Combined Endpoint Research Articles

Tremelimumab plus durvalumab prior to chemoradiotherapy in unresectable, locally advanced non-small cell lung cancer: the Induction trial.

The phase I Induction trial (NCT04287894) assessed the feasibility and safety of induction immunotherapy (IIT) prior to concurrent chemoradiotherapy (cCRT) in patients with locally advanced non-small cell lung cancer (NSCLC). Patients with unresectable stage II/III NSCLC were eligible for inclusion. Patients received either one cycle of tremelimumab (75mg) with two cycles of durvalumab (1500mg) in cohort I, one cycle of tremelimumab (300mg) with two cycles of durvalumab in cohort II or one cycle of tremelimumab (300mg) with one cycle of durvalumab in cohort III. After IIT, a comprehensive radiological and pathological restaging was performed followed by cCRT. The combined primary endpoint was feasibility and safety of IIT-cCRT. Fifteen of seventeen included patients were treated per-protocol. IIT-cCRT was completed in 13/15 of the patients within the predefined feasibility criteria. Grade ≥3 immune-related adverse events (irAEs) occurred in 7/15 patients, of which 6 were treated in the high-dose tremelimumab cohorts, thereby violating the safety criteria in cohorts II and III. The low-dose tremelimumab cohort (I) complied with safety criteria. Eleven patients had multilevel N2 or N3 disease at baseline, eight of these patients were downstaged to either N0/1 or single level N2 after IIT. Multiparametric MRI accurately identified nodal downstaging in 7/7 patients. Induction with high-dose tremelimumab plus durvalumab prior to cCRT in unresectable locally advanced NSCLC was associated with unacceptable toxicity, although ITT resulted in clinically relevant nodal downstaging in 8/11 of patients with baseline multilevel N2 or N3 disease. Multiparametric MRI showed potential evaluating treatment response.

Predictive value of CT-based and AI-reconstructed 3D-TAPSE in patients undergoing transcatheter tricuspid valve repair

BackgroundThe tricuspid annular plane systolic excursion (TAPSE) assessed by echocardiography has failed in predicting outcomes in patients with severe tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI). Considering the complex shape of the tricuspid annulus and right ventricle, as well as the difficult echocardiographic image acquisition of the right heart, cardiac computed tomography (CT) might be superior for the analysis of the annular excursion. Thus, this study aimed to analyze whether CT-captured TAPSE provides additional value in predicting outcomes after TTVI.Methods and resultsFor TTVI procedure planning, 75 patients (mean age, 77 ± 8 years; 61% female) with severe TR underwent full cardiac cycle CT. Septal, lateral, anterior, and posterior TAPSE, as well as TAPSE- volume, were analyzed. Indexed anterior and posterior (iTAPSE) and TAPSE volume were reduced in patients with right ventricular ejection fraction <45%. At 1 year after TTVI (mean follow-up, 193 ± 146days), the combined endpoint of death and rehospitalization occurred in significantly fewer patients with posterior iTAPSE >4.5 mm/m2 (17.2% vs. 63.6%; HR 0.225, CI 0.087–0.581; P < 0.001) and in patients with iTAPSE volume >9 ml/m2 (16.4% vs. 57.1%; HR: 0.269 CI 0.105–0.686; P = 0.003). Echocardiographic TAPSE correlated best with lateral CT-based TAPSE, although both failed in predicting outcomes after TTVI. In multivariate Cox regression, posterior iTAPSE was found to be a significant predictor of outcome 1 year after TTVI.ConclusionsPosterior iTAPSE is an independent predictor of cardiovascular outcomes among patients undergoing TTVI. Furthermore, CT-measured TAPSE has incremental value and refines risk stratification for clinical outcomes in patients undergoing TTVI.

Prognostic value of left atrioventricular coupling index in heart failure.

To investigate the distribution of left atrioventricular coupling index (LACI) among patients with heart failure and left ventricular ejection fraction (LVEF)<50% and to explore its association with the combined endpoint of all-cause death or HF hospitalization at long term follow-up. Patients with HF and LVEF<50% undergoing cardiac magnetic resonance (CMR) were evaluated. Patients with atrial fibrillation or flutter were excluded. LACI was measured as the ratio between the left atrial (LA) and the LV end-diastolic volumes. Patient population was divided according to LACI tertiles and followed-up. Total of 478 patients (mean age 62±12 years, 78% male) were included. The median value of LACI was 27.1% (interquartile range 19.9-34.5). Patients within the worst LACI tertile (≥30.9%) showed smaller LV volumes and larger LA volumes as compared to patients in the first or second tertile (LACI 6.2-22.2 and LACI 22.3-30.9; respectively). LACI was significantly associated with the combined endpoint (hazard ratio [HR] 1.87, p=0.01). After adjusting for sex, age, ischemic HF aetiology, LVEF, LA reservoir strain, diabetes mellitus, LV scar, mitral regurgitation and LVEDVi, LACI remained significantly associated with the combined endpoint (HR 1.77, p=0.02). Patients with highest LACI values had worse outcomes compared to patients in first and second tertiles (HR 1.69, p=0.02 and HR 1.77, p=0.02; respectively). In patients with HF and LVEF <50%, LACI is independently associated with adverse events. Patients with most impaired left atrioventricular coupling have the worst clinical outcomes.

