Prospective Multicenter Study Research Articles

Prognostic impact of symptom relief under low and normal physical performance in patients hospitalized for worsening heart failure

Abstract Background Subjective symptoms, represented by the New York Heart Association (NYHA) class, are well-established prognostic indicators and treatment goals of heart failure (HF). However, older patients may be less likely to develop subjective symptoms due to an impaired physical performance. Purpose To evaluate the prognostic impact of symptom relief under low and normal physical performance in patients hospitalized for worsening HF. Methods We carried out a sub-analysis of FRAGILE-HF, a prospective multicenter study, including 1272 consecutive older (>=65 years) hospitalized patients with HF (median age 80; 57.2% male; left ventricular ejection fraction 46±17%). NYHA class and gait speed were documented before discharge. The patients were prospectively followed-up for two years after discharge. Results At the time of discharge, 715 patients (56%) remained symptomatic (NYHA2-4) whereas 557 patients (44%) were asymptomatic (NYHA1). Patients were classified into 4 groups according to symptom relief and physical performance represented by slow (<0.8 m/s) or normal (>=0.8 m/s) gait speed: 279 slow-asymptomatic, 278 normal-asymptomatic, 402 slow-symptomatic, and 313 normal-symptomatic patients, respectively. During the follow-up period, 266 patients (20.9%) died. Slow-asymptomatic (hazard ratio (HR) 1.72[1.09-2.72], p=0.019 in comparison with normal-asymptomatic patients as a reference) and slow-symptomatic (HR 1.85[1.21-2.82], p=0.004) status was associated with high mortality in a Cox regression analysis adjusted for the Meta-analysis Global Group in Chronic Heart Failure score and B-type natriuretic peptide level (Figure). Furthermore, the combined endpoint of HF rehospitalization and all-cause death within 90 days were more frequently observed in slow-asymptomatic (HR 1.94[1.05-3.60], p=0.034), normal-symptomatic (HR 1.89[1.06-3.36], p=0.031), and slow-symptomatic (HR 1.97[1.10-3.52], p=0.022) patients than normal-asymptomatic patients (Figure). Conclusions Symptom relief achieved at the time of discharge was not associated with a lower mortality in patients with low physical performance, for whom careful follow-up may be needed especially in the early period after discharge because the symptoms may be masked due to low physical performance.

Relation between wearable heart rate monitor derived training load and cardiac adaption in endurance athletes

Abstract Background No studies have effectively measured training load (TL) from wearable heart rate (HR) monitors and determined its relation to exercise induced left and right ventricular (LV, RV) remodeling. A better insight into drivers of exercise induced cardiac remodeling is of clinical relevance to guide training advice in athletes at risk of adverse remodeling. Purpose We determined the TL, based on HR monitoring by commercial wearables[1]. The number and duration of training sessions was quantified during a period of 3 months. Training-intensity was calculated as Edwards TRIMP (eTRIMP) based on the product of training duration in one of 5 HR zones (1=light, 5=very vigorous) and the coefficient related to the respective HR zone. Methods Training data was collected in 2 prospective multicenter studies. Master@Heart comprises endurance trained middle-aged men aged 45 to 70years[2]. Pro@Heart consists of elite athletes aged 16 to 23years[3]. For this analysis, all male athletes with complete training data recorded using a chest-worn HR monitor for 3 months were included. Using an in-house developed pipeline, maximal HR and TL were calculated from raw training data. Cardiac magnetic resonance imaging was performed to measure indexed LV/RV end-diastolic volume (LVEDVi, RVEDVi), end-systolic volume (LVESVi, RVESVi), ejection fraction (LVEF, RVEF) and LV mass (LVMi). Results Pro@Heart athletes (n=69; age 21.9 ± 4.2 years) trained more than Master@Heart athletes (n=82; age 55.2 ± 6.5 years) and their total 3-month TL (eTRIMP) was also higher (9718 ± 3190 vs. 5499 ± 3775min; P<0.05 and 22339 ± 7350 vs. 13438 ± 8880 AU; P< 0.05; Table 1). Considering all athletes, there was a strong correlation between both training duration and eTRIMP and LVEDVi, LVESVi, LVMi, RVEDVi and RVESVi. Training duration in zone 1&2 correlated well with LVEDVi, LVESVi, LVSV, LVMi, RVEDVi and RVESVi (Table 2). We found small significant negative correlations between duration and eTRIMP compared to LVEF and RVEF (Table 2). To filter out individual training factors influencing cardiac remodeling we used a partial least squares method which included time and percentage of time spent in training zones and age. Accordingly, training duration in zone 1&2 and age were the main predictors of cardiac volumes and LVMi. For LVEF, age and time in zone 3 was most predictive, whereas for RVEF zone 3 and to a lesser degree zone 1&2 were the main predictors, irrespective of age. Interestingly, time spent in high intensity zones 4 and 5 was not predictive. Conclusion We prospectively quantified TL in comparison to CMR-derived measures of cardiac remodeling and demonstrated that training duration in low intensity training zones is most predictive for cardiac volumes and mass, whereas LVEF and RVEF are more closely associated to time in zone 3. Very vigorous intensity exercise was not predictive, likely due to limited time training in zone 4 and 5.

Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study.

Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment. This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction. In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity). A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity. This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS.

Strategy optimization for the combined procedure of left atrial appendage occlusion plus catheter ablation in patients with atrial fibrillation (COMBINATION): a multi-center, randomized study

Abstract Background The long-term efficacy and safety of combining left atrial appendage closure (LAAC) plus catheter ablation (CA) in patients with atrial fibrillation (AF) in a single procedure have been established. However, the optimal combining strategy has not been well elucidated. Objective To determine the impact of different combining strategies on long-term clinical outcomes. Methods In this prospective multicenter study, patients with non-valvular AF referred for the combining procedure were randomly assigned to the ablation-first or occlusion-first groups at a 1:1 ratio. We evaluated the outcomes of LAAC with a Watchman device and CA using a contact-force sensing catheter during long-term follow-up. Results Of the 202 randomized patients, 194(96.0%) completed the trial with 97 patients in each group. Baseline characteristics were comparable between groups. All procedures were accomplished with acute successful LAAC and restoration of sinus rhythm. Incidences of periprocedural complications were similar. Higher chronic peri-device leak (PDL, 15.5% vs 5.2%, P=0.031) and device-related thrombus (DRT, 8.2% vs 1.0%, P=0.035) rates were observed in the ablation-first group. The event-free survival rate of the primary endpoint (composite of stroke/transient ischemic attack, thromboembolism, clinically-relevant bleeding, cardiovascular rehospitalization/death) was significantly higher in the occlusion-first group (83.5% vs 71.1%, log-rank P=0.036, HR 0.53, 95%CI 0.29-0.95) during a median 2.5-year follow-up. Patients with male gender and higher CHA2DS2-VASc score were at lower risk in the subgroup analysis. Long-term freedoms from AF (77.3% vs 63.5%, log-rank P=0.039) and atrial tachyarrhythmias (70.1% vs 55.7%, log-rank P=0.044) were higher in the occlusion-first group, respectively. Conclusions The occlusion-first approach is recommended for combined procedures where a plug-like device is implanted due to its superior long-term clinical benefits.Flowchart of the COMBINATION trialIncidences of primary endpoint

Interplay between strain pattern-based classification of dyssynchrony and myocardial scar in CRT patients

Abstract Introduction Echocardiography-derived septal strain patterns are valuable for predicting volumetric reverse remodelling and survival in patients undergoing cardiac resynchronization therapy (CRT). Nevertheless, presence of myocardial scarring in the left ventricle (LV) is known to attenuate CRT treatment response. Purpose This study aims to investigate the interplay between septal strain patterns and myocardial scarring in CRT candidates, and how they link to outcome after CRT. Methods In this prospective multicentre study, CRT candidates from five European institutions underwent pre-implantation assessments using speckle-tracking strain analysis on echocardiography and cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). Dyssynchrony was graded through analysis of septal strain curves, categorizing patients into five distinct patterns, denoted as strain Stage-0 through strain Stage-4 (Fig. A). LGE of the LV wall was quantitatively assessed using CMR (as a percentage). The study endpoints were volumetric reverse remodelling (volume responder = more than 15% decrease LV end-systolic volume) after one year, and all-time all-cause mortality. Results A total of 267 patients, with a mean age of 66±11 years (69% males, 90% left bundle branch block [LBBB]) presented with an average LV ejection fraction (EF) of 30±7%. With each stepwise increase in strain stage, global LV scarring decreased (p<0.01; Fig. B) and the proportion of volume responders increased (all p<0.0001; Fig. C). ROC curves demonstrated that the predictive power of strain stages for CRT volumetric response was not significantly improved when scarring percentage was added (AUC 0.78 [95% CI: 0.69-0.83] vs. 0.81 [95% CI: 0.71-0.90]; p>0.05; Fig. D). In a multivariate cox regression model – including clinical characteristics that were significantly related to survival in univariate analysis – a patients’ strain stage was the only significant predictor of survival, also outperforming scar burden as determinant of outcome (HR 0.68; p=0.041; Fig. E). Conclusions Septal strain patterns show a strong association with the extent of reverse remodelling and outcome in CRT-treated patients. An inverse relationship is observed between pre-implant strain stages and the extent of myocardial scarring. However, scar burden did not provide incremental predictive value over the strain stages. Strain-pattern-based dyssynchrony assessment is a meaningful predictive marker which integrates information on myocardial dysfunction due to dyssynchrony as well as scar burden.

