1-year All-cause Mortality Research Articles

5-year valve academic research consortium-3 outcomes and predictors of mortality in a 10-year Asian transcatheter aortic valve implantation registry

Abstract Background Transaortic valvular implantation (TAVI) has revolutionised the management of aortic stenosis (AS). Uptake in Asia has caught up in recent years, after an initial lag due to expensive cost, limited subsidies, and scarce accessibility. Hence, longitudinal outcomes of TAVI remain largely unknown in Asian patients. Purpose This study aims to present the 5-year mortality endpoints in an Asian cohort followed up over a decade. Methods 253 patients with symptomatic severe aortic stenosis status post TAVI were retrospectively enrolled at a tertiary academic hospital from 2010-2021. The main outcomes were defined as short-term (30-day), mid-term (1-year) and long-term (5-year) all-cause mortality. Baseline demographics, procedural findings and clinical outcomes were analysed. Kaplan-Meier curves and multiple Cox regression analyses were constructed. Results The mean age was 75.2 + 10.2 years. 120 (47.4%) patients were female and 167 (66%) were Chinese. 168 patients (66.7%) received balloon-expandable valves, 80 patients (31.7%) underwent self-expandable valves, and 4 patients (1.6%) had mechanical-expandable valves. Malignancy was associated with worse short-term mortality at 30-days (HR 3.65, p = 0.054), while pulmonary disease and previous stroke were associated with worse long-term mortality at 5-years (HR 2.27, p = 0.012 and HR 2.02, p = 0.064). Worse all-cause mortality at 30-days, 1-year and 5-years were associated with high NT-Pro BNP levels (HR 1.04, p = 0.046; HR 1.05, p = 0.002 and HR 1.04, p < 0.001), the presence of peripheral arterial disease (PAD) (HR 4.32, p = 0.056; HR 4.48, p = 0.006 and HR 2.43, p = 0.023) and chronic kidney disease (CKD) (HR 6.19, p = 0.006; HR 6.77, p < 0.001 and HR 2.09, p = 0.008). Society of Thoracic Surgery (STS) score (HR 1.11, p = 0.001; HR 1.13, p < 0.001 and HR 1.12, p < 0.001) and Valve Academic Research Consortium (VARC) III endpoints of acute kidney injury (AKI) (HR 6.68, p = 0.047, HR 10.8, p < 0.001 and HR 6.99, p < 0.001), cardiogenic shock (HR 26.3, p < 0.001, HR 12.0, p < 0.001 and HR 4.29, p = 0.011) and structural complications (HR 40.3, p < 0.001, HR 18.1, p < 0.001 and HR 5.18, p = 0.008) were associated with worse all –cause mortality at time-points of 30-days, 1-year and 5-years respectively. On multivariate analyses adjusted for comorbidities and outcomes, STS score and structural complications were independent predictors of 30-day, 1-year, and 5-year all-cause mortality (HR 1.16; p = 0.003, HR 1.09, p = 0.003 and HR 1.10, p < 0.001) and (HR 62.7, p < 0.007; HR 18.9, p < 0.001 and HR 10.6, p = 0.001) respectively. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use was protective of survival within 1-year (HR 0.37, p = 0.022). Conclusions STS score and VARC III endpoints of structural complications were reliable predictors of all-cause mortality in Asian patients with TAVI. ACE inhibitor and ARB use was protective against mortality at 1-year.Cox regression analysesKaplan-Meier curves

Growth differentiation factor-15 and 5-years cardiovascular risk in chest pain patients presenting to the emergency department: a multicenter cohort study

Abstract Background Growth differentiation factor 15 (GDF-15) has been explored as a prognostic biomarker in multiple disease entities, including ischemic heart disease and heart failure (HF), but its role as a prognostic marker in chest pain patients presenting to the emergency department (ED) is unknown. Purpose To investigate the association between GDF-15 and 5-year all-cause mortality, cardiovascular mortality, and major adverse cardiac events (MACE), and to evaluate its prognostic incremental value. Methods Patients presenting to the ED with acute chest pain were prospectively enrolled in an international multicenter diagnostic study. GDF-15 concentrations were measured in a blinded fashion upon ED presentation. Follow-ups were performed at 3 months, 1-, 2- and 5-years. MACE was defined as the composite of cardiovascular mortality, acute myocardial infarction, stroke, and HF rehospitalization. Associations between GDF-15 and each prognostic outcome were modeled using multivariable Cox proportional hazard regression fitting restricted cubic splines to continuous variables. The magnitude of the effect of each GDF-15 unit change on multivariable-adjusted models was assessed graphically using dose-response plots. To compute an HR for the dose-response plots we chose a GDF-15 value of 1200 pg/mL as a reference value as this has been chosen in previous literature1. For the restricted cubic splines three knots were used. The added prognostic value of GDF-15 was evaluated by the increase in the C-statistic between a base and an extended model and the fraction of new information (FNI) provided by GDF-15. Results A total of 4779 chest pain patients had baseline GDF-15 values available. The median age was 61 [48-74] and 33% were female. Higher GDF-15 levels were more strongly associated with heart failure, kidney dysfunction, older age, hypertension, diabetes and coronary artery disease. GDF-15 was independently associated with 5-years all-cause mortality, cardiovascular mortality and MACE (Figure). When adding GDF-15 to a rich-for-prior-information base model which included age, sex, cardiovascular risk factors, creatinine, cardiac troponin and NT-proBNP, GDF-15 provided relevant incremental prognostic discrimination for 5-years all-cause death and cardiovascular death. (Table). Conclusions In chest pain patients presenting to the emergency department, GDF-15 concentration on admission was associated with 5-years all-cause mortality, cardiovascular mortality, and MACE. In addition, it provided relevant incremental prognostic information when added on top of troponin and NT-proBNP, the two current prognostic gold standard biomarkers.FigureTable

