Cohort Of Patients Research Articles

Sex-specific models to predict 5-year mortality after ST-elevation myocardial infarction using machine learning: insight from FAST-MI registry

Abstract Background Most prognostic stratification tools in acute myocardial infarction (AMI) have been derived from populations including both women and men and including only a small proportion of women. Purpose Using supervised machine learning (ML), we examined the performance of 2 models assessing 5-year mortality after AMI, one derived from a population of women only and one from a population of men only, to determine whether sex-specific models improved outcome prediction. Methods This cohort study used the French registry on acute ST-elevation and non-ST-elevation myocardial infarction (FAST-MI) 2010 and 2015 surveys. This multicentric registry led in more than 200 French hospitals, enrolled all consecutive patients with acute myocardial infarction during a 1-month recruitment period. Our analysis included all men and women presenting STEMI who underwent invasive coronary angiography (ICA). To build and validate the models, the data set were split with a 70%/30% ratio into training and testing sets. The primary outcome was 5-year all-cause mortality. Then, 52 clinical, laboratory, ECG, echocardiographic, and ICA parameters were evaluated for feature selection using Boruta algorithm. Different supervised machine learning algorithms, including random forest (RF), were assessed for model building, and their performance were compared in women and men. To compare prediction accuracy according to sex, we evaluate the performance of the women-based ML model in men from the same cohort. Results 1,189 consecutive women and 3,685 men with STEMI (mean age 61±13 and 69±15 years, respectively) were recruited; 12% of men and 20% of women experienced 5-year all-cause mortality. Using Boruta algorithm, the 10 most important variables for prediction were selected (Figure 1). For women-based ML model building, the RF algorithm exhibited the best performance to predict mortality with an area under the receiver-operating characteristic curve (ROC-AUC) of 0.82 (95% CI: 0.77 – 0.88), an area under the precision-recall curve (PR-AUC) of 0.59 (95% CI: 0.54 – 0.64); and a F1-score of 0.58. The women-based ML model exhibited lower performance in men (ROC-AUC: 0.78; PR-AUC: 0.43; Figure 2). Conversely, the men-based model exhibited better accuracy in men than in women. Conclusion In a large multicentric cohort of STEMI patients, a women-based ML-model exhibited a good accuracy to predict 5-year all-cause mortality in women, but a drop of accuracy when applied to men. In mirror, the accuracy of the men-based model was lower in women. This suggests that sex-specific models might be superior to general models to predict mortality after AMI.Features selection and ML model buildingML model performance according to sex

Beating the clock: the impact of heart failure duration on CRT efficacy

Abstract Background Cardiac Resynchronization Therapy (CRT) stands as an established intervention for selected patients with heart failure (HF) presenting with a wide QRS complex. The optimal timing for CRT implantation remains uncertain. Current evidence suggests superior outcomes post-CRT in patients who have not been previously hospitalised for HF and those receiving the implant during their initial hospitalisation for HF.1 Purpose The primary objective of this study is to investigate the long-term clinical outcomes following CRT implantation relative to the duration of HF previous to the implant. It was analysed in a cohort of consecutive patients from a HF Unit who met the criteria for CRT as recommended by the ESC guidelines (QRS duration ≥150ms, left bundle branch block morphology, and left ventricular ejection fraction (LVEF) ≤35% despite optimal medical therapy). Methods We evaluated all patients who received CRT from January 2011 through September 2022. Follow-up ended in September 2023. Patients with CRT indicated for ventricular pacing due to high-degree atrioventricular block were excluded. Patients were categorized into two groups based on the duration of HF progression prior to CRT implantation: more than 3 years and 3 years or less. The primary outcome was all-cause mortality (ACM). Secondary outcomes included a composite of ACM and HF hospitalisation and the proportion of patients who demonstrated a significant improvement in LVEF (defined as an increase of ≥10% from baseline and a subsequent measurement of LVEF ≥40%). Results The cohort consisted of 127 patients, mean age 65.8±10.7 years, 23.6% were women, mean LVEF was 28.4±8.6% and 36.2% had ischaemic aetiology (Table 1). 62 patients either died or were hospitalized for HF. Mean follow-up was 4.9±2.7 years. After adjusting for age, sex and baseline LVEF, patients with HF for more than three years before CRT implantation had a worse prognosis: HRs of 2.31 for ACM (p=0.016) and 2.13 for the combined endpoint of ACM+HFH (p=0.010) (Figure 1). The proportion of patients with improved LVEF after CRT was significantly higher in the group with shorter HF duration (68.25%) compared to the group with longer HF duration (25%), p <0.001. Conclusions Our findings reveal that patients with a shorter history of HF (less than three years) prior to CRT implantation exhibit significantly better clinical outcomes. These results highlight the role of early intervention with CRT in patients with HF, suggesting that shorter HF duration prior to CRT may lead to more favourable long-term outcomes.

