1-year Follow-up Research Articles

Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after TAVI: insights from an international multicenter registry

Abstract Background The impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve implantation (TAVI) is controversial. Purpose Our study aims to evaluate the impact of PPM on mortality and clinical-echocardiographic progression of cardiac damage in a "real world" cohort of patients at intermediate and low surgical risk and to characterize its main predictors. Methods 963 patients who underwent TAVI procedure between 2017 and 2021, from an international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations (VARC-3 criteria). Results 18% of patients developed post-TAVI PPM, (7.7% of the whole cohort severe). At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, p=0.33), aged 82y (interquartile range (IQR) 79-85y) vs 82y (IQR 78-86y; p=0.46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, p=0.04); they had smaller left ventricular outflow tract (LVOT) diameter (20mm, IQR 19-21 vs 20mm, IQR 20-22, p=0.02), reduced Stroke Volume index (SVi) (34.2 vs 38 ml/m2, p<0.01) and transaortic flow rate (190.6 vs 211 ml/s, p<0.01). At pre-discharge FU patients with PPM had more paravalvular aortic regurgitation (AR) (moderate/severe AR 15.8% vs 9.2%, p<0.01). At a median FU of 1.46 years (IQR 1-4), there was no evidence of a significant impact of PPM on overall mortality (15.3% vs 13.1%, p=0.46) nor on rehospitalization rate for heart failure (4.3% vs 8.0%, p=0.10). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in endsystolic diameter (ESD) (33 vs 28mm, p=0.03) and a statistically non-significant increase in LV mass index (121 vs 106g/m2, p=0.07). Interestingly, trajectory parameters of patients with PPM from baseline to 1-year FU showed a reduced cardiac remodeling compared to patients without PPM, including no LVEF improvement (p=0.88), absent reduction of LV end-diastolic volume (p=0.70), indexed LV mass (p=0.31), ESD (p=0.48) and pulmonary artery systolic pressure (p=0.82), and an increase of basal RV diameter (p<0.001). Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, p=0.03). Independent predictor of PPM at multivariable logistic regression was male gender (OR=1.93, p=0.04); while SVi (OR=0.86, p<0.001), prosthetic size >23mm (OR=0.62, p=0.03) and LVOT diameter (OR=0.79, p=0.02) had protective effect. Conclusions There was no evidence of a short- or medium-term impact of PPM on mortality. However, clinical-echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations associated with a significant deterioration in NYHA class at 1 year.

Ablation outcome in elderly women with atrial fibrillation undergoing pulsed-field ablation for electrical isolation of pulmonary veins and left atrial posterior wall

Abstract Background Documented evidences indicate higher prevalence of non-paroxysmal atrial fibrillation (AF) as well as in elderly women but also demonstrate the need to go beyond the pulmonary veins (PV) when treating these patients. Objective We compared the ablation outcome in elderly women (>70 years) with that in men in the same age group as well as in younger women (≤70 years) undergoing pulsed-field ablation (PFA) for persistent AF (PerAF). Methods This multicenter study included consecutive PerAF patients undergoing PFA as their first procedure. Patients were divided into 3 groups: Group 1: women >70 years, Group 2: men ≥70 years and Group 3: women ≤70 years. All received PV isolation (PVI) and isolation of left atrial posterior wall (LAPWI). Concentric overlapping lesions were placed in the LAPW. Number of applications were determined on a case-by-case basis. Isolation was confirmed by electrograms recorded on the multispline catheter. In all patients, ICE and fluoroscopy were used to optimize contact between the PFA catheter and the targeted tissue. Arrhythmia-monitoring was performed for 1-year with periodic clinic visits, event recorders and 7-day Holter monitoring. Results A total of 229 patients (group 1: 73; group 2: 47 and group 3: 109) were included in this analysis. Baseline characteristics of the study population is presented in table 1. At 1-year follow-up, 15 (20.5%), 3 (6.38%) and 10 (9.17%) from group 1, 2 and 3 respectively, experienced arrhythmia recurrence off-antiarrhythmic drugs. Recurrence rate in group 1 was significantly higher than that in group 2 (p=0.034) and group 3 (p=0.029). Conclusion In women aged ≤70 years and in elderly men (>70 years), PVI plus isolation of LAPW using ICE-guided PFA was associated with significantly lower recurrence rate compared to that in the elderly women. Given the higher recurrence rate following PVI+LAPWI in the elderly females, the operators should consider addressing all other AF-initiating extra-PV triggers for better ablation-outcome in this subset of the AF population.

Interleukin 6 in asymptomatic patients with nonsevere aortic valve stenosis: a post-hoc study of the SEAS trial