A propensity score matched analysis of transcatheter aortic valve replacement in failed bioprosthetic valves

Abstract Introduction While recently published data indicate similar long-term results of transcatheter aortic valve replacement (TAVR) compared to surgical procedures, surgical aortic valve replacement (SAVR) remains the standard of care in low-risk patients. However, since life expectancy increases, a non-negligible number of patients experience bioprosthetic valve dysfunction with the need for reintervention, but long-term data of TAVR in failed bioprosthetic valves is scarce. Purpose The aim of the study was to analyse long-term data of patients with TAVR in failed bioprosthetic valves compared to patients with native valve TAVR. The primary endpoint was 6-year all-cause mortality and the main secondary endpoint was echocardiographic valve function. Methods Patients undergoing TAVR for severe aortic valve disease between December 2012 and December 2020 were retrospectively analysed. Prior TAVR or aortic valve homografts led to exclusion from the study. A 2:1 propensity score matching by the optimal neighbor matching algorithm was performed to overcome differences in baseline characteristics. Results Between December 2012 and December 2020, 3,423 patients received TAVR for severe aortic valve disease and met inclusion criteria for the study. Of those, 3,287 patients underwent native valve TAVR, whereas 136 patients experienced bioprosthetic valve dysfunction and were treated with TAVR-in-SAV. After 2:1 propensity score matching, baseline characteristics without any relation to prior SAVR were similar between both groups. Concerning postprocedural echocardiographic function, a less pronounced gradient reduction (57.0 vs. 71.0 %, p < 0.01, Figure 1) and a higher number of patients with elevated mean pressure gradient > 20 mmHg could be found after prior SAVR (19.4 vs. 3.0 %, p < 0.01). However, there was no difference regarding 6-year all-cause mortality between both groups (log rank test p = 0.8, Figure 2). Conclusions Besides a less pronounced gradient reduction and higher mean aortic pressure gradients after TAVR-in-SAV compared to patients with native valve TAVR, no differences in 6-year all-cause mortality could be observed in a propensity score matched analysis.Reduction of mean pressure gradient6-year all-cause mortality

Prognostic significance of type 4a myocardial infarction and periprocedural myocardial injury in NSTEMI patients

Abstract Background Type 4a myocardial infarction (MI) and periprocedural myocardial injury (PMI) might occur in patients with non-ST-elevation MI (NSTEMI) after percutaneous coronary intervention (PCI) procedures. Purpose This study investigated the incidence and prognostic relevance of type 4a MI and PMI, according to current definitions, in NSTEMI patients undergoing PCI. The best cardiac troponin (cTn) threshold of PMI for prognostic stratification is also identified. Methods In this observational cohort study, we enrolled consecutive NSTEMI patients undergoing PCI with stable or falling pre-PCI cTn levels. According to the 4th Universal Definition of Myocardial Infarction (UDMI), we stratified the study population into three subgroups: those experiencing 1) type 4a MI; 2) PMI; 3) no periprocedural ischemic events. The primary endpoint was 1-year all-cause mortality. The secondary endpoint consisted in a composite of major adverse cardiovascular events (MACE) at 1-year, including all-cause mortality, non-fatal reinfarction, urgent revascularization, non-fatal ischemic stroke and hospitalization for heart failure. Results Among 1412 NSTEMI patients undergoing PCI with stable or falling cTn levels at baseline, 240 (17.0%) experienced type 4a MI, 288 (20.4%) PMI, and 884 (62.6%) no periprocedural ischemic events. Patients with type 4a MI had the highest 1-year all-cause mortality and MACE rates. PMI defined by the 4th UDMI (post-PCI delta cTn >20%) did not show significant associations with primary and secondary endpoints. PMI redefined as post-PCI delta cTn >40% was significantly correlated with 1-year all-cause mortality and MACE. Conclusion Periprocedural ischemic events are common in NSTEMI patients undergoing PCI and influence patient outcomes. Type 4a MI and PMI redefined as post-PCI delta cTn >40% are strongly associated with 1-year death and MACE. This study highlights the importance of identifying periprocedural ischemic events to aid risk stratification and management of NSTEMI patients.PMI and type 4a MI: mortality 1-yearPMI and type 4a MI: MACE 1-year

Transcatheter aortic valve replacement with balloon-expandable and self-expandable valves in Japanese patients with large annulus: the OCEAN-TAVI registry

Abstract Background East Asians have smaller aortic valve complexes than individuals from Western countries, and few studies have reported transcatheter aortic valve replacement (TAVR) outcomes in Asian patients with a large annulus. Purpose We aimed to compare the acute and long-term outcomes of TAVR using balloon-expandable valves (BEVs) and self-expandable valves (SEVs) in Asian patients with a large annulus. Methods We retrospectively analyzed the data from the Optimized transCathEter vAlvular interveNtion Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry. A large annulus was defined by annular area ≥ 500 mm2 and average diameter ≥ 25 mm in computed tomography scans. The primary endpoint was the 3-year all-cause mortality. Secondary endpoints were 3-year heart-failure rehospitalization (HFR) after TAVR, acute outcomes of TAVR, and changes in valve function on echocardiography 2 years after TAVR. Results Among 773 patients, 671 (86.8%) underwent BEV-TAVR. The SEV-TAVR group showed a significantly higher incidence of above-moderate perivalvular leakage (2.1% vs. 7.8%; P < 0.001), and included a significantly greater percentage of patients who required postoperative pacemaker implantation (6.1% vs. 11.8%; P = 0.035). The incidence of moderate-to-severe prosthesis–patient mismatch did not differ between the two groups. The Kaplan–Meier curve showed no significant intergroup differences in the 3-year all-cause mortality and HFR rates (log-rank P = 0.900), and the echocardiography-indexed effective orifice area and mean transaortic valve pressure gradient at 2 years post-TAVR did not differ significantly between the two groups. Conclusions The benefits of BEV-TAVR may outweigh those of SEV-TAVR in patients with a large annulus.