Prognostic scores in patients with severe tricuspid regurgitation: An external validation study.

Four scores have been published in 2022 for assessing mortality risk of patients with tricuspid regurgitation (TR): the TRI-SCORE, those reported by Hochstadt and Wang and the TRIO score. Our objective was to perform an external validation of available scores for predicting mortality and the combined endpoint of mortality and heart failure (HF) admission, in an independent cohort of patients with severe TR and to compare their discriminative ability. Discriminative ability of the scores for predicting events was assessed by means of receiver operating characteristics (ROC) curves. The validation cohort retrospectively included 614 consecutive patients (69 ± 13 years, 72% women) with severe TR studied with echocardiography in a tertiary care hospital and followed for up to 14 years (median 5 years, p25-75 2-7 years), with 358 deaths and 620 HF admissions on follow-up. Discriminative abilities for predicting death (C-statistic .72 [95% CI .68-.76] for the TRI-SCORE; .75 [.71-.78] for the Hochstadt score; .72 [.68-.76] for the Wang score; and .74 [.70-.78] for the TRIO score, p < .0005 for all) or the combined endpoint (C-statistic .74 [.70-.78]; .74 [.70-.78], .73 [.69-.77] and .76 [.72-.80], respectively, p < .0005 for all) on follow-up were statistically significant for all of them. Paired comparisons among them for predicting both endpoints were all non-significant. All tested scores showed significant and similar discriminative ability for predicting the combined endpoint of mortality or HF admission in this independent validation study of patients with severe TR.

The Screening Tomosynthesis Trial with Advanced Reader Methods (STREAM): design and rationale of a population-based breast cancer screening trial.

It is uncertain what the effects of introducing digital breast tomosynthesis (DBT) in the Dutch breast cancer screening programme would be on detection, recall, and interval cancers (ICs), while reading times are expected to increase. Therefore, an investigation into the efficiency and cost-effectiveness of DBT screening while optimising reading is required. The Screening Tomosynthesis trial with advanced REAding Methods (STREAM) aims to include 17,275 women (age 50-72 years) eligible for breast cancer screening in the Netherlands for two biennial DBT screening rounds to determine the short-, medium-, and long-term effects and acceptability of DBT screening and identify an optimised strategy for reading DBT. The control group will consist of 86,400 women selected from the database of the Dutch breast cancer screening programme screened with digital mammography. The intervention group will undergo DBT examinations only. Four different reading strategies will be evaluated on a subset of first-round screening exams. These four strategies will also be evaluated combined with replacing one of the two readers with AI predictions. The Microsimulation Screening Analysis (MISCAN)-Breast model will be used to estimate the long-term outcomes of DBT screening assuming the best-performing reading method. The primary outcome measure is the IC and advanced cancer rate at the second round (combined endpoint) in the DBT group compared to the control group. Secondary outcome measures are participation, recall and detection rates, positive predictive value, acceptability, reading method with the best case-based area under the curve and reading time, predicted breast cancer mortality, number of cancers overdiagnosed, and cost-effectiveness. Question The short-, medium-, and long-term effects of digital breast tomosynthesis (DBT)imaging in the Dutch breast cancer screening programme are unknown, but essential to decide about implementation. Findings This protocol paper describes the primary endpoint of the STREAM trial: the combined interval and advanced cancer detection rate at the second DBT round. Clinical relevance The STREAM trial is a prospective, non-randomised, population-based study in the Dutch breast cancer screening programme, that aims to evaluate the effects and acceptability of two rounds of DBT screening to determine if DBT can enhance the programme's outcomes.

Statin therapy in ischemic stroke patients with atrial fibrillation: Efficacy and safety outcomes.