Abstract Background Inflammation plays a pivotal role in the pathogenesis of aortic valve stenosis (AS) through cytokine-mediated valve calcification. Studies of explanted valves found associations of an elevated pro-inflammatory cytokine, Interleukin 6 (IL-6), with increased postoperative mortality. However, limited knowledge exists regarding the prognostic value of elevated circulating IL-6 in asymptomatic patients with nonsevere AS. Purpose To investigate the hypothesis that elevated plasma IL-6 concentration ≥7 pg/mL (above the upper limit of normal 95th percentile) correlates with more severe AS and a higher risk of adverse outcomes in asymptomatic patients with nonsevere AS. Methods We analyzed data of 1574 asymptomatic patients who had mild-to-moderate AS, preserved systolic and kidney function, no overt cardiovascular diseases, and an event-free follow-up one year after enrollment in the randomized Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial. We ascertained the correlation of year-0 and year-1 IL-6 levels with echocardiographic AS severity, defined as moderate-severe AS in the presence of ≥2 measurements at year-0: aortic valve area <1 cm², mean pressure gradient ≥40 mmHg, maximal transaortic velocity ≥4 m/s, and velocity ratio <0.25. Multivariable regression examined correlations between IL-6 at year-0 and clinical variables. Cox proportional hazard models and competing risk analyses examined associations of elevated IL-6 at year-1 and 4-year risk of the primary composite endpoint of major cardiovascular events (MACE) comprising the first event of cardiovascular death, aortic valve replacement, hospitalization with heart failure, myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or ischemic stroke. Results At year-0, among 1574 patients with a mean (SD) age of 67.5 (9.7) years, 629 (40.0%) were women, 263 (16.7%) had moderate-severe AS, and 194 (12.3%) had elevated IL-6. The median relative IL-6 change from year-0 to year-1 was 1.0 (IQR, 0.8-1.4) across AS-severity groups (P=0.12) (Figure 1). In adjusted models, IL-6 at year-0 did not correlate with AS-severity (P=0.30). In mild AS, an elevated IL-6 at year-1 was associated with an increased 4-year MACE risk (HR 1.40; 95% CI, 1.02-1.92; p=0.04) in adjusted Cox regression analyses (Figure 2A). In sensitivity analyses, the annual IL-6 increase >50% combined with normal IL-6 was associated with an increased 4-year MACE-risk of HR 1.48 (95% CI, 1.10-2.00; P=0.009) in patients with mild AS and 1.82 (95% CI, 0.68-1.74; P=0.73) in patients with moderate-severe AS (all P for interaction>0.25) (Figure 2C-D). Conclusion In asymptomatic patients with nonsevere AS, circulating IL-6 remains stable within the reference range in 7 out of 8 patients during a 1-year follow-up, regardless of AS severity. An elevated IL-6 was associated with a 1.4-fold increased 4-year MACE-risk in patients with mild AS, suggesting its possible role as an early risk marker.Figure 1Figure 2

Atrial fibrillation recurrence rates in patients with transthyretin cardiac amyloidosis undergoing pulmonary vein isolation: a comparative retrospective study with propensity score matching

Abstract Background Atrial fibrillation (AF) affects up to 70% of individuals diagnosed with transthyretin cardiac amyloidosis (ATTR CA) [1]. AF ablation is frequently considered in the management of these patients, but there is a lack of data about outcomes of the procedure in this population. Purpose This study aims to evaluate AF recurrence rates and long-term AF recurrence-free survival in patients with ATTR CA undergoing pulmonary vein isolation (PVI). Methods A single-center retrospective study was conducted, including all patients diagnosed with ATTR CA who underwent PVI from 2016 to 2023. We compared patients with amyloidosis (cases) to those without (controls), employing propensity score matching for age, gender, AF type (paroxysmal vs. persistent), BMI, diabetes, arterial hypertension diagnosis, antiarrhythmic drug therapy post-index ablation, and left atrium (LA) volume assessed by 3D rotational angiography (3DRA). Results 16 patients with CA were matched to 16 patients without (32 patients in total). After matching, the populations demonstrated comparable baseline characteristics (figure 1). The study consistently revealed a higher AF recurrence rate, after PVI, in the CA group (81.3%) compared to the control group (37.5%) at the last follow-up (p-value 0.01) (median follow-up 1255 ± 1055 days in CA and 1491 ± 464 days in control group), as well as a significantly lower long-term AF-recurrence free survival (log-rank p = 0.01 – figure 2). Additionally, the recurrence rate at 1-year post-procedure was 56.25% in the CA group and 18.75% in the control group (p-value 0.03). Conclusions Pulmonary vein isolation remains a viable treatment option for individuals with ATTR CA. However, it proved less effective (or less durable) than in the general population without the disease, both at 1-year follow-up and for longer periods, as shown also with recurrence-free survival rate. Further studies are warranted to determine the optimal treatment strategy for this specific population.Baseline Characteristics fig. 1Kaplan Meyer fig. 2

O2 consumption overshoot in patients with heart failure: crossing the line

Abstract Background Cardiopulmonary exercise testing (CPET) is among the most valuable clinical tools for evaluating disease severity and physical activity limitations in heart failure (HF) patients. Peak oxygen uptake (pVO2) reflects maximal cardiac output during exercise, and it is considered a major parameter in selecting candidates for cardiac transplantation. VO2 overshoot, a transient increase in VO2 during recovery from maximal exercise, has been frequently observed in HF patients and is attributed to the transient increase in cardiac output caused by the mismatch between cardiac contractility and afterload reduction. However, the prognostic significance of this phenomenon remains to be fully established. Purpose This study aimed to characterize the prognostic significance of VO2 overshoot following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF, with left ventricular ejection fraction (LVEF) <50%, who underwent CPET between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sitting passively for 2 minutes). VO2 overshoot kinetics during recovery were measured and described as the time until post-exercise VO2 fell below pVO2 for at least 15 seconds. Please refer to Figure 1A for an example of normal and prolonged VO2 overshoot. The study endpoint was time to cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) over 1-year follow-up. Results A total of 254 patients were included (mean age 59 ± 12 years; 83% males; mean LVEF 34 ± 9%; 70% with ischemic HF; 77% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean predicted pVO2% 52 ± 16%; mean VE/VCO2 slope 41 ± 13). The VO2 overshoot had a normal distribution (Figure 1B) and lasted on average for 45 ± 33 seconds. There were no differences between patients that had an overshoot higher and below average. Overall, during follow-up, 25 patients met the composite endpoint (12 CV deaths, 9 urgent heart transplants, and 4 LVAD). Univariate analysis showed a significant relationship between VO2 overshoot and the outcome of interest (HR 1.01, 95% CI 1.00 – 1.02, p=0.027). In multivariate analysis, this association remained significant, even after adjusting for pVO2 and VE/VCO2 slope (HR 1.01, CI 95% 1.00– 1.02, p=0.026). Conclusion This study delves into the intriguing phenomenon of VO2 overshoot in patients with heart failure, shedding light on its potential prognostic significance. The independent association between VO2 overshoot and the composite endpoint suggests that this transient increase in oxygen consumption may carry prognostic value. Further studies should confirm these findings.

