Endpoint Of Mortality Research Articles

Impact of Diagnosis to Ablation Time on Recurrence of Atrial Fibrillation and Clinical Outcomes After Catheter Ablation: A Systematic Review and Meta-Analysis With Reconstructed Time-to-Event Data.

Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing of atrial fibrillation (AF) ablation relative to the diagnosis time. We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on clinical outcomes after AF ablation. We searched PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials through August 2024. Pairwise, prognostic, and reconstructed time-to-event data meta-analyses were conducted using R V. 4.3.1. Our primary end point was time to first AF recurrence, with secondary end points of all-cause mortality, tamponade, stroke, and heart failure. Our cohort included 23 studies with 43 711 patients. Shorter DAT was significantly associated with reduced AF recurrence across both paroxysmal and persistent AF subgroups (P<0.01). There was a significant decrease in benefit for paroxysmal AF over time and a slight decrease in benefit for persistent AF over time. However, the benefit remained significant in both over time. DAT per year was significantly associated with a 10% increased risk of AF recurrence. Reconstructed Kaplan-Meier analysis showed that DAT >1 year was significantly associated with a 70% increased risk of AF recurrence in paroxysmal AF and 30% in persistent AF. DAT ≤1 year was significantly associated with decreased all-cause mortality (P<0.01) and showed a trend toward an association with a lower incidence of stroke (P=0.08). However, there was no significant difference in heart failure between DAT ≤1 year and DAT >1 year. Early ablation is more beneficial in paroxysmal AF, with a notable decrease in benefit over time, while in persistent AF, the benefit remains significant but slightly decreases over time. Shorter DAT was significantly associated with decreased all-cause mortality and showed a trend toward an association with a lower incidence of stroke. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42024525542.

Impact of Mandatory Preoperative Dental Screening on Infective Endocarditis in Patients Undergoing Surgical Valve Replacement.

Guidelines recommend preoperative dental screening (PDS) prior to surgical valve replacement (SVR) to reduce risk of prosthetic valve infective endocarditis (IE). Nonetheless, limited data support these recommendations. The objective of this study was to investigate the impact of mandatory preoperative dental screening (MPDS) on risk of IE in patients undergoing SVR. Patients undergoing SVR in Western Denmark from 2020 to 2022 were included in this observational study. Patients were considered based on 2 applied PDS practices: MPDS, and no routine referral to preoperative dental screening (NPDS). Data were retrieved from Danish registries and adjudicated using medical records. The primary endpoint was incidence of IE. Secondary endpoints were all-cause mortality, and the composite endpoint of IE and all-cause mortality. A total of 1,207 patients undergoing SVR were included. Of 805 patients in the MPDS, 93% (n=751) underwent subsequent PDS, compared to 5% (n=21) among 402 patients in the NPDS. Patients in the MPDS were older with higher rates of coexisting comorbidities. During a median follow-up of 2.6years, 3.3% (n=40) developed IE. The IE incidence rate for MPDS and NPDS was 16.0 (95%CI: 11.3-22.6) and 8.0 (95%CI: 4.0-16.0) per 1,000 person-years, respectively. Mortality rate was higher in MPDS (2-year mortality: 6.2% (95%CI: 4.7-8.1) vs 2.8% (95%CI: 1.6-5.0). Differences in IE rates, all-cause mortality but not composite endpoint were abolished in 370 propensity score-matched patients. Risk of IE was low regardless of PDS practice. MPDS prior to surgery did not alter the risk of IE orall-cause mortality in patients undergoing SVR in Denmark.

P-1865. Immunotherapy with Nebulized Toll-Like Receptor Agonists Restores Severe Immune Paralysis and Improves Outcomes in Mice with Influenza-Associated Pulmonary Aspergillosis

