Predictor Of Adverse Outcomes Research Articles

Cardiovascular disease history as a predictor for adverse outcomes in frail older adults admitted to acute geriatric settings: 12-month outcomes from an Australian frailty registry

Abstract Introduction Frailty is common in older adults with cardiovascular disease (CVD), with prevalence between 25-62% (1). The incidence of CVD increases with age, yet the outcomes of frail older adults with a history of CVD who present to acute geriatric settings, is not well understood. Purpose To report the association of CVD and rehospitalisation and/or mortality at 12 months in a cohort of frail older adults enrolled in an Australian frailty registry. Methods A convenience sample of participants enrolled in the frailty registry, with 12-month follow-up completed. The frailty registry is a prospective cohort study of adults admitted to the rehabilitation and aged care departments at two Australian hospitals. Frailty was assessed using the Clinical Frailty Scale (CFS), a score of 1-4 is ‘non-frail’, 5-6 is ‘mild-moderately frail’ and 7-9 is ‘severely frail’ (2). For this study, ‘CVD’ was defined as having a history of either heart failure, stroke, or atrial fibrillation. The cumulative incidence of first rehospitalisation and/or death during the first 12 months post discharge was estimated using one minus the Kaplan-Meier estimate of the survival function. Association between CVD (history of CVD, and type of CVD condition) and the composite endpoint were analysed. Adjusted Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox models incorporating variables of interest and potential confounders. Results A total of 592 participants were included, median age was 82 years, 59% (n= 349) were female. The majority were frail with 50% (n= 295) classified as mild-moderately frail and 21% (n= 123) classified as severely frail. Almost half (45%, n= 265) had a history of CVD. The incidence of frailty (CFS score ≥5, mild-severely frail) was higher in those with CVD compared to those without CVD (76% vs 66%). A history of CVD was significantly associated with higher rate of first readmission or death within 12 months, compared to no history of CVD (p=0.017) (Figure 1). Of the three CVD conditions, heart failure was the only independent predictor of the composite endpoint (HR 1.60 [CI 1.14 -2.24], p=0.007). A CFS score of mild-moderately frail (HR 1.51 [CI 1.18 - 1.93, p=0.001) and severely frail were also independent predictors of the composite endpoint (HR 1.83 [CI 1.35- 2.48], p=<0.001) (Table 1). Conclusions A history of CVD has a significant impact on adverse outcomes in frail older adults admitted to acute geriatric settings. Frailty according to the CFS was independently predictive of rehospitalisation and mortality in this cohort. Heart failure was the only independent predictor of the composite endpoint. These findings underscore the importance of identifying and addressing CVD and in the context of frailty, emphasising the need for targeted interventions to improve outcomes in this vulnerable population.Figure 1.Table 1.

Estimated aortic pulse wave velocity predicts adverse events in females with thoracic aortic aneurysms

Abstract Introduction Despite being more common in males, thoracic aortic aneurysms (TAAs) have worse prognosis in females. Females with TAA are 3x more likely to experience acute aortic syndromes, and 40% more likely to die than their male counterparts, but mechanisms underlying this paradox are incompletely understood. The estimated aortic pulse wave velocity (e-PWV) is a marker of aortic stiffness that can be used widely due to its simplicity, as it does not require specialized equipment. We have previously shown that e-PWV was independently associated with faster TAA growth,(1) and that this association was twice as strong in females than males, but the role of e-PWV as a predictor of adverse outcomes in TAA remains unknown. Purpose We sought to evaluate the sex-specific association of e-PWV with adverse outcomes in patients with TAA. Methods We performed a prospective study of 102 males and 48 females with TAA. e-PWV was calculated according to validated equations utilizing age, mean arterial pressure, and presence/absence of cardiovascular risk factors.(2) The primary outcome was a composite of acute aortic syndromes, death, or elective aortic surgery. We used a Cox proportional hazard model to determine the independent association of e-PWV with the primary outcome, adjusted for age, BSA, aneurysm size and location, hypertension, and pulse pressure. Sex-specific models were performed if the interaction of sex*e-PWV was significant (P≤0.05). Univariate logistic regression models were performed to determine the c-statistic for e-PWV in predicting adverse outcomes, and the best e-PWV cutoff for this prediction was established based on sensitivity and specificity. Kaplan-Meier curves were performed using this cut-off. Results A summary of study design and results is presented in Picture 1. Mean age was 62±12 years, 70 (47%) had degenerative etiology, baseline aneurysm size was 46.3±4.3mm, and e-PWV was 9.5±1.9 m/s (not different between sexes, P>0.07 for each). Mean follow-up was 4.6±2.4 years in females and 5.5±2.3 years in males, P=0.031. The primary outcome occurred in 37 (25%) participants (3 dissections, 3 intramural hematomas, 1 aortic rupture, 22 elective surgical repairs and 11 deaths - 3 of which followed surgery). The interaction term sex*e-PWV was significant (P=0.0001), so sex-specific models were performed. e-PWV independently predicted the primary outcome in females (HR for 1m/s increase in e-PWV: 3.4; 95% confidence interval (CI): 1.1-14.7, P=0.033), but not in males (HR: 0.87; 95% CI: 0.50-1.51, P=0.622). In females, e-PWV had a c-statistic of 0.860 for the detection of the primary outcome, with a best e-PWV cutoff of 11.58 m/s (73% sensitivity, 92% specificity). Kaplan-Meier curves for the primary outcome in females using this cutoff are shown in Picture 2. Conclusion e-PWV independently predicts adverse outcomes in females with TAA, highlighting a novel marker for risk stratification and therapeutic targeting.Study summaryKaplan-Meier curves

Association of Neutrophil extracellular traps burden with clinical and angiographic characteristics in patients with ST-elevation myocardial infarction