Comparing the ability of GRACE 2.0 scores for predicting mortality in patients with and without diabetes

Abstract Background The GRACE 2.0 (G2) was an improvement on GRACE. Neither contains DM in the model. In the GRACE, DM independently predicted in-hospital but not the 6-month post-discharge mortality. Similar analysis for GRACE 2.0 score is unavailable. Purpose Assess the ability of the GRACE 2.0 score in predicting mortality in patients with and without diabetes. Methods Retrospective cohort analysis of data on non-STEMI and UA patients admitted in two hospitals between 2010 and 2019 entered into the Myocardial Infarction National Audit Project database. All baseline characteristics of the population and G2 scores were recorded. Death at 1 year was recorded from hospital and general practice records. Follow up was censored at the last recorded contact of the patient with a medical professional. The discriminative power of the G2 score in patients with and without diabetes in predicting mortality was determined by comparing the area under the receiver operating characteristic curve (c-statistics). Accuracy of calibration was evaluated by plotting the mean predicted vs observed mortality in each decile of predicted risk. Results Of 2841 patients entered, complete data was available for 2768 patients (age 69±14yrs, 62.3% male, 877(31.7%) with diabetes). G2 risk was higher in DM (8.3, IQR 3.9 to 19.0 v 5.5, IQR 2.6 to 13.0; p<0.0001). 337 patients died, 156 with DM. Higher deaths occurred in DM group (17.8% vs 16.3; adjusted OR 1.81, 95% CI 1.41-2.33, p<0.0001) (fig 1D). G2 discriminated between events well in whole cohort (AUC 0.81, p<0.001) with no difference between DM and non-DM patients (AUC DM: 0.78, 95% CI 0.75 to 0.81; non-DM 0.81, 0.79 to 0.83; δAUC 0.0301, p=0.242) (fig1E). Calibration of predictions by G2 was excellent across all deciles of risk for the whole cohort (fig 1A). However, G2 underestimated mortality in DM versus non-DM (fig1B,C), especially in the higher deciles of risk (fig 1 F,G). Conclusion(s) Discrimination of the GRACE 2.0 model was excellent for mortality at 1-year with no difference between patient with and without diabetes in our cohort of NSTEMI and UA patients. However, calibration plots suggest GRACE 2.0 underestimates mortality in diabetic compare to non-diabetic patients. This may suggest that risk stratification with GRACE 2.0 in diabetic patients may have to be considered with caution.Figure 1.

Prolonged dual antiplatelet therapy in an extended Phase 3 Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Prolonged dual antiplatelet therapy (P-DAPT) is recommended in selected patients beyond 12 months after myocardial infarction (MI). Several risk scores have been developed to estimate the ischemic and bleeding risk and individualize the decision-making process. Purpose We aim to analyse the factors, including ischemic and bleeding scores, associated with P-DAPT prescription in MI patients submitted to a Cardiac Rehabilitation Program (CRP). Methods Patients with ST-segment elevation MI (STEMI) or occlusion MI (OMI) who were submitted to our CRP underwent Phase 2 CRP and were prospectively included. Patients were followed in an extended Phase 3 CRP, and a follow-up visit was scheduled 12 months after hospital discharge. Baseline and follow-up clinical characteristics and treatment after the 12-months visit were registered, specifically P-DAPT. Ischemic (DAPT score) and bleeding (PRECISE-DAPT and CRUSADE scores) risk scores were retrospectively computed. Predictors of P-DAPT were studied by univariate analysis and multivariable binary logistic regression. The model was tested by area under the curve (AUC) analysis in receiver operating characteristic curves. A p<0.05 was considered statistically significant. Results The cohort comprised 78 patients (mean age 61±11 years, 84.6% male). Anterior and inferior STEMI were the most common presentations (43.6% and 47.4%, respectively). The most prevalent cardiovascular risks factors were hypercholesterolemia (85.9%), hypertension (53.8%), smoking habit (46.2%) and diabetes mellitus (23.1%). P-DAPT was prescribed in 39 (50%) patients beyond 12 months after MI, primarily combining aspirin 100mg o.d. and ticagrelor 60mg b.i.d. (n=33, 84.6%). On multivariate analysis, variables associated with P-DAPT prescription were hypertension (HR 4.92 [1.37-17.68], p=0.02), diabetes mellitus (HR 5.13 [1.09-24.09], p=0.04), multivessel disease (HR 5.54 [1.55-19.79], p=0.008), and stent diameter <3mm (HR 5.46 [1.25-23.78], p=0.02). The predictive power of the model was excellent (AUC 0.88 [0.8-0.96], p<0.001). Ischemic (DAPT score) and bleeding (PRECISE-DAPT and CRUSADE) risk scores were not associated with P-DAPT neither in continuous form nor by using their standard cutoffs (≥2, <25 and >40 points, respectively). Conclusions In a real-life cohort of MI patients undergoing extended Phase 3 Cardiac Rehabilitation, P-DAPT was prescribed in half of the population. Clinical (hypertension and diabetes mellitus) and angiographic (multivessel disease and stent diameter <3mm) variables straightforwardly predict the likelihood of receiving P-DAPT, unlike ischemic and bleeding risk scores. The clinical consequences of this management should be further explored.Prolonged DAPT in Cardiac Rehabilitation

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.