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

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

The implementation of modern guideline-directed medical therapy among hospitalized patients with heart failure with reduced ejection fraction: real-world experience from two tertiary cardiac centers

Abstract Background According to the 2021 ESC HF Guidelines (GLs), the conventional triple therapy (TT) (RASi+βB+MRA) of HFrEF has been supplemented with the SGLT2 inhibitor dapa- and empagliflozin as the fourth pillar of the foundational quadruple therapy (QT) recommended for all HFrEF patients. Aim To assess the changes in the implementation of GDMT and investigate its impact on the prognosis among hospitalized HFrEF patients in light of the 2021 HF GLs. Patients and methods A retrospective data analysis of a consecutive cohort of HFrEF patients hospitalized due to HF between 01/01/2019 and 31/12/2023 at two tertiary cardiac centers was performed. Patients were classified into two groups: those hospitalized before and those after the publication of the 2021 ESC HF GLs (27/08/2021). Differences in the implementation of the drug therapy were analysed using the Chi-square test. 1-year all-cause mortality (ACM) was compared using Kaplan-Meier method and log-rank test. The independent predictors of the 1-year ACM were investigated with uni-, and multivariate Cox-regression analysis. Results A total cohort of 560 patients (male: 76%, age: 63 [51-72] years, coronary artery disease: 46%, diabetes: 38%, atrial fibrillation: 44%, LVEF: 25 [20-30]%, eGFR: 57 [43-74]mL/min/1.73m²; NT-proBNP: 5574 [2529-10960]pg/mL) was treated with a high proportion of TT (80%) and with QT (TT + SGLT2i) in 34% at discharge. After the publication of the 2021 ESC HF GLs, the proportion of patients on these SGTL2is improved (10% vs 57%, p<0.001; in the group before vs. after the publication of the GLs), resulting in an increased proportion of patients on QT (10% vs. 52%, p<0.001). There was no significant difference between groups regarding the use of TT (6% vs. 3%) or QT (1% vs. 3%) at target doses. The 1-year ACM was more favourable for those receiving QT (non-QT and non-TT: 41% vs. TT: 16% vs. QT: 11%, p<0.001). According to the multivariate Cox-regression analysis, older age, and more advanced left ventricular systolic dysfunction proved to be negative independent predictors of 1-year ACM, while "de novo" diagnosis of HFrEF and the application of TT/QT (adjusted HR: 0.303, 95% CI: 0.207-0.445, p<0.001) resulted in better outcomes. Conclusions The 2021 ESC HF GLs have led to a breakthrough regarding the modern drug treatment recommended for all patients in HFrEF. Our results demonstrated that the introduction of SGLT2is and the use of QT was feasible even in the everyday practice among complex, multimorbid HFrEF patients requiring hospitalization and the implementation of TT/QT was accompanied by a better prognosis.

Can a chest pain virtual ward be used to safely manage patients with low-risk acute coronary syndrome?

Abstract Background Acute coronary syndrome (ACS) accounts for approximately 2-6% of emergency department (ED) presentations and contributes at least 20% of the overall acute hospital admissions(1-3). Patients presenting with low-risk ACS may be suitable for remote monitoring(4) while awaiting angiogram in chest pain virtual ward(CPVW) thereby improving patient flow and resource utilisation. Purpose We aimed to assess outcomes for patients with low-risk ACS admitted in a district general hospital with a view to establish an onboarding pathway for CPVW whilst ensuring a safe monitoring without effecting the readmission rate or all-cause mortality. Methods We retrospectively analysed the Myocardial Ischaemia National Audit Project (MINAP) registry of from March 2022 to April 2023 for patients who presented to ED with a diagnosis of confirmed ACS. Patients were stratified into low-risk (GRACE score <140, HEART score <4, non-dynamic ECG, non-dynamic troponin, without ongoing chest pain), all other patients were deemed intermediate-to-high-risk ACS. Baseline demographics, the total length of acute admission days, waiting time before and after coronary investigation ,adverse events (escalation of therapy, death)whilst awaiting for invasive inpatient angiogram were calculated. The primary endpoint was 30-day readmission and all-cause mortality. Results 1077 patients were coded as ACS diagnosis in ED. 561(52.1%) had a confirmed diagnosis of ACS. Data to allow stratification was available for 538 patients, included in final analysis. 377(70.1%) were male with a mean age of 66.8 ± SD 13.1 years. A significant number of patients had other comorbidities, including hypertension (66.1%), diabetes (45.3%), hyperlipidaemia (51.3%), and previous history of IHD (46.5%). Total number of patients stratified into low-risk ACS was 55(10.2%), intermediate-to-high-risk group contained 483(89.8%) patients. The median total-length-of-stay (LOS) for low-risk ACS patients was 4 days(IQR 2-7), waiting time to have an inpatient angiogram was 3 days(IQR 0-5), and discharge time post-angiogram was 1 day(IQR 0-2). 4 patients(7.3%) in low-risk cohort required CCU admission for GTN infusion due to ongoing chest pain, among them 3 patients(5.5%) had abnormal coronary angiogram. 5 patients(9.1%) in low-risk cohort were readmitted due to chest pain post-angiogram and no patients had 30-days or 1-year all-cause mortality. The result depicts 51 patients from low-risk cohort would have been eligible for CPVW reducing the LOS from median 4 days to 1-2 days, this is a saving of 102-153 acute bed days per year. Assuming the costing of a bed day is £320 this equates to £32,640 - £48,960 cost saving without any adverse outcomes. Conclusion Our data suggests that there is a large cost saving with minimal risk in managing patients with low-risk ACS via a CPVW. This pathway of management is likely to have benefit in patient flow and resource utilisation in our district general hospital trust.Comparison of different ACS cohortsCPVW flow-diagram

