Impact of smoking on procedural outcomes and all-cause mortality following acute myocardial infarction: A misleading early-stage pseudoparadox with ultimately reduced survival.

Background: Smoking has conflicting results on outcomes following acute myocardial infarction (AMI). We evaluated the independent influence of smoking status on patient outcomes. Methods: We included patients with AMI undergoing invasive coronary angiography with available self-reported smoking status. The incidence of death of any cause was evaluated during a median follow-up of 1.14 years (range 0.36-3.40 years). Association between smoking status and long-term mortality was evaluated using multivariable adjusted Cox regression analysis. Results: From 1612 AMI patients (aged 65.7 ± 13.3 years, 72.1 % male), 378 patients (23.4 %) were current-smokers, 311 (19.3 %) ex-smokers, and 923 (57.3 %) non-smokers. Compared with non-smokers, current-smokers were younger (68.5 ± 13.0 vs. 58.6 ± 12.5, p < 0.0001) and more frequently presented with STEMI (21.6 % vs. 35,4 %, p < 0.0001), while ex-smokers with similar frequency of STEMI-manifestation as non-smokers (22.5 %, p = 0.79) constituted an intermediate-group in terms of age (65.8 ± 11,6 years). Although smoking status was not significantly associated with long-term survival in unadjusted-analysis, active-smokers had 56 % higher long-term mortality than non-smokers when adjusting for age, gender, medications and other traditional risk factors, whereas ex-smokers possessed comparable survival probability (current-smokers: 1.56[1.14-2.14], p = 0.006, ex-smokers 1.16[0.84-1.59], p = 0.37). Current-smokers had unadjusted lower NT-proBNP and modestly higher absolute in-hospital left ventricular global longitudinal strain (LV GLS) values that did not differ among groups after the same adjustments (NT-proBNP: -0.08[-0.31; 0.15], p = 0.5, LV GLS: 0.65[-0.26; 1.55], p = 0.16). Conclusion: Active smoking is associated with increased adjusted long-term mortality, earlier onset and more frequent manifestation as STEMI, compared to non-smoking. Comparable adjusted results for LV GLS and NT-proBNP between groups support the presence of the pseudoparadox.

Impact of overweight and obesity on radiation dose and outcome in patients undergoing pulmonary vein isolation by cryoballoon and pulsed field ablation.

Background: Pulmonary vein isolation (PVI) using pulsed field ablation (PFA) or cryoballoon ablation (CBA) are commonly used single-shot techniques for the treatment of patients with atrial fibrillation (AF). The number of overweight (BMI 25-30 kg/m2) and obese (BMI>30 kg/m2) patients undergoing PVI is increasing, but data on this patient population is limited. Methods: Consecutive AF patients with a BMI ≥25 kg/m2 undergoing PFA- or CBA-PVI were included in this retrospective analysis. Baseline characteristics, procedural parameters and 1-year AF-freedom were retrospectively analyzed and compared for both ablation modalities. Results: Of 115 patients (66 % men, 64 years [IQR: 58-71 years], 57 % overweight and 43 % obese) PFA- was performed in 68 % and CBA-PVI in 32 %. Contrast-dye volume (PFA: 80 ml [IQR: 60 - 117 ml] vs. CBA: 130 ml [IQR: 95 - 200 ml], P=0.001) and radiation exposure (PFA: 2196 cGy·cm2 [IQR: 1398 - 2973 cGy·cm2] vs. CBA: 3239 cGy·cm2 [IQR: 1288 - 5062 cGy·cm2], P=0.009) was lower in patients undergoing PFA-PVI. Logistic regression analysis identified obesity (OR: 5.58, 95 % CI: 1.63-19.06; P=0.006) and CBA-PVI (OR: 12.93, 95 % CI: 3.51-47.68; P <0.001) to be associated with increased radiation exposure. Both techniques were comparably safe (PFA: 4 % vs. CBA: 0 %; P=0.3). The median follow-up time was 145 days [IQR: 103 - 294 days]. AF-freedom after 1-year was similar in overweight (82 %) and obese patients (67 %) (HR: 0.61; 95 % CI: 0.29-1.28; P=0.19) as well as in PFA- and CBA-PVI patients (76 % vs. 76 %, HR: 1.37; 95 % CI: 0.63-2.99; P=0.42). Conclusion: Overweight and obese patients undergoing PFA-PVI had lower contrast-dye volume compared to CBA-PVI. Obesity was associated with increased radiation exposure. Both techniques were comparably safe. The 1-year AF-freedom was similar in overweight and obese patients.

