Long-term Failure Research Articles

Surrogate Endpoints in APOL1-Associated Kidney Disease: Evaluation in Three Cohorts.

Surrogate endpoints for the clinical outcome of kidney failure have been accepted by the United States Food and Drug Administration. However, they have not been specifically evaluated in Apolipoprotein L1 (APOL1)-associated kidney disease. This random-effects meta-analysis included African-American participants in the Atherosclerosis Risk in Communities (ARIC) study (N=3071), the Chronic Renal Insufficiency Cohort (CRIC; N=998), and the African American Study of Kidney Disease and Hypertension (AASK; N=609). Surrogate endpoints included three-year 30% and 40% decline in glomerular filtration rate (GFR), doubling of urine protein-to-creatinine ratio (UPCR), and >3 ml/min/1.73 m2 per year decline in GFR. Clinical outcomes included kidney failure requiring kidney replacement therapy, heart failure, cardiovascular disease, and death after three years.Results: 22% in AASK, 18% in CRIC, and 13% in ARIC had the APOL1 high risk genotype. Participants with the APOL1 high-risk genotype had higher risk of all three-year GFR outcomes but not doubling of UPCR, as well as kidney failure after three years. The three-year outcomes were strongly associated with kidney failure, with weaker but statistically significant associations with the development of heart failure, cardiovascular disease, and mortality. There were no differences in associations between short-term and long-term clinical outcomes by APOL1 risk status. Individuals with the APOL1 high risk genotype were more susceptible to three-year GFR-related endpoints and long-term kidney failure than individuals with the APOL1 low-risk genotype. There was no consistent difference in short-term-clinical outcome associations by APOL1 genotype, supporting the use of surrogates in APOL1-associated kidney disease.

Comparative analysis of post-PCI fractional flow reserve and quantitative flow ratio in predicting long-term Target Vessel Failure and hard endpoints

Abstract Background The role of functional assessment after angiographically acceptable post-PCI result is debatable. Purpose We sought to investigate the correlation between Fractional Flow Reserve measured directly after drug eluting stent (DES) implantation (post-PCI FFR) and post-PCI Quantitative Flow Ratio (post-PCI QFR), clarify their relationship with clinical parameters, and long-term target vessel failure (TVF: cardiac death (CD), non-fatal target vessel myocardial infarction (MI) and target vessel revascularisation (TVR)), and a composite of CD and MI (CD/MI). Method Coronary arteries that underwent post-PCI FFR measurement at our centre between 2012 and January 2021 were consecutively included in this registry. Post-PCI QFR was calculated blinded to the post-PCI FFR value. We analysed the influence of LAD vs. (non-LAD) location, gender, age, hypertension, diabetes mellitus, hyperlipidemia, indication (acute (ACS) vs. chronic coronary syndrome), stent diameter, in-stent restenosis (ISR) vs. de novo lesion category, estimated glomerular filtration rate, proximal vs. distal lesions, severe aortic stenosis, atrial fibrillation during the procedure (AF), and prior myocardial infarction in the supply area (prior MI) on post-PCI FFR and QFR. Optimal cut-off was determined by ROC curves. Results A total of 400 coronary arteries were analysed. LAD location (p<0.001), male gender (p=0.0029) and smaller stent diameter (p=0.0073) proved to be predictors of a lower post-PCI FFR. LAD location (p=0.001), ISR (p=0.02), distal location (p=0.0019), AF (p=0.042) and prior MI (p=0.029) were predictors of a lower post-PCI QFR. There was a systematic bias in post-PCI QFR compared to post-PCI FFR (bias 0.0614, 95% CI, 0.053 - 0.069). During a median follow-up of 45 months, 31 CD, 20 MI and 35 TVR occurred. Follow-up was complete in 100%. There was a significant inverse correlation between post-PCI FFR and TVF (p<0.001) as well as between post-PCI QFR and TVF (p=0.045). In-stent restenosis (p=0.014) and prior MI (p=0.002) were also predictors of higher TVF rate. The predictors of CD/MI were lower post-PCI FFR (p<0.001), smaller stent diameter (p=0.03), higher age (p=0.031) and ACS indication (p=0.048), whereas post-PCI QFR was not. The best post-PCI FFR cut-off to predict TVF was 0.87 (p<0.0001). There was no single optimal post-PCI QFR cut-off to predict TVF. Conclusion Post-PCI QFR shows a systematic bias compared to post-PCI FFR. Post-PCI FFR is a significant predictor of TVF as well as CD/MI, whereas post-PCI QFR predicts TVF. No significant correlation between post-PCI QFR and CD/MI could be demonstrated. Our findings underscore the importance of considering multiple clinical parameters in predicting long-term outcomes. The best post-PCI FFR cut-off to predict TVF was 0.87. However, there was no single, universally applicable post-PCI QFR threshold to predict TVF.