Abstract Background Given the poor outcomes of influenza-associated pulmonary aspergillosis (IAPA), there is a major unmet need for innovative therapeutic strategies. Impairment of pathogen recognition receptor (PRR) signaling is a known pathomechanism and prognostic factor in IAPA patients. Therefore, we performed immunotherapy with nebulized PRR agonists in a murine IAPA model and studied its impact on infection outcomes and pulmonary immunopathology. Timeline of experimental interventions. Abbreviations: AF = Aspergillus fumigatus, CA = cortisone acetate (10 mg intraperitoneally), IAV = nebulization with influenza A virus (7.5% of the 90% lethal dose), PBS = phosphate-buffered saline (mock therapy), P/O = Pam2/ODN, VPS = viral pneumonia score (0 = healthy – 12 = moribund). Methods 8-week-old BALB/c mice were infected with influenza A virus (IAV, H3N2), immunosuppressed with cortisone acetate (CA) on days (d) 5 and 8 after IAV infection, and infected intranasally with 50,000 Aspergillus fumigatus (AF) conidia on d9 (Fig. 1). Mice received nebulized Pam2+ODN (P/O, 4 µM/1 µM) or phosphate-buffered saline (mock therapy) before and after AF super-infection (d8/d12). Therapeutic outcomes were assessed using a combined morbidity (viral pneumonia score ≥ 7/12) and mortality endpoint. On d14, nCounter-based transcriptomics with Ingenuity pathway enrichment analysis was performed on lung tissue, along with histopathology and flow cytometry. Event-free survival (A; Mantel-Cox log-rank test) and median viral pneumonia scores of survivors (B) depending on the treatment arm. Results All mock-treated mice with IAPA reached the morbidity/mortality endpoint by d13 (Fig. 2). Compared to CA-immunosuppressed mice with IAV infection only (100% survival), nCounter analysis revealed minimal incremental inflammatory response and suppression of several PRR pathways, interferon signaling, and neutrophil activation in the IAPA group. P/O therapy led to 80% event-free survival until d21 (p &amp;lt; 0.001 vs. mock therapy) and full recovery of all survivors (Fig. 2). Histopathology revealed significantly reduced fungal burden and hemorrhagic lesions in P/O-treated animals. nCounter analysis showed induction of PRR signaling, several key effector cytokine pathways, and epithelial signaling after P/O therapy. Moreover, nCounter and flow cytometry revealed enhanced recruitment of macrophages, natural killer cells, and T cells in P/O-treated mice (Fig. 3). Summary of nCounter and flow cytometry results. Conclusion Consistent with previous studies in human IAPA patients, our data revealed severe immune paralysis in mice with IAPA. Immunotherapy with nebulized P/O strongly improved infection outcomes, enhanced mobilization of key immune effector cells, and re-invigorated PRR and cytokine signaling. Disclosures Sebastian Wurster, MD, MSc, Astellas Pharma: Grant/Research Support|Gilead Sciences: Grant/Research Support Dimitrios P. Kontoyiannis, MD, AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Knight: Advisor/Consultant|Merck: Advisor/Consultant|Scynexis: Advisor/Consultant

Mean pulmonary arterial pressure over cardiac output slope for risk stratification in patients with unexplained dyspnea: does the math matter?

Abstract Background Pulmonary artery pressure corrected for cardiac output (mPAP/CO) assessed by exercise echocardiography and calculated as the mPAP/CO slope improves risk stratification in various populations. However, it is unclear whether simplified alternatives have a similar predictive ability for outcomes. Purpose To evaluate whether the methodology employed to calculate the mPAP/CO slope affects prognostic assessment. Methods This is a secondary analysis of a multicenter cohort study that included patients with unexplained dyspnea who underwent exercise echocardiography. The primary analysis evaluated the additional prognostic value of the mPAP/CO slope. The mPAP was derived from the colloid-enhanced peak tricuspid regurgitation velocity using the Chemla formula. Cardiac output was calculated by multiplying heart rate by stroke volume, determined by the velocity time integral of the left ventricular outflow tract. The mPAP and CO were measured at rest, intermediate, and peak effort. The mPAP/CO relationship was calculated in six different ways: (1) linear regression based on three points, (2) delta from rest to peak, (3) delta from rest to intermediate, (4) delta from intermediate to peak effort, (5) mPAP/CO at intermediate effort and (6) mPAP/CO at peak effort. The primary outcome was the composite endpoint of all-cause mortality or non-elective cardiovascular hospitalizations. Receiver Operating Characteristic (ROC) curve analysis was used to assess the diagnostic performance of the different calculation methods, and the DeLong approach was used to compare differences in the area under the curve (AUC). Results Out of 2538 exercise echocardiography exams performed between January 2016 and March 2023, 2022 exams were included (age 62±15 years, 53% women) The patients' characteristics are shown in Figure 1. After 19 (11-36) months of follow-up, the overall event rate was 11.23%. Five of the six methods performed equally (Figure 2; AUC between 0.603 and 0.615, p&amp;gt; 0.05 for comparisons). The delta from intermediate to peak effort method was significantly less accurate than the other methods (Figure 2; AUC: 0.543; 95% CI: 0.521, 0.565; p-values ranging from 0.03 to &amp;lt; 0.001). Conclusion For risk stratification of patients with unexplained dyspnea, the 3-point linear regression method is not superior to more straightforward methods such as a 2-point slope (rest to peak; rest to intermediate effort) or a single-point mPAP/CO ratio during intermediate or peak effort. These findings can enhance the implementation of the mPAP/CO relationship in clinical practice. Figure 1. Patient characteristics Figure 2. ROC curves for each calculatio

TRIVO score: a new tool for predicting outcome in patients with secondary tricuspid regurgitation.