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

Clinical outcomes of patients with heart failure with improved ejection fraction after acute MI: a multicenter prospective study from the COREA-AMI Registry

Abstract Background The 2021 Universal Definition of Heart Failure introduce a new classification, heart failure with improved ejection fraction (HFimpEF). As yet, little is known about the long-term clinical outcomes of patients with HFimpEF after acute myocardial infarction (AMI). Methods From a multicenter, prospective cohort of AMI patients undergoing PCI, patients with an initial echocardiogram at the time of PCI and at least one follow-up echocardiogram one month to two years after the initial event were considered for analysis. HFimpEF was defined as initial left ventricular ejection fraction (LVEF)≤40% and at least one follow-up LVEF>40% with an increase of ≥10% from baseline. Persistent HFrEF was defined as LVEF ≤40% without interval improvement. Patients with LVEF>40% were defined as having preserved LVEF. The primary endpoint was all-cause mortality. Results In total, 3038 patients with repeated echocardiogram measurements were selected for initial analysis. 187 patients were identified as having HFimpEF, 190 patients had persistent HFrEF, 631 patients had HFmrEF, and 2030 patients had preserved EF. Kaplan-Meier analysis revealed that HFimpEF was associated with improved survival compared to chronic HFrEF, but inferior to preserved LVEF (log-rank p<0.001). Even after multivariate Cox regression analysis was done to account for confounding variables, HFimpEF was associated with reduced mortality compared to persistent HFrEF (HR 0.49, 95% CI 0.31-0.78). Compared to patients with preserved LVEF, HFimpEF patients had a tendency toward higher mortality, but did not reach statistical significance (HR 1.18, 95% CI 0.80-1.76). Conclusion HFimpEF is associated with decreased all-cause mortality compared to persistent HFrEF in patients with AMI.

Outcomes of bilateral temporomandibular joint arthroscopy: an international multicentric prospective study including 524 joints.

This study aimed to evaluate the efficacy of bilateral TMJ arthroscopy in patients with different Wilkes stages, comparing the results obtained in different arthroscopic levels on a larger scale, unifying similar populations. A multicentric prospective clinical study was conducted in three TMJ departments performing temporomandibular joint surgery in Portugal and Brazil, with an enrolling window active from January 1, 2019, to December 1, 2022. The primary clinical outcome was TMJ pain evaluated through a visual analogue scale. The secondary clinical outcome was the maximum mouth opening (MMO). TMJ arthroscopy was performed with a 1.9-mm arthroscope, including a video system with a 2.8-mm outer protective cannula. 262 patients, representing a total of 524 operated joints were enrolled. The mean age was 35.3 years. A significant decrease postoperatively in VAS pain was observed for all Wilkes stages. The lowest value of VAS pain was observed in Wilkes II compared to Wilkes III and IV. In the secondary outcome, MMO was observed to have a significant improvement in all Wilkes stages. In this multicentric study, bilateral TMJ arthroscopy was shown to be an effective procedure to reduce pain and increase maximum mouth opening in patients with different Wilkes stages, representing a valid minimally invasive solution.

Managing Perforated Diverticulitis: An Overview of Treatment Trends and Clinical Outcomes at a Single Centre in the United Kingdom.

Introduction Perforation represents the most critical manifestation of complicated diverticulitis. In 2008, it was estimated that about 2,000 cases of perforated diverticulitis (PD) were diagnosed in the United Kingdom (UK). Management of PD is evolvingwith considerable variation in approaches between hospitals and countries with an increased trend towards a conservative approach. Objective Our aim is to provide a comprehensive overview of the management strategies and treatment outcomes for PD, with a particular focus on the influence of abscess size and the presence of distant air (DA) on the successof conservative management. Methods Data from 112 patients admitted with PD to a single district hospital in the UK between 2013 and 2018 were retrospectively analysed.CT scan reports and images were examined to assess the size and number of abscesses, as well as the presence of DA. Failed initial management was defined as the need for an alternative therapeutic option after 48 hours during the index admission or readmission within 12 weeks. Follow-up data were also reviewed to evaluate the need for elective resection and stoma reversal. Result In this cohort of 112 patients with PD, a variety of treatment strategies were employed. Antibiotic therapy alone was successful in 46 patients (41%). Radiological management was successful in only six patients (5%). Surgical washout was required in 12 cases (11%), while resection was performed in 40 cases (36%). Best supportive care was provided to eight patients (7%) who were considered unfit for invasive interventions. The success rate was higher in cases with smaller abscesses and no DA (p <0.05). Specifically, 30 out of 45 patients (66.6%) with abscesses less than 4 cm and no DA were managed successfully with conservative treatment, whereas the success rate dropped to 14 out of 30 patients (47%) when DA was present (p<0.05). For abscesses larger than 4 cm, the success rate was seven out of 20 patients (35%) without DA and significantly lower at two out of 20 patients (10%) with DA (p=0.01). The data also show a shift towards increased conservative management over the six-year period, with a steady reduction in the number of surgical interventions. However, 12 patients (19%) were readmitted with complicated diverticulitis after the initial non-resectional management. Conclusion We observed a shift towards more conservative, non-operative management of acute complicated diverticulitis with perforation over the six-year period, likely influenced by advancements in diagnostic and interventional radiology, antibiotic therapy, and minimally invasive techniques. Our data also stress that cases of PD with distant extraluminal air or larger abscesses are less suited to conservative treatment, often necessitating traditional surgical interventions. Long-term follow-up showed a moderate rate of readmissions after non-resectional management, and while stoma reversal was successful in a proportion of patients, many either opted to live with the stoma or were deemed unsuitable for reversal. A larger, multicentre prospective study would likely provide more robust data on this subject.