Abstract Background The precise triggers for arterial plaque rupture and the underlying pathophysiology of thrombogenesis remain elusive. Polymorphonuclear neutrophils (PMN), particularly their formation of Neutrophil Extracellular Traps (NETs), have garnered attention in the context of coronary atherothrombosis. This study sought to explore the association of NETs burden with clinical and angiographic characteristics in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI) and thrombus aspiration (TA). Methods This study included 336 consecutive STEMI patients undergoing pPCI and TA. Aspirated thrombi underwent histological analysis and NETs quantification via immunohistochemistry. Potential associations of clinical variables and angiographic outcomes with NETs burden were assessed. Results Manual TA was selectively performed in 72 cases with increased thrombotic burden and 60 thrombi were suitable for analysis. Most thrombi specimens displayed lytic features (63%) and almost three out of four specimens were identified as white thrombi. Increased NETs burden was significantly associated with prolonged pain-to-balloon time (>300 minutes) OR=10.29 (95% CI 2.11-42.22, p=0.001) and stress-induced hyperglycemia (SIH) OR=6.58 (95% CI 1.23-52.63, p=0.04) after multivariate regression analysis. Additionally, distal embolization (DE), a predictor of adverse outcomes, was more frequent among patients with an elevated NETs burden OR=16.9 (95% CI 4.23-44.52, p<0.001). Conversely, no significant association between NETs burden and final TIMI flow=3 was observed. Conclusion Elevated NETs burden in STEMI thrombi is linked to delayed reperfusion, SIH and increased risk of DE. Further research is needed to elucidate the role of NETs as a potential therapeutic target in acute atherothrombosis.

The effect of exercise on RV-PC coupling in asymptomatic patients with significant primary mitral regurgitation

Abstract Background Right ventricular–pulmonary circulation (RV-PC coupling) serves as an index to evaluate RV function in relation to underlying RV afterload. Although impaired RV-PC coupling has been proposed as a predictor of adverse outcomes in heart failure (HF) patients with secondary mitral regurgitation (MR), there is limited data available for patients with primary MR. Purpose The objective of this study was to assess and compare alterations in RV-PC coupling during exercise with bicycle stress echocardiography in individuals with asymptomatic moderate to severe primary MR (MR group) and normal subjects (Control group). Μethods All patients and controls underwent stress echocardiography with a supine bicycle. RV systolic function was evaluated with TAPSE and S’. The non-invasively measured RV-PC coupling was evaluated by indexing TAPSE and S’ to right ventricular systolic pressure (RVSP) during baseline echocardiogram and peak workload stages of bicycle SE. Results Among the 48 patients in the MR group (mean age 53.5±15.16 years, 58.3% female), 39 patients had moderate MR(81.3%), 5 patients had moderate-to-severe MR(10.4%), and 4 patients had severe MR(8.3%). The duration of stress echocardiogram was significantly shorter in the MR group compared to control group (8.11±2.39 min vs 10.5±1.05 min, respectively; p<.001). Left Ventricular Ejection Fraction (LVEF) was within normal limits in both groups {70.7±11.9 % vs 72.6±12.1 %(p=NS} and the dimensions of left ventricular cavity (end-diastolic and end-systolic diameters) were significantly larger in the MR group compared to control group (49.25±5.21 mm vs 45.6±4.08mm (p .016) and 31.81±4.27mm vs 29.07±4.21mm (p .033) respectively}. TAPSE and RVSP increased from baseline to peak dose [23.48 ±3.05mm vs 29.94±3.48mm (p < .001), 8.54±4.56mmHg vs 43.79±5.27mmHg (p < .001), respectively]. There were no significant differences in TAPSE/RVSP and S’/RVSP between the two groups at rest. However, a significantly steady decrease was observed from baseline to peak dose (0.84±0.16 mm/mmHg vs 0.72±0.19mm/mmHg (p <.001) and 0.52±0.11 cm/sec/mmHg vs 0.50±0.15 cm/sec/mmHg (p .004), respectively). Conversely, these parameters did not exhibit a significant decrease in the control group. Finally, there was no significant correlation observed between the changes in the index TAPSE/RVSP , ratio E/E’ and systolic blood pressure. Conclusions RV-PC coupling decreases during exercise in asymptomatic patients with moderate to severe MR, independently of left ventricular dynamic changes. In contrast , there is no significant change in RV-PC coupling observed in the control group. Therefore, future studies should aim to evaluate the incremental role of this novel index not only in the assessment and evaluation of patients with MR but also as a potential prognostic marker.TAPSE/RVSP GraphTable of echocardiographic measurements

Peak atrial longitudinal strain to replace atrial volume in diastolic function grading: associations with long-term outcomes in a community-based sample with normal left ventricular ejection fraction

Abstract Background Diastolic dysfunction (DD) often precedes symptomatic heart failure and is a predictor of adverse outcomes; thus, accurate assessment and grading are crucial for early interventions. Current guidelines recommend combining multiple echocardiographic parameters, including left atrial volume index (LAVi), for diagnosing DD in patients with normal left ventricular ejection fraction (LVEF). Recently, peak atrial longitudinal strain (PALS) emerged as a more sensitive marker of left atrial function, although its added value in the grading of DD and associated adverse outcomes is scarcely explored. Purpose We aimed to investigate the impact of replacing LAVi with PALS on DD grading by its associations with long-term all-cause mortality in a low-risk, community-based sample. Methods We retrospectively identified 1319 volunteers from a population-based screening program (mean age 53.8±14.9 years, 59.1% female) with LVEF>50%. Subjects underwent echocardiography to measure mitral annular early diastolic velocities (e’), the ratio between mitral inflow early diastolic velocity (E) and e' (E/e'), tricuspid regurgitation peak velocity, LAVi, and PALS by speckle tracking. Diastolic function was initially classified according to the 2016 ASE/EACVI guidelines into normal, indeterminate, and DD groups and then reclassified by replacing LAVi>34 ml/m² with a standard PALS cut-off of <24%. The primary endpoint was all-cause mortality. Results During the median follow-up time of 11 years, 135 (10,2%) subjects met the primary endpoint. According to guideline definitions, 59 subjects were diagnosed with DD, 128 were indeterminate, and 1132 showed normal function. Kaplan-Meier analysis (Figure 1) showed significant differences in mortality between normal versus indeterminate and DD groups (log-rank p<0.001), with a three-fold (HR [95% CI]: 3.363 [1.802 - 6.274], and nearly five-fold increased risk (HR [95% CI]: 4.935 [1.919 - 12.690], respectively. Notably, no significant difference was observed between the outcomes of the indeterminate and DD groups. When subjects were reclassified using PALS instead of LAVi, 35 had DD, 75 were indeterminate, and 1209 had normal function. This classification resulted in different outcomes between groups (Figure 2, log-rank p=0.003). Compared to the normal, the indeterminate group exhibited a two-fold increase in mortality risk (HR: 2.277 [95% CI: 1.038-4.997]), while the DD group had a ten-fold increased risk (HR: 10.180 [95% CI: 2.870-36.130]). DD was associated with a nearly five-fold increase in mortality risk (HR: 4.724 [95% CI: 2.177-10.250]) compared to the indeterminate group. Conclusions In a community-based sample with normal LVEF, replacing LAVi with PALS in diastolic function classification separated groups with significant differences in their long-term all-cause mortality. This adjustment also reduced the size of the indeterminate group and refined its mortality risk.Figure 1Figure 2