The efficacy and safety of statins for secondary prevention in patients who have experienced a cardioembolic stroke are not well-defined. However, previous observational data reported hyperlipidemia as a risk factor for both ischemic and bleeding complications in patients with AF and previous stroke. Based on these premises, we conducted a sub-analysis of the RAF and RAF-NOAC studies to evaluate the efficacy and safety of statins in secondary prevention in patients with acute ischemic stroke and AF. We combined patient data from the RAF and RAF-NOAC studies, prospective observational studies conducted across Stroke Units in Europe, the United States, and Asia from January 2012 to June 2016. We included consecutive patients with AF who suffered an acute ischemic stroke with a follow-up of 90 days. Our outcomes were the combined endpoint, including stroke, transient ischemic attack, systemic embolism, symptomatic intracerebral hemorrhage, and major extracranial bleeding. Furthermore, both ischemic and hemorrhagic outcomes were evaluated separately. A total of 1742 patients were included (46% male), and 898 (52%) received statins after the index event, of whom 436 (48.6%) were already taking statins before the index event, 462 (51.4%) started treatment after. At multivariable analysis, statin use was statistically associated with age (OR 0.92, 95% CI 0.97-0.99, p = 0.001), male sex (OR 1.35, 95% CI 1.07-1.70, p = 0.013), anticoagulation (OR 2.53, 95% CI 1.90-3.36, p < 0.0001), hyperlipidemia (OR 5.52, 95% CI 4.28-7.12, p < 0.0001), paroxysmal AF (OR 1.40, 95% CI 1.12-1.75, p = 0.003), leukoaraiosis (OR 1.39, 95% CI 1.11-1.75, p = 0.004) and heart failure (OR 0.72, 95% CI 0.53-0.98, p = 0.034). Statin use was not associated with the combined outcome event (OR 0.84, 95% CI 0.58-1.23, p = 0.3) and ischemic outcome event (OR 1.17, 95% CI 0.73-1.88, p = 0.5) while was associated with a lower risk of hemorrhagic outcome event (OR 0.51, 95% CI 0.28-0.91, p = 0.02). Statins protect cerebral arterial vessels (particularly small vessels) from subacute damage due to hypertension, diabetes, and other harmful agents (such as reactive oxygen species, proinflammatory cytokines, etc.) due to their systemic anti-inflammatory and endothelium-protective effects. Our data show that statins seem to protect against global bleeding events in cardioembolic stroke patients; this may be due to the pleiotropic effect of statins. More data are warranted to confirm these findings.

Application of urinary peptide-biomarkers in trauma patients as a predictive tool for prognostic assessment, treatment and intervention timing

Treatment of severely injured patients represents a major challenge, in part due to the unpredictable risk of major adverse events, including death. Preemptive personalized treatment aimed at preventing these events is a crucial objective of patient management; however, the currently available scoring systems provide only moderate guidance. Biomarkers from proteomics/peptidomics studies hold promise for improving the current situation, ultimately enabling precision medicine based on individual molecular profiles. To test the hypothesis that peptide biomarkers could predict patient outcomes in severely injured patients, we initiated a pilot study involving consecutive urine sampling (on days 0, 2, 5, 10, and 14) and subsequent peptidome analysis using capillary electrophoresis coupled to mass spectrometry (CE-MS) of 14 severely injured patients and two additional intensive care unit patients. The urine peptidomes of these patients were compared to those of age- and sex-matched controls. Moreover, previously established urinary peptide-based classifiers, CKD273, AKI204, and Cov50, were applied to the obtained peptidome data, and the association of the classifier’s scores with a combined endpoint (death and/or kidney failure and/or respiratory insufficiency) was investigated. CE-MS peptidome analysis identified 191 significantly altered peptides in severely injured patients. A consistent increase in the abundance of peptides from A1AT, AHSG, and HBA1 was observed, while peptides derived from PIGR and UROM were consistently decreased. Most of the significant peptides (adjusted p < 0.05) were from COL1A1, and most were reduced in abundance. Two of the previously defined and validated peptidomic classifiers, CKD273 and AKI204, showed significant associations with the combined endpoint, which was not observed for the routine scores generally applied in the clinics. This prospective pilot study confirmed the hypothesis that urinary peptides provide information on patient outcomes and may guide personalized interventions in severely injured patients based on individual molecular changes. The results obtained allow the planning of a well-powered prospective trial investigating the value of urinary peptides in this context in more detail.

The Impact of Right Atrial Function on Prognosis and Renal Function in Patients With Tricuspid Regurgitation.