Sex differences in clinical characteristics, phenotypes, management, and long-term outcomes of myocardial injury: an international cohort study

Abstract Background Several studies have demonstrated sex differences in patients presenting to the emergency department (ED) with myocardial infarction, heart failure or syncope. Whether sex-specific differences in chest pain patients with myocardial injury exist is unknown. Purpose To determine whether sex-specific differences in the clinical characteristics, phenotypes, management, and long-term outcomes of patients with myocardial injury exist. Methods Patients presenting to the ED with chest pain suggestive of MI were consecutively enrolled into a prospective multicenter international diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists, applying the fourth universal definition of myocardial infarction, using all available medical records, including serial hs-cTn and cardiac imaging. Follow-ups were performed at 3 months, 1-, 2- and 5-years. The primary outcome was 5-year all-cause mortality. Secondary outcomes included 5-year cardiovascular mortality and non-cardiovascular mortality. Multivariable flexible parametric (Royston-Parmar) models assuming proportional hazards were fitted. Models were adjusted for age, history of coronary artery disease, history of malignancy, diabetes, hypertension, smoking status, history of liver disease, and renal function. Results Among 8046 chest pain patients presenting to the ED, 1158 (14.4%) had myocardial injury, of which 358 (31%) were females and 800 (69%) males. Women were older (79 years, vs. 73 years), had fewer cardiovascular risk factors and comparable non-cardiovascular comorbidities except for lung disease which was more commonly found in men. Myocardial injury phenotypes varied between sexes (Figure). The most common phenotype in both sexes was heart failure, yet it was more common in men (37.2%) than in women (22.3%). The second most common phenotype in women was hypertension (15.4%) and arrhythmia (15.4 %), while in men was myocarditis (17.8 %), followed by arrhythmia (15.8%). Women underwent less invasive coronary angiography (19.8% vs 26.9%) or stress testing (12% vs 21.5%). In the angiographic findings, women presented more often with normal findings (30.4% vs. 19.6%) or mild CAD (20.3% vs. 11.2%) whereas men displayed more frequently 3-vessel disease (14.5% vs. 36.4%), Table. After adjusting for known confounders, women were associated with a lower 5-years risk for all-cause mortality (HR 0.69; 95%CI: 0.56–0.83) and cardiovascular mortality (HR 0.61; 95%CI: 0.46–0.79). No statistically significant difference in non-cardiovascular mortality risk was found (HR 0.79; 95%CI: 0.59-1.04). Conclusions Women presenting with chest pain to the ED and having myocardial injury were less likely than men to undergo coronary angiography or non-invasive cardiac imaging. Long-term risk for all-cause or cardiovascular mortality was lower for women compared to men.Myocardial Injury phenotypesPatient management

Red-cell omega-3 fatty acids associate with increased hippocampal volume and superior longitudinal cognition in atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with cognitive impairment and dementia. Omega-3 Fatty Acids (n-3 FAs) have anti-thrombotic, anti-inflammatory and anti-oxidative properties; however, their neuroprotective effects remain controversial. Here, we report the association of n-3 FAs with both structural (hippocampal volume) and functional (cognition) readouts in a large cohort of AF pts. Purpose a) To determine the association of n-3 FAs and left and right hippocampal volume at baseline in AF pts. b) To assess the predictive value of HV and n-3 FAs for the risk of cognitive impairment after a 7-year follow-up period. Methods This prospective ongoing multicenter Swiss Atrial Fibrillation study (Swiss-AF) included 2,359 pts with documented AF and baseline red-cell n-3 FAs levels, measured by gas chromatography and mass spectrometry. Hippocampal volume (HV) and segmentation based intracranial volume (ICV) were analyzed by FreeSurfer's (v 7.4.0) subregion segmentation module and Sequence Adaptive Multimodal SEGmentation from brain MRI in 1,736 pts. Detailed neurocognitive assessments in pts at baseline and follow up periods were performed. We used mixed-effect linear regression models to determine the association of n-3 FAs and HV. For conversion to cognitive impairment (defined as MoCA score &amp;lt; 26), we performed cox-proportional hazards regression model. Two adjustment models were applied as described in the figures. Results Patients with AF (mean age, 73 years old [±8.5 SD]; 157 women [27%]) with 9569 cognitive evaluations (mean follow-up, 3.6 years [±2.3 SD]) were assessed. At baseline, we observed statistically significant associations between total n-3 FAs levels (EPA + DHA + ALA + DPA) and individual n-3 FAs (EPA, DHA, DPA) with increased HV after adjustment for ICV and other covariates (Fig1A, 1B). After all adjustments, EPA remained associated with both bilateral HV and right HV. Furthermore, we observed a significant association between HV and neurocognitive assessments, as measured both in global (MoCA, CoCo) and specific tests (TMT-A, TMT-B, DSST, SF) (Fig1C). Over time, quartile 4 (Q4, highest n-3) compared to quartile 1 (Q1, lowest), had a 16% lower risk of cognitive impairment (HR, 0.84 [CI 0.75-0.93]; P=0.001) for total n-3 FAs and even 30% lower specifically for EPA (HR, 0.7 [CI 0.63-0.78]; P&amp;lt;0.001). The risk of cognitive impairment was 47% lower (HR, 0.53 [CI 0.45-0.63]; P&amp;lt;0.001) when the highest HV Q4 was compared to lowest HV Q1 (Fig2A). In combination, the highest quartile of bilateral HV and EPA demonstrated an increased probability of being cognitive impairment-free and they had a 72% lower (HR, 0.28 [0.18-0.43]; P&amp;lt;0.001) risk of cognitive impairment (Fig2B). Conclusions 1. Red cell n-3 FAs levels are associated with higher HV in AF pts. 2. Higher baseline levels of n-3 FAs, particularly of EPA, are associated with both an increased HV and a decreased risk of cognitive impairment after 7 years follow up.