Examining prognostic scores for short-term major adverse cardiovascular events prediction following primary PCI: a comparative analysis

Abstract Background Accurately predicting short-term MACE (major adverse cardiac events) following primary PCI remains a clinical challenge. This study aims to assess the effectiveness of four established risk scores in predicting short-term MACE after primary PCI (percutaneous coronary intervention). Methodology We enrolled a cohort of consecutive adult patients diagnosed with STEMI (ST elevation myocardial infarction) undergoing primary PCI in this prospective observational study. Patients were followed at the interval of 3 months up for up to 12 months, and MACE events were recorded. Additionally, we obtained TIMI, PAMI, CADILLAC, and GRACE scores. Results A total of 2839 patients (79.3% male, mean age 55.6 ± 11.2 years) were included. Over a median follow-up of 244 days, the composite MACE rate was 18.3% (519). All-cause mortality was 13.5% (384), re-infarction requiring revascularization was 4.3% (121), heart failure-related re-hospitalization was 2.6% (74), stent thrombosis occurred in 5.6% (160), and CVA (cerebrovascular accident) events were documented in 1% (28). The AUC (area under the curve) for TIMI, PAMI, CADILLAC, and GRACE scores were 0.658 [0.630-0.685], 0.658 [0.632-0.684], 0.669 [0.644-0.695], and 0.675 [0.649-0.701], respectively, for the prediction of MACE. On multivariable Cox regression, medium and high-risk categories based on GRACE score were independent predictors of MACE with adjusted HR (hazard ratio) of 1.52 [1.21-1.92]; p<0.001 and 1.92 [1.34-2.75]; p<0.001, respectively. Conclusion A significant proportion of patients experienced short-term MACE after primary PCI. While none of the assessed scores demonstrated significant predictive power, the GRACE score exhibited comparatively better predictive ability than TIMI, PAMI, and CADILLAC scores

Timing of inopressor initiation in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Introduction Inotropes and vasopressors (inopressors) are commonly used in the treatment of acute myocardial infarction complicated by cardiogenic shock (AMICS). The characteristics of patients subjected to early or late initiation of inopressors are not yet described, and the impact of timing on outcomes remains uncertain. Purpose This retrospective real-world data study aims to identify patient-, treatment-, and outcome characteristics of AMICS patients treated with early- or late initiated inopressors. Methods The Netherlands Heart Registration (NHR) prospectively records baseline, procedural, and outcome data for PCI patients. Between 2017-2021, additional retrospective data on CS patients were collected by fourteen Dutch hospitals. Patients were categorized based on the timing of inopressor initiation, either early (pre PCI) or solely late (at the cathlab or within 24 hours after PCI). Patients presenting with an out of hospital cardiac arrest were excluded. Missing data were imputed through multiple imputation (30x). Multivariable logistic regression analysis was performed to evaluate the association between the timing of inopressor initiation and 30-day mortality, adjusting for univariate significant confounders among variables known at admission. Results A total of 956 consecutive CS patients were included of whom 418 (43.7%) and 538 (57.3%) patients were subjected to early and late initiation of inopressors respectively. The most frequently used drug in both groups was noradrenaline. At baseline, patients in the early initiation group were younger (67.4 vs. 70.0 years, p <0.001), presented with a lower mean arterial pressure (MAP) (72.5 vs. 76.3, p = 0.048) and higher lactate (4.2 vs. 3.6, p = 0.012), and presented with a NSTEMI more often (36.0% vs. 14.2%, p <0.001). They also had a higher prevalence of previous myocardial infarction (33.9% vs. 22.9%, p <0.001) and previous CABG (14.3% vs. 6.2%, p <0.001). Moreover, 30-day mortality rates were higher in the early initiated group (48.6% vs. 37.6%, pLogrank <0.001). After multivariate adjustment for age, admission MAP and lactate, early inopressor initiation remained independently associated with 30-day mortality (OR 1.44, 95%-CI 1.08-1.98) compared to late initiation. Conclusion In this Dutch cohort of CS patients undergoing PCI, baseline- treatment- and outcome characteristics differed between patient categories receiving either early or late initiated inopressors. Patients who were subjected to early initiated inopressors were younger, presented with worse hemodynamics, had a more extensive cardiovascular medical history and higher 30-day mortality rates. The results of this study reemphasize the importance of identifying patients who benefit from inopressors.30-day mortality late vs. earlyTable patient characteristics

Functional capacity by cardiopulmonary exercise testing is not related to health status in obstructive hypertrophic cardiomyopathy