Tricuspid regurgitation (TR) is related to survival, and right atrial (RA) size and function may play a role. This study aimed to assess the impact of RA function measured by strain (RA strain [RAS]) on outcome and end-organ congestion. We enrolled 134 patients (mean age 73 ± 13 years, 62% women) with any TR grade or etiology and a complete echocardiogram, clinical follow-up, and renal function assessment. The primary end point was a combination of overall mortality and right-sided heart failure hospitalization, and the secondary end point was worsening renal function (WRF). After a median follow-up of 23.5 months (interquartile range 12 to 34 months), the combined end point was reached by 31% of patients. Patients with RAS ≤18% showed lower event-free survival (log-rank p <0.001). In the multivariable analysis, RAS ≤18% (HR 3.1, 95% CI 1.1 to 8.8) and pulmonary artery systolic pressure (PASP) (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1 to 1.05) were independent predictors of the primary end point. Patients with RAS ≤18% and PASP >45 mm Hg had the worst outcome (HR 4.3, 95% CI 2 to 9.5). RAS ≤18% (odds ratio 3.22, 95% CI 1.11 to 9.33) and PASP >45 mm Hg (OR 3.2, 95% CI 1.15 to 8.88) were independent predictors of WRF, adjusting for TR severity, left and right ventricular function, age, gender, diabetes, diuretics, atrial fibrillation. The addition of RAS ≤18% had incremental power over PASP and echocardiographic variables of TR severity and right or left ventricular function to predict WRF (p = 0.026). In conclusion, RA function measured by RAS independently predicts mortality and hospitalizations in patients with TR and independently and incrementally predicts WRF over time.

Growth Differentiation Factor-15 IsAssociated With Congestion-Related Anorexia and Weight Loss in AdvancedHeartFailure.

Growth differentiation factor (GDF)-15 is a pleiotropic cytokine that is associated with appetite-suppressing effects and weight loss in patients with malignancy. This study aims to investigate the relationships between GDF-15 levels, anorexia, cachexia, and clinical outcomes in patients with advanced heart failure with reduced ejection fraction (HFrEF). In this observational, retrospective analysis, a total of 344 patients with advanced HFrEF (age 58 ± 10 years, 85% male, 67% NYHA functional class III), underwent clinical and echocardiographic examination, body composition evaluation by skinfolds and dual-energy x-ray absorptiometry, circulating metabolite assessment, Minnesota Living with HeartFailure Questionnaire, and right heart catheterization. The median GDF-15 level was 1,503ng/L (Q1-Q3: 955-2,332ng/L) (reference range:<1,200ng/L). Higher GDF-15 levels were associated with more prevalent anorexia and cachexia. Patients with higher GDF-15 had increased circulating free fatty acids and beta-hydroxybutyrate, lower albumin, cholesterol, and insulin/glucagon ratio, consistent with a catabolic state. Patients with higher GDF-15 had worse congestion and more severe right ventricular dysfunction. In multivariable Cox analysis, elevated GDF-15 was independently associated with risk of the combined endpoint of death, urgent transplantation, or left ventricular assist device implantation, even after adjusting for coexisting anorexia and cachexia (T3 vs T1 HR: 2.31 [95%CI: 1.47-3.66]; P< 0.001). In patients with advanced HFrEF, elevated circulating GDF-15 levels are associated with a higher prevalence of anorexia and cachexia, right ventricular dysfunction, and congestion, as well as an independently increased risk of adverse events. Further studies are warranted to determine whether therapies altering GDF-15 signaling pathways can affect metabolic status and clinical outcomes in advanced HFrEF.

Assessment of results of using three types of vascular access for isolated hepatic chemoperfusion

INTRODUCTION: Uveal melanoma (UM) is an oncological disease, which develops metastases mainly to the liver. One of treatments for this pathology is isolated hepatic chemoperfusion (IHCP). The implementation of this method requires surgical isolation of the liver from the systemic circulation and the use of a heart-lung machine. Due to a small number of observations of this treatment method in the world, the optimal vascular access for its implementation has not been determined so far. AIM: To analyze the in-hospital results of IHCP in patients with UM metastases performed from three different vascular accesses. MATERIALS AND METHODS: Over three years, 38 IHCP procedures were performed of the Kostroma Clinical Oncological Dispensary. Depending on the vessels into which the cannula for perfusion with Melphalan was inserted, patients were divided into 3 groups: group 1 with cava-porto-arterial access (perfusion into the inferior vena cava, portal vein, and common hepatic artery), n = 14; group 2 with cava-arterial access (perfusion into the inferior vena cava and common hepatic artery), n = 21; group 3 with a forced access, n = 3. The study took into account major complications: death, bleeding; and minor complications: tumor lysis syndrome, abscess of the left lobe of the liver, peritonitis, a systole, deep vein thrombosis of the lower limbs, hydrothorax, acute liver failure, anasarca, polyserositis, ischemic cholangiopathy, thrombosis of the common hepatic artery, detachment of the common hepatic artery intima. A combined endpoint was the achievement of at least one of the listed complications. In case of several complications in one patient, they were not summed up and were considered as ‘1’. RESULTS: In the postoperative period, the highest number of bleedings including those requiring revision, was noted in groups 1 and 3. The combined endpoint in the total sample made 42.11% and was lowest in group 2. Fatal outcomes were recorded in 3 cases (2 in group 1 and 1 in group 2), and were caused by increasing liver failure. CONCLUSION: The lowest number of complications IHCP was identified with cava-arterial access. Further continuation of the study is necessary to investigate the immediate and remote outcomes of IHCP.