Acute kidney injury as a risk factor for heart failure hospitalisation after major non-cardiac surgery

Abstract Aim The importance of acute kidney injury (AKI) after major non-cardiac surgery is incompletely understood. The aim of this study was to evaluate the association of AKI with short-term complications (e.g. perioperative myocardial injury (PMI); acute heart failure (AHF)), and long-term adverse outcomes (e.g. readmission for AHF, all-cause mortality). Methods The prospective observational international multi-center BASEL PMI study screened inpatients aged 40-85 at high cardiovascular risk undergoing non-cardiac surgery at tertiary hospitals to detect asymptomatic PMI. This secondary analysis focused on AKI, with prospective adjudication of AKI, PMI and AHF by blinded experts. Results In 11'133 patient cases, the incidence of AKI within 7 days was 11.1%, classified as KDIGO stage one (68.3%), two (15.4%) and three (16.3%). Pre- and perioperative determinants for AKI were perioperative myocardial infarction / injury (PMI, OR 3.63), the need for intra-operative blood transfusion (OR 1.48), chronic heart failure (CHF, OR 1.42), surgery duration (OR 1.37), male sex (OR 1.27), preoperative GFR (OR 0.80) and preoperative hemoglobin concentration (OD 0.84). Median time to occurrence of AKI was 2 days (IQR 1-4), similar to PMI (median 1, IQR 1-2) and in contrast to AHF (median 4, IQR 2-9). 41% of all AKI patients experienced additionally a PMI. In multivariable Cox regression analysis, AKI (aHR 1.76, 95% CI 1.51-2.06, p &amp;lt; 0.001) and PMI (aHR 1.21, 95% CI 1.02-1.45, p = 0.025) were both independently associated with prediction of one-year all-cause mortality after adjustment for each other and confounding factors, whereas AHF was marginally not (aHR 1.28, 95% CI 0.98-1.68, p = 0.070). However, testing the assumed proportional hazards assumption, the impact of AKI, PMI and AHF on mortality depended significantly on time. AKI had significantly increased short- and long-term mortality, in contrast to PMI and AHF with just elevated short-term mortality. The coincidence of AKI and PMI resulted in an additive effect on overall mortality. Importantly, patients with AKI showed more in-hospital AHF (aHR 2.08, 95% CI 1.49-2.91) within 30 days and higher hospitalization rates for HF within one year (aHR 1.40, 95% CI 1.01-1.98, p = 0.046) than patients without AKI, particularly patients without known heart failure (aHR 1.65, 95% CI 1.05-2.60, p = 0.029). Conclusion AKI is a common complication, occurring in 11% after non-cardiac surgery. The occurrence of AKI was associated with increased risks for in-hospital AHF, hospitalizations for heart failure and all-cause mortality. Notably, AKI patients without known history of heart failure faced hospitalizations for de novo heart failure. The occurrence of AKI unveiling de novo heart failure highlights the importance of systematic monitoring for AKI after surgery and gives clinicians a window of opportunity to take action at an early stage.

A systematic assessment of myocardial involvement and cardiovascular events up to six months in patients hospitalised with COVID-19

Abstract Background Retrospective cohort studies indicate that myocardial injury occurs in approximately 25% of patients hospitalised with COVID-19. However, prospective studies with a systematic assessment of myocardial involvement and major adverse cardiovascular events (MACE) after COVID-19 are scarce. Purpose The primary objective was to determine the incidence of MACE within six months of hospitalisation. MACE was defined as a composite of cardiac death, sudden death, life-threatening ventricular arrhythmia's, heart failure, non-fatal myocardial infarction, and/or non-fatal stroke. The main secondary objective was to determine the frequency of other cardiac complications not covered by this definition. Methods We conducted a prospective multicenter cohort study in 13 Dutch medical centers. Adult patients hospitalised with COVID-19 were consecutively recruited (May 2021-April 2023). Exclusion criteria were age ≥70 years, a history of new cardiac disease in the past six months, or dependency in the activities of daily living. Cardiac involvement was evaluated by a standardised healthcare pathway that was implemented in participating hospitals. All patients received an electrocardiogram, transthoracic echocardiogram, and troponin measurement at admission and at six months follow-up. Furthermore, a questionnaire was distributed at three and six months after admission to collect information on post-COVID symptomatology. Results In total 190 patients were included, median age of 57 years [IQR 48; 64], mostly male (n=110, 60%) and white (n=136, 72%). Cardiovascular risk factors were present in 116 (61.1%) patients and 33 (17.4%) had a history of cardiac disease. At admission, troponin was above the upper limit of normal in 68 (35.8%) patients. Seven (3.7%) patients died during follow-up. The cumulative incidence of MACE was 2.6% at discharge with no additional events during follow-up. Other cardiac complications were detected in 18 (9.5%) patients during admission with 3 (1.6%) additional events at six months follow-up. Supraventricular tachycardias (n=8, 4.2%) were the most common cardiac complication. Other complications were myocarditis (n=2, 1.1%), pericarditis (n=1, 0.5%), non-sustained ventricular tachycardia (n=1, 0.5%), and other arrhythmias or conduction disorders (n=5, 2.6%). At six months follow-up, three (2.3%) patients reported chest pain, with one requiring a percutaneous coronary intervention. Palpitations and dizziness were experienced by 88.9% and 83.3% of patients three months after admission but the prevalence of these symptoms decreased to 9.8% and 11.8% at six months. Conclusion With a systematic assessment, one in three patients hospitalized with COVID-19 have elevated troponin levels at admission. However, the overall incidence of MACE within six months is low. Palpitations and dizziness are commonly reported after discharge but these symptoms disappeared for most participants within six months.