Exercise stress testing recovery kinetics: the forgotten phase

Abstract Background Impaired exercise capacity is a cardinal feature of heart failure (HF). Peak oxygen uptake (pVO2) and ventilatory efficiency (VE/VCO2 slope) during exercise are well-consolidated prognostic markers in patients with HF. A previous study suggested that abnormally prolonged VO2 recovery, specifically the failure to decrease VO2 from peak exercise by 10.5 mL/kg/min at 180 seconds of the recovery phase, predicts adverse outcomes in HF. However, it is unknown to what extent the recovery of VEqCO2, a marker of ventilation/perfusion mismatch, adds prognostic value to the already existing parameters. Purpose The aim of this study was to characterize the functional and prognostic significance of VEqCO2 kinetics following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF with left ventricular ejection fraction (LVEF) <50% who underwent cardiopulmonary exercise testing (CPET) between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sittng passively for 2 minutes). VO2 and VEqCO2 kinetics during recovery, described as the absolute difference to peak VO2 (difVO2) and VEqCO2 (difVEqCO2), were measured at 30, 60, 120, and 180 seconds. Outcomes were assessed as a composite of cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) implantation at 1 year. Results A total of 238 patients were included (mean age 58 ± 12 years; 82% males; mean LVEF 34 ± 10%; 68% with ischemic HF; 75% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean VE/VCO2 slope 41 ± 12). During the 1-year follow-up, 19 patients met the endpoint (8 CV deaths, 8 urgent heart transplants, and 3 LVAD). ROC curve analysis showed that the best correlation between difVEqCO2 and outcomes was apparent at difVEqCO2 of 180 seconds (AUC 0.83) with a cut-off value of 1 (sensitivity 93%, specificity 58%). These patients, who had a decrease in VEqCO2 (difVEqCO2 >1) at 180 seconds, were significantly older (p=0.02), had a lower LVEF (p<0.001), and higher NYHA (p<0.001). They were at an increased risk of cardiovascular events compared to those with an increase in VEqCO2 (difVEqCO2 <1) at 180 seconds (event-free survival at 1 year 86% vs. 98%, log-rank p<0.001). In multivariate analysis, the statistical association between difVEqCO2 and outcomes remained significant, even after adjusting for difVO2 at 180 seconds (HR 4.315, CI95% (1.349-13.804), p=0.014). Conclusion Abnormal VEqCO2 kinetics in the recovery period of CPET is an easily recognizable non-invasively derived measurement that predicts outcomes in HF. VEqCO2 may complement the evaluation of VO2 and other parameters during recovery to further improve prognostic risk stratification in HF.

Incidence of 1-year mortality, heart failure admissions and decompensation in patients with heart failure followed in HF units in Spain. Differences according to type of units

Abstract Introduction Heart failure is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. The introduction of specific multidisciplinary HF units has improved the management of patients with this disease, thanks to better organization and management of available diagnostic and therapeutic resources. The HF Association of the ESC and the Spanish Society of Cardiology have defined 3 types of HF units (community, specialized, and advanced) according to their structure, complexity, and portfolio of services. Purpose To analyze in a contemporary registry of patients with HF followed up in HF units in Spain whether the results in terms of mortality and HF decompensations during follow-up are similar or different between the 3 types of units. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1,716 patients with HF included between 2019 and 2021 by 45 SEC-accredited HF units. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. Units were defined as community, specialized, and advanced according to ESC HFA and SEC criteria. We compared the incidence of death, HF admissions and total decompensations at 1-year follow-up between community and specialized/advanced units. Results Of the 1716 patients, 55.5% were treated in community units, 65.9% in advanced units, and 20.9% in advanced HF units. Figure 1 shows the main characteristics and treatment used in the 3 types of units. The community units treated older patients and more HFpEF, and the use of NRA and AID was lower, with no differences in the remaining characteristics, comorbidities, or treatments (Figure 1). Figure 2 shows the incidence of events at 1 year. Total mortality was 27.5% in community and 15.5% in specialized/advanced (p<0.001). HF admissions (39.7 vs 29.2%; p=0.019), HF decompensations without admission (16.4 vs 11.3%; p=0.074), total decompensations (56.1 vs 40.5%; p=0.003), and combined HF death/admissions (45.2 vs 31.4%; p=0.005) were statistically higher in community units. Control in specialized/advanced units was an independent protector factor for all events (mortality: HR 0.59, 0.43-0.82; p=0.002; HF admissions: HR 0.61, 0.42-0.90; p=0.012; total HF decompensations: HR 0.58, 0.42-0.81; p=0.001). Conclusions One-year prognosis of HF patients continues to be poor, with high rates of mortality and decompensations. Patients attended in community HF units was significantly worse in our country during the study period. Although this may be due in part to the small differences between the characteristics of the patients followed in the different types of units, it seems necessary to improve the network organization of HF care with the aim of achieving greater equity in the treatment of HF in Spain.