Examining the Effects of Different Exertion Levels and Reference Standards on the Diagnostic Accuracy of Exercise ECG for Detecting Coronary Artery Disease - A Pilot Study.

Exercise electrocardiogram (ECG) is frequently used for evaluating patients with suspected coronary artery disease (CAD). However, it has been downgraded in international guidelines due to a limited sensitivity and specificity, compared with other non-invasive tests. We hypothesized, that a sufficient exertion going beyond 85% of the age predicted maximal heart rate (APMHR), by considering the achieved level of workload can improve sensitivity and specificity of the exercise ECG. Secondly, the performance of exercise ECG, when evaluated against a functional reference standard has barely been investigated, although an improved diagnostic accuracy has been reported for other non-invasive tests in this case. Therefore, in this pilot study, a total of 147 patients without known CAD who underwent exercise ECG followed by coronary angiography within 90 days were retrospectively evaluated. The combined end point of 85% of APMHR and 75% of the predicted workload showed a slight but not statistically significant benefit over APMHR alone (66.7% vs. 58.1%; p = 0.545). The sensitivity of ST-segment depression was 51.3% for detecting anatomically defined CAD and 62.5% for functionally relevant CAD (p = 0.378). Although the results of this pilot study lack statistical significance, the numeric differences clearly justify further research on this topic.

Guideline-directed medical therapy for heart failure in arrhythmia-induced cardiomyopathy with improved left ventricular ejection fraction.

No study has analyzed the impact of guideline-directed medical therapy in preventing heart failure (HF) relapse in patients with arrhythmia-induced cardiomyopathy (AiCM) following left ventricular ejection fraction (LVEF) improvement. We analyzed data from a single-center cohort of 200 patients admitted for HF, LVEF <50% and cardiac arrhythmia considered by cardiologists to be the precipitating cause of the episode. The primary endpoint was time-to-HF relapse, defined as the composite of readmission for HF, Emergency Department (ED) visit for HF, or significant decline in LVEF. Changes in medication were recorded and a time-varying multivariate Cox regression was performed. After a median follow-up period of 6.14 years, diagnostic confirmation was achieved in 188 out of the initial 200 patients with suspected AiCM. A total of 89 patients (47.3%) met the primary endpoint. RAS inhibitors (adjusted hazard ratio (HR) 0.50 [0.31-0.81]; p = 0.005) and beta-blockers (adjusted HR 0.48 [0.28-0.81]; p = 0.006) were associated with a lower incidence of relapse. Mineralocorticoid receptor antagonists were associated with a significantly lower incidence of ED visits for HF (adjusted HR 0.38 [0.15-0.95]; p = 0.038), but did not achieve statistical significance for the combined primary endpoint. Antiarrhythmic drugs did not show a significant impact on the primary endpoint. Maintaining RAS inhibitors and beta-blockers was associated with a significantly lower incidence of relapse in the setting of AiCM with improved LVEF.

Long-term outcomes of carotid endarterectomy with eversion technique in patients with an open circle of Willis: A multicenter registry study.

Carotid endarterectomy (CEA) is a surgery aimed at removing atherosclerotic plaque from the carotid artery. There are classical and eversion CEA techniques. The eversion technique is the most popular because it does not require the use of implants. Eversion CEA is also associated with a lower risk of restenosis in the late postoperative period. During the surgery, the carotid artery is clamped and blood flow to the brain comes from the contralateral carotid artery and vertebral arteries. However, if the circle of Willis (COW) is not closed, compensatory mechanisms for protecting the brain are reduced, which can lead to the development of an intraoperative stroke. To analysis of in-hospital and long-term CEA outcomes in patients with different types of closed and non-closed COW. This is a multicenter Russian study. In the period from 2010 to 2020. 641 eversion CEA were performed. Depending on the type of structure of the COW, six groups of patients were formed: Type 1 - Closed posterior part (CRS) - in the presence of the posterior communicating (PCOMA) and P1 segment of the posterior cerebral (PCA) arteries; Type 2 - Intermediate type of structure of the posterior part (ISRP) - with hypoplasia of PCOMA or PCA; Type 3 - Open back part (OBP) - in the absence of PCOMA or PCA; Type 4 - Closed anterior part (CFS) - in the presence of the anterior communicating artery (ACOMA) and the A1 segment of the anterior cerebral artery (ACA); Type 5 - Intermediate type of anterior part structure (IFPS) - with ACOMA or ACA hypoplasia; Type 6 - Open Front Section (OFS) - in the absence of ACOMA or ACA. The long-term follow-up period was 107.3 ± 14.6 months. The end points of the study were death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction (MI), ICA thrombosis, hemodynamically significant restenosis of the internal carotid artery, bleeding, and combined endpoint (death + ischemic stroke + TIA + MI).The type of distribution was determined using the Kolmogorov-Smirnov criterion. Group comparisons were performed using the Kruskal-Wallis and Pearson chi-square tests. Differences were assessed as significant at p < .05. According to clinical and demographic characteristics, the majority of patients were male and elderly. In 20% of cases, patients had a history of MI and/or stroke/TIA. Diabetes mellitus was diagnosed in 10%. There were no significant differences between groups in EuroSCOREII. In the long-term postoperative period, the largest number of deaths occurred in groups 5 and 6 (13 (45.1%) and 12 (30.1%)). The majority of strokes were diagnosed in groups 3 (OBP) and 5 (IFPS) (7 (13.5%) and 9 (17.6%)). The highest value of the combined end point (death + stroke/TIA + MI) was obtained in groups 3 (OBP), 5 (IFPS), and 6 (OFS) (23 (44.2%), 26 (50.1%), and 23 (58.9%)). The eversion technique of carotid endarterectomy for carotid artery stenosis is the most preferred. The greatest number of complications of eversion CEA in the hospital and long-term follow-up periods is observed in patients with OBP, IFPS, and OFS. In the presence of an unstable plaque, a temporary shunt can be used, which will exclude the pharmacological increase in blood pressure and the associated risk of embolization.