CMR-derived pulmonary artery to aorta ratio as a predictor of adverse outcome in patients with cardiac transthyretin amyloidosis

Abstract Introduction Cardiac transthyretin amyloidosis (ATTR) represents a heart failure phenotype often accompanied by pulmonary hypertension. The pulmonary artery to aorta ratio (PA/Ao), as assessed on cardiac computed tomography or cardiac magnetic resonance (CMR), has demonstrated to indicate risk for adverse events in a variety of cardiovascular diseases, particularly in heart failure and pulmonary hypertension. However, its prognostic value in cardiac ATTR remains unknown. Aim We aimed to investigate the prognostic value of the PA/Ao ratio in patients with cardiac ATTR. Methods Data of consecutive patients diagnosed with cardiac ATTR undergoing CMR were prospectively collected. PA/Ao ratios were measured from CMRs using axial images (Figure 1A). Adverse outcome, defined as heart failure related hospitalizations and/or mortality, was recorded during follow-up. Results Among the 190 confirmed cardiac ATTR patients (mean age 76±11 years, 79% males), encompassing hereditary transthyretin (vATTR, n=22) and senile (wtATTR, n=168) types, the median pulmonary artery diameter was 28mm (IQR 25-31) and the median ascending aorta diameter was 35mm (IQR 33-39). Over the median follow-up period of 28 months (IQR 11-50 months), 84 (44%) patients experienced an adverse event. Kaplan Meier curves demonstrated an increased risk for adverse outcome in patients with PA/Ao ratios above the median of ≥0.8 (p<0.001 by log rank test, see Figure 1B). In univariate analysis, a high PA/Ao ratio was associated with adverse outcome (HR=10.3, 95% CI=2.59–41.1, p<0.001). When adjusted for age, sex, body mass index and right ventricular function, the PA/Ao ratio remained significantly related to adverse outcome (adj. HR=10.8, 95% CI=1.76–65.8, p=0.010). Conclusion A PA/Ao ratio ≥0.8 on CMR is associated with heart failure hospitalization and death in patients with cardiac ATTR. This threshold, notably lower than the commonly reported ≥1.0 in other patient populations, holds promise for future risk stratification.

Refining risk stratification in hypertrophic cardiomyopathy: the role of late gadolinium enhancement and syncope in predicting adverse outcomes

Abstract Background The presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (MRI) is recognized as a significant marker of myocardial fibrosis and a predictor of adverse outcomes in hypertrophic cardiomyopathy (HCM). Nevertheless, the specific quantity of LGE that correlates with poor outcomes is still under debate. Therefore, this study sought to assess the combined impact of LGE presence and a history of syncopal events and its association with clinical prognosis. Methods Between May 2018 and June 2023, a total of 230 HCM patients was prospectively enrolled at our Medical University, a tertiary referral center. The primary endpoint was a composite of new-onset ventricular tachycardia (VT), appropriate ICD therapy, and all-cause mortality. Results Median age of enrolled patients was 56 (IQR 44-64) years and 40% (n=94) were female. Median interventricular septal thickness (IVS) was 21 (IQR 18–25) mm and 43 % (n=84) had significant left ventricular outflow tract obstruction (LVOTO). Over a median follow-up of 3.2 years, 30 patients (13%) met the composite endpoint. These patients had a significantly higher LGE quantity compared to the non-event group (1.1 % vs. % 9.0, P=0.012). An LGE threshold of 5.2% was identified as an optimal predictor of the composite endpoint, with an area under the curve of 0.72, which increased to 0.77 when including at least one syncopal event in medical history. LGE > 5.2% and/or syncope were independently associated with adverse outcomes after multivariable adjustment (Adj HR 7.26 [95%CI 2.54-20.72]). Furthermore, NTproBNP and hsTnT were associated with the presence of LGE or syncope (OR for a 1-unit increase in standardized log-transformed biomarker NTproBNP 3.35 [95%CI 1.42-10.85]; hsTnT 3.48 [95%CI 1.48-10.24], respectively). Interestingly, typically used variables for risk stratification, such as age, IVS or LVOT were not significantly associated with these cardiac biomarkers. Conclusion An extent of LGE > 5.2% and the history of at least one syncope are associated with unfavorable clinical outcomes in HCM patients. These findings call for detailed MRI appraisal and suggest adopting a holistic approach to accurately identify high-risk patients.

The correlation between the confusion assessment method for intensive care units 7-item, the intensive care delirium screening checklist and adverse outcomes after post-cardiac surgery delirium