Abstract Background In obstructive hypertrophic cardiomyopathy (HCM), the primary goal of therapy is to improve patient quality of life by decreasing symptom burden. Increasingly, cardiopulmonary exercise testing (CPET), with peak oxygen consumption (pVO2) and ventilator efficacy (VE/VCO2), is used to assess efficacy of novel therapies in clinical studies and selectively in clinical practice to determine treatments. However, the relationship of CPET variables to symptom burden in HCM is not well established. Therefore, we examined the relationship between CPET variables and health status measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) and NYHA functional classification in a cohort of obstructive HCM patients. Methods Consecutive patients with HCM and resting left ventricular outflow tract (LVOT) obstruction (≥50 mmHg) underwent CPET between October 2022 to January 2024. Patients with a peak RER <1.0 were excluded (n=4). To investigate distribution of patient reported health status (KCCQ) and NYHA functional classification, patients were stratified into groups for pVO2 (<14, 14-20, and >20 mL/kg/min) to reflect moderate to severe, mild to moderate, and little to no functional limitation, respectively. Results Of 58 patients, clinical evaluation was at 59 ± 13 years of age, 55% male, with LVOT gradient of 83 ± 28 mmHg at rest with 84% NYHA class II or III and 76% with KCCQ overall summary (OS) <75. Both pVO2 and VE/VCO2 had significant but weak correlation with NYHA class and KCCQ scores (Table 1), with the strongest correlation observed with pVO2 and KCCQ-OS (R2= 0.13, p=0.004). In contrast, % predicted pVO2 was not significantly correlated with NYHA or KCCQ. Notably, despite 14 patients being classified as having little to no limitations by pVO2, 29% of these patients had mild to moderate disability and 29% had moderate to severe disability by KCCQ-OS (Figure 1). Conclusion In patients with symptomatic obstructive HCM, objective measures of exercise performance, including pVO2 and VE/VCO2, correlate poorly with measurements of health status. These data suggest that CPET results should not be considered a surrogate marker of heart failure symptom burden in obstructive HCM.

Mortality related to left ventricular ejection fraction and obstructive coronary artery disease in non-ST-segment elevation myocardial infarction

Abstract Background Extent of coronary artery disease (CAD) and the severity of reduced left ventricular ejection fraction (LVEF) have both been associated with the prognosis after non-ST-segment elevation myocardial infarction (NSTEMI). However, the contemporary mortality associated with the extent of obstructive CAD over a range of LVEF remains uncertain. Purpose The aim of this study was to assess the impact of CAD and LVEF on all-cause death following a first-time NSTEMI. Methods We included consecutive first-time NSTEMI patients undergoing coronary angiography from 2010 to 2021 in Western Denmark. Patients were stratified by extent of obstructive vessel disease (VD; 1, 2, or 3VD) and LVEF (≥51%, 41-50%, or 10-40%). Patients with previous myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting were excluded. The primary outcome was all-cause death. We calculated 5-year cumulative incidence proportions (CIP) as a measure of absolute risk and adjusted hazard ratios (HR). Results A total of 8,770 patients with first-time NSTEMI and obstructive CAD were examined with coronary angiography. Two-thirds were male and median age was 68 years (Q1-Q3: 58-78). The increase in mortality associated with decreasing LVEF was greater than observed by extent of CAD (Table). Thus, the 5-year mortality increased stepwise by extent of CAD from 14% for 1VD to 31% for 3VD (adjusted HR 1.35, 95% CI:1.19-1.54), but from 12% for LVEF ≥51% to 40% for LVEF 10-40% (adjusted HR 2.32, 95% CI: 2.04-2.65). When combining LVEF and extent of CAD, an increase in 5-year mortality was found from 9% for 1VD and LVEF ≥51% to 46% for 3VD and LVEF 10-40% (risk difference of 37.1%; Figure). Correspondingly, using 1VD and LVEF ≥51% as reference, the adjusted HRs increased gradually with extent of CAD and decline in LVEF to 3.05 (95% CI: 2.51-3.70) for patients with 3VD and LVEF 10-40% (Table). Conclusion In a contemporary all-comers cohort of first-time NSTEMI patients, increasing extent of CAD and declining LVEF are both associated with a gradual increase in 5-year mortality. Our data suggest that the level of LVEF reduction was more strongly associated with 5-year mortality than CAD extent.

Incremental prognostic value of late gadolinium enhancement granularity in patients with hypertrophic cardiomyopathy

Abstract Background The prognostic stratification of hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance (CMR) is based on the extent of late gadolinium enhancement (LGE). To enhance risk stratification for sudden cardiac death (SCD), the ESC has recently added LGE extent in the guidelines, at ≥15% of LV mass. However, SCD has become an uncommon event in this population, and mortality is now mostly related to other phenotypes, such as atrial fibrillation, stroke, and heart failure. While previous studies have showed the prognostic value of LGE to predict all-cause mortality, the prognostic impact of additional LGE features is not well established. Therefore, we aimed to assess the incremental prognostic value of the granularity of LGE including extent, location, and pattern in patients with HCM to predict all-cause death. Methods Between 2008 and 2021, all patients referred for HCM assessment using CMR, without history of coronary artery disease (CAD) or clinical history of myocarditis were prospectively recruited in two French centers. The outcome was all-cause death using the French National Registry of Death. The concept of "LGE granularity" was defined as a comprehensive model combining all the following LGE features with extent (by segment), location (septal or others), and pattern (midwall and/or subepicardial). Using nested Cox proportional hazard models, the additional predictive value of LGE features was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 2,672 included patients (52±7 years, 56% males), 862 (32%) had LGE. After a median (IQR) follow-up of 9 (7–11) years, 447 (17%) patients died. Survival curves show an increased risk for LGE presence (log-rank p<0.001, Figure 1A). After adjustment for traditional prognosticators in the overall population (N=2,672), the presence of LGE was strongly associated with all-cause death (adjusted hazard ratio (HR) 3.96, 95% CI: 3.26-4.80, p<0.001). In the subgroup of patients with LGE (n=862), survival curves showed that all parameters defining the LGE granularity were associated with a higher risk of all-cause death (all p<0.001, Figure 1B). A nested Cox model adjusted on traditional prognosticators showed that the LGE extent, location and pattern were all independently associated with all-cause death (all p<0.001, Figure 2). The model of "LGE granularity" combining all independently significative LGE features showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.90; NRI=41.9%; IDI=13.2%, Chi-2 global=450, all p<0.001; LR-test p<0.001, Figure 2). Conclusion In a large cohort of HCM patients, the "LGE granularity" model combining the extent, location, and pattern of LGE had an incremental prognostic value over and above traditional prognosticators to predict all-cause death.Prognostic value of LGE granularityIncremental prognostic value LGE granula