The Clinical Impact of Mitral Gradient Post Transcatheter Edge-To-Edge Repair: A Systematic Review and Meta-Analysis.

Mitral transcatheter edge-to-edge repair (TEER) is a minimally invasive therapy for severe mitral regurgitation (MR) in patients with high surgical risk. TEER results in a tissue bridge that decreases mitral valve area, potentially leading to elevated mean gradient. The clinical impact of elevated gradient on outcomes is unclear. This systematic review and meta-analysis was based on a comprehensive search of five databases. We included studies that evaluated post mitral TEER gradient on one of the following outcomes: all-cause mortality, combined endpoints, symptoms, hospitalizations, and mitral valve re-intervention. Meta-analysis was conducted using the random-effects model. Out of 6458 citations, 17 studies were included (2017-2024) reporting on 7748 patients. There was significant heterogeneity between studies related to the cutoff used to define elevated gradient, etiology of MR, and outcomes. Elevated mitral gradient post TEER (4, 4.5, 5 mmHg) was associated with worse combined endpoint (HR = 1.35, 95% CI 1.07-1.71; I2 64%), but not all-cause mortality (HR = 1.25, 95% CI 0.97-1.59; I2 45%) or risk of hospitalization. For the combined endpoint, this association was mainly significant in patients who had mitral gradient assessed using discharge echocardiogram (HR = 1.39, 95% CI 1.07-1.81; I2 62%) for all patients and for those with degenerative MR. Despite the heterogeneity between studies, the current analysis suggests that patients with elevated mitral gradient post TEER are at risk of worse clinical outcomes, particularly in patients who had mitral gradient assessed using discharge transthoracic echocardiogram.

Extracorporeal Photopheresis for the prevention of rejection after lung transplantation - a prospective randomized controlled trial.

Lung transplant recipients have the worst long-term outcomes of all solid organs due to acute rejection and chronic lung allograft dysfunction (CLAD). To investigate the efficacy of ECP as a prophylactic treatment to prevent acute cellular rejection (ACR), CMV infections and reduce the risk of CLAD. Single-center prospective randomized controlled trial conducted at Medical University of Vienna between 2018 and 2020. It included 31 COPD recipients per group. Treatment group underwent extracorporeal photopheresis in addition to standard triple-drug immunosuppression protocol after lung transplantation. Control group received standard triple-drug immunosuppressive therapy. The primary outcome was a composite outcome defined as incidence of high-grade ACR, CMV infection or CLAD within 24 months after lung transplantation. In the control group, 19 patients (61.3%) achieved the primary combined endpoint, compared with only 6 patients (19.4%) in the treatment group (p<0.001). Freedom from high-grade ACR was significantly greater in the ECP group (p=0.045). Cumulative A scores were significantly lower in the ECP group than in the control group at 3 months (0.18±0.44 versus 0.56±0.94, p<0.05) and at 12 months (0.25±0.48 versus 1.0±1.45, p=0.002). The rate of infections was lower in the ECP group with 5 cases and 67 cumulative hospital days compared to 22 cases and 309 days in the control group (p=0.002). Freedom from CLAD at three years was significantly greater in the ECP group (p=0.015). Adding ECP to standard triple immunosuppression resulted in a significant reduction of the number of ACR episodes and significantly lower incidence of CLAD.

