Predictors Of Outcome Research Articles

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

Single-cell and bulk transcriptomic datasets enable the development of prognostic models based on dynamic changes in the tumor immune microenvironment in patients with hepatocellular carcinoma and portal vein tumor thrombus.

Hepatocellular carcinoma (HCC) patients exhibiting portal vein tumor thrombosis (PVTT) face a high risk of rapid malignant progression and poor outcomes, with this issue being compounded by a lack of effective treatment options. The integration of bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) datasets focused on samples from HCC patients with PVTT has the potential to yield unprecedented insight into the dynamic changes in the tumor microenvironment (TME) and associated immunological characteristics in these patients, providing an invaluable tool for the reliable prediction of disease progression and treatment responses. scRNA-seq data from both primary tumor (PT) and PVTT cells were downloaded from the Gene Expression Omnibus (GEO) database, while the International Cancer Genome Consortium (ICGC) and Cancer Genome Atlas (TCGA) databases were used to access bulk RNA-seq datasets. scRNA-seq, clustering, GSVA enrichment, mutational profiling, and predictive immunotherapeutic treatment analyses were conducted using these data with the goal of systematically assessing the heterogeneity of PT and PVTT cells and establishing a model capable of predicting immunotherapeutic and prognostic outcomes in patients with HCC. These analyses revealed that PVTT cells exhibited patterns of tumor proliferation, stromal activation, and low levels of immune cell infiltration, presenting with immune desert and immune rejection-like phenotypes. PT cells, in contrast, were found to exhibit a pattern of immunoinflammatory activity. Core PVTT-associated genes were clustered into three patterns consistent with the tumor immune rejection and immune desert phenotypes. An established clustering model was capable of predicting tumor inflammatory stage, subtype, TME stromal activity, and patient outcomes. PVTT signature genes were further used to establish a risk model, with the risk scores derived from this model providing a tool to evaluate patient clinicopathological features including clinical stage, tumor differentiation, histological subtype, microsatellite instability status, and tumor mutational burden. These risk scores were also able to serve as an independent predictor of patient survival outcomes, responses to adjuvant chemotherapy, and responses to immunotherapy. In vitro experiments were used to partially validate the biological prediction results. These results offer new insight into the biological and immunological landscape of PVTT in HCC patients, By utilizing individual patient risk scores, providing an opportunity to guide more effective immunotherapeutic interventional efforts.

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.

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.

Extracellular volume analysis on cardiac computed tomography is useful to predict prognosis after cardiac resynchronization therapy

Abstract Background Left-ventricular (LV) extracellular volume (ECV) (LVECV) is often evaluated on magnetic resonance imaging (MRI), and the value is well correlated with biopsy-identified myocardial fibrosis. Recently, mechanical development has been achieved, and ECV analysis on cardiac computed tomography (CCT) has been eligible using the latest software, and the ECV on CCT is well correlated with the ECV on MRI. Cardiac resynchronization therapy (CRT) has been usually performed in cases with severe heart failure, but almost 30 percent of them are non-responders. Therefore, the indicators to predict non-responders to cardiac resynchronization therapy (CRT) have been sought in advance. Purpose The purpose of this study is to reveal the utility of LVECV on CCT for the prediction of patient prognosis in the candidates of cardiac resynchronization therapy (CRT) who have low LV function. Methods We analyzed 53 patients (30 males, 65 ± 14 years old) with heart failure who underwent CCT, including late phase scan, using 320-row detector CT (Aquilion One or Aquilion One ViSion Edition, Cannon Medical Systems) or 256-row detector CT (Revolution CT Apex, GE Healthcare), before the implantation of a CRT device from December 2008 to January 2024. The primary outcomes were defined as cardiac death, hospitalization due to HF, and fatal arrhythmia after CRT implantation. CRT responders were defined as the patients whose LV endo-systolic volume was decreased by 15% or more on transthoracic echocardiography. Results Twenty-two patients (42%) had primary outcomes (10 cardiac death, 7 fatal arrhythmia, 5 hospitalization due to HF). LVECV was lower in CRT responder (n = 23) than the others (n = 25) (35 ± 6.3% vs 41 ± 6.8%, P = 0.006). LVECV was higher in the patients with primary outcomes (n = 22) than the others (n = 31) (35 ± 5.0% vs 41 ± 7.8%, P = 0.019). Based on the receiver-operating characteristics curve analysis, the best cut-off of LVECV for predicting primary outcomes was 44.03% (B). In the survival analysis using the Cox proportional hazard model, LVECV on CCT was a significant predictor of primary outcomes (HR, 1.07; 95% CI, 1.13-1.01; P = 0.012). On Kaplan-Meier analysis, the higher LVECV group (≥ 44.03%) had a significantly greater number of primary outcomes than the others (P = 0.010) (C). Conclusion LVECV on CCT may be useful for predicting responders of CRT and prognosis after CRT implantation.ROC curve and Kaplan-Meier analysis