Long-term heart failure risk after atrial septal defect closure in elderly

Abstract Background There is concern that atrial septal defect (ASD) closure will unmask underlying diastolic dysfunction or left heart disease in elderly causing heart failure. It is controversial whether fenestrated devices should be used in elderly patients. Purpose To assess the long-term heart failure risk after ASD closure in elderly and risk factors associated with heart failure hospitalization in a single centre. Method From 2003-2023, all elderly patients aged more that 60 years old who had ASD closure performed successfully in this centre were retrospectively studied. Baseline demographics, underlying risk factors and survival without heart failure hospitalization were analyzed. Result From 2003-2023, 73 patients aged more than 60 years old underwent successful ASD closure in our centre. None of these patients had balloon occlusion test for assessment of left atrial pressure. Median age was 66 years old (60-84) at operation and 27 (37.0%) of them were male. Common risk factors included diabetes (n=9, 12.3%), hypertension (n=31, 42.5%) and ischaemic heart disease (n=8, 11%). Thirty-nine (53.4%) patients had pre-existing atrial fibrillation and 17 (23.3%) of them had moderate to severe left sided valvular lesions. Heart failure symptoms were present in 31 (42.5%) of them (Figure 1). During a median follow-up time of 4 years (1-15 years), 80.8% of patients did not experience heart failure hospitalization (Figure 2). Pre-existing atrial fibrillation and left-sided valvular lesions were associated with higher risk of heart failure hospitalization (OR 4.06, 95% CI 1.03-16.06 p=0.036 and OR 4.9, 95% CI 1.41-17.09 p=0.009). Conclusion In a median follow-up time of 4 years, patients aged more than 60 years old had low rate of heart failure hospitalization after ASD closure. Pre-existing atrial fibrillation and left-sided moderate to severe valvular lesions were associated with higher risk of heart failure admission. Further studies should be conducted on ASD closure in these group of patients.Figure 1Figure 2

Heart failure hospitalization reduction and long-term safety with remote pulmonary artery pressure monitoring: results of the CardioMEMS HF System OUS Post-Market Study

Abstract Background Heart failure (HF) is increasing in prevalence and is responsible for frequent hospitalization and readmissions, despite current guideline recommended therapies. Hemodynamic guided HF management using frequently remotely obtained pulmonary artery (PA) pressure information using a permanently implanted PA sensor (CardioMEMSTM HF System, Abbott) consistently reduced HF hospitalizations (HFH) in multiple healthcare settings. The safety and efficacy of the CardioMEMS HF System has been shown previously in several clinical studies, which reported significant reductions in HFH compared to a control (CHAMPION: 33%, 18M; GUIDE-HF: 28%, 1 yr; and MONITOR-HF: 44%, 1 yr) and longitudinally (MEMS-HF: 62%, 1 yr; and CardioMEMS US PAS: 57%, 1 yr) across varying health systems. Purpose The CardioMEMS HF System OUS Post-Market Study (COAST) aimed to evaluate the safety and effectiveness of hemodynamic guided HF management in patients with NYHA Class III HF in varying health systems across Europe and Australia. Methods COAST is a prospective, multi-centre, open-label clinical trial that consented 321 patients at 38 European and Australian centres. The primary endpoint is a combination of safety (freedom from DSRCs and freedom from pressure sensor failure at 2 years after implant) and efficacy endpoints (annualized HFH rate at 1-year vs the HFH rate in the year prior to enrolment). In this analysis we report these primary results of the study. Results Out of 321 consented patients, 17 subjects were withdrawn before implant, while the PA sensor was implanted successfully in 299 out of 304 patients who underwent the procedure (98.3% success rate). Seventy-three percent (73%) of the patients were male, the mean age was 68.4±11.7 years with ischemic cardiomyopathy in 45.4%. At baseline, all patients had NYHA Class III symptoms and an average EQ-5D-5L VAS score of 60.0±21.6. After 2 years follow-up there was 100% freedom from DSRCs and 99.7% freedom from pressure sensor failure. The annualized HFH rate after 1 year decreased by 69%, from 1.586 (pre-implant) to 0.488 (post-implant) (p<0.0001). The patient’s quality of life (EQ-5D-5L VAS) increased 8.1 units (68.2 ± 20.1, p=0.0008). Conclusion The COAST Study demonstrated that hemodynamic-guided remote HF management using PA pressure information is both safe and effective, with consistent implant safety and low risk for long-term sensor failure. At 1 year post implant, HFH were significantly reduced and quality of life improved. These results are also consistent with long-term clinical follow-up (2 yr) in other geographies with no late-stage adverse events or adverse events from sensor implant, demonstrating the generalizability of this type of hemodynamic-guided HF management.