Recreational drugs use as prognostic factor of major adverse cardiovascular and cerebrovascular events in patients hospitalised for acute cardiovascular events

Abstract Background Among patients admitted to the intensive cardiac care unit (ICCU), systematic screening for recreational drugs evidenced a significant prevalence of recent use and was associated with a higher rate in-hospital outcomes. However, long-term cardiovascular consequences of recreational drug use remain uncertain. Purpose We aimed to evaluate the prognostic impact of recreational drugs use at 1-year follow-up to predict major adverse cardiovascular and cerebrovascular events (MACCE) in consecutive patients admitted to ICCUs for acute cardiovascular events from the Addiction in Intensive Cardiac Care Units (ADDICT-ICCU) study. Methods In this prospective multicentric study, all consecutive patients admitted to ICCUs over two weeks in April 2021 at 39 centres across France were included. Screening for recreational drugs use was performed by systematic urinary testing. One-year follow-up consisted of a clinical visit or direct contact with the patient and the referring cardiologist. The primary composite outcome was the occurrence of one of the combined MACCE defined as cardiovascular death, nonfatal myocardial infarction (MI) or stroke. Subgroup analysis was performed in patients hospitalised at baseline for acute coronary syndrome. Results Of the 1499 consecutive patients screened, 1392 (93%) patients (63±15 years, 70% males) had a complete 1-year follow-up. Among them, 157 (11%) had an initial positive test for recreational drug use (cannabis, opioids, cocaine, amphetamines, 3,4-methylenedioxymethamphetamine [MDMA]). After 1-year of follow, 94 (7%) patients experimented MACCE. Patients with positive testing exhibited a higher rate of MACCE than non-users (13% vs 6%, respectively, p=0.002). After adjustment for traditional prognosticators, recreational drug use was independently associated with the occurrence of MACCE (HR=2.99; 95% CI: 1.73-5.16, p<0.001). In the subgroup analysis of 713 patients hospitalised at baseline for acute coronary syndrome, 96 (14%) had a positive recreational drug test and 50 (7%) experienced MACCE. Using a multivariable Cox analysis in this population, recreational drug use was still independently associated with MACCE after adjustment for traditional prognosticators (HR=2.98; 95% CI: 1.43-6.21, p=0.004). Conclusions In a large cohort of consecutive patients admitted to ICCUs for acute cardiovascular events, the prevalence of recreational drug use was 11%. Recreational drug use was strongly associated with the occurrence of 1-year MACCE even after adjustment for traditional prognosticators.Central illustrationPrognostic impact of drug use

Visit-to-visit HbA1c variability and risk of potentially avoidable hospitalisations in adults with type 2 diabetes receiving outpatient care at a tertiary hospital.

This study aims to investigate the relationship between long-term visit-to-visit within-person HbA1c variability and hospitalisation outcomes in adults with type 2 diabetes (T2D). We conducted a cohort study at a tertiary hospital in Singapore involving people aged 21 to 101 years with T2D who had ≥3 HbA1c tests over 2 years. HbA1c variability was assessed using coefficient of variation (CV), variability independent of the mean (VIM) and HbA1c variability score (HVS). A 1-year follow-up was performed after the last HbA1c measurement to identify all-cause and potentially avoidable hospitalisations (PAH), categorised as overall, acute, chronic and diabetes composites. The study included 14 923 patients (mean age: 62.9 ± 12.9 years; 55% male). The median HbA1c variability was 8.6% CV (IQR: 5.1-14.3). Higher quartiles of HbA1c variability were associated with greater risks of PAH and all-cause hospitalisations, independent of glycaemic control. Compared to Q1, for example, the risk ratios and 95% confidence intervals for diabetes-related PAH based on HbA1c CV were as follows: Q2, 1.32 (0.93-1.88); Q3, 1.65 (1.18-2.31) and Q4, 2.16 (1.54-3.03). For all-cause hospitalisations, they were as follows: Q2, 0.97 (0.90-1.05); Q3, 1.08 (1.00-1.17) and Q4, 1.16 (1.07-1.26). When stratified by glycaemic control, elevated risk of PAH persisted even in those with optimal glycaemic control. Consistent findings were observed using HbA1c VIM and HVS measures. In individuals receiving care at specialist outpatient clinics of a tertiary hospital, HbA1c variability is associated with a higher risk of PAH. Comprehensive diabetes management strategies addressing both glycaemic control and variability may offer benefits.

Adherence to anti-hypertensive therapy with perindopril-based single-pill versus free-pill combinations: a 10-year real-world analysis in Italy

Abstract Background/Introduction Despite the growing availability of blood pressure-lowering drugs, hypertension remains poorly controlled and a significant mortality cause worldwide. The silent course of the disease, suboptimal adherence, and complexity of therapeutic schedules are important factors in reducing the effectiveness of anti-hypertensive treatments at the population level. With the purpose of simplifying patients’ medication self-management, guidelines have strongly endorsed the use of anti-hypertensive therapy with single-pill combinations (SPCs). Perindopril (PER)-based SPCs, including both two- and three-drug combinations, have been available since 2008. Purpose We explored treatment adherence over 10 years in patients receiving PER-based regimens (SPC or free-pill combination) in Italy. Methods A retrospective real-world analysis was conducted on administrative databases covering 6.7 million Italian health-assisted residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, those with PER-based prescriptions were identified, considering combinations with amlodipine (AML) and/or indapamide (IND), either as SPC or free-pill or mixed (SPC+separate pill). The index-date (ID) was that of the first prescription of a PER-based regimen throughout the inclusion period. All patients with at least 12 months of available data before and after the ID were included. A cross-sectional analysis evaluated the yearly adherence for the period 2012-2021, calculating the proportion of days covered (PDC) by drug prescriptions on 1-year follow-up (PDC≥80% indicated high-adherence). Results Over 2012-2021, of 121,397 patients on a PER-based therapy, those treated with SPC ranged from 87% (during 2012) to 94.4% (during 2021), while free-pill and SPC+separate pill cohorts represented, respectively, 10.6-3.5% and 2.4-2.1% of all hypertensive patients. Over the decade, the proportion of adherent patients in SPC users was markedly higher than in free-pill and SPC+separate pill cohorts (Fig. 1). The sudden reduction of adherent patients during 2018-2019 was possibly due to a temporary shortage of PER/AML/IND as SPC in Italy from Nov-2018 to Mar-2019. Multivariate analysis showed that over 2012-2021 decade, free-pill and SPC+separate pill regimens resulted in significantly lower adherence (more than 80% reduction) than SPC formulation, while male gender and older age were predictive of better adherence (Table 1). Conclusions These findings from real clinical practice in Italy highlighted a growing attitude from clinicians to prescribe more manageable anti-hypertensive schemes based on SPC formulations, in line with current guidelines. The higher proportion of adherent patients among the users of PER-based SPCs corroborates the importance of alleviating pill burden, that is a key component in blood pressure control, and so in the reduction of hypertensive complications and cardiovascular risk.