Abstract Background Predicting outcomes in patients with significant secondary tricuspid regurgitation (STR) is extremely challenging. Purpose This study sought to develop and validate the TRIVO-SCORE, utilizing advanced echocardiographic parameters, for predicting hospitalization for heart failure (HF) and mortality in moderate and severe STR patients. Methods We retrospectively studied 504 consecutive STR outpatients (mean age 74 ± 13 years, 44% men), randomly divided into derivation (49%) and validation (51%) cohorts. The primary endpoint included all-cause death and/or heart failure HF hospitalization, whereas the secondary endpoint focused on HF hospitalization or all-cause death. Score discrimination was assessed using time-dependent area under the receiver operating characteristic curve (AUROC), and calibration was evaluated via the Hosmer-Lemeshow goodness-of-fit test. In a subset of patients (162/504, 29%) with severe STR and comprehensive clinical, laboratory, and echocardiographic data, we compared TRIVO-SCORE with TRI-SCORE and TRIO-SCORE. Results After Multivariable Cox Regression Analysis, four variables were incorporated into the final model: moderate to severe chronic kidney disease (CKD, GFR &amp;lt;30 mL/min), effective Right Ventricular Ejection Fraction (eRVEF &amp;lt;20%), right Ventricular free wall longitudinal strain/pulmonary artery systolic pressure (RVFWLS/PASP) &amp;lt;0.48, and effective regurgitant orifice area (EROA) &amp;gt;0.41cm². The final score ranged from 0 to a maximum of 5 points. The TRIVO-SCORE demonstrated satisfactory performance in both the derivation cohort (AUROC 0.78, 95% CI 0.73-0.84) and the validation cohort (AUROC 0.71, 95% CI: 0.65-0.77) at 2-year. TRIVO-SCORE accurately predicted separate endpoints for HF hospitalization or mortality. Per each point of TRIVO-SCORE, the risk of experiencing the composite endpoint increased by 1.5 times (HR 1.55 [95% CI 1.35–1.80], p&amp;lt;0.001, for each stage increase). This progressive increase in risk persisted when stratifying the population into atrial and ventricular STR. The discrimination and calibration for mortality prediction were superior to those of TRI-SCORE (1) (AUROC 0.61) and TRIO-SCORE (2) (AUROC 0.57). Conclusions The TRIVO-SCORE, integrating both clinical and advanced echocardiographic variables, proved to be a robust tool for enhancing risk stratification in patients with moderate to severe STR, providing a stronger association with outcomes than previously validated risk scores.

Myocardial strain and work parameter changes predict long term mortality and rehospitalization in an acute heart failure patient population after levosimendan use

Abstract Introduction Decompensated acute heart failure (HF) in patients with reduced ejection fraction (HFrEF) signifies a pivotal stage in the progression of chronic HF. This condition is closely linked to increased rates of rehospitalization and a higher risk of mortality and morbidity due to inadequate decongestion. Recently, the field of quantitative echocardiography has experienced significant advancements, particularly in myocardial work analysis (MWA), which measures the energy the heart uses during each cardiac cycle. Purpose This study aimed to investigate the immediate effects of levosimendan on myocardial mechanics and to determine if these effects can predict the composite endpoint of HF-related rehospitalization and cardiovascular mortality. Methods 60 patients with HFrEF have been enrolled in the present study (age: 63.8±14.1, 46 males, 25 ischemic HFrEF, 35 non-ischemic HFrEF). or all patients, detailed baseline echocardiography, including strain imaging and myocardial work analysis (MWA), was conducted. Follow-up echocardiography was performed an average of 13.1±12.5 days after levosimendan administration. The clinical follow-up period lasted 496±191 days. Results Before levosimendan administration there was no significant difference in baseline echocardiographic, strain imaging and MWA parameters between ischemic and non-ischemic HFrEF groups. After the drug administration, left ventricular global wasted work (179±89 Hgmm% vs. 319±220 Hgmm%, p &amp;lt;0.05) was higher in the ischemic HFrEF group compared to non-ischemic HFrEF group. Among advanced echocardiographic parameters, global longitudinal strain (GLS) showed no significant improvement, however out of the MWA parameters, global work index (376±215 Hgmm% vs. 460±272 Hgmm%, p &amp;lt;0.05) improved significantly. The prognostic role of hemodynamic and novel echocardiographic parameters has been also assessed. Kaplan-Meier analysis revealed that LV stroke volume index improvement of 0.145 ml/m2 (p=0.01), LVEF improvement of at least 10% or more (p=0.032), LV GLS improvement of 0.85% (p=0.018) and lastly global constructive work improvement of 100 Hgmm% or more (p=0.021) resulted in significantly better event-free survival during the follow up period. Conclusion Levosimendan administration produces substantial immediate effects on hemodynamic parameters, myocardial deformation, and MWA metrics. These alterations appear to hold significant long-term prognostic value for predicting the composite endpoint and event-free survival.