Left ventricular dysfunction, pulmonary congestion, or both and cardiovascular risk after acute myocardial infarction

Abstract Background Patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD), pulmonary congestion, or both are at increased risk for adverse cardiovascular events, including long-term heart failure. The EMPACT-MI trial studied the efficacy and safety of early initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) in this population. We set out to evaluate the contemporary real-world risk associated with AMI presenting with LVSD and/or congestion and the projected impact of implementing early SGLT2i post-MI across the spectrum of risk. Purpose To evaluate the independent risk of presenting with LVSD, congestion, or both in patients with AMI. We will further explore the potential impact of the implementation of early initiation of SGLT2i in real-world clinical practice. Methods We conducted a retrospective population-based cohort study in Ontario, Canada, analyzing AMI hospitalizations from April 2009 to March 2022, emulating the EMPACT-MI trial cohort. Patients that survived to hospital discharge were stratified by baseline presentation with LVSD (defined as LVEF<50%), signs or symptoms of congestion or both and compared with a referent group without either risk factor (none). Exclusion criteria were previously established heart failure, prior SGLT2i use, eGFR < 20 ml/min/1.73m2 or chronic dialysis. The primary outcome was a composite of HF hospitalization or all-cause mortality at 30 days and 1 year. We used a multivariable logistic regression model to report an odds ratio (OR) and 95% confidence intervals (CI) adjusted for clinical risk factors. Results Among 36,837 AMI patients, 3% presented with congestion, 55% with LVSD, 10% with both, and 32% with none. Age/sex-adjusted 30-day event rates for the primary endpoint were 30%, 22%, 57%, and 7%, respectively. The corresponding adjusted ORs were 3.34 (95% CI: 2.05-5.46) for congestion, 3.58 (95% CI: 2.72-4.71) for LVSD, and 7.01 (95% CI: 5.09-9.65) for both, versus the reference group (none) (Figure 1). At year 1, a similar pattern of risk was observed (Figure 2). Based on the results of the EMPACT-MI trial being reported at the ACC conference in April 2024, relative and absolute risk differences in outcomes with implementation of early initiation of SGLT2i post-MI in real-world clinical practice across the spectrum of presentation will be reported. Conclusion Patients presenting with pulmonary congestion and/or LVSD remain at high risk of adverse cardiovascular events following AMI. This high-risk group represents an unmet need with a potential impact for improvement with novel interventions such as SGLT2i.

Systematic review and meta-analysis on the effects of physical activity-based interventions on frailty status and clinical outcomes in adults with long-term cardiac conditions

Abstract Introduction Frailty is common in patients with long-term cardiac conditions and is associated with poor clinical outcomes, but limited treatment options are available. Previous studies investigating interventions for frailty have shown positive results with physical activity interventions, however, these studies were largely based on general elderly populations. Aim To assess the impact of physical activity-based interventions on frailty and clinical outcomes in frail patients with long-term cardiac conditions. Methods A systematic review and meta-analysis was conducted based on the PRISMA guideline, using Medline, Embase, CENTRAL, PEDro, CINAHL electronic databases for articles published between 2000 and 2023. Studies which recruited adults >18 years with long-term cardiac conditions (including angina, acute coronary syndrome (ACS), valve disease, heart failure (HF), atrial fibrillation, cardiac surgery and congenital heart disease) who underwent physical activity-based interventions were included. The primary outcome was change in frailty (measured using a validated tool) post intervention. We also assessed the effect of interventions on mortality and hospitalisation. Results We screened 2697 records and reviewed 91 full-text articles; 12 studies (14 articles) were included, involving 1394 patients. Median age of participants ranged from 64 to 82 years. Five studies recruited participants with HF, 3 evaluated participants post transaortic valve implantation, 3 recruited cardiac surgical patients and 1 study evaluated participants post ACS. Physical activity-based interventions were multi-domain, including a mixture of aerobic, strength, balance, endurance and respiratory muscle training; the majority (N=10) had individualised exercise prescription. Meta-analysis of 8 randomised controlled trials (RCTs) showed statistically significant improvement in frailty associated with physical activity-based interventions compared to controls [pooled standardised mean difference (95% CI) = -0.34 (-0.59 to -0.08), p = 0.01, I2 = 48%]. Seven RCTs evaluated change in frailty by short physical performance battery (SPPB). Meta-analysis of these studies showed a statistically significant improvement in SPPB associated with physical activity-based interventions compared to controls [pooled mean difference (95% CI) = 0.83 (0.31-1.34), p = 0.002, I2 = 49%]. (Figure) The magnitude of improvement in SPPB exceeded the minimally clinically significant improvement of 0.5. Three studies evaluated the effect of physical activity-based intervention on clinical outcomes, all of which showed neutral effect on mortality and hospitalisation. Conclusion Physical activity-based interventions in patients with frailty and long-term cardiac conditions were associated with significant improvement in frailty status, with neutral effect on mortality and hospitalisation. Figure: Meta-analysis of 7 RCTs assessing effect of physical activity-based interventions on SPPB