Long-term prognosis of adverse cardiovascular events in patients with chronic heart failure depending on the rs1143634 polymorphism of the interleukin-1β gene

The course and prognosis of chronic heart failure (CHF) are associated with the activation of inflammatory cascades, the severity of which is genetically determined.Aim: To analyze adverse cardiovascular events in patients with chronic heart failure over 5 years depending on the rs1143634 polymorphism of the interleukin-1β gene.Material and Methods. Clinical signs were studied, genotyping was carried out at the polymorphic locus rs1143634 of the IL-1β gene in patients with CHF of ischemic origin (n = 445, average age 66.4 ± 10.4 years). Information on patient outcomes over 5 years was obtained by telephone interview with endpoints: all-cause death, cardiovascular death, fatal and non-fatal cardiovascular events formed a composite endpoint. Time to event was analyzed using the Kaplan-Meier method; hazard ratio – Cox regression. Statistical processing was carried out in the Jamovi, R 4.3.1 programs.Results and conclusions. The occurrence of genotypes of the rs1143634 polymorphism of the IL-1β gene in patients with CHF and the genetic control group did not differ and was commensurate with the theoretically expected Hardy–Weinberg equilibrium. Carriers of the TT genotype were characterized by a high level of inflammation and the development of myocardial infarction at a young age. In patients with CHF of the TT genotype, the risk of death from all causes is 2.85 times higher, achieving the combined endpoint is 3.3 times higher, fatal cerebral stroke is 17.1 times higher compared to CC, 14.9 times higher than compared to ST genotype. In patients with CHF and chronic kidney disease of the TT genotype, the risk of death from cerebral stroke is 29.33 times higher than the CC genotype, and 29.12 times higher for the CT genotype. In patients with CHF in combination with diabetes mellitus, the frequency of hospitalizations due to cardiac decompensation in the TT genotype is higher than in the CC and CT genotypes (χ2 = 6.33, p = 0.042).chronic heart failure; rs1143634 polymorphism of the IL-1β gene; prognosis; cardiovascular complications

An examination of sexual function & distress among sexual minority & heterosexual women seeking care at menopause and sexual health specialty clinics.

Sexual minority women (SMW) have worse mental and physical health outcomes compared to heterosexual women, but literature on sexual function in SMW compared to heterosexual women is lacking. To evaluate sexual function and sexual distress in women across sexual orientations. Questionnaire data were analyzed for women aged 18 and older who presented to women's health clinics at Mayo Clinic in Minnesota, Arizona, and Florida from 2016 to 2023. Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) scores assessed sexual dysfunction (FSFI ≤ 26.55 and FSDS-R ≥ 11). Multivariable logistic models adjusted for confounding factors. Our main outcome was female sexual dysfunction as defined by a composite of FSFI ≤ 26.55 and FSDS-R ≥ 11 to include both sexual function and sexual distress. Of 6241 sexually active women, 3% were SMW and 97% were heterosexual women. The majority were White (93%), with average age 51.6years old. There was no significant difference in sexual dysfunction rates between heterosexual and SMW by combined endpoint on univariate or multivariable analysis. SMW had higher total FSDS scores (17 vs 15, P = 0.037), indicating more sexual distress. Sexual health concerns may differ between SMW and heterosexual women emphasizing the need for inclusive, culturally competent care. This study assessed the association of sexual orientation and sexual dysfunction by incorporating sexual functioning problems and sexual distress. Limitations include a small number of SMW and a predominantly White, married, employed, and educated study sample, limiting the generalizability of the findings. Rates of sexual dysfunction were similar between mostly White SMW and heterosexual women presenting to tertiary care centers. SMW reported more sexual distress than heterosexual women. Evaluating these variables in larger, more diverse cohorts is a critical next step.

Curricular Self-management for patients on ventricular assist device support decreases depression: A multicenter randomized controlled trial.

Utilization of ventricular assist device (VAD) support in patients with end-stage heart failure is well advanced. Recent studies emphasize the need to develop and evaluate evidence-based psychosocial support interventions for patients following VAD implantation. A national, multi-center study in four established German heart centers was initiated. An evidence-based VAD curriculum was developed; a randomized controlled trial evaluated the impact of the interprofessional intervention over time. Primary combined endpoint was the occurrence of adverse events (thromboembolic events, driveline infections, bleeding, rehospitalization, and death); secondary endpoints were psychosocial outcomes (anxiety, depression [HADS], quality of life [QoLVAD], social support [FSoZu], and self-management [SELMA]). A total of 140 patients were randomized block-wise to intervention (IG n = 70) or control (CG n = 70). Center-effects were considered. Instruments were completed at four time points (T0-T3). At baseline, intervention group (IG) patients were 19% female (control group [CG] 19%; p = 0.982); 58 ± 11 years. (CG 58 ± 11 years.; p = 0.966); 80% were implanted electively (CG 79%; p = 0.968). No significant difference in primary endpoint was found between IG versus CG (p > 0.05). For secondary endpoints, mixed linear regression revealed a significant reduction in depression scores in IG compared to CG (est. 1.18; 95% CI -2.17 to -0.18; p = 0.021). Clinically significant reductions in anxiety were greater in IG patients between T0 and T3 (IG 51.9%; CG 40.7%); increased anxiety was reported in 3.7% IG (11.1% CG). Mixed linear regression analyses favored IG (all >0.05) for QoL, social support, and self-management. A comprehensive curricular VAD intervention has potential to decrease depression levels and improve psychosocial outcomes of patients on VAD support.