Ablation outcome in patients with atrial fibrillation undergoing ICE-guided pulsed-field ablation

Abstract Background Prior experiences from preclinical studies indicate the critical need of catheter-tissue- contact for creation of consistent transmural lesions in pulsed-field ablation (PFA). Intracardiac echocardiography (ICE) not only provide real-time visualization of cardiac structures, but also ensure adequate contact with the tissue. Objective We evaluated ablation outcome and reconnection rate following ICE-guided PFA procedure in patients with atrial fibrillation (AF). Methods Consecutive patients receiving ICE-guided PFA procedure were included in this multi-center analysis. All patients received isolation of PVs (PVI). Additional ablation of left atrial posterior wall (LAPW) was decided based on operator’s discretion. Concentric overlapping lesions were placed in the LAPW. Number of applications were determined on a case-by-case basis. ICE and fluoroscopy were used to optimize contact between the PFA catheter and the targeted tissue. All procedures were performed under uninterrupted anticoagulation. Mapping was done before and after ablation to confirm electrical isolation. Arrhythmia-monitoring was done for 1-year with periodic clinic visits, event recorders and 7-day Holter monitoring. Results A total of 372 patients [age: 62.69 ± 10.41 years, male: 201 (71.3%), paroxysmal AF: 67 (18%)] were included in this analysis of which 48 (12.9%) underwent PVI-only and the remaining subjects received additional ablation of LAPW. Mean number of applications were 34.67 ± 8.88 and 73.65 ± 37.21 for PVI-only and PVI+LAPWI cohorts respectively (p<0.001). No major procedural complications such as esophageal injury, atrio-esophageal fistula, pericardial effusion requiring drainage or cerebrovascular accidents were reported. During 1-year follow-up, 38 (10.2%) patients underwent repeat procedure for recurrence. Reconnection of PV and LAPW were found in only 2 (5.2%) patients. In all 38 patients, new triggers initiating AF were detected to be originating from interatrial septum: 25 (65.8%), superior vena cava: 9 (23.7%), coronary sinus: 7 (18.4%) and left atrial appendage: 6 (15.8%). Conclusion ICE-guided PFA procedures are safe and produce durable lesions leading to very low reconnection rate. The recurrence was mostly due to new triggers initiating AF.

Impact of procedural and patient-related risks on 1-year outcomes for patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent implantation

Abstract Background While early de-escalation of dual antiplatelet therapy (DAPT) and P2Y12 inhibitor monotherapy following short DAPT are becoming standard treatments for patients after percutaneous coronary intervention (PCI), the impact of procedural and patient-related risks on clinical outcomes of PCI for patients receiving the above DAPT regimen has never been established. Purpose To evaluate the impact of procedural and patient-related risk factors on 1-year cardiovascular and bleeding outcomes in patients with 1-month DAPT followed by P2Y12 inhibitor monotherapy after biodegradable-polymer drug-eluting stent (BP-DES) implantation. Methods Using data from the multi-centre regional-wide REIWA registry, we assessed clinical outcomes according to each risk factor and compared between patients with and without either procedural or patient-related risk factors. The primary end point was net adverse clinical events (NACE), defined as a composite of cardiovascular outcomes (cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic or hemorrhagic stroke) and bleeding outcomes (TIMI major or minor bleeding), which was same with that for STOPDAPT-2 trial. Procedural risk was defined as a factor of complex PCI which was previously published and included the follows: treatment of three vessels, three or more lesions, three or more stents, bifurcation with two stents, long stenting (total stent length >60 mm) and target of chronic total occlusion. Additionally, patient-related risk factors were defined as chronic kidney disease, anaemia, peripheral vascular disease, heart failure and advanced age (≧75 years). Results Among 1,202 patients treated BP-DES with 1-month DAPT, 276 patients (23.0%) had at least one procedural factors and 510 patients (42.4%) had one or more patient-related risks. Compared with each risk factor, patients with patient-related risk factor were more likely to have higher NACE rates, whereas low NACE rates were observed in patients with each procedural risk factor (Figure 1). In addition, during 1-year follow-up, patients with patient-related risk factors had a significantly higher incidence of NACE compared with patients without such risks (4.90 % vs. 1.73 %, p = 0.002) (Figure 2). However, no significant differences in NACE rates was observed between patients with and without procedural risk factors (2.54% vs. 3.24%, p = 0.555). Conclusion In patients undergoing BP-DES implantation and 1 month DAPT followed by P2Y12 inhibitor monotherapy, patient-related risk factors had an impact on 1-year clinical outcomes, while procedural risk factors no longer had small impact on those outcomes.

