreated patients. Treatment with MRAs was associated with a reduction of in-hospital mortality [HR 0.372 (95% CI, 0.261–0.532), p < 0.001]. This association remained significant after adjustment for known prognostic factors and co-administered intravenous and oral HF therapies [HR: 0.618 (95% CI, 0.383–0.995), p = 0.048]. In conclusion, MRA therapy administered during hospitalization for AHF was associated with reduced in-hospital mortality. The role of MRAs in AHF deserves further examination in adequately powered randomized controlled studies.

Left ventricular contractile reserve is a prognostic indicator for adverse outcome in patients with severe chronic heart failure with reduced ejection fraction (HFrEF). We investigated the dobutamine-induced changes of LV multidimensional deformation and their predictive value for cardiac mortality of patients with severe chronic HFrEF. In this prospective study, out of 130 patients with severe HFrEF who underwent a low-dose dobutamine stress echocardiography (LDSE) study using speckle tracking imaging, 100 patients were followed up for the occurrence of cardiac death over a period of 4 years. Compared with survivors, non-survivors (n = 32) had lower radial strain (RS) and strain rate (RSR) (10.7 ± 5.9 vs. 20.1 ± 8% and 0.5 ± 0.2 vs. 0.8 ± 0.3 L/s, P < 0.001), a smaller increase of global longitudinal strain (GLS) and strain rate after LDSE (0.9 ± 1.5 vs. –3.3 ± 3.5% and −0.1 ± 0.1 vs. –0.3 ± 0.3 L/s, P < 0.001), and a lack of change in the circumferential and radial deformation. The dobutamine-induced changes of all speckle tracking indices predicted cardiac mortality, while, among resting echocardiographic parameters, only RS and RSR predicted survival, after adjusting for age, sex, cardiomyopathy aetiology, NYHA class, AF, BNP levels, resting LVED, and LV outflow tract velocity–time integral, and their respective changes produced by dobutamine (P < 0.05). The dobutamine-induced change of GLS and resting RS were the best additive predictors of mortality with a net reclassification improvement of 0.518 (P = 0.022) In severe chronic HFrEF, resting RS and the dobutamine-induced change of GLS are independent predictors of cardiac mortality.