Long-term outcomes after stress echocardiography in real-world practice: five year follow-up of the EVAREST study

Abstract Background/Introduction Stress echocardiography is widely used to assess patients with chest pain. The clinical value of a positive or negative test result to inform on likely longer-term outcomes when applied in real-world practice across a national healthcare system has not been previously reported. Purpose We report patient outcome up to five years after stress echocardiogram for patients undergoing a clinically-indicated stress echocardiogram for ischaemic heart disease in a real-world, multi-centre national healthcare system and determine the event-free ‘warranty’ period following a normal stress echocardiogram. Methods Patients participating in the EVAREST/BSE-NSTEP (Echocardiography: Value and Accuracy at Rest and Stress/ British Society of Echocardiography National Review of Stress Echo Practice) prospective cohort study were recruited from 32 UK NHS hospitals between 2018 and 2022. Medical outcome data up to 2023 was available from NHS England. Stress echocardiography results were related to outcomes, including death, procedures, hospital admissions and relevant cardiovascular diagnoses, using Kaplan-Meier analysis and Cox proportional hazard ratios. Warranty period following a negative stress echocardiogram was defined as time the cumulative event rate of myocardial infarction or cardiac-related death remained below 5%. Results 5503 patients were included in the analysis with a median follow-up of 829 days (IQR 224 – 1434). A positive stress echocardiogram was associated with a greater risk of myocardial infarction (HR 2.71, 95% CI 1.73 – 4.24, P&amp;lt;0.001), revascularisation (HR 10.52, 95% CI 8.26 – 13.42, P&amp;lt;0.001) and reaching a composite endpoint of cardiac-related mortality and myocardial infarction (HR 2.04, 95% CI 1.41 – 2.93, P&amp;lt;0.001). Hazard ratios for all events increased with ischaemic burden identified at stress echocardiography (Figure 1). A negative stress echocardiogram identified an event-free ‘warranty period’ of at least five years in patients with no prior history of coronary artery disease, and four years for those with disease (Figure 2). Conclusions In real-world practice, the degree of ischaemia recorded by clinicians at stress echocardiography correctly categorises risk of future events over the next five years. Reporting a stress echocardiogram as negative correctly identifies patients with no greater than a background risk of cardiovascular events over a similar time period. Figure 1 Figure 2

External validation of two different cardiac damage staging systems for aortic stenosis in a surgical cohort of patients who underwent surgical aortic valve replacement

Abstract Purpose In recent years, several cardiac damage staging systems for severe aortic stenosis (AS) have been proposed. These systems may help to stratify patients’ risk and select the adequate timing for intervention. Our aim was to perform an external validation of two staging systems (1,2) in patients who underwent surgical aortic valve replacement (SAVR). Methods Retrospective analysis of a prospective cohort of patients with AS who underwent SAVR in a tertiary care center from 2017 to 2022. Echocardiographic parameters measured prior to surgery were analyzed, and patients were classified into the different stages of two published staging systems. The area under the ROC curve (AUC ROC) was used to measure the discriminatory capacity of the two staging models to predict the primary endpoint of 1-year mortality after SAVR. Results 244 patients were analyzed. Mean age was 69 (9.5) years, and 37.7%f were female. Mean EuroSCORE II was 2.6 (3.3). The primary endpoint occurred in 11 (4.5%) patients. The distribution of patients in the different stages of cardiac damage is displayed in Figure 1. According to Staging system 1, the majority of patients (50%) were intervened on in a Stage 1 of cardiac damage (left ventricular subclinical damage, considered when global longitudinal strain [GLS] was ≥ −17%). In the case of Staging system 2, 29% of patients were classified as left ventricular damage and 47.9% as left atrium or mitral damage. The area under the ROC curve of Staging system 1, which incorporated cardiac mechanics, was 0.688 (95% CI: 0.510-0.865), and showed better predictive performance than Staging system 2 [0.593 (95% CI 0.432–0.736)] (Figure 2). Conclusions In a surgical cohort of patients with AS, a cardiac staging system that include GLS and right ventricular-arterial coupling showed better discriminatory yield for one-year mortality. Therefore, when available, assessing LV mechanics and the interrelation between right ventricular function and afterload could help in better risk stratification and prognostic assessment in this context. Cardiac damage staging systems AUC curve for 1-y mortality

Association of the right ventricular ejection adjusted by the regurgitant volume with outcomes in patients with secondary tricuspid regurgitation - a three-dimensional echocardiographic study