Real-world evidence supports superior efficacy of prasugrel over ticagrelor in individuals with acute coronary syndrome

Abstract Background In patients with acute coronary syndrome (ACS) undergoing invasive treatment, ticagrelor and prasugrel are guideline-recommended P2Y12 receptor inhibitors. Preference for one of the two drugs is under debate although the ISAR-REACT5 trial revealed advantages for prasugrel. This real-world data study evaluated the efficacy and safety of ticagrelor versus prasugrel in individuals with ACS undergoing invasive treatment by emulating a target trial analogous to ISAR-REACT5. Methods Following the Population, Intervention, Comparator, Outcome, and Timing (PICOT) framework, within a German health claims database, we adapted the inclusion and exclusion criteria from ISAR-REACT5 and identified a 1:1 propensity score-matched cohort with ACS being treated after hospital discharge with either ticagrelor or prasugrel (n=9,380, each). End points were defined as in ISAR-REACT5 at 1-year follow-up. Additionally, subgroup analyses of individual ACS components ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) and unstable angina (UA) were conducted. Results The primary composite end point occurred in 9.2% of ticagrelor and 7.4% of prasugrel treated individuals (hazard ratio 1.22; 95% confidence interval 1.10-1.35). Likewise, the secondary end points MI and stroke occurred significantly more often in the ticagrelor arm. All-cause mortality, stent thrombosis, and the safety end point bleeding revealed no significant differences. Subgroup analysis revealed superiority for prasugrel particularly in individuals with STEMI. Statistically, test results and hazard ratios of this real-world data study were in agreement with the findings of ISAR-REACT5. Conclusions With over four times the cohort size of ISAR-REACT5, this study indicates superior efficacy of prasugrel over ticagrelor in individuals with ACS undergoing invasive strategy.Cumulative incidence of primary endpointGraphical abstract

The prognostic impact of intra-procedural mitral valve gradient following transcatheter edge-to-edge repair for primary mitral regurgitation

Abstract Background/Introduction The impact of intra-procedural mitral valve gradient following transcatheter edge-to-edge repair (TEER) in primary mitral regurgitation (MR) is a matter of controversial debates. Purpose The aim of this study was to investigate the prognostic impact of intra-procedural mean mitral valve gradient (MPG) in patients with primary MR undergoing TEER. Methods The PRIME-MR registry included consecutive patients with primary MR undergoing TEER from 2008-2022 at 27 international sites. Clinical outcomes were assessed according to intra-procedural mean MPG measured at the end of the procedure by transesophageal echocardiography. The evolution of mean MPG from intra-procedural to discharge and follow-up was documented. Baseline characteristics and clinical outcomes of patients were investigated according to intra-procedural mean MPG using a cut-off of 5mmHg (low MPG: ≤5mmHg, high MPG: >5mmHg). The prognostic impact of intra-procedural mean MPG was evaluated in multivariable Cox regression analysis. The primary endpoint was 2-year all-cause mortality or heart failure (HF) hospitalization. Results Intra-procedural MPG was available in 1,516 patients (median age 82 years [IQR 76.0, 86.0], 55.1% male). Patients with high intra-procedural MPG presented with less atrial fibrillation and less severe MR but were more symptomatic at baseline than patients with low MPG. Moreover, patients with high intra-procedural MPG had higher baseline MPG and smaller LV dimensions (LVEDV and LVESV). The rate of patients with mean MPG >5mmHg increased from intra-procedural (18.3%) to discharge (31.3%), while remaining stable thereafter (1-year follow-up: 30.9%; last follow-up: 29.6%). At 1-year follow-up the rate of patients presenting with New York Heart Association (NYHA) functional class I or II did not differ between patients with low (82.3%) and high MPG (83.6%, p=0.93). Kaplan-Meier analysis according to mean MPG showed no difference between patients with low and high MPG for the primary endpoint (32.4% vs. 42.1%, p=0.12), as well as for the single endpoints of all-cause mortality (22.3% vs. 27.7%, p=0.47) and HF hospitalization (17.6% vs. 27.5%, p=0.087) through 2 years (Figure 1). Unadjusted spline analyses were provided to depict the prognostic impact of continuous intra-procedural MPG (Figure 2). Following multivariable Cox regression neither MPG >5mmHg (HR 0.91, 95%-CI 0.56-1.49, p=0.72), nor continuous MPG (HR 1.05, 95% CI 0.96-1.15, p=0.28) were independently associated with adverse clinical outcomes. Conclusions Based on a large international cohort of patients with primary MR undergoing TEER, intra-procedural mean MPG did not significantly affect clinical and functional outcomes at 2 years. The long-term impact of elevated post-procedural MPG warrants further investigation.Figure 1Figure 2

Mortality rates by therapeutic approaches for isolated severe tricuspid regurgitation: a systematic review

Abstract Background Managing isolated severe tricuspid regurgitation (TR) poses significant challenges, with questions recently arising about the efficacy of surgical and percutaneous therapies compared to conservative approaches in improving survival. Purpose This systematic review aims to evaluate the mortality associated with various treatment modalities for isolated severe TR. Methods A comprehensive search of medical databases was conducted. Studies reporting mortality of isolated TR at 1-year follow-up, with TR severity classified as moderate-to-severe or worse, were included. Exclusion criteria were TR associated with left-heart disease and combined procedures (treating other valves). The primary endpoint was all-cause mortality at 1-year, with secondary outcomes including in-hospital, 2 and 5 years mortality. Patients with isolated severe TR were categorized by management type: medical, percutaneous, or surgical. Percutaneous treatment included all types of transcatheter therapy (repair or replacement), and surgical interventions encompassed both repair and replacement procedures. Results Twenty-nine studies met the inclusion criteria. Mean age was 72 years among the 5970 patients managed medically, 77 years among the 1205 patients treated percutaneously, and 60 years among the 1754 patients managed surgically. In medically managed patients, 1-year, 2-year, and 5-year mortality rates were 23.6%, 32.5%, and 45.9% respectively. Among percutaneously managed patients, there was an in-hospital mortality of 2.5% and a 1-year mortality rate of 16.9%, which increased to 27.9% at 2 years. Surgically managed patients experienced an in-hospital mortality of 8.6% (p<0.001 compared to percutaneous treatment), with 1-year, 2-year, and 5-year mortality rates of 19.8%, 21.7% and 33.5%, respectively. Compared to medical management, both transcatheter therapy and surgical management demonstrated significantly lower mortality rates at 1 year (p<0.001 vs. percutaneous treatment; p=0.02 vs. surgery), with no significant differences between surgical and percutaneous treatment (p=0.16). At 2-year follow-up, patients undergoing surgical management exhibited significantly lower mortality compared to the other groups (p<0.001 vs. medical treatment; p=0.02 vs. percutaneous treatment), while mortality rates between medical and percutaneous treatment was not different (p=0.11). Conclusion The findings underscore the significant long-term mortality associated with isolated severe TR. While selection bias should be considered, invasive management, through either percutaneous or surgical interventions, demonstrates superior 1-year survival rates compared to medical management. Surgical therapy appears to offer the lowest long-term mortality in selected, operable patients, potentially due to their younger age. Further research is warranted to refine patient selection criteria and optimize therapeutic strategies to improve outcomes in the management of isolated TR.