Abstract Background Postoperative Delirium(POD) and Subsyndromal Delirium(SSD) remain prevalent, particularly among the cardiovascular surgical population due to the utilization of cardiopulmonary bypass. Adverse outcomes, such as prolonged ICU stay, extended length of stay, and increased incidence of adverse events, are associated with individuals diagnosed with Postoperative Delirium or those experiencing fluctuations between Postoperative Delirium and Subsyndromal Delirium during ICU stays. Therefore, early delirium screening is of utmost importance. The Intensive Care Delirium Screening Checklist(ICDSC) and the Confusion Assessment Method for the Intensive Care Unit 7-item(CAM-ICU-7) are validated delirium screening instruments for critical patients. Purpose This study aims to determine whether the ICDSC or the CAM-ICU-7 is the superior predictor for adverse outcomes following Postoperative Delirium among the cardiovascular population. Methods In this prospective cohort study, 84 patients who underwent elective cardiovascular surgery underwent a total of 833 paired assessments(ICDSC and CAM-ICU-7) twice daily by the researcher. The correlation between the results of ICDSC and CAM-ICU-7 was evaluated. Multiple linear regression was employed to explore associations between ICDSC and CAM-ICU-7 and length of ICU stay, length of overall stay, and the total number of adverse events. The best model was selected after testing with Pearson's correlation coefficient, Hotelling's t, and Steiger's Z tests. Logistic regression explored associations between ICDSC and CAM-ICU-7 and adverse events. Results Postoperative Delirium incidence evaluated by the ICDSC and CAM-ICU-7 was 47.61% and 45.23%, respectively. The incidence of fluctuations between Postoperative Delirium and Subsyndromal Delirium evaluated by the ICDSC and CAM-ICU-7 was 34.52% and 21.43%, respectively. The agreement between the ICDSC and CAM-ICU-7 is high(kappa = 0.835, p<0.001) in detecting Postoperative Delirium but fair in detecting Subsyndromal Delirium(kappa = 0.213, p<0.001). Our research revealed that the length of ICU stay can be predicted by POD(detected by ICDSC and CAM-ICU-7) and fluctuated POD and SSD(detected by ICDSC but not CAM-ICU-7). However, only fluctuated POD and SSD detected by ICDSC could predict hospital length of stay. The total number of adverse events and incidence could be predicted by POD either detected by ICDSC or CAM-ICU-7 but only fluctuated POD and SSD detected by ICDSC, not CAM-ICU-7, could predict the total number of adverse events. Conclusions Both ICDSC and CAM-ICU-7 can detect Postoperative Delirium with high agreement. However, ICDSC could identify more individuals with both Postoperative Delirium and Subsyndromal Delirium, thus predicting more adverse outcomes than CAM-ICU-7. Therefore, ICDSC emerges as the superior delirium screening instrument for the cardiovascular population.

The gut-microbiome derived phenylacetylglutamine predicts adverse events in patients with acute coronary syndromes

Abstract Background and Introduction The gut microbiota-derived metabolite phenylacetylglutamine (PAG) is associated with incident cardiovascular events(1). Acute coronary syndromes (ACS) present a major health challenge, especially as population ages(2). Data from our group show increased PAG levels during aging in humans. However, the predictive potential of PAG for mortality and major adverse cardiovascular events (MACE) in patients (pts) with ACS is unknown. Purpose Here, we investigated the potential of PAG to predict ischemic and fatal events in pts with acute coronary syndromes (ACS). We also compared the predictive potential of PAG to another relevant gut-microbiota derived metabolite involved in CVD, namely Trimethylaminoxyde, (TMAO), and we evaluated their cumulative risk potential. Methods A total of 1’848 patients were enrolled in Cohort I of the SPUM-ACS study – a multi-center prospective ACS cohort study from Switzerland. Overall survival and incident MACE after 1 year follow-up were analyzed using Kaplan-Meier (KM) estimates and compared by log-rank test after patient stratification into PAG tertiles. Uni- and multivariable Cox-regression models were fit to calculate the hazard ratios for 1-year MACE in a crude model and adjusted model (adjusted for established confounders). Healthy controls served as additional controls. PAG plasma levels were quantified using LC-HRMS. Results The median PAG plasma level in the healthy control group was 1.76µM, whereas for the whole ACS patient population it was 1.92µM (Table 1). Pts in the third PAG tertile had a two times higher MACE rate and a four times higher mortality rate compared to pts in the first PAG tertile (p<0.001). (Table 2). PAG levels were significantly higher in pts who presented with MACE (2.63µM) or died (3.1µM) within the 1-year follow-up compared to the healthy control subjects (p<0.0001) (Figure 1A). Spearman correlation analysis revealed that plasma PAG levels were positively associated with age (r=0.43, p<0.0001), while a negative association with eGFR was observed (r=-0.51, p<0.0001) (Figure 1B). KM estimates indicated that pts in the highest PAG tertile had significantly higher 1-year MACE risk relative to those with low levels (Figure 1C; p<0.001 log rank). Following multivariable adjustment, PAG remained an independent predictor for MACE at 1-year follow-up with a hazard ratio (HR) of 1.8 (95% CI, 1.1–3.2, p=0.048) (Figure 1D). KM estimates of both, high levels of PAG and high levels of TMAO together, indicate that the combination of these two detrimental metabolites leads to an even higher risk of 1-year MACE relative to lower levels (Figure 1E). Conclusion PAG is a novel and independent predictor of adverse outcomes in patients with ACS. This study indicates the role of the gut-microbiome and its metabolites in predicting ischemic and fatal outcomes of pts with established CVD.

Right atrio-ventricular strain as a predictor of death in left-sided heart failure

Abstract Background Right ventricular (RV) strain is an established outcome predictor in heart failure (HF). However, the role of right atrial (RA) strain in the setting of left-sided HF is incompletely understood. Purpose We sought to evaluate the RV, RA and combined right atrio-ventricular (RAV) strain using speckle-tracking echocardiography in a cohort of patients with left-sided HF and to assess their prognostic role. Methods 121 consecutive patients (mean age 59±14 years, 74% men) with HF with reduced ejection fraction (HFrEF) referred to our echocardiography department were prospectively enrolled. The main endpoint was all-cause death. RV strain was measured as the average longitudinal strain of the basal, mid, and apical segments of the RV free wall and was reported as a positive value, thus a lower RV strain reflecting a greater longitudinal dysfunction. RA strain was defined as the maximal longitudinal displacement of the atrial wall at end-systole, corresponding to atrial reservoir function. RAV strain was defined as the sum of RV strain and RA strain. Results During a median follow-up of 19±11 months, 26 patients (21%) died. Patients who reached the endpoint had lower left ventricular ejection fraction (LVEF) (21±7% vs. 26±7%, p=0.001), lower tricuspid annular plane systolic excursion (16±3 vs. 18±5, p=0.02) and lower RA strain (13± 10% vs. 18±11%, p=0.03). In univariable Cox regression, RV, RA and RAV strain were all predictors of death: HR=1.05 [95% CI, 1.00-1.11], p=0.045 for RV strain, HR=0.95 [95% CI, 0.91-0.99], p=0.02 for RA strain, HR=0.97 [95% CI, 0.94-0.99], p=0.01 for RAV strain. We constructed a multivariable model with well-established event predictors in HFrEF and one strain index at a time. After adjustment for LVEF, maximal left atrial volume, tricuspid regurgitation severity and pulmonary artery systolic pressure, only RAV strain remained an independent predictor of death (HR=0.97 [95% CI, 0.94-1.00], p=0.04), while RV strain and RA strain did not (p=0.07 for both). LVEF did not emerge as a predictor of death in multivariable regression (p=0.57). Conclusion In left-sided HF, RV and RA strain were predictors of death. Combining the longitudinal strain of both right heart chambers might improve risk stratification, since RAV strain remained the only independent predictor of adverse outcome after adjustment for confounders.