Prognostic Impact of Admission Time in Infarct-Related Cardiogenic Shock: An ECLS-SHOCK Substudy.

BACKGROUND: The outcomes of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) and the efficacy and safety of extracorporeal life support (ECLS) may be affected by the timing of hospital admission. OBJECTIVES: The present ECLS-SHOCK substudy sought to investigate the prognostic impact of on-hours vs off-hours admission and the efficacy of ELCS according to the timing of hospital admission time in AMI-CS. METHODS: Patients with AMI-CS enrolled in the multicenter, randomized ECLS-SHOCK trial from 2019 to 2022 were included. The prognosis of patients admitted during regular hours (ie, on-hours) was compared to patients admitted during off-hours. Thereafter, the prognostic impact of ECLS was investigated stratified by the timing of hospital admission. The primary endpoint was 30-day all-cause mortality. Statistical analyses included Kaplan-Meier, univariable, and multivariable logistic regression analyses. RESULTS: Of 417 patients enrolled in the ECLS-SHOCK trial, 48.4% (n = 202) were admitted during off-hours. Patients admitted during off-hours were younger (median age = 62 years [Q1-Q3: 55-69 years] vs 63 years [Q1-Q3: 58-71 years]; P = 0.036) and more commonly treated using initial femoral access for coronary angiography (79.0% [n = 158/200] vs 67.9% [n = 146/215]; P = 0.011). However, off-hours admission was not associated with an increased risk of 30-day all-cause mortality (off-hours vs on-hours: 46.0% [n = 93/202] vs 50.7% [n = 109/215]; OR: 0.83; 95% CI: 0.56-1.22). Furthermore, ECLS had no prognostic impact on 30-day all-cause mortality in patients with AMI-CS admitted during on-hours (50.5% [n = 52/103] vs 50.9% [n = 57/112]; P = 0.95; OR: 0.98; 95% CI: 0.58-1.68) or in patients admitted during off-hours (45.3% [n = 48/106] vs 46.9% [n = 45/96]; P = 0.82; OR: 0.94; 95% CI: 0.54-1.63). Finally, ECLS was associated with an increased risk of bleeding events, especially in patients admitted during on-hours. CONCLUSIONS: The prognosis in AMI-CS was not affected by admission time with a similar effect of ECLS during on- and off-hours.

Hospitalization of Symptomatic Patients With Heart Failure and Moderate to Severe Functional Mitral Regurgitation Treated With MitraClip: Insights From RESHAPE-HF2.