Safety and efficacy of transcatheter aortic valve implantation (TAVI) for pure aortic regurgitation; a systematic review and meta-analysis

Abstract Background Although Transcatheter Aortic Valve Implantation (TAVI) has gained ground in the management of severe aortic stenosis (AS), evidence about its safety and efficacy for patients with pure native aortic regurgitation (AR) remains limited. Purpose The aim of the study is to systematically review and summarize available data regarding the safety and the outcomes of TAVI in pure AR. Methods This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 1, 2024, for studies assessing the characteristics and outcomes of patients undergoing TAVI for pure AR. Primary endpoint of our systematic review and meta-analysis is the in-hospital, 30-days and 1-year mortality rates. Secondary endpoints comprised in-hospital stroke, major bleeding, and permanent pacemaker implantation (PPM) implantation. Endpoint definitions followed the Valve Academic Research Consortium 2 criteria. The cumulative incidence of primary and secondary endpoints and the corresponding 95% confidence intervals (CI) were estimated. A random effects model (DerSimonian-Laird) was used to account for heterogeneity among the included studies. Results Our meta-analysis included a total of 22 studies and 6,710 patients undergoing TAVI for pure-AR. Our analysis showed that patients undergoing TAVI for pure AR had 3.4% (95% CI: 2%-4.7%), 7.9% (95% CI: 5.2%-10.6%) and 15.5% (95% CI: 9.9%-21.2%) in-hospital, 30-days and 1-year all-cause mortality. In-hospital stroke occurred in 1.9% (95% CI: 1.5%-2.2%) of the patients, while 4.9% (95% CI: 3.3%-6.6%) of the patients suffered from major bleeding events. Finally, considering the PPM implantation rates, patients had a 10.7% (95% CI: 7.4%-13.9%) in-hospital incidence. Conclusion Our systematic review and meta-analysis shows a promising safety profile for TAVI treating pure AR. It demonstrated relatively low in-hospital, 30-days and 1-year mortality incidence, comparable to the TAVI treating severe AS, according to the existing literature. Taking into consideration that TAVI for pure-AR might be the only therapeutic option for an increasing number of patients, further studies are needed to further assess the safety and efficacy of the procedure.TAVI for pure AR mortality rates

One-year prognosis difference of MINOCA versus MI-CAD in developing countries: insights from the Moroccan experience

Abstract Introduction The debate remains open as to the difference in prevalence of mortality and occurrence of acute events in patients with Myocardial infarction with non-obstructive coronary arteries (MINOCA) and others with Myocardial infarction with coronary arteries disease (MI-CAD) (1). Purpose We carried out an analysis of the clinical characteristics and one-year prognosis of MINOCA versus MI-CAD. Methods We conducted a prospective study for patients admitted for Acute coronary syndrome (ACS) during 2-years, to analyze the clinical and prognostic characteristics of patients with MINOCA versus MI-CAD. We defined 1-year all-cause mortality as the primary outcome, and the secondary outcome as a composite of 1-year readmission for myocardial infarction or acute heart failure (AHF). The primary and secondary outcomes was studied using a Cox proportional hazards regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for variables described in the literature. Results Our study included 1077 patients, 95.3% with MI-CAD and 4.7% with MINOCA. At admission, 71.1% patient were diagnosed STEMI and 28.9% with NSTEMI. The difference between the two groups was found on age (p<0.001), hypertension, diabetes with consecutive p-values of 0.007 and 0.001, as well as Ejection fraction (p<0.001). For the outcomes studied, we found, firstly before adjustment, that patients in the MINOCA group had a better prognosis than the MI-CAD group, for all-cause 1-year mortality (HR=0. 442; 95%CI 0.227-0.760; p=0.041) with a significant difference in the Kaplein Meier survival analysis with a log-rank test (p-value =0.02) (Figure 1), and a lower risk of readmission for ACS (HR=0.297; 95%CI 0.316-0.821; p=0.034), as well as for readmission for AHF (HR=0.555; 95%CI 0.329-0.836; p=0.045) also with a significant difference between the two groups in the Kaplein Meier analysis with consecutive log-rank test p-values of 0.033 and 0.035 (Figure 2). After adjustment for age, arterial hypertension, diabetes, active smoking, EF<40%, proximal LAD or LM as culprit artery, TIMI 0-I flow, CRP >300mg and cardiogenic shock during hospitalization, the results remained significantly in favor of a better prognosis for MINOCA: (HR=0. 672; 95%CI 0.376-0.872; p=0.003) for 1-year all-cause mortality, (HR=0.301; 95%CI 0.482-0.879; p=0.012) for readmission for ACS and finally (HR=0.604; 95%CI 0.309-0.812; p=0.039) for readmission for AHF. Conclusion Despite the ambiguity in the genesis of MINOCA, the short- and long-term prognosis of these patients remains generally favorable.Figure 1.Figure 2.

Safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with previous TAVI; a systematic review and meta-analysis

Abstract Background Transcatheter Aortic Valve Implantation (TAVI) has gained ground in the management of severe aortic stenosis, even in low-surgical risk patients. However, TAVI prostheses, like bioprostheses, have a finite lifetime; thus, TAVI in patients with previous TAVI (TAVI-in-TAVI) rates are radically increased. Although data regarding TAVI indicate low mortality and stroke rates within the first year, TAVI-in-TAVI is less studied. Purpose The aim of the study is to systematically review and summarize available data regarding the safety and the outcomes of TAVI-in-TAVI. Methods This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 10, 2024, for studies assessing the characteristics and outcomes of patients undergoing TAVI-in-TAVI. Primary endpoint of our systematic review and meta-analysis is the in-hospital, 30-days and 1-year mortality rates. Secondary endpoints comprised in-hospital, 30-days and 1-year stroke rates, in-hospital vascular complications, conversion to surgery, coronary compression or obstruction, and perforation with or without tamponade, and in-hospital and 30-days permanent pacemaker implantation (PPM) implantation. Endpoint definitions followed the Valve Academic Research Consortium 3 criteria. The cumulative incidence of primary and secondary endpoints and the corresponding 95% confidence intervals (CI) were estimated. A random effects model (DerSimonian-Laird) was used to account for heterogeneity among the included studies. Results Our meta-analysis included a total of 5 studies and 2,145 patients undergoing TAVI-in-TAVI, 72.9% (N=1,564) of whom were treated with a balloon-expandable valve. Our analysis showed that patients undergoing TAVI-in-TAVI had 3.7% (95% CI: 1.6%-5.9%), 3.9% (95% CI: 3%-4.7%) and 12.5% (95% CI: 11%-14%) in-hospital, 30-days and 1-year all-cause mortality, while stroke occurred in 1.8% (95% CI: 1.2%-2.4%), 2.1% (95% CI: 1.4%-2.9%) and 3% (95% CI: 2.3%-3.8%) of the patients in-hospital, 30-days and 1-year, respectively. Notalby, conversion to surgery, coronary compression/obstruction and perforation with or without tamponade occurred in <1% of the patients, while 6.1% (95% CI: 2.2%-9.9%) of the patients had vascular complications during the procedure. Considering the PPM implantation rates, patients had a 1.8% (95% CI: 1.2%-2.4%) for in-hospital and a 6.8% (95% CI: 5.2%-8.3%) for 30-days incidence. Conclusion Our systematic review and meta-analysis is the first to present that TAVI-in-TAVI has an acceptable safety profile with relatively low in-hospital, 30-days and 1-year mortality and stroke rates, comparable to the native-valve-TAVI. Taking into consideration that TAVI-in-TAVI might be the only therapeutic approach for an increasing number of patients, further studies are warranted to further assess its safety and efficacy and to provide additional procedural techniques.TAVI-in-TAVI mortality rates

Prognostic significance of the estimated pulse wave velocity in critically ill patients with coronary heart disease

Abstract Background The estimated pulse wave velocity (ePWV) has emerged as an alternative measurement of arterial stiffness which has been suggested as a potential marker for mortality and cardiovascular risk. Nonetheless, its prognostic significance in critically ill patients with coronary heart disease (CHD) remains uncertain. Methods Patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) were grouped into quartiles according to the ePWV levels. We conducted logistic and Cox regression analyses to examine the association between ePWV and both in-hospital and 1-year all-cause mortality among critically ill patients with CHD. Additionally, we employed restricted cubic spline (RCS) analysis to explore the relationship between ePWV as a continuous variable and mortality. Results A total of 11001 patients (men: 63.6%, age: 71.94 [IQR: 62.69-81.31]) were included in this study. In-hospital mortality and 1-year mortality rates were 9.1% and 25.1%, respectively. Multivariable logistic regression models demonstrated that ePWV was independently associated with an elevated risk of in-hospital mortality (OR 1.27; 95%CI [1.14-1.41]; p<0.001) and 1-year mortality (OR 1.49; 95% CI [1.38-1.60]; p<0.001]. The restricted cubic splines regression model revealed a linear relationship between ePWV and both in-hospital and 1-year mortality (p for non-linearity = 0.098 and p for non-linearity = 0.156, respectively). Conclusion Our findings indicate a linear association between ePWV levels and short- and long-term mortality in critically ill patients with CHD.

The prognostic impact of intra-procedural mitral valve gradient following transcatheter edge-to-edge repair for primary mitral regurgitation