Abstract Introduction In patients with secondary tricuspid regurgitation (STR), the chronic volume overload caused by the regurgitant volume (RegVol) may lead to an overestimation of the right ventricular (RV) systolic function when evaluated using traditional echocardiographic parameters. Purpose We sought to overcome this limitation in patients with STR by investigating whether the effective RV ejection fraction (eRVEF) – which is the RVEF calculated after subtracting the RegVol from the total RV stroke volume – has a stronger association with outcomes compared to tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), RV free-wall strain (RV-FWS), and RVEF. Methods The study included consecutive patients with a first diagnosis of STR (ranging from mild to severe) undergoing complete two-, three-dimensional (3D), and Doppler echocardiography. eRVEF was computed as forward RV stroke volume (fRVSV)/ RV end-diastolic volume, where fRVSV was obtained by subtracting the STR RegVol obtained with the PISA method from the total RVSV obtained with 3D echocardiography. The endpoint was a composite of heart failure hospitalization (HHF) and all-cause death. Results 513 patients (mean age 75±13 years, 53% female, 39% atrial STR, 58% severe STR) were included in the final cohort. After a mean follow-up of 18±15 months, 195 patients (38%) reached the composite endpoint (97 HHF and 98 all-cause deaths). At time-dependent receiver operating characteristic analysis, eRVEF (AUC 0.72, 95%CI 0.68-0.77) demonstrated a stronger association with outcome than TAPSE (AUC 0.64, 95%CI 0.59-0.69, p= 0.01), FAC (AUC 0.55, 95%CI 0.50-0.60, p&amp;lt;0.001), RV-FWS (AUC 0.63, 95%CI 0.58-0.68, p= 0.003), and RVEF (AUC 0.65, 95%CI 0.59-0.70, p=0.006) (Figure 1). The spline curve of mortality risk showed that the cut-off value of eRVEF associated with an excess event rate was 20%, whereas, for the conventional RVEF, it was 45%. By separating the study population into 4 groups according to eRVEF value (higher and lower than 20%) and RVEF value (higher and lower than 45%), the highest cumulative rate of events was observed in the patients with both eRVEF and RVEF reduced values (event rate at 2 years 74 ± 5%, log-rank &amp;lt;0.0001) (Figure 2). Interestingly, patients with eRVEF&amp;lt;20% and RVEF≥45% had a significantly worse outcome than patients with eRVEF≥20% and RVEF&amp;lt;45%. At univariate Cox regression analysis, eRVEF &amp;lt;20% was associated with a 3-fold increased risk of experiencing the composite outcome [hazard ratio (HR): 3.54 [2.61-4.79], p&amp;lt;0.0001]. On three different models of multivariable Cox regression analysis, eRVEF as a continuous variable remained independently associated with the composite outcome (HR: 0.96; 95% CI= 0.94 -1.0; p&amp;lt;0.001). Conclusions eRVEF showed a stronger association with the composite endpoint of all-cause mortality and HHF compared to the conventional echocardiographic indices of RV function in a large group of STR patients. Figure 1. Figure 2.

P-2021. How Have COVID-19 Treatment Guidelines and the Scientific Evidence Evolved throughout the Pandemic and Endemic Eras?

Abstract Background With progressive understanding of the natural history of COVID-19 and accumulation of knowledge on clinical management, treatment guidelines recommended several options including remdesivir (RDV), a broad-spectrum antiviral. Given the evolving nature of COVID-19, it is critical to capture the totality of scientific evidence to inform clinical decision making. We conducted a systematic literature review (SLR) to summarize the mortality endpoint for RDV among hospitalized adults throughout COVID-19 eras and contrasted with evidence informing treatment recommendations in clinical guidelines. Methods We systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining RDV efficacy. Clinical trial registries, Cochrane COVID-19 Study Register, and conference abstracts were hand-searched (Fig1). Case reports and case studies were excluded. A review of most recent RDV recommendations across guidelines was conducted. Results From Dec ’19 to Dec ’22, 123 relevant publications were identified. In ’23, the evidence grew significantly, with 70 new publications. In total, 193 publications were evaluated, and 122 unique studies were included. While early randomized clinical trials (RCT) and small sample size observational studies did not universally demonstrate a significant difference in mortality in all severity groups of RDV-treated patients, real-world studies with larger sample sizes showed a significant impact across disease severity levels, regardless of COVID-19 era (Table1). Guideline recommendations for COVID-19 treatment with RDV are based on early RCTs (Table2) and most have not been updated (Fig2). Conclusion Our comprehensive evaluation of scientific literature indicates that evidence of RDV impact on mortality in hospitalized COVID-19 patients continued to grow and cover full range of disease severity. Guideline recommendations have not evolved in parallel which may explain differing recommendations in certain subgroups (e.g. IMV/ECMO). To assure that providers in the hospital setting are aware of and deploy evidence-based optimal care for patients with COVID-19, recommendations should rely on current evidence, including real-world data. Disclosures Essy Mozaffari, PharmD, MPH, MBA, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Michele Bartoletti, MD, PhD, Advan pharma: Advisor/Consultant|Advan pharma: Honoraria|Biomereux: Honoraria|Gilead: Advisor/Consultant|Gilead: Honoraria|Infectopharma: Advisor/Consultant|Msd: Advisor/Consultant|Msd: Grant/Research Support|Msd: Honoraria|Pfizer: Honoraria Alpesh N. Amin, MD, MBA, Alexion: Advisor/Consultant|Aseptiscope: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Bayer: Advisor/Consultant|Dexcom: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Ferring: Advisor/Consultant|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|Heartrite: Advisor/Consultant|Nova Nordisk: Advisor/Consultant|Pfizer: Advisor/Consultant|Renibus: Advisor/Consultant|Reprieve: Advisor/Consultant|Salix: Advisor/Consultant|Seres: Advisor/Consultant|Spero: Advisor/Consultant Yohei Doi, MD, PhD, bioMerieux: Lecture fees|Entasis: Grant/Research Support|Fujifilm: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|GSK: Advisor/Consultant|KANTO CHEMICAL CO.,INC.: Grant/Research Support|KANTO CHEMICAL CO.,INC.: Patent for genotyping kit|MeijiSeika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|MSD: Lecture fees|Pfizer: Advisor/Consultant|Shionogi &amp; Co., Ltd.: Grant/Research Support|Shionogi &amp; Co., Ltd.: Lecture fees Paul LOUBET, MD, PhD, Astrazeneca: Advisor/Consultant|Gilead: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Board Member Michael Roshon, MD/PhD, MD/PhD, Gilead: Honoraria Thomas F. Oppelt, PharmD, BCPS, Gilead Sciences, Inc: I am an employee of Gilead Sciences, Inc|Gilead Sciences, Inc: Stocks/Bonds (Public Company) Mel Chiang, Ph.D., Gilead Sciences: I am an employee of Gilead Sciences|Gilead Sciences: Stocks/Bonds (Public Company)