BACKGROUND: For patients with functional mitral regurgitation (FMR) and symptomatic heart failure (HF), randomized trials of mitral transcatheter edge-to-edge repair (M-TEER) have produced conflicting results. OBJECTIVES: This study sought to assess the impact of M-TEER on hospitalization rates, and explore the effects of M-TEER on patients who did or did not have a history of recent HF hospitalizations before undergoing M-TEER. METHODS: RESHAPE-HF2 (Randomized Investigation of the MitraClip Device in Heart Failure: 2nd Trial in Patients with Clinically Significant Functional Mitral Regurgitation) included patients with symptomatic HF and moderate to severe FMR (mean effective regurgitant orifice area 0.25 cm2; 14% >0.40 cm2, 23% <0.20 cm2) and showed that M-TEER reduced recurrent HF hospitalizations with and without the addition of cardiovascular (CV) death and improved quality of life. We now report the results of prespecified analyses on hospitalization rates and for the subgroup of patients (n = 333) with a HF hospitalization in the 12 months before randomization. RESULTS: At 24 months, the time to first event of CV death or HF hospitalization (HR: 0.65; 95% CI: 0.49-0.85; P = 0.002), the rate of recurrent CV hospitalizations (rate ratio [RR]: 0.75; 95% CI: 0.57-0.99; P = 0.046), the composite rate of recurrent CV hospitalizations and all-cause mortality (RR: 0.74; 95% CI: 0.57-0.95; P = 0.017), and of recurrent CV death and CV hospitalizations (RR: 0.76; 95% CI: 0.58-0.99; P = 0.040), were all lower in the M-TEER group. The RR of recurrent hospitalizations for any cause was 0.82 (95% CI: 0.63-1.07; P = 0.15) for patients in the M-TEER group vs control group patients. Patients randomized to M-TEER lost fewer days due to death or HF hospitalization (13.9% [95% CI: 13.0%-14.8%] vs 17.4% [95% CI: 16.4%-18.4%] of follow-up time; P < 0.0001, and 1,067 vs 1,776 total days lost; P < 0.0001). Patients randomized to M-TEER also had better NYHA functional class at 30 days and at 6, 12, and 24 months of follow-up (P < 0.0001). A history of HF hospitalizations before randomization was associated with worse outcomes and greater benefit with M-TEER on the rate of the composite of recurrent HF hospitalizations and CV death (Pinteraction = 0.03) and of recurrent HF hospitalizations within 24 months (Pinteraction = 0.06). CONCLUSIONS: These results indicate that a broader application of M-TEER in addition to optimal guideline-directed medical therapy should be considered among patients with symptomatic HF and moderate to severe FMR, particularly in those with a history of a recent hospitalization for HF.

Regional wall motion abnormalities on focused transthoracic echocardiography in patients presenting with acute chest pain: a predefined post hoc analysis of the prospective single-centre observational EPIC-ACS study.

OBJECTIVES: We evaluated the ability of the assessment of regional wall motion abnormalities (RWMA) detected via transthoracic echocardiography to predict the presence of obstructive coronary artery disease (CAD) in patients presenting with acute chest pain to the emergency department. DESIGN: Prospective single-centre observational study. SETTING: Tertiary care university hospital emergency unit. PARTICIPANTS: Patients presenting to the emergency department with acute chest pain suggestive of obstructive CAD. PRIMARY OUTCOME MEASURE: The primary endpoint was defined as the presence of obstructive CAD, requiring revascularisation therapy. RESULTS: Overall, 657 patients (age 58.1±18.0 years, 53% men) were included in our study. RWMA were detected in 76 patients (11.6%). RWMA were significantly more frequent in patients reaching the primary endpoint (26.2% vs 7.6%, p<0.001). In multivariable regression analysis, the presence of RWMA was associated with threefold increased odds of the presence of obstructive CAD (3.41 (95% CI 1.99 to 5.86), p<0.001). Adding RWMA to a multivariable model of the Thrombolysis in Myocardial Infarction (TIMI) risk score, cardiac biomarkers and traditional risk factors significantly improved the area under the curve for prediction of obstructive CAD (95% CI 0.777 to 0.804, p=0.0092). CONCLUSION: RWMA strongly and independently predicts the presence of obstructive CAD in patients presenting with acute chest pain to the emergency department. TRIAL REGISTRATION: The study has been registered online (NCT03787797).

Comprehensive strain assessment and mortality after acute myocardial infarction: a retrospective observational study based on the Essen Coronary Artery Disease registry.