Prognostic value of alveolar surfactant type-B in acute heart failure: a long-term comparative analysis vs NT-proBNP

Abstract Background In heart failure (HF) biomarkers are an integral component of prognostic assessment. Natriuretic peptides are the gold standard, but they do not directly reflect lung vascular injury. Surfactant type B (Surf-B) is released by type 2 alveolar cells under pressure induced trauma, with few reports just addressing its plasmatic levels in stable chronic HF (CHF). Information on acute HF (AHF) is lacking. Purpose To clarify the prognostic value of Surf-B changes vs NT-proBNP levels after decongestion therapy and to compare their prognostic ability at 1-year follow-up. Methods Patients with acute pulmonary edema (APE) underwent a combined evaluation of Surf-B and NT-proBNP serum levels with quantification of B-lines at hospital admission (time 0), discharge (time 1) and at 1 year (time 2). Results 54 patients (mean age 72.1 ± 11 years; mean LVEF 36% ± 13%; 65% men) were enrolled. At time 1, the average Surf-B, NT-proBNP and B-lines were significantly reduced compared to time 0 (p<0.0001). No correlation between Surf-B and NT-proBNP was observed either at time 0 (r=-0.21; p=0.12) or at time 1 (r=0.05; p=0.71). Despite the significant decrease in Surf-B levels from time 0 to time 1, 18.5% of patients behaved as non-responders exhibiting no changes in Surf-B; conversely, only 5.5% did not show significant reduction in NT-proBNP, despite significant decongestion. 38 patients were followed up to time 2: of these, 13 (34%) reached the composite endpoint of death or hospitalization for HF. Surf-B measured at time 1 was a strong predictor of adverse outcome. Patients with Surf-B above median at discharge displayed a worse survival-free from HF hospitalization compared to the remainders (Log rank p=0.012) (Figure). Also, patients with Surf-B above median at discharge had a more than 4-fold increased risk of the composite endpoint (HR 4.5, 95%CI 1.4-20.2, p=0.023). Conversely, NT-proBNP at discharge was not significantly associated with HF-free survival (Log rank p=0.26) (Figure) and was not a significant predictor of the composite outcome (HR 1.9, 95%CI 0.6-9.3, p=0.25). At ROC analysis, discharge Surf-B levels showed a higher area under the curve (AUC=0.763, p=0.011) than NT-proBNP values (AUC=0.69, p=0.063). Conclusions These data suggest that Surf-B, an organ specific biomarker of lung injury, is highly sensitive to the effectiveness of decongestion therapy, outperforming NT-proBNP. Given the high rate of patients who do not improve their Surf-B levels over time, the reparative processes of alveolar break damage may dissociate from mere decongestion and cardiac healing in AHF.Figure:1yr Kaplan-Meier survival curves

Unveiling the prognostic journey: renal function trajectories in 'de novo' heart failure with reduced ejection fraction - insights from a cohort study and their impact on patient outcomes

Abstract Background HFrEF poses significant clinical challenges globally. Renal dysfunction frequently coexists with HF, exacerbating prognosis. However, the dynamic trajectory of renal function in 'de novo' HFrEF patients and its prognostic implications remain understudied. Methods We conducted a prospective cohort study involving 370 'de novo' HFrEF patients. Renal function was initially assessed upon admission and re-evaluated at the end of the titration period. The CKD-EPI formula was used for renal function assessment. Patients were followed up for a median of 15 months. Statistical analyses were performed to evaluate predictors of adverse outcomes. Results Baseline renal function significantly influenced outcomes, with eGFR < 45 ml/min associated with higher mortality and heart failure readmissions. Among patients with available renal function data at discharge (n=354), 87 (24.6%) had eGFR < 45 ml/min, while 267 (72.2%) ≥ 45 ml/min. Patients with eGFR < 45 ml/min exhibited older age, higher prevalence of comorbidities, lower haemoglobin levels, and higher creatinine and NT-proBNP levels, both at admission and discharge. Furthermore, they were less likely to receive certain heart failure medications at discharge. During follow-up, 46 deaths (13.0%) and 105 events of combined all-cause death and readmission due to heart failure (29.6%) occurred. Patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.29, p < 0.001) and all-cause death and heart failure readmissions (HR: 0.32, p < 0.001) both in univariate and multivariate analysis (HR: 0.63, p = 0.028 for mortality; HR: 0.53, p = 0.038 for combined endpoint). See Figure 1. Among patients with available renal function data at follow-up (n=304), 240 (78.9%) had eGFR ≥ 45 ml/min (stabilization or improvement), and 64 (21.1%) had eGFR < 45 ml/min (deterioration or previously < 45 ml/min). Patients with eGFR < 45 ml/min at follow-up exhibited older age, lower BMI, higher prevalence of comorbidities, lower haemoglobin levels, and higher NTproBNP levels at admission and discharge. They were also less likely to receive certain crucial heart failure medications at discharge and follow-up (Table 1). During follow-up, 31 deaths (10.1%) and 87 events of combined death and readmission due to heart failure (38.6%) occurred. In univariate analysis, patients with eGFR ≥ 45 ml/min exhibited a lower overall mortality (HR: 0.27, p < 0.001) and admissions (HR: 0.30, p < 0.001), which remained significant in multivariate analysis (HR: 0.43, p = 0.048 for mortality; HR: 46, p = 0.014 for admissions). See Figure 1. Conclusion Our findings underscore the importance of integrated heart-kidney care in 'de novo' HFrEF patients. Continuous monitoring of renal function and interventions to prevent deterioration are crucial for optimizing outcomes. Further research is needed to validate these findings and explore targeted therapeutic strategies for renal protection in HFrEF.