Evaluation of Prospective ECG-Triggered CT Scan as a Practical Alternative to Standard Retrospective ECG-Gated Scan for Pre-TAVI Patients

Purpose: CT-TAVI is a critical component of pre-TAVI assessment. The conventional method, retrospective ECG-gated scan, covering a complete cardiac cycle, measures the annulus during optimal systolic phases. Recently, prospective ECG-triggered scans acquiring images at a specific interval of the cardiac cycle were evaluated, allowing faster acquisition and lower contrast doses. Moreover, these scans might be beneficial for elderly patients, reducing the need for breath-holding and easing cooperation requirements. Still, their impact on annular measurement and procedural success has yet to be fully evaluated. Methods: This retrospective, single-center study included 419 patients who underwent CT-TAVI scans, by either prospective or retrospective scanning methods. Baseline data and calculated surgical risk scores were collected, with propensity score matching performed, followed by univariate analysis, Cox regression, and multivariable regression analysis. Results: A total of 171 patient pairs were generated via propensity score matching, ensuring that both groups had similar distributions of age (81 ± 8 years), sex (55% males), and baseline comorbidities. The patients in the prospective ECG-triggered group were exposed to a smaller amount of contrast material (40.0 ± 12 mL vs. 70.0 ± 48 mL, p &lt; 0.001) and radiation (4.4 ± 3.6 mSv vs. 8.0 ± 10.3 mSv, p &lt; 0.001). The prospective ECG-triggered group had a smaller aortic annulus area and diameter (426.6 ± 121.0 mm2 vs. 469.1 ± 130.8 mm2, p = 0.006 and 23.3 ± 3.2 mm vs. 24.5 ± 3.6 mm, p = 0.004) but no excess paravalvular leak was observed. Multivariable analysis showed no significant differences in mortality and composite endpoints between the two groups after 23 months of follow-up. Conclusion: Prospective ECG-triggered, ultra-fast, low-dose, high-pitch scan protocol, used in selected patients offers comparable safety and clinical procedural outcomes along with time and contrast savings.

Defining Fulminant Clostridioides difficile Infections: Assessing the Utility of Hypotension as a Diagnostic Criterion.

Fulminant Clostridioides difficile infection (FCDI) is associated with a 30%-40% mortality rate. Guideline definitions for FCDI severity classification include ileus, megacolon, shock, or hypotension. However, no hypotension definition is provided, making application of the definition challenging. The objective of this study was to assess optimal hypotension definitions for FCDI severity criteria. This was a multicenter cohort study involving 1172 hospitalized patients diagnosed with C difficile infection (CDI) from 2015 to 2022 (Houston cohort). Patients were assessed for a composite endpoint of colectomy or mortality within 30 days of diagnosis. The ability of the CDI severity criteria to predict the composite endpoint was assessed using 2 definitions of hypotension (systolic blood pressure [SBP] ≤90 mm Hg and mean arterial pressure [MAP] ≤65 mm Hg) through multivariable regression models. A separate CDI cohort of 494 hospitalized patients validated the results (Midwest cohort). The composite endpoint was similar in the Houston cohort (98 patients [8.4%]) and the Midwest cohort (26 patients [5.3%]). Using either a MAP ≤65 mm Hg or SPB ≤90 mm Hg as criteria for hypotension was the best-performing model in both the development and validation cohorts. Removal of hypotension was the worst-performing model in both cohorts. Inclusion of hypotension, defined as SBP ≤90 mm Hg or MAP ≤65 mm Hg, was an important component of FCDI severity criteria, significantly improving the predictive ability to identify FCDI patients at risk for poor outcomes.

Sex Differences in the Prognostic Value ofCirculating Biomarkers in Patients Presenting With Acute Chest Pain.