Impact of prolonged QTc interval on mortality risk with hypertrophic cardiomyopathy.

The association between corrected QT (QTc) interval and life-threatening cardiac events in patients with hypertrophic cardiomyopathy (HCM) remains unclear. This study sought to investigate whether the prolonged QTc was associated with HCM-related death in patients with HCM. We included 445 patients with HCM (mean age 51 ± 16 years, 67% men). The QTc interval was measured at the time of the initial evaluation and the patients were classified into those with and without QTc prolongation, which was defined as a QTc interval >450 ms. HCM-related death was defined as a combined endpoint of sudden death or potentially lethal arrhythmic events, heart failure-related death, and stroke-related death. Prolonged QTc interval was found in 120 patients (26.4%) at the time of enrollment. Over a median (IQR) follow-up period of 8.1 (4.6-11.9) years, a total of 67 patients (15.1%) experienced HCM-related deaths including 57 (12.8%) with the endpoint of sudden death or potentially lethal arrhythmic events. In a multivariable analysis that included prolonged QTc interval and the risk factors for life-threatening events, prolonged QTc interval was independently associated with an HCM-related death (adjusted hazard ratio [HR]: 1.91; 95% confidence interval [CI]: 1.16-3.16; p = .011) and this trend also persisted for the combined endpoint of sudden death or potentially lethal arrhythmic events (adjusted HR: 2.01: 95% CI: 1.17-3.46; p = .012). In this cohort of patients with HCM, QTc prolongation may be associated with HCM-related death, including the endpoint of sudden death or potentially lethal arrhythmic events.

Inappropriate Therapy and Shock Rates Between the Subcutaneous and Transvenous Implantable Cardiac Defibrillator: A Secondary Analysis of the PRAETORIAN Trial.

Inappropriate therapy (IAT) is an undesirable side effect of implantable cardiac defibrillator (ICD) therapy. Early studies with the subcutaneous ICD (S-ICD) showed relatively high inappropriate shock (IAS) rates. The PRAETORIAN trial demonstrated that the S-ICD is noninferior to the transvenous ICD (TV-ICD) with regard to the combined end point of IAS and complications. This secondary analyses evaluates all IAT in the PRAETORIAN trial. This international, multicenter trial randomized 849 patients with an indication for ICD therapy between S-ICD (n=426) and TV-ICD therapy (n=423). ICD programming was mandated by protocol. All analysis were performed in the modified intention-to-treat population. In both groups 42 patients experienced IAT (48-month Kaplan-Meier estimated cumulative incidence, 9.9% and 10.1%, respectively; hazard ratio (HR), 0.99 [95% CI, 0.65-1.52]; P=0.97). There was no significant difference in patients experiencing IAS between both groups (P=0.14). In the S-ICD group, 81 IAT episodes with 124 IAS and 1 inappropriate antitachycardia pacing occurred versus 89 IAT episodes with 130 IAS and 124 inappropriate antitachycardia pacing in the TV-ICD group. IAT episodes were most frequently caused by supraventricular tachycardias in the TV-ICD group (n=83/89) versus cardiac oversensing in the S-ICD group (n=40/81). In the TV-ICD group, a baseline heart rate >80 bpm (HR, 1.99 [95% CI, 1.05-3.76]; P=0.03), a history of atrial fibrillation (HR, 2.66 [95% CI, 1.41-5.02]; P=0.003), and smoking (HR, 2.46 [95% CI, 1.31-4.09]; P=0.005) were independent predictors for IAT. A QRS duration >120 ms was an independent predictor for IAT caused by cardiac oversensing in the S-ICD group (HR, 3.13 [95% CI, 1.34-7.31]; P=0.008). Post-IAS interventions significantly reduced IAS recurrence in both groups (P=0.046). There was no significant difference in IAT and IAS rates between the S-ICD and TV-ICD in a conventional ICD population, but causes and predictors for IAT differed between the devices. After the first IAS, an intervention significantly reduced the recurrence rate of IAS. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01296022.