Nighttime blood pressure reductions after radiofrequency renal denervation through 24 months in patients with uncontrolled hypertension: pooled analysis from the SPYRAL HTN trials

Abstract Introduction Studies have shown that elevated nighttime and early morning systolic blood pressure (SBP) are associated with the highest risk for cardiovascular (CV) events. Radiofrequency renal denervation (RF RDN) is an interventional therapy to reduce BP in patients with uncontrolled hypertension (HTN). Although sustained, durable reductions in office and 24-h ambulatory systolic BP (SBP) after RDN have been observed, whether the therapy produces similar, durable nighttime and early morning SBP reductions requires further evaluation. Objective To assess whether RF RDN significantly reduces nighttime SBP through long-term follow-up, in addition to other times of the day. Methods We pooled data from patients with uncontrolled HTN undergoing RF RDN using the latest-generation Symplicity SpyralTM multi-electrode catheter from the published SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-h ambulatory SBP were evaluated from baseline through 24 months. We also assessed BP changes during specific, diurnal time ranges including nighttime (1am-6am), early morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urine and plasma drug testing were tabulated from baseline through 24 months. Results Outcomes from 388 patients undergoing RF RDN were pooled for this analysis. Patients were on average 54±10yrs old, 26.8% female, mean BMI was 31.3±6.0, 45.1% with >10yrs diagnosis of hypertension, 7.7% with type 2 diabetes, 9.8% with obstructive sleep apnea, 47.7% with a history of smoking. The baseline nighttime SBP was 139±11mmHg, morning SBP was 154±15mmHg, and daytime SBP was 156±9mmHg. At baseline, 92.5% of patients had nocturnal hypertension (BP ≥120/70 mmHg) and took 1.0±1.2 antihypertensive drugs. 12 months after RF RDN, 30.6% of patients no longer had nocturnal hypertension (p<0.0001). The mean nighttime SBP change at 12 months was -10.8±15.4mmHg, morning changed was -12.8±20.4mmHg, and daytime changed was -12.2±13.6mmHg (Figure). The mean 24-h ambulatory SBP change at 12 months was -11.9±12.4mmHg, and the office SBP change was -17.7±15.4mmHg . Patients took 1.8±1.1 antihypertensive drugs at 12 months. Results from 24 months, not currently available, will also be presented for the first time. Conclusions In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. Clinically meaningful reductions at 12 months throughout the 24-hr circadian cycle, including at nighttime and early morning SBP, are consistent with the "always on" effect of RDN. Results from 24 months will also be presented for the first time at ESC. As an adjunctive therapy to pharmacotherapy, RDN may help to reduce CV risk by lowering nighttime and morning SBP.

Long term follow up of Implantable Cardioverter Defibrillators (ICD) in hypertrophic cardiomyopathy: is subcutaneous the way forward?

Abstract Introduction Young patients have greater risks of longer-term complications including inappropriate therapy (IT) from Implantable Cardioverter Defibrillators (ICD) than older ICD patients. In prevention of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM), these complications are critical in determining treatment thresholds. When comparing transvenous ICDs (TV), subcutaneous ICDs (SICD) may have different risks & benefits that define their relative utility. We investigated TV & SICD outcomes in a propensity matched cohort of HCM patients. Methods We used electronic health records in a retrospective study of HCM patients receiving an ICD between 2006-22 at tertiary centre. Indications for ICD implantation, including type of device, were determined by the treating cardiomyopathy team according to ESC guidance. All TV device types were included & eligibility for SICD included passing screening in at least 1 sensing vector. Outcome data included patients lost to follow-up until the last device check & patients who had both device types were included twice. Patients were censored after their first IT for an analysis of IT, & their first ‘ICD complication’ for that analysis. ICD complications are defined as all other complications that resulted in a re-intervention procedure (excl SICD battery advisory), or extra procedure at box change. The audit was registered with local institutional review board for ethical approval. Propensity scoring was used for stratification and covariate adjustment. Matching was conducted using the 12 baseline variables. Associations with IT, ICD complications and their composite were assessed using proportional hazard regression (Cox) models, with time to event starting at implant date. Univariable & multivariable regression analyses were used as appropriate. Hazard ratios (HRs) of 95% confidence intervals were estimated by fitting a model with the propensity score and dichotomous variable (TV vs SICD). A p value of <0.05 was considered statistically significant. Analyses were conducted using R- Version 2023.06.0+421. Results Mean age was 55±14.2 years with follow-up of 73±63 months; 70.7% were male. Of a total of 611 patients, with 469 in the TV group & 164 in the SICD. SICD patients had fewer complications, with no differences in IT across all and propensity matched analyses (CI 0.64), fig 1. Conclusion In HCM, when compared to TV, SICDs are associated with fewer ICD complications & not associated with more frequent IT. Intriguingly, there was a higher rate of IT with the first generation SICD, causing the wide IT errors at longer durations. Complications over long term follow up require more assessment, but the absence of TV lead intervention creates reduced risks for SICD complications. In HCM patients without pacing needs, SICDs may be preferred for HCM-SCD prevention. In addition, the lower risks associated with SICD could lead to lower treatment thresholds for people with elevated lifetime HCM-SCD risk.