Biomarkers are used for long-term risk prediction of cardiovascular (CV) events in patients presenting with suspected acute coronary syndromes. This study investigated whether there are sex differences in the long-term prognostic value of biomarkers in patients presenting with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS). High-sensitivity cardiac troponin (hs-cTn), hs-cTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, and C-reactive protein (CRP) concentrations were measured in 1,476 patients admitted with suspected NSTE-ACS. Patients were followed up for a median of 1,547 (IQR: 873-1,842) days until a primary composite endpoint of all-cause mortality, incident myocardial infarction, or heart failure hospitalization. A secondary endpoint of CV death was also registered. For the primary endpoint, a log2 increase of hs-cTn and hs-cTnI concentration was associated with a higher adjusted hazard ratio in women (hs-cTn: 1.3, 95%CI: 1.2-1.5; hs-cTnI: 1.2, 95%CI: 1.1-1.2) than in men (hs-cTn: 1.1, 95%CI: 1.0-1.2; hs-cTnI: 1.0, 95%CI: 1.0-1.1); P value for interaction with sex: 0.009 (hs-cTn) and 0.005 (hs-cTnI). Asimilar interaction was shown for NT-proBNP (P for interaction: 0.043). GDF-15 and CRP were independent predictors of the primary endpoint, but the interaction by sex was nonsignificant. In contrast to CRP and GDF-15, increasing concentrations of hs-cTn, hs-cTnI, and NT-proBNP areassociated with higher risk of death and CV events in female than in male patients presenting with suspected NSTE-ACS. Sex-adjustment of hs-cTn and NT-proBNP may increase the accuracy of long-term CV prognostication in women and men.

Prognostic Implications of Sex in Patients With Heart Failure With Mildly Reduced Ejection Fraction: Results From a Large-Scaled Registry.

The study investigates the prognostic impact of sex and sex-related differences in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). More data regarding the characterization of patients and their outcomes in the presence of HFmrEF are needed. Consecutive patients hospitalized with HFmrEF (ie, left ventricular ejection fraction 41%-49% and signs or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Female patients were compared with male patients with regard to the primary end point of all-cause mortality at 30 months (median follow-up). Statistical analyses comprised Kaplan-Meier, multivariable Cox proportional regression analyses and propensity score matching. From a total of 2184 patients hospitalized with HFmrEF, 64.6% were male. Female patients with HFmrEF were older than male patients (median age 78 versus 73 years; P=0.001) and had lower rates of ischemic cardiomyopathy (46.6% versus 63.6%; P=0.001). Within the entire study cohort, sex was not associated with the risk of all-cause mortality (hazard ratio [HR], 0.931 [95% CI, 0.797-1.088]; P=0.372). However, male sex was associated with a lower risk of HF-related rehospitalization at 30 months (HR, 0.761 [95% CI, 0.600-0.966]; P=0.026), which was confirmed after multivariable adjustment (HR, 0.759 [95% CI, 0.592-0.973]; P=0.029) and propensity score matching (HR, 0.722 [95% CI, 0.539-0.967]; P=0.029). Although almost two thirds of patients hospitalized with HFmrEF were male, sex was no predictor for the risk of all-cause mortality at 30 months. However, female sex was associated with a higher risk of HF-related rehospitalization. URL: https://clinicaltrials.gov; Unique identifier: NCT05603390.

Insights from 3D echocardiography: unveiling the prognostic value of RV function in pulmonary hypertension: a systematic review and meta-analysis.

The role of right ventricular (RV) dysfunction in pulmonary hypertension (PH) has garnered increasing interest in terms of outcomes. This systematic review and meta-analysis evaluated the prognostic utility of three-dimensional echocardiography (3DE) derived right ventricular ejection fraction (RVEF) in PH. A systematic review and meta-analysis were performed using MEDLINE, Embase, and Scopus databases for publications reporting the hazard ratio (HR) of 3DE-derived RVEF in PH patients for the clinical end-points of composite outcome or all-cause mortality. Nine articles totaling 885 subjects were included, among which 67.23% had pulmonary arterial hypertension (PAH), with the remainder having a range of PH etiologies. The mean value of 3DE-derived RVEF was 35.5 ± 9.07% reflecting impaired RV function. The primary endpoint was all-cause mortality in three studies, while the rest of the studies reported composite outcomes. Follow-up duration ranges from 6 to 44months. From seven publications, the pooled HR by 3DE-derived RVEF was 0.91 (95% CI: 0.85 to 0.97, p = 0.001; heterogeneity: I2 = 62%, p = 0.004). In subgroup analysis, 3DE-derived RVEF was a significant prognostic factor for group 1 PH (HR: 0.90, CI: 0.86-0.94; heterogeneity I2 = 43%, p < 0.0001). From meta-regression analysis, only follow-up duration was found statistically significant with the HR of RVEF in the population (estimate: 0.028, p = 0.026). 3DE-derived RVEF provides important prognostic value in a large population of PH patients, especially for group 1 PH. Further accumulation of evidence is needed to perform a detailed subgroup analysis in each type of PH.

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.

Hemoglobin, albumin, lymphocyte and platelet (HALP) score for predicting early and late mortality in elderly patients with proximal femur fractures.