BACKGROUND AND AIMS: Current ESC guidelines on the management of patients after acute myocardial infarction only include the evaluation of left ventricular (LV) function by assessment of the ejection fraction in addition to clinical risk scores to estimate the patient's prognosis. We aimed to determine, whether comprehensive evaluation of cardiac function using LV and right ventricular (RV) global longitudinal strain (GLS) and left atrial (LA) reservoir strain improves the prediction of survival in patients with acute myocardial infarction. METHODS: In patients with non-ST segment elevation or ST segment elevation myocardial infarction receiving echocardiography within 1 year after revascularisation, LV-GLS, RV-GLS and LA reservoir strain were quantified. In multivariable Cox regression analysis, HRs and 95% CIs were calculated per 1 SD increase in strain measure, adjusting for age, sex, systolic blood pressure, low-density lipoprotein cholesterol, smoking, diabetes and family history of premature coronary artery disease. RESULTS: During a median follow-up of 1.5 (0.5-4.2) years, 157 (11.1%) out of 1409 patients (64.4±13.5 years, 24.7% female) died. LV-GLS (1.68 (1.37-2.06), p<0.001), RV-GLS (1.39 (1.16-1.67), p<0.001) and LA reservoir strain (0.57 (0.47-0.69), p<0.001) were associated with mortality. Adding LV ejection fraction, tricuspid annular plane systolic excursion (TAPSE) or LA volume index to these models did not alter the association of strain measures of the LV (1.41 (1.06-1.89), p=0.02), RV (1.48 (1.03-2.13), p=0.04) or LA (0.61 (0.49-0.76), p<0.001). In receiver operating characteristics, combining the three strain measures improved the prediction of mortality above risk factors (AUC: 0.67 (0.63-0.71) to 0.75 (0.70-0.80)), while further addition of LV ejection fraction, TAPSE and LA volume index did not (0.75 (0.70-0.81)). CONCLUSION: The comprehensive evaluation of contractility of various cardiac chambers via transthoracic echocardiography using myocardial strain analysis, when routinely performed after acute myocardial infarction, may help to detect patients at increased mortality risk.

Establishing Medical Intelligence - Leveraging FHIR to Improve Clinical Management: a retrospective cohort and clinical implementation study.

BACKGROUND: FHIR (Fast Healthcare Interoperability Resources) has been proposed to enable health data interoperability. So far, its applicability has been demonstrated for selected research projects with limited data. OBJECTIVE: Here, we designed and implemented a conceptual medical intelligence framework to leverage real-world care data for clinical decision-making. METHODS: A Python package for the utilization of multimodal FHIR data (FHIRPACK) was developed and pioneered in five real-world clinical use cases, i.e., myocardial infarction (MI), stroke, diabetes, sepsis, and prostate cancer (PC). Patients were identified based on ICD-10 codes, and outcomes were derived from laboratory tests, prescriptions, procedures, and diagnostic reports. Results were provided as browser-based dashboards. RESULTS: For 2022, 1,302,988 patient encounters were analyzed. MI: In 72.7% of cases (N=261) medication regimens fulfilled guideline recommendations. Stroke: Out of 1,277 patients, 165 patients received thrombolysis and 108 thrombectomy. Diabetes: In 443,866 serum glucose and 16,180 HbA1c measurements from 35,494 unique patients, the prevalence of dysglycemic findings was 39% (N=13,887). Among those with dysglycemia, diagnosis was coded in 44.2% (N=6,138) of the patients. Sepsis: In 1,803 patients, Staphylococcus epidermidis was the primarily isolated pathogen (N=773, 28.9%) and piperacillin/tazobactam was the primarily prescribed antibiotic (N=593, 37.2%). PC: Three out of 54 patients who received radical prostatectomy were identified as cases with PSA persistence or biochemical recurrence. CONCLUSIONS: Leveraging FHIR data through large-scale analytics can enhance healthcare quality and improve patient outcomes across five clinical specialties. We identified i) sepsis patients requiring less broad antibiotic therapy, ii) patients with myocardial infarction who could benefit from statin and antiplatelet therapy, iii) stroke patients with longer than recommended times to intervention, iv) patients with hyperglycemia who could benefit from specialist referral and v) PC patients with early increases in cancer markers.

Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation.