A graded association between mobility limitation and prognosis in patients with heart failure

Abstract Background In the era of an aging population worldwide, geriatric conditions have become a high-priority clinical concern in treating heart failure (HF). Although mobility limitation is one of the most common geriatric conditions, no study has quantified the dose-response relationship between the level of mobility limitation and the risk of adverse clinical outcomes in patients with HF. Purpose This study aimed to characterize the association between the level of mobility limitation and prognosis in patients with HF. Methods This study was conducted as a patient-level pooled analysis of data from two prospective multicenter cohort studies. The analysis included consecutive patients hospitalized for HF without any exclusion criteria, with a total of 2103 participants. We categorized the patients into four groups based on their level of mobility limitation: Category I, independent outdoor walking; Category II, independent indoor walking; Category III, indoor walking with assistance; and Category IV, abasia. The primary endpoint was a 2-year composite outcome of re-hospitalization for HF or all-cause mortality after hospital discharge. Results During the 2820.7 person-year follow-up period, 998 patients experienced the composite outcome. The cumulative incidences of the composite outcome for Categories I to IV were 24.9, 47.0, 59.3, and 84.8 per 100 person-years, respectively (Figure). After adjusting for potential confounders, a 1-point increase in the mobility limitation category was associated with a 19% higher risk of the composite outcome (hazard ratio: 1.19; 95% CIs: 1.10–1.29; p&amp;lt;0.001). Conclusions A strong and graded association exists between the level of mobility limitation and prognosis in patients with HF. Even among patients with mobility limitations, the risk of adverse clinical outcomes varies in a dose-response manner depending on the magnitude of mobility limitation. Our findings contribute to a more individualized approach for managing older patients with HF.Figure

Prediction of 10-year risk for recurrent atherosclerotic cardiovascular events in a secondary prevention population: Insights from CHART-2 and Suita studies in the Japanese population

Abstract Background Despite the European Society of Cardiology (ESC) guidelines advocating risk prediction models for secondary prevention in established atherosclerotic cardiovascular disease (ASCVD) patients, such models for Japanese individuals remain limited, owing to their comparatively lower ASCVD risk than Western populations. Given this gap, there is a need to develop tailored risk assessment tools for Japanese ASCVD patients to optimize secondary prevention strategies. Purpose Leveraging data from two large-scale, long-term cardiovascular cohorts in Japan, our aim was to develop and externally validate a 10-year risk model predicting recurrent cardiovascular events among patients with established ASCVD. Methods The CHART-2 and Suita studies, large-scale prospective observational multicenter cohort studies in Japan, served as the primary data sources for this investigation. From the CHART-2 study, which comprised 3,560 patients with a history of coronary artery disease or ischemic stroke, we derived our risk model. External validation was conducted using data from the Suita study, which included 445 patients with similar ASCVD backgrounds. The primary outcome of interest was a composite endpoint encompassing cardiovascular death, myocardial infarction, or stroke. Variable selection was performed based on clinically relevant factors previously employed in established risk scores (SMART, REACH, and TRS 2°P risk scores). Logistic regression was utilized for model development, and the predictive performance was assessed using the C-index. Results Over a median follow-up of 10.1 years, the derivation cohort experienced 756 cardiovascular events. Patients in the derivation cohort had an average age of 68.9 ± 10.6 years, with 91% and 24% having a history of coronary artery disease and ischemic stroke, respectively. Using logistic regression, the multivariate model revealed a higher recurrent risk associated with several factors including age, smoking status, systolic blood pressure, diabetes, renal function, number of ASCVD events, atrial fibrillation, lipid levels, left ventricular systolic dysfunction, and statin use. A simple risk score based on these predictors demonstrated a &amp;gt;5-fold gradient of 10-year recurrent risk with a C-index of 0.65 (95% CI 0.63-0.68, Figure). The prediction model was externally validated in the Suita study wit 245 cardiovascular events and a median follow-up of 10.4 years, showing good discriminative ability with a C-index of 0.64 (95% CI 0.60–0.68). Conclusion Our newly developed prediction model offers a valuable tool for identifying individuals at heightened risk of recurrent cardiovascular events over a 10-year period, thereby facilitating more targeted and effective secondary prevention strategies tailored to the unique characteristics of Japanese ASCVD patients.