Predicting mortality and morbidity poses a significant challenge to physicians, leading to the development of various scoring systems. Among these, the hemoglobin, albumin, lymphocyte and platelet (HALP) score evaluates a patient's nutritional and immune status. The primary aim of this study was to determine the predictive effect of the HALP score on 30-day and 1-year mortality in elderly patients with proximal femoral fractures (PFFs). Patient demographic, clinical, laboratory, and prognostic data were obtained. The patients were categorized into two groups: survival and nonsurvival at mortality endpoints. The HALP score was calculated and compared among the groups and with other mortality biomarkers such as C-reactive protein (CRP) and C-reactive protein to albumin ratio (CAR). The ability of the HALP score to predict mortality was compared between the groups. The mortality risk was also calculated at the optimal threshold. The HALP score had a statistically significant predictive effect on mortality endpoints and was lower in the non-surviving group. The ability of the HALP score to predict 1-year mortality at the optimal cut-off value (17.975) was superb, with a sensitivity of 0.66 and specificity of 0.86 (AUC: 0.826, 95% CI: 0.784-0.868). In addition, the power of the HALP score to differentiate survivors and non-survivors was more significant than that of other indices (p < 0.001). Patients with a HALP score ≤ 17.975 had a 1-year mortality risk 11.794 times that of patients with a HALP score ≥ 17.975 (Odds ratio: 11.794, 95% CI [7.194-19.338], p < 0.001). The results indicate that the HALP score demonstrates efficacy and utility in predicting 30-day and 1-year mortality risk among elderly patients with PFFs.

Association of Total Mortality and Cardiovascular Endpoints With the Timing of the First and Second Systolic Peak of the Aortic Pulse Wave.

Prognostic significance of the timing in the cardiac cycle of the first (TP1) and second (TP2) systolic peak of the central aortic pulse wave is ill-defined. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of adverse health outcomes associated with TP1 and TP2, estimated by the SphygmoCor software, were assessed in the International Database of Central Arterial Properties for Risk Stratification (IDCARS) (n = 5529). Model refinement was assessed by the integrated discrimination (ID) and net reclassification (NR) improvement. Over 4.1 years (median), 201 participants died and 248 and 159 patients experienced cardiovascular or cardiac endpoints. Mean TP1 and TP2, standardized for cohort, sex, age, and heart rate, were 103 and 228ms. Shorter TP1 and TP2 were associated with higher mortality and shorter TP1 with a higher risk of cardiovascular and cardiac endpoints (trend p ≤ 0.004). The HRs relating total mortality and cardiovascular endpoints to TP2 were 0.82 (95% confidence interval [CI]: 0.72-0.94) and 0.87 (0.77-0.98), respectively. The HR relating cardiac endpoints to TP1 was 0.81 (0.68-0.97). For total mortality and cardiovascular endpoints in relation to TP2, NRI was significant (p ≤ 0.010), but not for cardiac endpoints in relation to TP1. Integrated discrimination improvement (IDI) was not significant for any endpoint. The HRs relating total mortality to TP2 were smaller (p ≤ 0.026) in women than men (0.67vs. 0.95) and in older (≥ 60 years) versus younger (< 60 years) participants (0.80vs. 0.88). Our study adds to the evidence supporting risk stratification based on aortic pulse analysis by showing that TP2 and TP1 carry prognostic information.

Differential effects of pharmaceuticals and insecticides on swimming behaviour and survival in Gammarus pulex.

Many freshwater systems are continuously exposed to waste streams like municipal wastewater and agricultural runoff, leading to exposure to chemicals that can cause mortality and behavioural changes in aquatic organisms. While research has advanced our understanding of pesticide effects on behaviour of aquatic organisms, the impacts of pharmaceuticals are less understood. Psychopharmaceuticals are particularly interesting because they can act on nervous systems, potentially affecting the behaviour of aquatic organisms. Sublethal behavioural effects can be crucial in ecotoxicological research for environmental pharmaceuticals and are often detected below lethal concentrations. Gammarids, especially Gammarus pulex, are widely used in ecotoxicological studies due to their ecological role and sensitivity to pollutants. This study aims to evaluate the sensitivity of six swimming behaviour endpoints in G. pulex compared to the conventional endpoints immobility and mortality, using different chemicals with distinct modes of action: insecticides imidacloprid and chlorpyrifos and the pharmaceuticals carbamazepine and citalopram. After a 2-hour exposure, the mobile organisms were assessed for their swimming speed, acceleration, curvature, thigmotaxis and startle response (magnitude and duration). Our study reveals that G. pulex exhibits varied behavioural responses to different chemical pollutants. While behavioural endpoints can indicate harmful effects on aquatic organisms, they are not consistently more sensitive than traditional endpoints, such as immobility and mortality. The insecticides imidacloprid and chlorpyrifos show development of immobility and mortality without prior sublethal behavioural effects, suggesting a limited utility of behavioural endpoints as early warning indicators. In contrast, the pharmaceuticals carbamazepine and citalopram demonstrate adverse effects through behavioural changes before immobility and mortality occur. Further research is essential to understand the mechanisms underlying these varying sensitivities of behavioural endpoints to different compounds, emphasising the importance of considering both chemical type and endpoint relevance in toxicity testing protocols.

Impact of porcelain aorta on outcomes in transfemoral aortic valve implantation (TAVI) with balloon-expandable valves

BackgroundCurrent guidelines recommend transcatheter aortic valve implantation (TAVI) for patients with aortic stenosis and porcelain aorta (PA). Neurological outcomes of patients with PA undergoing TAVI with modern valves require clarification...