Radiographic Indicators of Craniocervical Instability: Analyzing Variance of Normative Supine and Upright Imaging in a Healthy Population.

Single-institution retrospective review. To establish baseline ranges and variability of 7 radiographic measurements of the cervical spine in a healthy patient population as potential diagnostic tools for craniocervical instability. Craniocervical instability, common in patients with connective tissue disease such as Ehlers-Danlos Syndrome, often presents with a wide range of symptoms, including neck pain. Current diagnostic methods employ a range of clinical and radiographic features, but diagnostic challenges remain due to missed indications on static imaging and a lack of standardized measurement values and normalized variance. Seventy-two healthy patients with cervical imaging were analyzed. Surgimap software was used to annotate supine computed tomography images, flexion, extension, and neutral x-ray images for measurement. These measurements included the atlanto-dental interval, clival-axial angle, basion-dens interval, basion-axis interval, perpendicular basion to the inferior aspect of C2, also known as Grabb Oakes measurement, and the hard palate to C1 and hard palate to C2. Statistical analysis assessed differences among imaging modalities, and coefficients of variation were calculated for each measurement. Our cohort consisted of a total of 72 patients with a mean age of 64 (SD: 13.54). All measurements except for the basion-axial interval and atlanto-dental interval demonstrated a significant difference between extension and flexion x-ray measurements. clivo-axial angle, hard palate to C1, and hard palate to C2 demonstrated the lowest coefficients of variance across imaging modalities. Understanding normal variance in cervical measurements is invaluable for accurate CCI diagnosis. Using a cohort of healthy patients, this study delineates the distribution and spread of 7 cervical measurements, delineating reference values and variability in these key measurements and highlighting their potential for use as imaging markers for CCI. Level III.

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

Characterizing Non-T2 Asthma: Key Pathways and Molecular Implications Indicative of Attenuated Th2 Response.

Non-Type 2 (non-T2) asthma is characterized by a lack of allergic sensitization and normal to low total IgE levels. We aimed to explore molecular mechanisms and pathways differentiating non-T2 from T2-high pediatric asthma. We analyzed peripheral blood RNA samples from 11 non-T2 and 17 T2-high pediatric asthma patients using bulk RNA sequencing. Differentially expressed genes (DEGs) were identified, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Protein-Protein Interaction (PPI) network construction. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were employed to explore significance of these DEGs. We utilized independent public datasets GSE145505 to validate our findings. We investigated Th cytokine profiles in an independent cohort of pediatric patients with non-T2 asthma (n = 38) and T2-high asthma (n = 64). We demonstrated that the total serum IgE levels of children with non-T2 asthma (128.4 ± 159.5IU/mL) was significantly lower than that of those with T2-high asthma (405.8 ± 252.1IU/mL). Our analysis revealed 136 DEGs distinguishing non-T2 from T2-high asthma. IPA identified predicted inhibition of IgE-FcεRI signaling pathways in non-T2 asthma. Our DEG data showed the expression of IGHV4-39, IGLV1-40, IGLV1-47, IGLV1-44, IGHV1-69, IGLV6-57, IGLV3-19, IGLV3-1, and IGLC7 were downregulated in our non-T2 asthma patient. The non-T2 group exhibited significantly higher concentrations of IL-2, IFN-γ, IL-6, and IL-17A compared to the T2-high group. Our integrated analysis differentiated non-T2 from T2-high asthma by revealing downregulation of specific immunoglobulin genes influencing FcεRI signaling, elevated Th1 cytokines and Th17 cytokines might affect IgE associated sensitization and alter Th2 allergic response.

Prognostic staging system correctly identifies high risk groups in cardiac transthyretin amyloidosis treated with tafamidis