The role of fibrosis and inflammation for response and outcome prediction in candidates to cardiac resynchronization therapy: is response the right answer?

Abstract Background Cardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT "response" and outcome. Purpose Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT. Methods 86 consecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. An echocardiographic reduction of LV end-systolic volume ≥15% was used to define a patient as responder to CRT. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years. Results 44% of patients experienced the primary outcome. the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 38.5 ng/ml, AUC: 0.63, p=0.03, (OR 7.13 [1.12;45.41], p=0.03), together with TAPSE>17.5 mm (OR 10.86 [3.15;37.44], p<0.001) significantly correlated with the structural response to CRT in several prediction models. Baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p<0.001, HR 8.33 (1.88–33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p<0.001, HR 333 (250–1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood (Table). At Kaplan-Meyer curve patients with both high baseline sST2 and Gal-3 had the lowest survival probability (Figure). Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08–1.22), p < 0.001; HR: 0.84 (0.74–0.91), p = 0.04; HR: 1.26 (1.10–1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome. Conclusion In HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.

Lipid-lowering prescription patterns after a non-fatal acute coronary syndrome

Abstract Introduction After an acute atherosclerotic cardiovascular event, high-intensity lipid-lowering therapy (LLT) is needed to reduce the risk of recurrence. Moreover, despite 2016/2019 ESC/EAS guidance on lipid management according to risk, several studies indicate that most patients do not attain low-density lipoprotein-cholesterol (LDL-C) goals. The present study aims to describe LLT prescription patterns after a non-fatal acute coronary syndrome (ACS) and identify opportunities for improvement in secondary preventive measures, namely LDL-C control. Methods Retrospective cohort study featuring adults aged 40-80 residing in a Portuguese municipality Portugal, using Electronic Health Records between 2016 and 2022. Selected patients had ≥1 general practice appointment three years before the occurrence of an ACS, which was considered an index date. Sub-analysis was made based on patients’ age (under and high or equal to 65 years), gender, and whether their LDL-C levels were controlled according to gradual upper thresholds of 100 mg/dL in the period before the ACS event and 55 mg/dL at one-year post-ACS. Results Among the 544 selected patients, 270 were younger than 65 years. Females comprised 30% (164 patients) of the total cohort, 27% of the under-65 group, and nearly 38% of the 65 and older group. In younger patients, LDL-C levels were higher at presentation (132 mg/dL) and had a significantly greater decrease during the follow-up period compared to the older group. In the period before the ACS, 71.1% of men and 56.7% of women had no previous prescription of LLT, and younger patients had worse levels of LDL-C control (24.1%) compared to older patients (46.0%). One year post-ACS, the pattern of LLT revealed a substantial drop in patients without any LLT prescription from 66.7% to 13.6% and an increase in high-intensity LLT from 2.4% to 16.5%. Still, moderate-intensity LLT (66%) remained the most frequently used LLT. An increase in LLT potency was observed in the follow-up, although there was a decrease in patients achieving LDL-C control. Previous to the ACS event, 35.3% of men and 34.8% of women had initially controlled LDL-C levels according to defined thresholds, which significantly reduced to 11.3% and 8.5%, respectively, at one-year post-ACS. Conclusion Despite initiating or intensifying LLT after ACS, LDL-C goals were not achieved in approximately 9 out of 10 patients at 1-year follow-up, highlighting that the LLT adjustment was insufficient. Therefore, there is a need for better optimisation of LLT after ACS, unveiling an alarming gap in guideline implementation in clinical practice.

Controlling Nutritional Status (CONUT) Score: a new tool for characterization and prognosis of patients with infective endocarditis

Abstract Background malnutrition is a marker of unfavorable prognosis in different medical conditions, however, the association between new objective immunonutritional indexes and outcomes for patients with infective endocarditis (IE) is not fully studied. Purpose the aim of this study was to assess the role of the Controlling Nutritional Status (CONUT) Score in the characterization of patients with IE and its association with prognostic outcomes. Methods a total of 184 cases of confirmed IE were consecutively collected and followed during one year after diagnosis in two tertiary hospitals. CONUT score was calculated using serum albumin, total cholesterol and lymphocyte count [(range 0-12), the higher, the worse] at diagnosis, and patients were categorised as CONUT-high (>=6, n=98), and CONUT-low (<6, n=86) based on the sample median value. Results mean age was 70 [SD 15] years, 64% were men and community-acquired infections were 69%. Median score value was 6 (4). As shown in Table 1 and 2, diabetes and frailty were more prevalent in CONUT-high group, who showed a worse profile of nutritional biomarkers. Overall, the most frequent pathogen was S. viridans (n=43). By groups, S. aureus was predominantly isolated in CONUT-high (20 vs 8%; p 0.02), and non-viridans streptococci in CONUT-low (9 vs 2%, p 0.03). Regarding infection site, IE of aortic bioprostheses was more common in CONUT-high, whereas mechanical aortic valves and mitral bioprostheses were more frequently involved in CONUT-low. Larger vegetations [14 (11) vs 11 (7) mm, p 0.02], and more periannular abscesses (25 vs 13%, p 0.04) were detected in CONUT-high, who presented more acute kidney injury and septic shock during hospitalization. Despite higher predicted surgical risk in CONUT-high, neither the proportion of patients who underwent surgery nor in-hospital mortality, differed between groups. When analyzing according to the therapeutic approach, only among those medically managed patients without surgical indication, in-hospital mortality was higher in CONUT-high. At 1-year follow-up, rehospitalization rate tended to be lower in those with a better nutritional status (35% vs 51%, p 0.07). Conclusions in patients with IE and a high CONUT score, diabetes and frailty were more prevalent. In addition, virulent pathogens, larger vegetations and periannular complications were more frequently reported. Although surgery performance and in-hospital mortality did not differ between groups, a worse nutritional status was associated with a higher rate of clinical complications and higher mortality among patients with conservative management who did not meet surgical criteria.

