Prospective Multicenter Study Research Articles

Romosozumab Versus Bisphosphonates for preventing subsequent vertebral fractures after Balloon Kyphoplasty: Comparison Using Data from Two Prospective Multicenter Studies

Abstract Preventing subsequent fractures after vertebral augmentation is a critical clinical concern. The purpose of this study was to compare the effect of romosozumab and bisphosphonate administration on the occurrence of subsequent vertebral fractures after balloon kyphoplasty (BKP) and to identify factors associated with the occurrence of subsequent vertebral fractures. The study compared 24 patients who underwent BKP and received romosozumab with 58 control patients who underwent BKP and received bisphosphonates, all within two months of acute osteoporotic vertebral fracture and showing unfavorable MRI prognostic factors. The primary outcome was the occurrence of subsequent fracture, and the secondary outcomes were improvement in back pain visual analog scale (VAS) score. Furthermore, logistic regression analysis was conducted to adjust for confounding factors and assess the effect of osteoporosis treatment type on subsequent vertebral fractures following BKP. Subsequent vertebral fractures occurred in 16 patients in the bisphosphonate group and in one patient in the romosozumab group (P=.02). There were no significant differences between the two groups in VAS scores and their change from preoperatively to 6 months after surgery. The multivariable logistic regression analysis identified the type of osteoporosis treatment as an independent factor associated with the occurrence of subsequent vertebral fractures (Odds ratio, 18.30, P=.02). This prospective, multicenter study demonstrates that romosozumab is more effective than bisphosphonates in preventing subsequent vertebral fractures within six months after BKP. Romosozumab’s superior efficacy in reducing subsequent vertebral fractures may lead to improved long-term outcomes and quality of life, potentially making it a preferred treatment option over bisphosphonates for patients undergoing BKP.

Prognosis and Risks for Probable Chronic Lung Allograft Dysfunction: A Prospective Multicenter Study.

Chronic lung allograft dysfunction (CLAD) hinders lung transplant success. A 2019 consensus refined CLAD diagnosis, introducing probable or definite CLAD based on persistence of lung function decline. Outcomes and risks for probable CLAD remain uncertain. Determine the prognosis and clinical risks for probable CLAD in a prospective multicenter cohort. Clinical Trials in Organ Transplantation-20 included 745 CLAD-eligible adult lung recipients at 5 centers and applied rigorous methods to prospectively adjudicate probable CLAD. The impact of probable CLAD on graft loss was determined using a Cox model that considered CLAD as a time-dependent covariate. Regularized Cox modeling with LASSO penalty was used to evaluate donor or recipient characteristics and the occurrence and timing of posttransplant events as probable CLAD risks. Similar analyses were performed for definite CLAD. Probable CLAD occurred in 29.7% of patients at 3 years posttransplant and conferred a marked increase in risk for graft loss (unadjusted HR 4.38, p<0.001). Most patients (80%) with probable CLAD progressed to definite CLAD. Cytomegalovirus infection and specifically late presence (>90 days posttransplant) of donor-specific alloantibodies, acute rejection, acute lung injury, or organizing pneumonia contributed the greatest independent information about probable CLAD risk. Definite CLAD risks were similar. Probable CLAD identifies patients at high risk for graft loss, supporting prospective identification of this condition for early initiation of CLAD-directed interventions. More effective strategies to prevent posttransplant cytomegalovirus, inhibit allospecific immunity, and reduce tissue injury are needed to reduce probable CLAD and improve lung recipient survival.

Inter-Reader Agreement for Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System Major Features and Final Categorization: A Subanalysis From a Prospective Multicenter Study.

Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is used to definitively diagnose hepatocellular carcinoma (HCC) in patients at risk. However, the user variability associated with CEUS LI-RADS has not been validated in North American and European patients. This study aims to evaluate the inter-reader agreements of CEUS LI-RADS features for, and final categorization of, HCC in patients at risk. This retrospective multicenter clinical study used the database of a previous prospective multinational study, evaluating the accuracy of CEUS LI-RADS for HCC diagnosis in patients at risk. All cases were first evaluated by a site physician performing/supervising the CEUS examination. Randomly selected cases were re-evaluated by a blinded central reader. Final diagnosis was confirmed with the reference standard, which was a composite of imaging tests and histology. Cohen's kappa test was used to evaluate inter-reader agreement. This study included 150 liver nodules and 58.0% (87/150) were confirmed as HCC, 4.7% (7/150) non-HCC malignancies, 22.7% (34/150) had no confirmed final diagnosis, and 14.7% (22/150) were nonmalignant. Inter-reader agreements were substantial for CEUS LI-RADS categorization (κ = 0.61; 95% confidence interval [CI]: 0.51-0.71) and major features assessment (ranged κ = 0.64-0.78), LR-5 (κ = 0.65; 95% CI: 0.52-0.77), and LR-M (κ = 0.67; 95% CI: 0.44-0.90), while for LR-1 and LR-2 categorization was almost perfect (κ = 0.85; 95% CI: 0.65-1.00). Our study reported a substantial inter-reader agreement for overall CEUS LI-RADS categorization, especially for LR-5 and LR-M, and major imaging features of HCC, further confirming CEUS LI-RADS as a valuable and reliable tool for diagnosis of HCC.

Revisits and frailty in older patients in the emergency department - a prospective observational multicenter study

BackgroundAn increased number of revisits may signal that the immediate medical needs of patients seeking care at Emergency Departments (EDs) are not being met. The prevalence and characteristics of revisits to the EDs in Sweden among older patients, and its association to frailty, are unknown. We aimed to investigate the prevalence of ED revisits among patients over 65 years of age, living with or without frailty, and its association with rate of admission, and mortality; in the Swedish ED setting.MethodsThis was a prospective, multicentre study of patients over 65 years of age with an index visit to one of three Swedish EDs during May-Nov 2021. Frailty was assessed in conjunction with standard triage, using the 9-level Clinical Frailty Scale (CFS) with a CFS score of 5 to 8 as cut-off for identifying frailty. For all patients who made a revisit within 90 days of their index visit, we collected information about the revisit, admission, and mortality.ResultsA total of 1835 patients made an index visit which were included, and out of those, 595 patients made a revisit within 90 days of the index visit. Patients living with frailty (CFS 5 to 8) were more likely to make a revisit to the ED at 8 to 30 days (17% vs. 11%, diff 6%, 95% CI 2–10%, p < 0.001) and at 31 to 90 days (19% vs. 12%, diff 7%, 95% CI 3–10%, p < 0.001) and be admitted to in-hospital care during their revisit (57% vs. 47%, diff 10%, 95% CI, 1–18%, p < 0.05), compared to patients living without frailty. Results also show that patients living with frailty had a higher overall mortality rate (17% vs. 5%, diff 12%, 95% CI 7–18%, p < 0.001). However, among patients living without frailty, making a revisit slightly increased the mortality rate compared to those who did not (5% vs. 2%, diff 3%, 95% CI 1–10%, p < 0.05).ConclusionsPatients living with frailty make more revisits, are more often admitted to in-hospital care, and have a higher overall mortality rate than patients not living with frailty. Frailty, assessed with the CFS may be a simple and useful indicator of increased risk of adverse events, including revisits, in the ED.

Head injuries in prehospital and Emergency Department settings: a prospective multicenter cross-sectional study in France

Head injuries in prehospital and Emergency Department settings: a prospective multicenter cross-sectional study in France

Lung Ultrasound in the Acute Phase of ST-Segment-Elevation Acute Myocardial Infarction: 1-Year Prognosis and Improvement in Risk Prediction.

Lung ultrasound (LUS) has emerged as a useful tool in the acute phase of patients admitted for ST-segment-elevation myocardial infarction. However, its long-term significance remains uncertain, and risk scores do not include LUS findings as a predictor. This study aims to assess the 1-year prognostic value of LUS and its ability to enhance existing risk scores. This is a multicenter prospective cohort study involving 373 patients with ST-segment-elevation myocardial infarction. LUS was performed during the first 24 hours after angiography. LUS results were assessed both as a categorical (wet/dry lung) and continuous variable (LUS score). The primary end point comprised the following major adverse cardiovascular events: all-cause mortality or hospitalization for heart failure, acute coronary syndrome, or stroke within 1 year. We also evaluated whether LUS could enhance the predictive value of the GRACE (Global Registry of Acute Coronary Events) score. Major adverse cardiovascular events occurred in 51 (13.7%) patients over a median follow-up of 368 days. After multivariate analysis, the LUS score was an independent predictor (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P=0.009] for each additional B-line), whereas the categorical classification was an independent predictor in patients with ST-segment-elevation myocardial infarction Killip I (HR, 3.12 [95% CI, 1.34-7.31]; P=0.009). Incorporating LUS into GRACE resulted in a net reclassification index of 31.6% and a significant increase in the area under the curve; GRACE alone scored 0.705 compared with GRACE+LUS 0.791 (P=0.002). Detecting B-lines on LUS at the acute phase predicts major adverse cardiovascular events at 1 year in patients with ST-segment-elevation myocardial infarction and enhances the predictive value of the GRACE score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04526535.