Frailty and MECKI score in predicting mortality in advanced heart failure

Abstract Background Physical frailty (PF), characterized by decreased physiological reserves and increased vulnerability to stressors, has emerged as a significant predictor of adverse outcomes in heart failure (HF). The MECKI (Metabolic Exercise Cardiac Kidney Index) score, a composite index derived from cardiopulmonary exercise testing parameters and renal function, has shown promise in predicting outcomes in HF patients. Purpose The aim of the study is to evaluate the independent prognostic role of the MECKI score and PF on mortality in patients with advanced heart failure (AHF). Methods Ninety-one patients with AHF were enrolled, including 42 on the heart transplant waiting list, 10 undergoing evaluation for listing, and 49 removed from the list due to transplant contraindications or reaching age limits. All patients included in the study were on medically optimized therapy. MECKI score assessment was conducted upon enrollment, along with hematological and biochemical evaluations including creatinine, hemoglobin, Na+, and NT-pro-BNP levels. Patients also underwent echocardiography assessing ejection fraction (EF), TAPSE, Inferior Vena Cava (IVC) diameters, and PASP. Additionally, all patients performed the 6-minute walk test (6MWT) and cardiopulmonary exercise testing with assessment of VO2max and VE/VCO2. Frailty was assessed based on modified Fried criteria. Results The mean age was 56.5±11.2 years. Mean NYHA class was 2.7±0.6, EF was 28.8±7.6, TAPSE was 17.5±4.2, and NT-proBNP was 2912.2±3249.0. Mean VO2max was 12.0±3.5 ml/kg/min, and mean distance walked during 6MWT was 278.8±137.2 meters. Mean frailty score was 3.2±1.2 while mean MECKI score was 15.2±14,2. During a mean follow-up of 32.0±15.3 months, there were 21 deaths, 15 patients received heart transplants, and 1 patient underwent LVAD implantation. Stratified data for mortality showed statistically significant differences in deceased patients compared to survivors regarding NYHA class (3.2±0.3 vs 2.6±0.7; p<0.001), Frailty Index (4.4±0.7 vs 2.7±1.13; p<0.001), NT-proBNP (5425.0±2863.0 vs 1731.0±1618.0; p<0.001), VE/VCO2 (42.7±12.3 vs 35.0±9.1; p<0.003), and MECKI score (29.4±15.2 vs 11.2±11.2; p<0.001). Linear regression analysis demonstrated a significant positive correlation for Frailty Index and MECKI score with age, NYHA class, VE/VCO2, IVC, and NT-proBNP, while showing a negative correlation with TAPSE, VO2max, and 6-minute walk test. Cox regression analysis on mortality demonstrated the predictive role of Frailty (HR=2.121; 95%CI=1.017-4.421; p=0.045) and MECKI score (HR=1.043; 95%CI=1.009-1.079; p=0.014) independently from age, sex, NYHA class, NT-proBNP, EF, TAPSE, VO2max, 6MWT, and IVC diameter. ROC curves demonstrated an AUC of 0.896 for MECKI score and mortality, and 0.884 for Frailty Index and mortality. Conclusions The MECKI score and physical frailty are both valid independent predictors of mortality in patients with advanced heart failure.

Elevated mitral valve pressure gradient following transcatheter edge-to-edge repair is independently associated with inferior outcomes in atrial, but not in ventricular secondary mitral regurgitation

Abstract Background In transcatheter mitral valve edge-to-edge repair (M-TEER), the goal of optimizing post-procedural residual mitral regurgitation inadvertently carries the risk of generating relevant mitral stenosis, resulting in an elevated mean mitral valve pressure gradient (MPG). In patients with primary mitral regurgitation, an elevated post-procedural MPG has been found to independently predict impaired outcomes. However, the effect of elevated post-procedural MPG on outcome after M-TEER in patients with secondary mitral regurgitation (SMR) has yet to be fully elucidated. This study investigated the impact of elevated MPG on outcome in the EuroSMR registry, a large, multi-center real-world cohort of patients with SMR. Methods This retrospective study included patients who underwent M-TEER for SMR between 2009 and 2021 in 12 centers. Patients were stratified into two groups based on SMR etiology: (1) ventricular SMR (vSMR), and (2) atrial SMR (aSMR). The etiology was considered as vSMR in patients with a left ventricular ejection fraction (LV-EF) <50% and aSMR in subjects with preserved left ventricular function (LV-EF ≥50%) and a markedly dilated left atrium (Left Atrial Volume Index [LAVi] ≥40ml/m2). According to the proposed M-VARC threshold, post-procedural MPG was assessed by discharge transthoracic echocardiography and was considered elevated if >5 mmHg. The primary endpoint was all-cause mortality after 5 years, with statistical analysis conducted using Kaplan-Meier and uni- and multivariable Cox Regression analysis. Results Among the 1703 patients in the study (vSMR: n=1420; aSMR: n=283), elevated post-procedural MPG was observed in 9.4% (n=133) of vSMR and 19.1% (n=54) of aSMR patients. Atrial fibrillation was significantly more prevalent in aSMR (78.4% vs. 57.1%, p<0.001). Patients with vSMR had a higher median surgical risk assessed by the EuroScore II (aSMR vs. vSMR: 7.0% [IQR 4.0, 13.1] vs. 4.9% [IQR 2.9, 8.5], p<0.001). Kaplan-Meier analyses for all-cause mortality after 5 years demonstrated significant differences in aSMR patients (low vs. elevated MPG: 48.9% vs. 69.8%, log-rank p<0.01), while there was no difference in vSMR patients (55.7% vs. 60.8%, log-rank p=0.66) (Figure 1). This observed effect remained significant even after accounting for common confounding factors: elevated MPG was an independent predictor for all-cause mortality in aSMR patients (HR=1.86; 95%-CI: 1.14-3.02, p=0.013) but not in vSMR patients (HR=1.00; 95%-CI: 0.74-1.35, p=0.99). Conclusion Our findings suggest that elevated post-procedural MPG is an independent predictor of adverse outcomes in patients with aSMR, but not in those with vSMR. This effect may partially be explained by a reduced left atrial function and higher rates of atrial fibrillation.Figure 1.Study flowchart