A higher adherence to perindopril-based anti-hypertensive therapy is associated with a reduced risk of cardiovascular outcomes and all-cause mortality in real clinical practice in Italy

Abstract Background Therapeutic management of hypertension is a landmark of cardiovascular (CV) risk prevention. Combined therapies with at least 2 anti-hypertensive agents are required in many patients in whom monotherapy and lifestyle interventions failed in blood pressure control. It is well-known that poor medication adherence remains a major barrier to achieving the therapeutic targets for all CV drugs, including anti-hypertensives. Purpose We evaluated the relationship between adherence to perindopril (PER)-based therapeutic regimen prescribed as single-pill combination (SPC) or free-pill and CV outcomes and all-cause mortality in a large Italian population. Methods A retrospective analysis was performed using administrative databases corresponding to around 6.7 million health-assisted residents. Hypertensive adults were first identified through hospitalization discharge diagnosis or exemption codes for hypertension between 2010 and 2021. Patients prescribed PER-based therapies were screened for all combinations of PER with amlodipine (AML) and/or indapamide (IND) (all formulations, single-pill or free-pill). Time of the first prescription of a PER-based regimen during the inclusion period was considered the index-date. The analysis included all hypertensive subjects prescribed a PER-based therapy, having available data at least 12 months before and 24 months after the index-date, respectively. Since the analysis was focused on the possible associations between adherence level and CV outcomes and all-cause mortality, adherence was assessed during the first year of follow-up on alive patients and outcomes were assessed during the second year. Adherence was assessed using the proportion of days covered (PDC) approach on 1-year follow-up, and considering a PDC<80% as poor-to-moderate adherence, and PDC ≥80% as good adherence. The Cox’s proportional hazard model was applied to estimate Hazard Ratio (HR) adjusting for baseline covariates, including comorbidity profile and pill burden. Results The included cohort (N=24,476) was divided into sub-groups according to adherence in poor-to-moderate (N=6,781) and good adherent patients (N=17,695) with a mean age of 64.8±13.3 and 64.6±11.9 years old, respectively. The Cox’s proportional hazard model showed that good adherence was associated with a relative risk reduction of 23% in all-cause mortality (Table 1A), 21% in all CV events (Table 1B), 17% in ischemic heart disease (Table 1C), 33% in cerebrovascular events (Table 1E), and 22% in the composite outcome of CV events/all-cause mortality (Table 1G). Conclusions The present analysis provided evidence from the Italian real clinical practice that good adherence to PER-based anti-hypertensive therapy results in significantly lower cardiovascular risk and all-cause mortality. These data further emphasize the importance of promoting cost-effective measures to increase medication adherence in patients on anti-hypertensive treatment.

The dynamics of urine sodium concentration after intra-venous furosemide in patients with acute heart failure

Abstract Background The urine sodium concentration measured at 2 hours after the administration of intravenous (IV) furosemide in patients with acute heart failure (AHF) is recommended as a marker to assess the responsiveness to IV furosemide. However, little is known regarding the dynamics of natriuresis in the very acute phase after IV furosemide and its association with prognosis in patients with AHF. Purpose The aim of this study is to investigate the dynamics of natriuresis in the very acute phase after IV furosemide and its prognostic implication in patients with AHF. Methods DIURESIS-AHF (Diuretic Resistance Measured by Sodium Excretion and Urine Output in Acute Heart Failure) is a multicenter, prospective, and observational study that evaluated the urine samples at the time of 0h, 1h, 2h, 6h, and 24h after the first administration of IV furosemide in hospitalized patients with AHF. Results After excluding 20 patients who needed additional IV furosemide within the first 6 hours, and 9 patients with missing data about 1h-spot urine sample, 84 patients with AHF (79±8 years, 55% men) were analyzed. Median N-terminal pro-brain natriuretic peptide levels at admission were 4722 [interquartile: 2616-8095] pg/mL, and median first IV furosemide doses were 20 [interquartile:20-20] mg. 29 combined event of all-cause death and heart failure rehospitalization were observed during a 1-year follow-up after registration. Urine sodium concentration corrected for urine creatinine concentration peaked 1 hour and decreased at 2 hours after IV furosemide. Kaplan-Meier curve analysis indicated that 1h urine sodium concentration below 50 mEq/L was significantly associated with a high incidence of composite endpoint (Log-rank P=0.033), and this association was retained even after adjusting for age and sex (hazard ratio, 2.37 [95% CI, 1.03-5.45]; P=0.042), but 2h urine sodium below 50 mEq/L was not associated with a poor prognosis (Log-rank; P=0.630). Conclusions Urinary sodium excretion after IV furosemide administration peaked at 1 hour after IV furosemide and decreased at 2 hours in patients with AHF. The urine sodium concentration below 50 mEq/L at 1 hour, but not 2 hours, was associated with adverse events.Urine Na trajectoriesKaplan Meier curves