Acute myocarditis presentation and intra-hospital prognosis: results of the multicenter prospective MYOCARDITIRM study

Abstract Background Acute myocarditis (AM) usually presents as chest pain with rising troponin and normal coronary arteries. Despite frequent favorable evolution at the acute phase, it is associated with heart failure and ventricular rhythm disorders and is considered the leading cause of sudden cardiac death in young apparently healthy adults. There is no recommendation for AM, only expert consensus, given the lack of important databases for a strong level of confidence. Methods We performed a multicenter prospective observational study of patients admitted for AM acknowledged by cardiac MRI to describe baseline characteristics, management, in-hospital and long-term outcomes of AM patients in France. Secondary objectives were to investigate determinants of prognosis, modalities of treatment and follow-up, and to identify gaps between expert consensus and real-life management. Results We enrolled 805 consecutive patients hospitalized for AM in 49 participating centers between May 2016 and February 2019. Median age was 31 (IQR 23-41) with 19% of female. Chest pain was the most frequent symptom (93%) and 112 (14%) had severity criteria upon admission (LVEF&amp;lt;50% or severe ventricular arrythmia or high-grade AV block or cardiogenic shock). ST elevation was observed in 49% of patients. One 26-years old patient died during initial hospital stay. Overall, 62 patients (8%) experienced intra-hospital complication of their AM, defined as a combined endpoint of death, LVEF&amp;lt;40% (MRI), sustained ventricular or supraventricular arrythmia, acute renal failure, cardiogenic shock, need for ventricular assistance device, need for inotropic drugs, temporary cardiac pacing, pace-maker or cardiac defibrillator implantation. Patients with initial severity criteria were 10 times more likely to present intra-hospital complication (33% vs 3.6%, p&amp;lt;0.001). Conclusion This prospective cohort represents the largest database on AM worldwide. Here we report baseline characteristics and in hospital events. Most patients had typical presentation with favorable outcomes but as much as 8% of patients did exhibit intra-hospital complication. The prospective follow up will provide valuable data to better identify subset of patients with poor prognosis that may be of interest to develop new therapeutic strategies.Acute myocarditis on cardiac MRI

Improving the prediction of major adverse cardiovascular events in patients with hypertrophic cardiomyopathy by adding plasma SVEP1 to conventional clinical model including NT-proBNP