Abstract Background/Introduction The impact of intra-procedural mitral valve gradient following transcatheter edge-to-edge repair (TEER) in primary mitral regurgitation (MR) is a matter of controversial debates. Purpose The aim of this study was to investigate the prognostic impact of intra-procedural mean mitral valve gradient (MPG) in patients with primary MR undergoing TEER. Methods The PRIME-MR registry included consecutive patients with primary MR undergoing TEER from 2008-2022 at 27 international sites. Clinical outcomes were assessed according to intra-procedural mean MPG measured at the end of the procedure by transesophageal echocardiography. The evolution of mean MPG from intra-procedural to discharge and follow-up was documented. Baseline characteristics and clinical outcomes of patients were investigated according to intra-procedural mean MPG using a cut-off of 5mmHg (low MPG: ≤5mmHg, high MPG: >5mmHg). The prognostic impact of intra-procedural mean MPG was evaluated in multivariable Cox regression analysis. The primary endpoint was 2-year all-cause mortality or heart failure (HF) hospitalization. Results Intra-procedural MPG was available in 1,516 patients (median age 82 years [IQR 76.0, 86.0], 55.1% male). Patients with high intra-procedural MPG presented with less atrial fibrillation and less severe MR but were more symptomatic at baseline than patients with low MPG. Moreover, patients with high intra-procedural MPG had higher baseline MPG and smaller LV dimensions (LVEDV and LVESV). The rate of patients with mean MPG >5mmHg increased from intra-procedural (18.3%) to discharge (31.3%), while remaining stable thereafter (1-year follow-up: 30.9%; last follow-up: 29.6%). At 1-year follow-up the rate of patients presenting with New York Heart Association (NYHA) functional class I or II did not differ between patients with low (82.3%) and high MPG (83.6%, p=0.93). Kaplan-Meier analysis according to mean MPG showed no difference between patients with low and high MPG for the primary endpoint (32.4% vs. 42.1%, p=0.12), as well as for the single endpoints of all-cause mortality (22.3% vs. 27.7%, p=0.47) and HF hospitalization (17.6% vs. 27.5%, p=0.087) through 2 years (Figure 1). Unadjusted spline analyses were provided to depict the prognostic impact of continuous intra-procedural MPG (Figure 2). Following multivariable Cox regression neither MPG >5mmHg (HR 0.91, 95%-CI 0.56-1.49, p=0.72), nor continuous MPG (HR 1.05, 95% CI 0.96-1.15, p=0.28) were independently associated with adverse clinical outcomes. Conclusions Based on a large international cohort of patients with primary MR undergoing TEER, intra-procedural mean MPG did not significantly affect clinical and functional outcomes at 2 years. The long-term impact of elevated post-procedural MPG warrants further investigation.Figure 1Figure 2

Sex differences in clinical characteristics, phenotypes, management, and long-term outcomes of myocardial injury: an international cohort study

Abstract Background Several studies have demonstrated sex differences in patients presenting to the emergency department (ED) with myocardial infarction, heart failure or syncope. Whether sex-specific differences in chest pain patients with myocardial injury exist is unknown. Purpose To determine whether sex-specific differences in the clinical characteristics, phenotypes, management, and long-term outcomes of patients with myocardial injury exist. Methods Patients presenting to the ED with chest pain suggestive of MI were consecutively enrolled into a prospective multicenter international diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists, applying the fourth universal definition of myocardial infarction, using all available medical records, including serial hs-cTn and cardiac imaging. Follow-ups were performed at 3 months, 1-, 2- and 5-years. The primary outcome was 5-year all-cause mortality. Secondary outcomes included 5-year cardiovascular mortality and non-cardiovascular mortality. Multivariable flexible parametric (Royston-Parmar) models assuming proportional hazards were fitted. Models were adjusted for age, history of coronary artery disease, history of malignancy, diabetes, hypertension, smoking status, history of liver disease, and renal function. Results Among 8046 chest pain patients presenting to the ED, 1158 (14.4%) had myocardial injury, of which 358 (31%) were females and 800 (69%) males. Women were older (79 years, vs. 73 years), had fewer cardiovascular risk factors and comparable non-cardiovascular comorbidities except for lung disease which was more commonly found in men. Myocardial injury phenotypes varied between sexes (Figure). The most common phenotype in both sexes was heart failure, yet it was more common in men (37.2%) than in women (22.3%). The second most common phenotype in women was hypertension (15.4%) and arrhythmia (15.4 %), while in men was myocarditis (17.8 %), followed by arrhythmia (15.8%). Women underwent less invasive coronary angiography (19.8% vs 26.9%) or stress testing (12% vs 21.5%). In the angiographic findings, women presented more often with normal findings (30.4% vs. 19.6%) or mild CAD (20.3% vs. 11.2%) whereas men displayed more frequently 3-vessel disease (14.5% vs. 36.4%), Table. After adjusting for known confounders, women were associated with a lower 5-years risk for all-cause mortality (HR 0.69; 95%CI: 0.56–0.83) and cardiovascular mortality (HR 0.61; 95%CI: 0.46–0.79). No statistically significant difference in non-cardiovascular mortality risk was found (HR 0.79; 95%CI: 0.59-1.04). Conclusions Women presenting with chest pain to the ED and having myocardial injury were less likely than men to undergo coronary angiography or non-invasive cardiac imaging. Long-term risk for all-cause or cardiovascular mortality was lower for women compared to men.Myocardial Injury phenotypesPatient management

Effects of Concurrent Administration of Spironolactone in Veterans with Metastatic Prostate Cancer Receiving Abiraterone: A Real-World Retrospective Study.