Plaque phenotyping using deep learning in optical coherence tomography imaging

Abstract Background Artificial intelligence (AI) techniques have emerged as powerful tools in various computer vision tasks, particularly in classification, detection, and segmentation. Purpose This study aimed to develop a deep learning model for categorizing optical coherence tomography (OCT) frames into different plaque phenotypes, including thin-cap fibroatheroma (TCFA) and fibroatheroma. Methods A prospective multicenter observational study enrolled 168 patients who underwent percutaneous coronary intervention (PCI) and received OCT imaging for non-target lesions with angiographically estimated diameter stenosis greater than 30% (177 vessels). Among them, 129 patients (135 vessels) underwent follow-up OCT imaging at 1 year. A total of 45,072 OCT frames were randomly divided into training and validation sets in a 4:1 ratio. An EfficientNet-B3 convolutional neural network model was developed to classify OCT frames into TCFA, thick-cap fibroatheroma, non-fibroatheroma, adaptive intimal thickening, and normal vessel categories. Results A confusion matrix comparing manually assessed plaque phenotypes with AI-predicted phenotypes was presented in Table. In the validation datasets (9,015 frames), the overall accuracy of the model was 85.1%. For predicting the presence of TCFA, sensitivity was 81.1%, specificity was 98.8%, positive predictive value was 63.9%, and negative predictive value was 99.5%. Regarding the presence of fibroatheroma, sensitivity was 90.3%, specificity was 89.4%, positive predictive value was 93.1%, and negative predictive value was 85.4%. Conclusions The deep learning algorithm demonstrated high accuracy in detecting TCFA and fibroatheroma with excellent reproducibility. This automated process enables operators to promptly identify high-risk lesions during PCI, potentially leading to improved clinical outcomes.

Beyond secondary prevention drugs: added benefit in survival and events of a healthy lifestyle in patients after an acute coronary syndrome

Abstract Background Despite advances in drug treatment and secondary prevention programs, cardiovascular disease remains the leading cause of death. The full extent and independent benefit of a healthy lifestyle, particularly after optimal medical therapy in secondary prevention, has not been widely reported. Purpose To quantify the added benefit on survival and events of a healthy lifestyle following an acute coronary syndrome (ACS). Our study seeks to answer the question: Is adherence to medical therapy sufficient or a healthy lifestyle provides additional improvement?. Methods This a prospective observational multi-center study of 685 patients included during admission for ACS. At 6 months patients were asked about their post-ACS lifestyle and were given a score (range: 0-7) with the following items: Intake of ≥3 fruits and vegetables/day, ≥2 fish servings/week, ≤7 alcohol beverages/week, feeling stress RESULTS: After adjusting for demographic variables, cardiovascular risk factors, characteristics of the index event, high-sensitivity C-reactive protein (hs-CRP), and drug therapy, multivariate Cox regression showed that the lifestyle SCORE was independently and inversely associated with both the incidence of the primary outcome (ischemic events [any ACS, stroke, or Transient Ischemic Attack] or death) (HR 0.65 (CI95% 0.44-0.96); p=0.029) and death (HR 0.41 [95%CI 0.18-0.91]; p=0.029). Statin therapy was also independently and inversely associated with both the incidence of the primary outcome. Kaplan-Meier curves showed a higher event-free survival for both outcomes in patients with SCORE≥4 than in those with SCORE&amp;lt;4 (p=0.03 and p&amp;lt;0.001, respectively). Additionally, patients with a SCORE≥4 had a significantly greater decrease of total cholesterol (-52 [-16.5, -79] vs -38 [-7.5, -68] mg/dl; p=0.040) and hs-CRP (-1.1 [-0.1, 2.5] vs -0.5 [0.7, -1.9] mg/L; p=0.001) at six months. Conclusions Among patients with ACS and similar medical therapy, a healthy lifestyle is an independent and added marker of a lower incidence of ischemic events and death. It is also associated with a better lipid profile and lower inflammation.

Direct annual healthcare costs in survivors of acute pulmonary embolism: estimates based on a prospective multicentre cohort study