Long-term outcomes after transcatheter aortic valve implantation: derivation and validation of the long-TAVI prediction model

Abstract Background Identification of high-risk individuals after transcatheter aortic valve implantation (TAVI) is essential to personalized care. Established risk models require a plethora of variables, fail to account for biomarker dynamics and imaging parameters, mostly focus on the short term, and offer limited predictive performance. Purpose We aimed to develop an easily applicable prediction model for long-term mortality or heart failure (HF) admission following TAVI. Methods Patients undergoing TAVI at a high-volume university centre in the United Kingdom (n = 990) were recruited into a prospective cohort study. Enrolled patients were divided into a development cohort (07/2007 – 12/2016) and a validation cohort (01/2017 – 11/2018) and followed for up to 15.1 (median 5.3, interquartile range [IQR] 2.8 – 7.4) years. Patient characteristics along with pre- and post-procedural imaging results and brain natriuretic peptide (BNP) levels before the procedure and at 3 months were recorded. A clinical risk score for long-term mortality and HF admission (i.e., Long-TAVI risk score) was derived using Cox regression and evaluated using time-dependent area under the receiver operating characteristics curve (AUC). Results Age at presentation was 79.8 (standard deviation [SD] 8.9) years, 961 (99.0%) patients had signs of heart failure, left ventricular ejection fraction was 52 (SD 11.2), and pre-TAVI BNP levels were 298.0 (interquartile range [IQR] 159.0 – 571.5) pg/mL. High BNP levels at presentation (higher vs. lower than 400 pg/mL: HR 1.50, 95% CI 1.17 – 1.92, P < 0.001) and dynamic changes in BNP with the first 3 months (low/high vs. low/low: 2.61, 95% CI 1.17 – 5.86, P = 0.020; high/high vs. low/low: 2.41, 95% CI 1.26 – 4.64, P = 0.008) were independent predictors mortality or HF admission. The simple 8-item Long-TAVI score accounts for periprocedural BNP dynamics and shows good discrimination (AUC 0.76, 95% CI 0.72 – 0.79) and calibration in the development cohort performing similarly well in the external validation cohort (AUC 0.70, 95% CI 0.63 – 0.77). Long-TAVI significantly outperformed the logistic EURO score (AUC 0.56, 95% CI 0.52 – 0.59, P < 0.001). Conclusion Both pre-TAVI BNP levels and periprocedural BNP trajectories are independently associated with long-term outcomes after TAVI. Accounting for clinical characteristics, imaging parameters, and circulating BNP levels, the newly developed Long-TAVI risk score achieves high performance and provides the first prediction model for long-term mortality or HF admission. Long-TAVI represents a novel tool for personalized risk assessment in patients undergoing TAVI.Correlation at baseline A) and FUP B)Score performance A) and risk groups B)

Postoperative atrial fibrillation following noncardiac surgery is associated with long-term heart failure: insights from a nationwide cohort

Abstract Background Atrial fibrillation (AF) is associated with the development of heart failure (HF). Whether postoperative AF (POAF) also confers a greater risk of HF is unclear. Purpose To investigate the long-term rate of incident HF in patients developing new-onset POAF after noncardiac surgery relative to patients who did not develop POAF after noncardiac surgery. Methods In this cohort study, the Danish nationwide registries were used to identify all patients aged ≥30 years who developed POAF following noncardiac, nonobstetric surgery from 1996 to 2020. These patients were matched in a 1:3 ratio by age, sex, type of surgery, selected comorbidities, and year of inclusion with patients without POAF after noncardiac surgery. The primary outcome was incident HF. Secondary outcomes were HF hospitalization and all-cause mortality. Results A total of 2,270 patients with POAF were matched with 6,810 patients without POAF (median age: 75 years [25th-75th percentile: 67-82 years]; 53.5% females). The median follow-up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long-term rate of incident HF (2.6 versus 1.2 events per 100 person-years; HR 2.39 [95% CI 2.06-2.78]]), HF hospitalization (2.2 versus 1.0 events per 100 person-years; HR 2.33 [95% CI 1.97-2.74]), and all-cause mortality (9.8 versus 7.4 events per 100-person-years; HR 1.55 [95% CI 1.45-1.66]) (Figure 1). Conclusions Patients with new-onset postoperative atrial fibrillation following noncardiac surgery had a higher associated long-term rate of incident heart failure compared to those without postoperative atrial fibrillation following noncardiac surgery. These findings highlight the importance of increased awareness among physicians of the risk of adverse outcomes, including heart failure, in patients with postoperative atrial fibrillation after noncardiac surgery. Closer postoperative follow-up and monitoring, as well as aggressive treatment of cardiovascular risk factors, may be warranted to reduce the risk of adverse outcomes in these patients.