BACKGROUND: Whether transcatheter mitral-valve repair improves outcomes in patients with heart failure and functional mitral regurgitation is uncertain. METHODS: We conducted a randomized, controlled trial involving patients with heart failure and moderate to severe functional mitral regurgitation from 30 sites in nine countries. The patients were assigned in a 1:1 ratio to either transcatheter mitral-valve repair and guideline-recommended medical therapy (device group) or medical therapy alone (control group). The three primary end points were the rate of the composite of first or recurrent hospitalization for heart failure or cardiovascular death during 24 months; the rate of first or recurrent hospitalization for heart failure during 24 months; and the change from baseline to 12 months in the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS; scores range from 0 to 100, with higher scores indicating better health status). RESULTS: A total of 505 patients underwent randomization: 250 were assigned to the device group and 255 to the control group. At 24 months, the rate of first or recurrent hospitalization for heart failure or cardiovascular death was 37.0 events per 100 patient-years in the device group and 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 to 0.85; P = 0.002). The rate of first or recurrent hospitalization for heart failure was 26.9 events per 100 patient-years in the device group and 46.6 events per 100 patient-years in the control group (rate ratio, 0.59; 95% CI, 0.42 to 0.82; P = 0.002). The KCCQ-OS score increased by a mean (±SD) of 21.6±26.9 points in the device group and 8.0±24.5 points in the control group (mean difference, 10.9 points; 95% CI, 6.8 to 15.0; P<0.001). Device-specific safety events occurred in 4 patients (1.6%). CONCLUSIONS: Among patients with heart failure with moderate to severe functional mitral regurgitation who received medical therapy, the addition of transcatheter mitral-valve repair led to a lower rate of first or recurrent hospitalization for heart failure or cardiovascular death and a lower rate of first or recurrent hospitalization for heart failure at 24 months and better health status at 12 months than medical therapy alone. (Funded by Abbott Laboratories; RESHAPE-HF2 ClinicalTrials.gov number, NCT02444338.).

Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion.

Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer's patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3-10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients.

Cardiovascular toxicities of immune therapies for cancer - a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology.

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.

Risk Factors of Ischemic Stroke in Patients With Atrial Fibrillation After Transcatheter Aortic Valve Implantation from the Randomized ENVISAGE-TAVI AF Trial.

In patients with prevalent or incident atrial fibrillation (AF) after successful transcatheter aortic valve implantation (TAVI) enrolled in the EdoxabaN Versus standard of care and theIr effectS on clinical outcomes in pAtients havinG undergonE Transcatheter Aortic Valve Implantation - in Atrial Fibrillation (ENVISAGE-TAVI AF) trial, the incidence of ischemic stroke (IS) and any stroke was numerically less in the edoxaban group than in the vitamin K antagonist (VKA) group. The present study aimed to identify risk factors associated with IS in an on-treatment subanalysis in patients from ENVISAGE-TAVI AF who received ≥1 dose of edoxaban or VKA. Baseline patient characteristics were compared in patients with and those without IS. Numerical variables were compared using a 1-way analysis of variance; categorical variables were compared using Fisher's exact test. Stepwise Cox regression determined patient characteristics associated with the first IS event. Of 1,377 patients, 41 (3.0%) experienced an IS, and 1,336 (97.0%) did not; baseline demographics and clinical characteristics were well balanced between groups. Most ISs occurred within 180 days of TAVI for edoxaban (57.9%) and VKA (68.2%). The rate of IS was 2.0/100 person-years for edoxaban versus 2.7/100 person-years for VKA. Independently associated with IS were history of systemic embolic events (hazard ratio 2.96, 95% confidence interval 1.26 to 7.00, p = 0.01) and pre-TAVI use of VKAs (hazard ratio 2.17, 95% confidence interval 1.12 to 4.20, p = 0.02). In conclusion, although the overall incidence of IS was small for patients with AF on edoxaban or VKA after successful TAVI, patients with a history of systemic embolic events or pre-TAVI use of VKAs may be at greater risk of IS after TAVI.

Early Outcomes of Two Large Mitral Valve Transcatheter Edge-to-Edge Repair Devices-A Propensity Score Matched Multicenter Comparison.