Prostate cancer is the most common cancer in men in the United States with low survival rates once metastasized. Abiraterone is approved for use in castrate-sensitive and castrate-resistant prostate cancer and is used extensively in the Veterans Affairs (VA) healthcare system. Spironolactone, a diuretic used to treat heart failure, edema, ascites, and hypertension, may increase androgen levels and reduce effectiveness of abiraterone when used concurrently to treat prostate cancer patients. While previous case studies support this, no large epidemiology studies have been conducted. The current study utilizes the large, VA prostate cancer data core and evaluates the effect of concomitant spironolactone on efficacy of abiraterone treatment in metastatic prostate cancer patients. The study selected 18,943 veterans with metastatic prostate cancer on abiraterone treatment. Of these, 581 patients (3.1%) were also on concomitant spironolactone. The concomitant treatment group, abiraterone + spironolactone, significantly differed from the abiraterone-only group in body mass index, prevalence rates of heart failure and liver disease, and being previously treated with docetaxel. A 1:1 propensity score matching method was used to balance sample sizes and baseline traits between the two treatment groups, abiraterone versus abiraterone + spironolactone. Kaplan-Meier curves and Cox proportional hazard model were used to compare 5-year overall survival and all-cause mortality outcomes, respectively, between the two groups. After propensity score matched, the abiraterone + spironolactone group was treated with abiraterone significantly longer than the abiraterone-only group (mean ± standard deviation days 549.0 ± 552.3 vs. 435.5 ± 474.1; p = 0.0002) and had a higher 5-year overall survival rate (44% vs. 37%; p = 0.0116). Veterans with metastatic prostate cancer treated with abiraterone + spironolactone also had a lower 5-year all-cause mortality compared to those only on abiraterone (hazard ratio 0.80, 95% confidence intervals 0.61-0.96; p = 0.012). This large VA observational study suggests that concomitant use of spironolactone does not compromise cancer control or survival of metastatic prostate cancer patients treated with abiraterone.

Small heart size and premature death in 366,484 individuals with normal ejection fraction

Abstract Background In patients with preserved left ventricular ejection fraction (LVEF), small ventricular size has been associated with reduced functional capacity, but its impact on clinical outcomes is unclear. Purpose The goal of this study was to determine the relationship between small heart size and premature mortality within a large multi-centre adult patient cohort with transthoracic echocardiographic examinations. Methods We divided 366,484 individuals with LVEF ≥ 50% (including a sub-set of 279,442 individuals with high-normal LVEF ≥ 60%) by sex and increasing quartiles for LV end-diastolic volume (LVEDV), LVEDV indexed to body surface area (LVEDVi) and LV end-diastolic diameter to assess associations with 5-year mortality through linkage with the National Death Index. Results During 2-million person-years of follow-up, 65,241 deaths occurred. Increasing LV chamber size was associated with reduced odds of 5-year all-cause mortality, particularly for higher LVEF. As compared with the larger quartiles, the smallest cardiac size quartiles were associated with higher 5-year all-cause mortality, even after adjusting for age (Figure 1). The smallest LVEDVi quartile was associated with a 14% and 18% higher odds of 5-year all-cause mortality for males and females, respectively, with a greater effect with high-normal LVEF. For cardiovascular-related mortality, females in the smallest quartile for LVEDVi had a 17% increased odds of mortality, which increased to 30% in those with LVEF was ≥ 60%. In men, there was no significant association between smallest cardiac size and cardiovascular-related mortality. Conclusions In individuals with normal LVEF, small ventricular size is associated with increased mortality, particularly among females and those with higher LVEF.

A novel risk score based on exercise capacity to predict all-cause mortality in adults with congenital heart disease

Abstract Background Impaired exercise capacity in adults with congenital heart disease is associated with mortality. Thus, exercise capacity is a potential tool for predicting risk in this population. The present study attempts to further explore the usefulness of exercise capacity in risk assessment of all-cause mortality, together with a limited number of easily accessible clinical variables. Methods The national register of congenital heart disease was searched for adults (18-60 years of age) with at least one bicycle ergometer exercise test and follow up in the register. The exercise capacity was classified based on percent of predicted exercise capacity (EC%pred); normal (> 70%), moderately impaired (50-70%) or severely impaired (<50%). All patients were followed for 10 years or until death, if occurring earlier than 10 years after the exercise test. Data were analyzed using logistic regression modelling. A risk evaluation model was constructed based on percent of predicted exercise capacity, age, and complexity of the heart lesion. Finally, the model was converted into a 5-point (p) risk score used to predict 10-year mortality (EC%pred >70%=0p, 50-70=1p, <50%=2p, age <25=0p, 25-40=1p, 40-60=2p, simple lesion=0p, moderate/severe complexity of heart lesion=1p). Results 1171 patients (mean age at exercise test 30.5 years, 44% women) were included with 70 deaths occurring within 10 years. A score 0-1 corresponded to <1% 10-year all-cause mortality, 2p 5%, 3p 9%, 4p 21% and 5p 33% mortality risk (Table 1). The area under curve for the model was 0.75 (95% CI 0.69-0.81). Conclusion An easily performed risk assessment containing % of predicted exercise capacity, age and complexity of heart lesion performs well in detecting patients at both low and high risk of all-cause mortality within 10 years after an exercise test.

Long-term clinical outcomes informed by artificial intelligence-enabled single-lead ECG detection of reduced ejection fraction