A larger reduction of spatial mean QRS-T angle during cardiac resynchronisation therapy is associated with a lower risk of mortality and heart failure hospitalisation

Abstract Background Predicting clinical outcome in heart failure patients undergoing cardiac resynchronization therapy (CRT) remains challenging, necessitating improved risk stratification for CRT recipients. Previous studies have shown an association between large spatial peak and mean QRS-T angles and cardiovascular disease. Little is known, however, about their relation to clinical outcome following CRT. Purpose To investigate the association between spatial peak and mean QRS-T angles and long-term clinical outcome following CRT initiation. Methods All patients with native LBBB receiving CRT at a large-volume tertiary care center between 2015 and 2020 were retrospectively evaluated. Spatial peak and mean QRS-T angles were derived from digital pre- and post-CRT 12-lead ECGs that were processed using Glasgow algorithm and Kors’ regression transformation. The QRS-T angles and their change after CRT were analyzed in relation to the primary composite endpoint of heart failure hospitalisation or all-cause mortality using Cox regression analysis adjusted for clinical covariates (age, gender, CRT-P or CRT-D, secondary ICD indication, ischemic etiology, NYHA class, LVEF, diabetes, atrial fibrillation, baseline QRS duration, NT-proBNP, and eGFR). Results The study group comprised 250 patients (a median age [Q1–Q3] of 72.2 years [64.5–76.3]; 22% female; 58% New York Heart Association (NYHA) class III-IV; LVEF 27% [22–30]) who were followed over a median follow-up time of 4.5 years [3.2–5.8] after CRT implantation. The median post-CRT spatial peak and mean QRS-angles were 142° [116–160] and 152° [127–166], and the median angle was decreased by 16° [-0.6–41] and 14° [-0.4–38], respectively. Both a larger post-CRT mean QRS-T angle (HR 1.20, 95%CI 1.08-1.33, p=<.001) and peak QRS-T angle (HR 1.08, 95%CI 1.01-1.17, p=0.046) were associated with the primary endpoint. A larger reduction of mean QRS-T angle, but not peak QRS-T angle, was associated with a risk reduction (HR 0.87, 95%CI 0.79-0.95, p<0.003). In Kaplan-Meier analysis, patients with a post-CRT mean QRS-T angle above median had a higher risk of reaching the endpoint (log-rank p=0.002, Figure 1). Conclusion Our results show that a larger magnitude of the post-CRT spatial peak and mean QRS-T angles, and a larger reduction of the latter, are associated with long-term heart failure hospitalisation and death. These findings suggest that spatial QRS-T angle may have a potential role in refined risk stratification of CRT patients.Figure 1.K-M curve spatial mean QRS-T

Competing and Noncompeting Risk Models for Predicting Kidney Allograft Failure.

Prognostic models are becoming increasingly relevant in clinical trials as potential surrogate endpoints, and for patient management as clinical decision support tools. However, the impact of competing risks on model performance remains poorly investigated. We aimed to carefully assess the performance of competing risk and noncompeting risk models in the context of kidney transplantation, where allograft failure and death with a functioning graft are two competing outcomes. We included 11,046 kidney transplant recipients enrolled in 10 countries. We developed prediction models for long-term kidney graft failure prediction, without accounting (i.e., censoring) and accounting for the competing risk of death with a functioning graft, using Cox, Fine-Gray, and cause-specific Cox regression models. To this aim, we followed a detailed and transparent analytical framework for competing and noncompeting risk modelling, and carefully assessed the models' development, stability, discrimination, calibration, overall fit, clinical utility, and generalizability in external validation cohorts and subpopulations. More than 15 metrics were used to provide an exhaustive assessment of model performance. Among 11,046 recipients in the derivation and validation cohorts, 1,497 (14%) lost their graft and 1,003 (9%) died with a functioning graft after a median follow-up post-risk evaluation of 4.7 years (IQR 2.7-7.0). The cumulative incidence of graft loss was similarly estimated by Kaplan-Meier and Aalen-Johansen methods (17% versus 16% in the derivation cohort). Cox and competing risk models showed similar and stable risk estimates for predicting long-term graft failure (average mean absolute prediction error of 0.0140, 0.0138 and 0.0135 for Cox, Fine-Gray, and cause-specific Cox models, respectively). Discrimination and overall fit were comparable in the validation cohorts, with concordance index ranging from 0.76 to 0.87. Across various subpopulations and clinical scenarios, the models performed well and similarly, although in some high-risk groups (such as donors over 65 years old), the findings suggest a trend towards moderately improved calibration when using a competing risk approach. Competing and noncompeting risk models performed similarly in predicting long-term kidney graft failure.

TRPC5 controls the adrenaline-mediated counter regulation of hypoglycemia.