Background/Objectives: Previous trials reported comparable results with PASCAL and earlier MitraClip generations. Limited comparative data exist for more contemporary MitraClip generations, particularly the large MitraClip XT(R/W). We aimed to evaluate acute and 30-day outcomes in patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) with one of the large devices, either PASCAL P10 or MitraClip XT(R/W) (3rd/4th generation). Methods: A total of 309 PASCAL-treated patients were matched by propensity score to 253 MitraClip-treated patients, resulting in 200 adequately balanced pairs. Procedural, clinical, and echocardiographic outcomes were collected for up to 30 days, including subgroup analysis for mitral regurgitation (MR) etiologies. Results: PASCAL and MitraClip patients were comparable regarding age (80 vs. 79 years), sex (female: 45.5% vs. 50.5%), and MR etiology (degenerative MR: n = 94, functional MR [FMR]: n = 96, mixed MR: n = 10 in each group). Technical success rates were comparable (96.5% vs. 96.0%; p > 0.999). At discharge, the mean gradient was higher (3.3 mmHg vs. 3.0 mmHg; p = 0.038), and the residual mitral valve orifice area was smaller in MitraClip patients (3.0 cm2 vs. 2.3 cm2; p < 0.001). At discharge, the reduction to MR ≤ 2+ was comparable (92.4% vs. 87.8%; p = 0.132). However, reduction to MR ≤ 1+ was more frequently observed in PASCAL patients (67.7% vs. 56.6%; p = 0.029), driven by the FMR subgroup (74.0% vs. 60.0%; p = 0.046). No difference was observed in 30-day mortality (p = 0.204) or reduction in NYHA-FC to ≤II (p > 0.999). Conclusions: Both M-TEER devices exhibited high and comparable rates of technical success and MR reduction to ≤2+. PASCAL may be advantageous in achieving MR reduction to ≤1+ in patients with FMR.

Preclinical models of cardiotoxicity from immune checkpoint inhibitor therapy.

Immune checkpoint inhibitor (ICI) therapy represents a ground-breaking paradigm in cancer treatment, harnessing the immune system to combat malignancies by targeting checkpoints such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). The use of ICI therapy generates distinctive immune-related adverse events (irAEs) including cardiovascular toxicity, necessitating targeted research efforts. This comprehensive review explores preclinical models dedicated to ICI-mediated cardiovascular complications including myocarditis. Tailored preclinical models of ICI-mediated myocardial toxicities highlight the key role of CD8+ T cells, emphasizing the profound impact of immune checkpoints on maintaining cardiac integrity. Cytokines and macrophages were identified as possible driving factors in disease progression, and at the same time, initial data on possible cardiac antigens responsible are emerging. The implications of contributing factors including thoracic radiation, autoimmune disorder, and the presence of cancer itself are increasingly understood. Besides myocarditis, mouse models unveiled an accelerated progression of atherosclerosis, adding another layer for a thorough understanding of the diverse processes involving cardiovascular immune checkpoint signalling. This review aims to discuss current preclinical models of ICI cardiotoxicity and their potential for improving enhanced risk assessment and diagnostics, offering potential targets for innovative cardioprotective strategies. Lessons from ICI therapy can drive novel approaches in cardiovascular research, extending insights to areas such as myocardial infarction and heart failure.

The Effect of Stress-Reducing Interventions on Heart Rate Variability in Cardiovascular Disease: A Systematic Review and Meta-Analysis.

Stress is recognized as a significant trigger and exacerbator of various medical conditions, particularly in the field of cardiovascular disease (CVD). Given that heart rate variability (HRV) offers insight into the functioning of the autonomic nervous system and has been identified as a predictive factor for increased cardiovascular mortality, exploring the correlation between stress and HRV is pertinent. We systematically reviewed trials where researchers investigated the effects of stress-reducing interventions on biomarkers and time-domain/frequency-domain parameters of HRV in CVD. Eligible studies underwent meta-analysis utilizing a random-effects model. The meta-analysis showed overall beneficial effects of stress-reducing interventions on HRV for the standard deviation of Normal-to-Normal intervals (SDNN) in short-term and 24 h assessments, as well as for the low-frequency power (LF) in short-term assessment. Overall effect sizes were notably high and showed significant p-values (short-term SDNN: MD = 6.43, p = 0.01; 24 h SDNN: MD = 10.92, p = 0.004; short-term LF: MD = 160.11, p < 0.001). Our findings highlight the significant impact of stress-reducing interventions in modulating HRV by influencing short-term SDNN and LF parameters, as well as the 24 h assessment of SDNN. These results emphasize the importance of stress-reducing measures in lowering the risk of further progression in CVD and improving patient outcomes.

Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

AIM: The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. METHODS AND RESULTS: The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. CONCLUSION: Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.