Abstract Background The development of different multiparametric staging systems improved the risk assessment of cardiac transthyretin amyloidosis (ATTR-CA) patients substantially. However, to date, all staging systems were validated in treatment-naive ATTR-CA patients. The introduction of tafamidis led to significant changes in the disease trajectory of ATTR-CA, indicating that it may also have an impact on the prognostic accuracy of these staging systems. Purpose Thus, we sought to assess whether the prognostic value of the National Amyloidosis Centre (NAC) staging system, currently considered as the most accurate, is sustained in ATTR-CA patients treated with tafamidis. Methods This retrospective observational study included ATTR-CA patients treated with tafamidis. Patients were continuously followed from treatment initiation to time of death. NT-proBNP and eGFR data collected at baseline were used to stratify patients into low (stage I), intermediate (stage II) and high-risk (stage III) subgroups according to the NAC staging system. Kaplan-Meier analyses were conducted to illustrate overall survival. Differences in overall survival between subgroups were assessed by log rank tests. P-values <0.05 were considered statistically significant. Results A total of 166 ATTR-CA patients (95.2% wild-type) were enrolled. 81 (48.8%), 51 (30.7%) and 34 (20.5%) patients were stratified into stages I, II and III, respectively. Median follow-up was 539 [323-865] days, during which 20 deaths were recorded. Overall survival of the subgroups over time is demonstrated in figure 1. The probability of overall survival was significantly lower for patients in stage III compared to patients in stages I (log rank; p=0.002) and II (log rank; p=0.031). However, no differences in the probability of overall survival were identified between patients in stage I and II (log rank; p=0.679). Conclusions In this cohort of ATTR-CA patients treated with tafamidis, the NAC staging system effectively identified patients at elevated risk of mortality. However, the distinction in survival rates between low- and intermediate-risk groups was less pronounced, suggesting that tafamidis may have a stronger prognostic impact in these groups.Overall Survival across NAC Stages

The triglyceride-glucose index is a marker of thromboembolic events in atrial fibrillation patient under oral anticoagulation therapy

Abstract Background Atrial fibrillation (AF) increases the risk of stroke and thromboembolism; and appropriate risk stratification is central for better targeted patient management. The triglyceride-glucose (TyG) index indirectly assesses insulin resistance, and has been associated with cardiovascular risk. Purpose To investigate whether the TyG index could be a biomarker for assessing the risk of thromboembolic events in patients with AF. Methods We performed an observational prospective cohort study including outpatients diagnosed with AF starting vitamin K antagonist (VKA) or direct-acting oral anticoagulants (DOAC) therapy from January, 2016 to November, 2021. The primary endpoint was a combination of thromboembolic events, considered as the composite of myocardial infarction, and/or venous thromboembolism, and/or ischemic stroke/transient ischemic attack, over 2 years of follow-up. The TyG index was calculated as the natural logarithm (Ln) of the product of baseline plasma glucose and triglyceride using the following formula: Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Patients were stratified into tertiles according to their TyG index (ie. first tertile: TyG index <4.59; second tertile: TyG index 4.59-4.83; third tertile: TyG index >4.83). Results We included 2907 patients (median age 77 [70-83] years; 52.5% female). The median TyG index was 4.71 (4.53-4.91), and 34% (989) where in the third tertile of TyG index. During a follow-up of 2 years, 209 (7.2%) patients suffered a thromboembolic event. Compared to patients in the first or second tertiles of TyG index, patients in the third tertile had an increased annual event rate of thromboembolic events (3.40 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.043; and 3.41 per 100 patient-years vs. 4.76 per 100 patient-years, p=0.044), and higher incidence rate ratio (1.41 [95% CI 1.01-1.98], p=0.044 vs. first tertile; 1.40 [95% CI 1.01-1.97], p=0.044 vs. second tertile). Cox regression analyses adjusted for several risk factors demonstrated that the TyG index was an independent predictor for thromboembolic events (aHR 1.82; 95% CI 1.15-2.89; p=0.011). Patients in the third tertile of TyG index presented a 64% higher risk of thromboembolic events (aHR 1.64; 95% CI 1.17-2.29; p=0.004) (Table), with significantly lower event free survival (log-rank test p-value = 0.016) (Figure). Conclusions In this real-world cohort of AF patients under oral anticoagulation therapy, elevated TyG index was an independent risk factor for thromboembolic events. The TyG index is a simple, low-cost indicator, that could be used as a screening tool in everyday clinical practice.

The influence of prolonged antibiotic treatment before lead extraction procedures on the outcomes of device reimplantation in cardiac implantable electronic device infections

Abstract Background Cardiac implantable electronic devices (CIED) related infections have a considerable clinical and economic burden in the cohort of CIED-implanted patients and require a complex and thoughtful approach of the "heart team". Complete CIED removal is recommended for all patients with confirmed CIED infection, but the optimal duration of antibiotic therapy (AT) before lead extraction (LE) and its impact on the time of reimplantation are still debatable [1-2]. This study was aimed to evaluate the impact of prolonged AT before LE on the outcomes of device reimplantation. Methods Consecutive cases of LE due to CIED infection at our centre from 2013 to 2022 were reviewed. Our approach assumed the duration of AT for a minimum of 2 weeks for patients with pocket infection (PI), and at least 4 weeks for endocarditis with the exception of non-response to the AT. The target time for reimplantation was 2-3 days after LE with the exception of uncontrolled infection, positive blood culture, logistical reasons or reevaluation of pacing indications during follow-up. Results From a total of 256 LE, 202 (in 198 patients) were due to CIED infection (pacemaker-67,8%, CRT-19,8%, ICD-12,4%). In 62,4% of the cases there was only PI, in 24,7% only endocarditis and in 12,9% it was concomitant. Systemic infection was found in 43,1% of the cases. The mean dwell time of the leads was 92.2±5.0 months (n=201, median 84, IQR 29.0-132.0). In cases of PI, the mean time of AT before LE was 21,7±1,0 days (n=124, median 21, IQR 14.0-28.0), whereas it was 31,6±1,7 days (n=76, median 28, IQR 21.0-42.0) in cases of endocarditis (p<0.05). The duration of AT after LE was 17.7±0.8 days (n=121, median 14, IQR 14.0-21.0) in cases of PI and 22.7±1.4 days (n=76, median 21, IQR 14.0-28.0) in cases of endocarditis (p<0.05). Procedural success was achieved in 98,5% and the procedural failure rate was 1,5%. Major complication rate was 2,5% and minor complication rate was 8,9%. There was no intraprocedural death. Device reimplantation after LE was performed in 68,8% (139) of all patients. The majority of reimplantations (57,6%) occurred within 7 days after LE (figure 1). The mean reimplantation time was 43.6±12.1 days (n=135, median 6, IQR 4.0-15.0), without statistically significant difference in time to reimplantation between PI and endocarditis (p=0.78). 9 patients were reimplanted with epicardial ventricular lead and 1 with leadless pacemaker. Total reinfection rate was 2% (4), all the cases were due to contralateral PI with reimplantation after LE in 11, 12, 38 and 596 days, respectively. One of the patients was also diagnosed with an allergy to silicone, nickel and palladium. Mortality rate during the first 30 days was 5%. Uneventful 12-month follow-up was achieved by 80,2%. Conclusions Appropriate prolonged AT before LE led to feasibility of early device reimplantation with a low rate of reinfection.Time to preimplantation