Hypoglycemia triggers autonomic and endocrine counter-regulatory responses to restore glucose homeostasis, a response that is impaired in patients with diabetes and its long-term complication hypoglycemia-associated autonomic failure (HAAF). We show that insulin-evoked hypoglycemia is severely aggravated in mice lacking the cation channel proteins TRPC1, TRPC4, TRPC5, and TRPC6, which cannot be explained by alterations in glucagon or glucocorticoid action. By using various TRPC compound knockout mouse lines, we pinpointed the failure in sympathetic counter-regulation to the lack of the TRPC5 channel subtype in adrenal chromaffin cells, which prevents proper adrenaline rise in blood plasma. Using electrophysiological analyses, we delineate a previously unknown signaling pathway in which stimulation of PAC1 or muscarinic receptors activates TRPC5 channels in a phospholipase-C-dependent manner to induce sustained adrenaline secretion as a crucial step in the sympathetic counter response to insulin-induced hypoglycemia. By comparing metabolites in the plasma, we identified reduced taurine levels after hypoglycemia induction as a commonality in TRPC5-deficient mice and HAAF patients.

Association between Respiratory Virus Infection and Development of De Novo Donor-Specific Antibody in Lung Transplant Recipients.

Chronic lung allograft dysfunction (CLAD) is the most common cause of long-term lung allograft failure. Several factors, including respiratory virus infection (RVI), have been associated with CLAD development, but the underlying mechanisms of these associations are not well understood. We hypothesize that RVI in lung transplant recipients elicits the development of donor-specific antibodies (DSAs), thus providing a mechanistic link between RVI and CLAD development. To test this hypothesis, we retrospectively evaluated for the presence of HLA antibodies in a cohort of lung transplant recipients with symptomatic RVI within the first four months post-transplant using sera at two time points (at/directly after the transplant and following RVI) and time-matched controls without RVI (post-transplant). We found a trend toward the development of de novo DSAs in those with symptomatic RVI versus controls [6/21 (29%) vs. 1/21 (5%), respectively, p = 0.09]. No cases or controls had DSA at baseline. We also found increased rates of CLAD and death among those who developed class II DSA versus those who did not (CLAD: 5/7 (71.4%) vs. 19/34 (54.3%), death: 5/7 (71.4%) vs. 17/35 (48.6%)). Prospective studies evaluating the temporal development of DSA after RVI in lung transplant patients and the subsequent outcomes are warranted.

Delta QRS and outcomes post CRT in the Resynchronization-Defibrillation for Ambulatory Heart Failure Trial

BackgroundFor patients with left ventricular systolic dysfunction and prolonged QRS duration, cardiac resynchronization therapy (CRT) can improve cardiac electromechanical synchrony and prevent adverse clinical outcomes. ObjectiveThis study sought to investigate the role of delta QRS duration (ΔQRSd) in predicting clinical response to CRT. MethodsThe RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study randomized 1798 patients to CRT with defibrillator or implantable cardioverter-defibrillator alone. Those who received CRT and had electrocardiograms available at baseline and after CRT implantation were included in this analysis. ΔQRSd was calculated as the absolute difference between QRS duration at baseline and with CRT pacing. The primary outcome was the composite of death and heart failure hospitalization. ResultsThere were 813 patients included in this analysis. The median age was 67 years, and 125 patients (15.2%) were female. The median ΔQRSd was −2 ms (−20 to 18 ms), and 447 (55%) patients had a ΔQRSd ≤0 after implantation. ΔQRSd was an independent predictor of the composite outcome for patients with CRT (hazard ratio, 1.012; 95% confidence interval, 1.008–1.017). CRT recipients with ΔQRSd >0 had higher rates of the composite outcome than patients randomized to implantable cardioverter-defibrillator alone. ConclusionFor patients receiving CRT for heart failure with left ventricular systolic dysfunction and QRS prolongation, ΔQRSd was an independent predictor of long-term mortality and heart failure hospitalization.

Populations particulières : impact de l’état général et des principales comorbidités et de leurs traitements sur la prise en charge thérapeutique locale des patients présentant un Cancer Bronchique Non à Petites Cellules

Numerous factors, whether linked to cancer or to comorbidities, can affect the Performance Status (PS). PS remains a major independent prognostic factor in lung cancer despite the heterogeneity of cancer patients with poor PS. Lung cancer occurs mainly at an advanced age and is linked in most of the cases to smoking, which can also lead to long-term organ failure. Comorbidities and PS should then be considered to determine the most suited local treatment. The aim of this review is to highlight the impact of PS and certain comorbidities (coronaropathy, cirrhosis, chronic kidney disease and interstitial lung disease) on the management and treatment of localized lung cancer.1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

TCT-219 Comparative Analysis of Post-PCI Fractional Flow Reserve and Quantitative Flow Ratio in Predicting Long-term Target Vessel Failure and Hard Endpoints

TCT-219 Comparative Analysis of Post-PCI Fractional Flow Reserve and Quantitative Flow Ratio in Predicting Long-term Target Vessel Failure and Hard Endpoints