Abstract Background * Reduced left ventricular ejection fraction (LVEF) is linked to poor clinical outcomes (1, 2). * Despite its increasing prevalence, reduced LVEF is often undetected due to resource-limited echocardiography and lack of suitable point-of-care diagnostic tools. * Previous studies have shown that an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm can accurately identify patients with reduced LVEF, but may also offer novel insights on long-term prognosis (3, 4). Purpose We aimed to determine if an AI-ECG algorithm designed for detecting reduced LVEF can also independently predict 2-year major adverse cardiovascular events (MACE) and all-cause mortality. Method * A retrospective multicentre observational study investigating the ability of AI-ECG to predict long-term clinical outcomes (i.e. over two years' follow up). * Analysis included a total of 1,007 consecutive unselected patients attending for routine echocardiography, with a single-lead ECG recording performed at the same time. * An AI-ECG algorithm, designed to identify impaired LVEF, was applied to each single-lead ECG. * Occurrence of MACE and all-cause mortality associated with AI-ECG results (Figure 1) was investigated using Cox regression; evaluating performance of AI-ECG results as a classifier (0 or 1) and as a probability score (0 to 1). * The study was approved by the UK Health Research Authority (reference 21/LO/0051). Results * The mean age was 62.3 years. 52.4% of patients were male and 57.5% of patients were White. * Appropriately, patients with a positive AI-ECG had a higher MACE rate compared to those with a negative AI-ECG (34.2% vs. 11.9%; adjusted hazard ratio (aHR) 2.02; 95% CI, 1.46 – 2.81; p < 0.005), primarily driven by increased mortality (23% vs. 9.6%; p < 0.0001; aHR 1.65; 95% CI, 1.12 – 2.43) and heart failure hospitalization (14.5% vs. 1%; p < 0.0001) – Figure 2. * AI-ECG probability score (per 10% increase) was significantly associated with MACE (aHR 1.17; 95% CI, 1.09 – 1.25; p < 0.005) and all-cause mortality (aHR 1.11; 95% CI, 1.02 – 1.20; p = 0.01). * Importantly, sub-analysis of AI-ECG for those who have a normal LVEF (i.e. ≥50%) continued to show association between positive AI-ECG and MACE (27.2% vs. 11.9%; p < 0.0001; aHR 1.70, 95% CI 1.17 – 2.48) and all-cause mortality (20.4% vs. 9.6%; p < 0.0001; aHR 1.53, 95% CI 1.00 – 2.36). Conclusion An AI-ECG algorithm designed to identify impaired LVEF can identify patients at risk of MACE and all-cause mortality from single-lead ECG screening – regardless of their LVEF. Such results may enable further risk stratification for cardiovascular investigations through the simple addition of single-lead ECG recording.

Association between life's essential 8 score and 5-year all-cause and cardiovascular mortality in people with prediabetes: based on a cohort study

Abstract Background The Life's Essential 8 (LE8) score, which evaluates cardiovascular health (CVH) status, is linked to premature mortality in individuals with diabetes. However, the relationship between LE8 score and the risk of all-cause and cardiovascular mortality in individuals with prediabetes remains unclearly. Purpose This study aims to investigate the association between LE8 score and both all-cause and cardiovascular mortality among prediabetic patients within the United States population. Methods Our retrospective cohort study was based on the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2016. We selected prediabetic patients with blood glucose levels between normal and type 2 diabetes range from this database. The CVH status of these patients was categorized into low group (0-49), medium group (50-79), and high group (80-100) based on the LE8 score, which was assessed on a scale of 0 to 100. We constructed a multivariable Cox proportional hazards model to explore the relationship between LE8 score and mortality, and used restricted cubic spline curves to assess their non-linear correlation. Additionally, we conducted stratified analyses by age, gender, BMI, comorbid hypertension, and ASCVD in different populations to investigate the association between LE8 score and mortality. Results This study enrolled a total of 4,912 individuals with prediabetes (577 with low LE8 scores, 3,549 with medium LE8 scores, and 786 with high LE8 scores). Compared to the other groups, prediabetic patients with high LE8 scores exhibited younger age, lower BMI levels, a smaller proportion of Non-Hispanic Black individuals, higher education levels, and fewer clinical comorbidities. After adjusting for covariates using Cox proportional regression risk models, we observed that a low LE8 score was significantly associated with an increased rate of cardiovascular mortality (HR 4.13; 95% CI = 1.16-14.72) and all-cause mortality (HR 3.42; 95% CI = 1.73-6.74) in prediabetic patients. Restricted cubic splines demonstrated a linear trend between high LE8 scores and decreased risks of all-cause and cardiovascular mortality (P>0.05). Stratified analysis indicated that compared to the group with high LE8 scores, the group with low LE8 scores had a significantly higher risk of death within subgroups defined by age (≥65), gender, BMI<30, presence of hypertension, and absence of ASCVD. Conclusions In the American population, as the LE8 score increases, the risk of all-cause and cardiovascular mortality decreases for individuals with prediabetes over a 5-year period. Maintaining an ideal LE8 score will provide long-term benefits for individuals with prediabetes.Cox proportional regression modelRestricted cubic spline curves

External validation of the CA-AKI score in patients with acute coronary syndrome: A real-world cohort analysis from Asia

Abstract Background Contrast-associated acute kidney injury (CA-AKI) is associated with long-term impairment of kidney function, the need for renal replacement therapy, and subsequent all-cause deaths. A practical risk score, the CA-AKI risk score is derived for the prediction of contrast-associated acute kidney injury. However, this novel score has not received sufficient evidence of external validation in real-world studies, especially in Asian individuals. Methods Short-term endpoints and long-term endpoints were assessed in 8,816 patients with acute coronary syndrome enrolled in a large Asia registry. Discrimination was assessed by Harrell’s C statistic, and calibration was assessed by calibration plots. The ability of the CA-AKI score to predict short-term and long-term prognosis was assessed. Results CA-AKI occurred in 5.3% of the patients, with a stepwise increase of CA-AKI rates from the lowest to the highest of the 4 risk categories. When predicting the risk of CA-AKI, both discrimination and calibration were helpful in model 2 (C-index: 0.72; slope: 0.97) and in model 1(C-index: 0.69; slope: 1.02). The risks of 1-year all-cause mortality and 1-year bleeding were higher in CA-AKI patients (HR: 2.70 [95% CI: 2.22-3.30] and HR: 1.76 [95% CI: 1.41-2.46]; respectively). Conclusion The updated CA-AKI risk score could accurately identify patients with contrast-associated acute kidney injury, the occurrence of which is strongly associated with long-term mortality and bleeding.