HFpEF is associated with a higher risk of hospitalization or death in men undergoing transcatheter edge-to-edge tricuspid valve repair

Abstract Aims There are fundamental differences between women and men regarding the pathophysiology and etiology of tricuspid regurgitation (TR) as well as underlying comorbidities. The aim of this study was to analyze differences between female and male patients undergoing transcatheter edge-to-edge tricuspid valve repair for TR (T-TEER) and to identify gender-specific predictors of adverse outcome. Methods and Results In this monocentric study 197 consecutive patients (96 women and 101 men) undergoing T-TEER at our university heart center were included. Prevalence of heart failure with preserved ejection (HFpEF) was higher in women than in men (63% vs. 37.3%; p=0.001) whereas men more often had heart failure with reduced ejection fraction (HFrEF; 62.7% vs. 37%; p=0.001). Women had more severe symptoms (86.2% in New York Heart Association (NYHA) class III-IV vs. 72.3% in men; p=0.022). Device success rates (p=0.64), procedural characteristics (e.g. number of clips, p=0.17) and postprocedural results (TR grade post clip, p=0.1) were comparable. One-year mortality did not differ between genders (5.9% in women, 8.6% in men; p=0.53). Likewise, no significant difference could be found with regard to heart failure hospitalizations within one year after T-TEER (20.3% in women, 18.8% in men, p=0.82). Strikingly, prevalence of HFpEF was substantially higher than of HFrEF in men that reached the combined endpoint of one-year mortality or rehospitalization for heart failure (61.5% vs. 38.5%; p = 0.08). In women, no relevant difference could be found (27.0% vs. 32.4%; p=0,623). To identify gender-specific predictors of the combined endpoint, a cox regression analysis was performed. In men, HFpEF emerged as an independent predictor (HR 2.703; 95% CI 1.069 – 6.837; p = 0.036). In women, NYHA functional class proved to be an independent risk factor (Hazard Ratio (HR) 3.362; 95% confidence interval (CI) 1.085 – 10.415; p=0.036) for the combined endpoint whereas HFpEF was not associated with adverse outcome (HR 0.865, 95% CI 0.259 – 2.885, p=0.81). Conclusions Women undergoing T-TEER were more symptomatic and had higher prevalence of HFpEF compared to men. Nevertheless, HFpEF emerged as an independent predictor of the combined endpoint of one-year mortality or rehospitalization for heart failure only in men. NYHA functional class independently predicted adverse outcome in women.

Mortality based right ventricle functional echocardiographic cutoffs in patients with compared to without tricuspid regurgitation

Abstract Introduction Tricuspid-annular-plane-systolic-excursion (TAPSE) and peak-lateral-tricuspid-annular-systolic-velocity (S’) are frequently used echocardiographic indices of right-ventricle (RV) function. Tricuspid regurgitation (TR) is present in 70-90% of the general population, and while trivial or mild TR may not have prognostic implications, several studies have demonstrated that ≥moderate TR is an independent predictor of adverse outcomes, and that increasing TR severity incurs an increased risk of mortality. The abnormality thresholds for TAPSE and S' are based on published mean and standard deviation data obtained from healthy adults, but not on outcome data. The effect of significant TR on the abnormality threshold of TAPSE and S’ prime is currently unknown. Purpose We aimed to re-examine the abnormality thresholds for TAPSE and S' based on their association with mortality in consecutive patients, stratified to with, or without, significant tricuspid regurgitation (TR). Methods We performed a retrospective analysis of consecutive patients undergoing echocardiography between 2011-2021 in a large tertiary center. TR was assessed using a semi-quantitative method. Cut-off values associated with excess mortality were assessed using spline curves in univariate, and multivariate Cox logistic regression analyses. Results A total of 24717 subjects were included in the current analysis with a median (interquartile range) follow up of 1321 (581-1902) days. 1143 (4.6%) subjects had clinically significant (≥moderate) TR. In the entire cohort, TAPSE<20.9 mm and S’ <10.9 cm/s were associated with excess mortality. In sub-group analysis, among subjects with significant TR, TAPSE<18.0 mm and S'<10.0 cm/s was the cutoff associated with excess mortality, while subjects without TR had a higher cutoff of TAPSE<21.5 mm and S'<10.9 cm/s. In a multivariate model adjusted for the presence of TR and baseline characteristics, TAPSE<20.9 mm (HR 1.20, 95% CI 1.14-1.27; p<0.001) and S’<10.9 cm/s (HR 1.07, 95% CI 1.01-1.13; p=0.015) were independent predictors for mortality. A sensitivity analysis, which included 14,664 patients with additional echocardiographic indices, demonstrated that low TAPSE remained an independent predictor of mortality (aOR=1.15; 95% CI: 1.07-1.24; p<0.001) Conclusion TAPSE and S’ thresholds associated with excess mortality are higher than those previously reported in healthy adults. The TAPSE and S' cutoffs associated with excess mortality were lower in patients with significant TR compared to patients without, suggesting that a personalized approach for their interpretation is needed.Central illustration

Frailty as a predictor of adverse outcomes in patients with hepatectomy - the importance of design studies to improve frailty: A systematic review and meta-analysis of 128 868 patients.

Frailty has been associated with increased mortality among patients with surgery. However, evidence about the frailty prevalence and outcomes in frail populations with hepatectomy is inconsistent and has not been clarified. The purpose of this study was to quantitatively synthesize the prevalence of frailty and the role of frailty on mortality in patients with hepatectomy. Embase, PubMed, Scopus, and Web of Science were searched for eligible studies that explored the prevalence and impact of frailty in hepatectomy from inception until January 24, 2024. The pooled prevalence of frailty and odds ratio (OR) corresponding 95% confidence intervals (CI) in mortality and major complications estimates were analyzed. A total of 26 studies containing 128 868 patients with hepatectomy were included. The prevalence of frailty in hepatectomy was 23% (95% CI: 17-28; p = .000). Frailty was associated with an increased odds ratio for mortality (adjusted OR = 3.06; 95% CI: 1.85-5.04; p = .000). Furthermore, frailty was significantly associated with an increased odds ratio for major complications (adjusted OR = 3.20; 95% CI: 2.04-5.04; p < .01). The prevalence of frailty in patients with hepatectomy is prevalent, which has a significant adverse impact on the outcomes of patients with hepatectomy. These findings highlight the importance of frailty assessment in this population, which may provide prognostic details.