Abstract Background Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease with a prevalence between 1 in 200 to 500 [1]. HCM can lead to major adverse cardiovascular events (MACE) such as heart failure (HF) hospitalization and cardiac death [2,3]. A protein named "sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1" (SVEP1) is a large extracellular matrix protein whose activity can be measured in plasma [4,5]. SVEP1 promotes inflammation and atherosclerosis [4,5]. SVEP1 is associated with risk of HF hospitalization and cardiac death in patients with HF with reduced ejection fraction [6]. However, no prior study has assessed the prognostic value of SVEP1 in patients with HCM. Purpose To test the hypothesis that the addition of SVEP1 improves the predictive performance of the conventional model based on clinical risk factors plus NT-proBNP for future MACE in patients with HCM. Methods We performed a multicenter prospective cohort study of patients with HCM [7]. The outcome was MACE, defined as a composite of HF hospitalization or cardiac death [6]. After dividing the cohort into four groups using the median values of SVEP1 and NT-proBNP, we compared the risk of the outcome event using the Cox proportional hazards model adjusting for 15 clinical risk factors known to be associated with MACE in HCM (Figure 1) [8-11]. We also developed the Lasso-regularized Cox proportional hazards model to predict the time to first MACE by adding SVEP1 to the 15 clinical risk factors with or without NT-proBNP in the training cohort (randomly selected 75% of the cohort). We then compared the predictive performance in the test cohort (25% of the cohort) using the C-statistic of each model. Results During a median follow-up of 1.9 (25 percentile-75 percentile, 0.7-4.3) years, the outcome event occurred in 63 (10%) of 610 patients. The four groups stratified by the median of SVEP1 and NT-proBNP levels had different risks of the outcome event (log-rank p&amp;lt;0.001: Figure 1). Even in the groups with lower-than-median NT-proBNP levels, the high-SVEP1 group had higher risks of MACE compared with the low-SVEP1 group (adjusted hazard ratio 4.52, p=0.042: Figure 1). In the prediction of time to first MACE, the addition of SVEP1 improved the C-statistic of the clinical model (p&amp;lt;0.001) and that of the clinical plus NT-proBNP model (p=0.01: Figure 2). The clinical plus SVEP1 model also outperformed the clinical plus NT-proBNP model (p=0.005: Figure 2). Conclusions In the present multicenter prospective cohort study of 610 patients with HCM, SVEP1 improved MACE risk stratification when added to the conventional model consisting of clinical risk factors plus NT-proBNP. SVEP1 also exhibited a superior predictive ability than NT-proBNP to predict MACE in patients with HCM. These data collectively indicate that SVEP1 provides additional risk stratification and may be a better biomarker than NT-proBNP for the prognostication of patients with HCM.Figure 1.Kaplan-Meier curves for MACEFigure 2.Time-dependent AUROC curves

Prospective evaluation of an AI algorithm for real-time LVEF assessment in acute coronary syndrome using left coronary angiograms: the CathEF multicenter study

Abstract Background Acute assessment of Left Ventricular Ejection Fraction (LVEF) is critical at time of percutaneous coronary intervention to optimize clinical management. The CathEF artificial intelligence algorithm offers a novel approach for real-time, intra-procedural LVEF assessment using routinely obtained left coronary artery angiograms without additional dye use[1]. Our objective was to evaluate the real-time application of the CathEF algorithm for LVEF measurement during coronary angiogram procedures in patients with acute coronary syndrome (ACS) and to compare its performance with transthoracic echocardiography (TTE) and left ventriculography. Methods The CathEF study is a prospective multi-center study that recruited ACS patients undergoing coronary angiography at two institutions from July 2022 to July 2023. Using the CathEF algorithm and the PACS-AI software, we analyzed 2 to 4 left coronary angiogram videos per procedure for LVEF assessment to compare to ventriculography (if indicated) and echocardiography performed during the same hospitalization. Operators were blinded to the CathEF AI-generated results. The primary measure was the algorithm's area under the receiving-operating characteristic curve (AUC) in identifying LVEF &amp;lt;40% or ≥40% compared to TTE-LVEF. Results 240 patients (32% female, average age 66 ± 12 years) were enrolled, with 207 undergoing TTE during index hospitalization (coronary angiogram to TTE mean delay of 0.8±6.3 days). The CathEF algorithm analyzed 881 coronary angiogram videos, averaging 3.12±1.66 per patient. Indications for angiography included unstable angina (18%), NSTEMI (47%), and STEMI (35%). The algorithm took under one minute to apply. CathEF’s performance yielded an AUC of 0.90 (95% CI, 0.840-0.96) and an MAE of 6.81% ± 0.43, with a Spearman correlation of 0.52. Conclusions This study provides proof-of-concept for prospective deployment of an AI algorithm at point-of-care with reliable LVEF measurement in real-time during ACS. This innovation holds the potential to ensure all ACS patients can receive prompt and appropriate care based on their LVEF.CathEF algorithm applied to an angiogramPACS-AI : Platform used to apply CathEF

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 (&amp;gt;=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 (&amp;lt;0.8 m/s) or normal (&amp;gt;=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&amp;lt;0.05 and 22339 ± 7350 vs. 13438 ± 8880 AU; P&amp;lt; 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&amp;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&amp;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&amp;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&amp;lt;0.01; Fig. B) and the proportion of volume responders increased (all p&amp;lt;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&amp;gt;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&amp;lt;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&amp;gt;40% with an increase of ≥10% from baseline. Persistent HFrEF was defined as LVEF ≤40% without interval improvement. Patients with LVEF&amp;gt;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&amp;lt;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.

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.