Abstract Background Patients surviving acute pulmonary embolism (PE) necessitate long-term care and follow-up. However, the economic impact of PE on healthcare systems after the acute event remains largely unknown. Purpose To estimate the direct cost of PE during the first year after discharge from hospital for the index event, focusing on rehospitalizations, anticoagulant medication, and outpatient follow-up. Methods We analyzed the data from a multicentre cohort study of 1017 unselected patients with confirmed acute symptomatic PE in Germany. After the index episode, the costs of which were not considered, patients prospectively followed an outpatient visit plan at 3, 12 and 24 months. All rehospitalisations were documented with the main and accompanying diagnoses; hospital costs were calculated based on current reimbursement in the German Diagnosis Research Groups (G-DRG) system. The duration and type (central unique drug identifier) of anticoagulant treatment was documented at each visit. Per-patient costs of ambulatory follow-up visits and tests were calculated by multiplying (i) the costs of each visit/test (German ambulatory healthcare services reimbursement catalogue) by (ii) the probability π (0.0≤π≤1.0) of needing that specific service, based on the PE follow-up algorithm of the ESC Guidelines which we populated with the actual results per step in the present study (Figure). The primary analysis was conducted in all patients with ≥3-month follow-up. An additional sensitivity analysis included only the patients completing ≥12-month follow-up. We additionally identified the baseline predictors for the number of rehospitalizations and costs using multivariable zero-inflated Poisson and hurdle regression and accounting for censored data. Results Of 1017 enrolled patients, 958 (94%) were included in the primary analysis. Of them, 24% were rehospitalized, for a marginal mean of 0.34 (bootstrapped 95% CI: 0.30-0.39) readmissions per PE survivor. Age, coronary artery, pulmonary and kidney disease, diabetes, and (in the sensitivity analysis) cancer, emerged as independent cost predictors by multivariable hurdle gamma regression (Table). Estimated overall rehospitalisation costs were €1138 (95% CI 896-1420) per patient (€1171 [908-1479] in the sensitivity analysis). Mean anticoagulation duration was 330 days, with estimated per-patient costs of €1050 (€1190 in the sensitivity analysis). Per-patient costs of ambulatory follow-up visits and tests were estimated at €182, yielding a total cost of illness per PE survivor of €2370-2543. For the entire country, the annual direct costs after acute PE would thus amount to €202-217 million. Conclusions By estimating per-patient costs and identifying major cost drivers of post-PE care, the present study may inform decisions concerning implementation and reimbursement of follow-up programmes aiming at improved overall cardiovascular prevention.TableFigure

Natural history of salivary gland secretory carcinoma: A REFCOR study.

Background and objectivesSalivary gland Secretory Carcinoma (SC), characterized by Skalova in 2010 is a rare tumor studied within the REFCOR (French Network of experts on Rare Head and Neck Cancers). We conducted a prospective multicentric cohort study of 108 SC cases in the REFCOR database up to July 2021, analyzing diagnostic, therapeutic, and survival data. MethodsData was collected prospectively from diagnosis to the last update. Each patient had two histological readings including one by a REFCORpath pathologist, and all cases underwent molecular testing to confirm diagnosis. Statistical analyses were performed using R software. ResultsMRI was not contributive to malignancy diagnosis. After 2 histological readings, 79 % of patients were diagnosed, with 21 % requiring molecular testing to confirm diagnosis. Surgical treatment typically involved tumor excision and lymph node dissection. The tumor exhibited low lymph node involvement, with 95 % of patients being cN0, and no nodal metastases post-dissection. Five-year overall survival and recurrence-free survival were 91.4 % {95 % CI (0.84–1)} and 89 % {95 % CI (0.81; 0.98)} respectively, indicating a favorable prognosis. ConclusionsSC is a rare and newly recognized tumor, with generally favorable outcomes. Our cohort, among the largest to date, provides valuable insights. Future research should refine treatment guidelines.

Prospective longitudinal evaluation of AI-ECG in newly diagnosed heart failure (PLANE-HF)

Abstract Background * In the United Kingdom, there are one million people suffering from heart failure (HF), with more than 60,000 new cases annually (1). * Monitoring for declining left ventricular ejection fraction (LVEF) could optimise treatment approaches and avert healthcare episodes. * Easy home-based tracking of cardiac function would be transformative. * Previous studies have validated the capability of artificial intelligence-enabled electrocardiogram (AI-ECG) to correlated with changes in LVEF (2). * We hypothesize that longitudinal changes in AI-ECG probability score is associated with changes in the left ventricular (LV) function. Method * A prospective multicentre longitudinal study recruiting newly diagnosed HF with reduced ejection fraction (HFrEF) cases to investigate application of AI-ECG using longitudinal single-lead ECG recordings via patient-administered smart ECG-stethoscope examination – Figure 1. * A total of 36 patients were included in the analysis, with invitation to return for repeat echocardiography at 6-8 weeks. * Adjusted logistic regression was performed to analyze changes in LVEF by 10% as the outcome variable, investigating the relationship with the trajectory of AI-ECG probability scores. This study was approved by the UK Health Research Authority (reference 22/LO/0701). Result * Out of 36 patients, 19 patients had ischaemic and 17 had a non-ischaemic HF. * The mean age was 56.3 years, 97.2% patients were male and 46.6% were White. * 328 longitudinal single-lead ECGs were captured and used in the analysis. * 12 (33.3%) patients had an increase of their LVEF by 10%; preceding AI-ECGs was predictive of this recovery (OR 1.36; 95% CI, 1.05 – 1.65, p value = 0.016 – Table 1) Clinical Importance: * Individualised predictions of deterioration and improvement * Proactive medication adjustment * Enhanced triage for echocardiography Conclusion * AI-ECG designed to identify left ventricular systolic dysfunction (LVSD) can predict changes in LVEF% among newly diagnosed HFrEF patients. * Such results can place AI-ECG as a remote monitoring tool to track improvement or deterioration in patients’ LVEF%, which facilitate a proactive management and prevention strategies.