Left atrial volume assessed by echocardiography identifies patients with high risk of adverse outcome after acute myocardial infarction

BackgroundThe left atrial (LA) volume has been demonstrated to be an important predictor of adverse outcome in patients with various cardiac conditions, including acute myocardial infarction (AMI). However, new treatment strategies in patients with AMI have led to better patient outcomes. We hypothesised that increased LA size could still predict mortality in patients with AMI despite improved treatment strategies.MethodsWe included patients with AMI in a prospective multicenter cohort study and the study patients were enrolled from 2014 to 2022. We recorded echocardiographic and clinical data during their index hospitalisation. Indexed LA volume (LAVi) was assessed in all patients and was used as a continuous variable in the univariate and multivariate Cox regression analysis. The study took place over a period of five years and median follow-up time was 3.8 years (range 3.1 to 5.0 years). The primary study outcomes were all-cause mortality and major adverse cardiac events (MACE). MACE was defined as hospital readmission due to myocardial infarction, cardiac arrest, stroke, heart failure, or onset of new atrial fibrillation.ResultsWe included 487 patients (69 ± 12 years old, 26% female) with AMI. During the follow-up period all-cause mortality was 50 (10.3%) and patients who reached the primary outcomes were 153 (31.4%). The deceased patients had higher LAVi compared to survivors (40.0 ± 12.9 mL/m2 vs. 29.7 ± 11.2 mL/m2, p < 0.001). Factors associated with all-cause mortality and MACE were age, year of enrollment, left ventricular (LV) ejection fraction, LV global longitudinal strain (GLS), LV filling pressure, moderate or severe mitral regurgitation and LAVi. GLS and EF were segregated into two distinct models due to their moderately high correlation (r = 0.57, p < 0.001). LAVi remained as an independent echocardiographic predictor of primary outcomes after adjusting for the covariates above in two separates multivariable Cox regression models (hazard ratio 1.02/1.02 mL/m2 [95% CI 1.01–1.03/1.01–1.03], p = 0.006/0.003).ConclusionsOur study demonstrated that LA dilatation is an independent echocardiographic predictor of mortality and MACE in patients with AMI despite improved treatment strategies. This finding highlights the potential of using LAVi as a marker for prognostication in these patients.

Importance of the Hemoglobin Glycation Index for Risk of Cardiovascular and Microvascular Complications and Mortality in Individuals with Type 2 Diabetes.

This study investigated the prognostic importance of the hemoglobin glycation index (HGI) for macrovascular and microvascular outcomes, mortality, and hypoglycemia occurrence in a type 2 diabetes cohort and compared it to glycated hemoglobin (HbA1c). Baseline and mean first-year HGI and HbA1c, and the variability thereof, were assessed in 687 individuals with type 2 diabetes (median follow-up, 10.6 years). Multivariable Cox regression was conducted to evaluate the associations of HGI and HbA1c parameters with macrovascular (total and major cardiovascular events) and microvascular outcomes (microalbuminuria, advanced renal failure, retinopathy, and peripheral neuropathy), mortality (all-cause and cardiovascular), and moderate/severe hypoglycemia occurrence. During follow-up, there were 215 total cardiovascular events (176 major) and 269 all-cause deaths (131 cardiovascular). Microalbuminuria developed in 126 patients, renal failure in 104, retinopathy in 161, and neuropathy in 177. There were 90 hypoglycemia episodes. Both HGI and HbA1c predicted all adverse outcomes, except microalbuminuria and hypoglycemia. Their adjusted risks were roughly equivalent for all outcomes. For example, the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), estimated for 1 standard deviation increments, of mean first-year HGI were 1.23 (1.05 to 1.44), 1.20 (1.03 to 1.38), 1.36 (1.11 to 1.67), 1.28 (1.09 to 1.67), and 1.29 (1.09 to 1.54), respectively, for cardiovascular events, all-cause mortality, renal failure, retinopathy, and neuropathy; whereas the respective HRs (95% CIs) of mean HbA1c were 1.31 (1.12 to 1.53), 1.28 (1.11 to 1.48), 1.36 (1.11 to 1.67), 1.33 (1.14 to 1.55), and 1.29 (1.09 to 1.53). HGI was no better than HbA1c as a predictor of adverse outcomes in individuals with type 2 diabetes, and its clinical use cannot be currently advised.

Dynamic prediction of pregnancy outcome after previous stillbirth or perinatal death: pilot study to establish proof-of-concept and explore method feasibility.

To establish proof-of-concept for the dynamic prediction of adverse pregnancy outcome in women with a history of stillbirth or perinatal death, repeatedly throughout the pregnancy. A retrospective cohort study of women in a subsequent pregnancy following previous perinatal loss, who received antenatal care at a tertiary hospital between January 2014 and December 2017, was used as the basis for exploratory prognostic model development. Models were developed to repeatedly predict a composite adverse outcome (stillbirth or neonatal death, 5-min Apgar score < 7, umbilical artery pH ≤ 7.05, admission to the neonatal intensive care unit for longer than 24 h, preterm birth (< 37 completed weeks) or birth weight < 10th centile) using the findings of sequential ultrasound scans for fetal biometry and umbilical and uterine artery Doppler. In total, 506 participants were eligible, of whom 504 were included in the analysis. An adverse pregnancy outcome was experienced by 110 (22%) participants. The ability to predict the composite outcome using repeated head circumference and estimated fetal weight measurements improved as the pregnancy progressed (e.g. area under the receiver-operating-characteristics curve improved from 0.59 at 24 weeks' gestation to 0.74 at 36 weeks' gestation), supporting proof-of-concept. Predictors to include in dynamic prediction models were identified, including ultrasound measurements of fetal biometry, umbilical and uterine artery Doppler and placental size and shape. The present study supports proof-of-concept for dynamic prediction of adverse outcome in pregnancy following prior stillbirth or perinatal death, which could be used to identify risks earlier in pregnancy, while highlighting methodological challenges and requirements for subsequent large-scale model development studies. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.