Outcomes and failure patterns after chemoradiotherapy for locally advanced rectal cancer with positive lateral pelvic lymph nodes: a propensity score-matched analysis

PurposeThis study aimed to use propensity score matching (PSM) to explore the long-term outcomes and failure patterns in locally advanced rectal cancer (LARC) patients with positive versus negative lateral pelvic lymph node (LPLN).Materials and methodsPatients with LARC were retrospectively divided into LPLN-positive and LPLN-negative groups. Clinical characteristics were compared between the groups using the chi-square test. PSM was applied to balance these differences. Progression-free survival (PFS) and overall survival (OS), and local–regional recurrence (LRR) and distant metastasis (DM) rates were compared between the groups using the Kaplan–Meier method and log-rank tests.ResultsA total of 651 LARC patients were included, 160 (24.6%) of whom had positive LPLN and 491 (75.4%) had negative LPLN. Before PSM, the LPLN-positive group had higher rates of lower location (53.1% vs. 43.0%, P = 0.025), T4 stage (37.5% vs. 23.2%, P = 0.002), mesorectal fascia (MRF)-positive (53.9% vs. 35.4%, P < 0.001) and extramural venous invasion (EMVI)-positive (51.2% vs. 27.2%, P < 0.001) disease than the LPLN-negative group. After PSM, there were 114 patients for each group along with the balanced clinical factors, and both groups had comparable surgery, pathologic complete response (pCR), and ypN stage rates. The median follow-up was 45.9 months, 3-year OS (88.3% vs. 92.1%, P = 0.276) and LRR (5.7% vs. 2.8%, P = 0.172) rates were comparable between LPLN-positive and LPLN-negative groups. Meanwhile, despite no statistical difference, 3-year PFS (78.8% vs. 85.9%, P = 0.065) and DM (20.4% vs. 13.3%, P = 0.061) rates slightly differed between the groups. 45 patients were diagnosed with DM, 11 (39.3%) LPLN-positive and 3 (17.6%) LPLN-negative patients were diagnosed with oligometastases (P = 0.109).ConclusionsOur study indicates that for LPLN-positive patients, there is a tendency of worse PFS and DM than LPLN-negative patients, and for this group patients, large samples are needed to further confirm our conclusion.

Late Survival Benefits of Concomitant Surgical Ablation for Atrial Fibrillation During Cardiac Surgery; A Systematic Review and Meta-Analysis

Long-term survival benefits following surgical ablation for atrial fibrillation (AF) during cardiac surgery were not confirmed in previous randomized controlled trials or meta-analyses. This study aimed to investigate the long-term efficacy of surgical ablation in patients with AF. MEDLINE, EMBASE, and CENTRAL were searched to identify studies comparing concomitant surgical AF ablation with no surgical ablation during cardiac surgery. The primary outcome was long-term all-cause mortality. Secondary outcomes were stroke, heart failure rehospitalization, major bleeding, freedom from atrial fibrillation, and permanent pacemaker implantation during follow-up. To minimize confounding, only adjusted outcomes were used from observational studies. A total of 38 studies met the inclusion criteria. Of those, nine RCTs and 15 observational studies with 41,678 patients (surgical ablation, n = 19,125; no surgical ablation, n = 22,553) were analyzed for all-cause mortality, with a weighted median follow-up of 62.0 months. Surgical ablation was associated with decreased risks of long-term mortality (hazard ratio (HR): 0.78; 95% confidence interval (CI): 0.71 to 0.84), stroke (HR: 0.60; 95% CI: 0.48 to 0.76), heart failure rehospitalization (HR: 0.92; 95% CI: 0.87 to 0.96), and more freedom from AF during follow-up (relative risk: 1.93; 95% CI: 1.50 to 2.49), whereas surgical ablation was associated with a higher risk of permanent pacemaker implantation during follow-up (HR: 1.35; 95% CI: 1.03 to 1.77). There was no significant difference in major bleeding during follow-up between the two groups. In patients with AF undergoing cardiac surgery, surgical ablation was associated with decreased risks of long-term mortality, stroke, and heart failure rehospitalization than patients with untreated AF. Given that the survival benefits were predominantly observed in observational studies, further randomized trials are necessary to confirm these findings.

Arthroscopic subscapularis augmentation of the classic Bankart repair leads to satisfactory clinical and functional mid-term outcomes in patients with recurrent anterior shoulder instability and less than a subcritical glenoid bone loss.