Insights into the gut microbiome of vitiligo patients from India

BackgroundVitiligo is an autoimmune disease characterized by loss of pigmentation in the skin. It affects 0.4 to 2% of the global population, but the factors that trigger autoimmunity remain elusive. Previous work on several immune-mediated dermatological disorders has illuminated the substantial roles of the gut microbiome in disease pathogenesis. Here, we examined the gut microbiome composition in a cohort of vitiligo patients and healthy controls from India, including patients with a family history of the disease.ResultsOur results show significant alterations in the gut microbiome of vitiligo patients compared to healthy controls, affecting taxonomic and functional profiles as well as community structure. We observed a reduction in the abundance of several bacterial taxa commonly associated with a healthy gut microbiome and noted a decrease in the abundance of SCFA (Short Chain Fatty Acids) producing taxa in the vitiligo group. Observation of a higher abundance of genes linked to bacteria-mediated degradation of intestinal mucus suggested a potential compromise of the gut mucus barrier in vitiligo. Functional analysis also revealed a higher abundance of fatty acid and lipid metabolism-related genes in the vitiligo group. Combined analysis with data from a French cohort of vitiligo also led to the identification of common genera differentiating healthy and gut microbiome across populations.ConclusionOur observations, together with available data, strengthen the role of gut microbiome dysbiosis in symptom exacerbation and possibly pathogenesis in vitiligo. The reported microbiome changes also showed similarities with other autoimmune disorders, suggesting common gut microbiome-mediated mechanisms in autoimmune diseases. Further investigation can lead to the exploration of dietary interventions and probiotics for the management of these conditions.

Clinical and laboratorial profile of patients with ATTR cardiomyopathy: comparison between wild type and p.Val142Ile forms in the Brazilian population

Abstract Background In Brazil, besides the wild type (wt) form, transthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly caused by hereditary form with Val142Ile mutation. Considering that both forms occur in elderly people, the clinical presentation may be similar. We sought to compare the clinical presentation of patients with wt and Val142Ile mutation in a Brazilian cohort of ATTR-CM patients. Methods Among the 642 patients enrolled in REACT/SP, 283 presented ATTR-CM, being 85 wt and 90 Val142Ile patients. We compared the main clinical characteristics between groups. Results The wt in comparison to Val142Ile patients, respectively, presented: older age (78.4+/-8.5 vs 74.2+/-8.1 y.o., p = 0.0009); similar proportion of males (82% vs 81%, p=0.85); lower proportion of blacks (11% vs 39%, p=0.0001); similar prevalence of heart failure (HF) symptoms (85% vs 79%, p=0.33); higher prevalence of syncope (13% vs 2%, p=0.008) and Pacemakers (PM) implantation (8% vs 1%, p=0.027); similar prevalence of neuropathy manifestations (38% vs 51%, p=0.17); lower creatinine (1.5+/-0.8 vs 2.1+/-2.1 mg/dL, p=0.02) and NT-ProBNP levels (2860.0+/-2843.3 vs. 5488.3+/-5455.6 pg/ml, p=0.0001); reduced interventricular septal thickness (15.6+/-3.3 vs 17.0+/-3.3 mm, p= 0.006), posterior left ventricular (LV) posterior wall thickness (14.2+/-2.4 vs 16.2+/-4.4 mm, p=0.0003), higher LV ejection fraction (52.0+/-10.1 vs 48.2+/-13.6%, p=0.038), higher global LV longitudinal strain (8.6+/-8.7 vs 3.4+/-9.8, p=0.0003), smaller LV diastolic diameter (45.9+/-6.1 vs 43.0+/-7.3 mm, p=0.005) at 2D-Echocardiogram. Conclusions In the Brazilian population wt and Val142Ile patients had similar clinical presentation regarding HF and neuropathy symptoms, but higher prevalence of syncope and PM in wt patients. Conversely, Val142Ile patients presented more severe amyloid cardiac infiltration.