The long-term failure rate of the arthroscopic Bankart repair may reach unacceptable values, raising the need to augment this classic procedure. Arthroscopic subscapularis augmentation is the tenodesis of the upper part of the subscapularis tendon to the anterior glenoid rim. The aim of the study was to evaluate the mid-term clinical and functional outcomes of patients operated with arthroscopic subscapularis augmentation of the classic Bankart repair due to recurrent anterior shoulder instability. This is a retrospective single-centre case series study with prospectively collected data. All patients suffered from recurrent anterior shoulder instability and had glenoid bone loss less than 13.5% of the inferior glenoid diameter (subcritical glenoid bone loss). Patients with greater anterior glenoid bone defect, engaging Hill-Sachs lesions, multidirectional instability or subscapularis insufficiency were excluded. Postoperatively, all patients were evaluated for recurrence and apprehension. The patient's shoulder range of motion and functional scores were recorded. The final study cohort included 34 patients with a mean age of 29.3 ± 10.2 years. The mean follow-up period was 42.4 ± 10.7 months (range, 24-62 months). Two out of 34 patients (5.8%) experienced a re-dislocation postoperatively, while one additional patient had a subjective feeling of apprehension. External rotation at the last follow-up was lower compared to preoperative values or the healthy side, but only one patient had restrictions in his sporting activities. The functional scores were significantly increased compared to the preoperative values. Twenty-two out of 26 patients (84.6%) returned to the same level of sporting activities, and 30/34 patients (88.2%) were highly satisfied with the results. Arthroscopic subscapularis augmentation of the classic Bankart repair reduces the dislocation recurrence rate and leads to satisfactory clinical and functional mid-term outcomes in patients with recurrent anterior shoulder instability and less than a subcritical glenoid bone loss. Level IV.

Unveiling the correlation between in vivo endodontic reciprocate instrumentation and crack formation

IntroductionDentinal microcracks have been supposedly associated with unrestorable vertical root fractures and consequently long-term treatment failure. This study aimed to investigate whether in vivo root canal instrumentation in mandibular incisors with vital pulps causes dentinal microcracks using two different irrigating solutions. MethodsFive patients with four vital mandibular incisors indicated for extraction were included. In vivo root canal preparation was performed using Reciproc R40 (tip #40 and taper 0.06). From these, two teeth were randomly assigned for root canal instrumentation irrigated with 5.25 % sodium hypochlorite irrigation (n = 10) or 2 % chlorhexidine gel with saline solution irrigation (n = 10). In sequence, all teeth were carefully extracted, stored in saline solution until microtomography (µCT) scan. Images were reconstructed and assessed for the presence or absence of dentinal microcracks where microcracks originating from the root canal lumen would be considered. All reconstructed samples were analysed dynamically and rendered in videos through the entire extension of the teeth, evaluating the axial cuts considering each third separately from the apex to the enamel-dentinal junction. Teeth were analysed using the DataViewer software at 100 % magnification without filters by three examiners blinded to the condition allocation. ResultsNo complete dentinal microcracks were observed after root canal instrumentation of mandibular incisors with vital pulps using Reciproc R40 regardless the irrigating solutions, 5.25 % sodium hypochlorite or 2 % chlorhexidine gel. ConclusionsIn vivo root canal instrumentation of mandibular incisors with vital pulps and bone/periodontal insertion does not cause dentinal microcracks and the irrigating solutions tested did not influence this occurrence. Microcrack evaluation must be performed in vivo conditions of dental tissue moist and periodontal support to avoid dryness dentinal alterations after extraction provoking false positive results. Clinical relevanceReciprocating instrumentation performed in vivo is safe and do not induce dentinal microcracks in mandibular incisors.

Long-term outcomes of 1,989 immediate implant-based breast reconstructions: an analysis of risk factors for failure and revision surgery.

Nipple- or skin-sparing mastectomy and immediate implant-based breast reconstruction (IBR) is potentially associated with long-term unfavorable outcomes such as revision surgery and reconstruction failure. This large patient cohort study aimed to provide long-term data on the incidence of these outcomes and identify predictive risk factors. Between 2012 and 2019 1,989 mastectomies with IBR were performed in 1,512 women in our institute. A direct-to-implant (DTI) method was used in 93% and a two-staged method with tissue-expander in 7%. Logistic regression analysis was used to identify patient- and treatment-related risk factors associated with revision surgery or reconstructive failure. Mean follow-up was 62.2 months. IBR failed in 6.7% of all breasts, thus a breast was present in 93.3%. Age older than 44 years old yielded a 2.6- and radiotherapy a 1.7-fold increased risk for reconstruction failure. Revision surgery was performed in 60% of all breasts. Mean number of revisions of all IBRs is 1.2 (range, 0-8; SD 1.37). Factors associated with significant higher rates of revision surgeries were age>44 years (OR=1.23), smoking (OR=1.53), specimen weight>492 grams (OR=1.39), implant volume>422 grams (OR=1.95) and radiotherapy (OR=1.51). Nipple preservation was protective for both outcomes (OR=0.71 and OR=0.42, respectively). DTI did not require any surgical revision in 43%. Despite the necessity of revision surgery in the majority of IBRs, nearly half of the breasts did not require any revision surgery, and long-term reconstruction failure rates are extremely low. Therefore, IBR should be offered to all eligible women undergoing mastectomy while understanding the risks.