Socio-economic gradients in urban green space access and respiratory health

Abstract Background This study investigates social disparities as one of the drivers influencing the access to green spaces and exposure to natural environments, potentially exacerbating disparities in respiratory health in children. Methods Longitudinal ELSPAC birth cohort study data included 4384 complete case participants born in cities of Brno and Znojmo, examined throughout the years 1990-2010. Estimates on socio-economic status (SES) scores of children’s parents and their education were used as socio-economical predictors. Tree cover density (TCD) calculated as mean canopy closure percentage in the individual walking distance neighbourhoods and the ownership and accessibility of a garden were used as indicators of green space accessibility. Multiple logistic regression models were employed to estimate odds ratios for predictors of respiratory health outcomes, controlling for several confounders. Results Parents’ SES was found to be positively associated with neighbourhood TCD, and this effect was even more pronounced for garden owners. Higher tree cover was then significantly negatively associated with development of acute bronchitis (OR 0.88, CI 95 % 0.84-0.94 for 1 SD of tree cover), while not having a garden (OR 1.81, CI 95 % 1.42-2.33) and living in area with lower tree cover (OR continuously decreasing from 1.88 to 1.68 for lowest and highest quartile respectively) was significantly associated with progression of acute bronchitis into chronic bronchitis in a fully adjusted model. Vice versa, higher tree cover was statistically significantly positively associated with development of allergic rhinitis (OR 1.09, CI 95 % 1.03-1.15), suggesting viability of the novel method of estimation of individual neighbourhood greenness. Conclusions The results suggest protective effect of access to urban green spaces against adverse respiratory outcomes in children. The socially uneven distribution of access emphasizes the importance of urban policies in promoting urban health. #NGEU Key messages • There is a significant protective effect of access to green spaces against respiratory diseases and their progression. • There’s an unequal, but varied distribution of access to green spaces, and social gradient in health, highlighting the importance of urban green space distributive politics.

Reduction of aortic stiffness in newly diagnosed persons with HIV-infection: modifiable vascular dysfunction after antiretroviral therapy?

Abstract Background People living with HIV (PLWH) are at an increased risk of cardiovascular disease (CVD), which is underestimated by contemporary risk stratification systems[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD. Aortic stiffness, as measured with pulse wave velocity (PWV), is a validated predictor of CVD [2,3] and has been shown to be elevated in PLWH at the time of HIV diagnosis compared to HIV-uninfected persons[4]. Purpose To prospectively assess the influence of contemporary antiretroviral therapy (ART) on aortic stiffness in a group of newly diagnosed PLWH in a low- to middle-income setting. Methods A group of ART naïve PLWH with modest cardiovascular risk and free from known CVD, was recruited at the time of HIV diagnosis from the Western Cape Province of South Africa. Aortic stiffness was measured using carotid-femoral PWV on a commercially available device that simultaneously measured the carotid and femoral waveforms on a supine patient in a temperature-controlled room utilising established methodology[4]. The algorithmically-calculated time delay between the upstroke of the carotid and femoral wave-forms provided the transit time (TT). Carotid femoral path distance (path length) was measured using surface anatomy. PWV was calculated as direct path length divided by TT. Aortic distensibility was expressed according to the Bramwell-Hill equation as 3.57/PWV(squared)[5]. ART was initiated and PWV was re-evaluated 9 months later. Results Seventy-three participants completed follow-up and were included. The cohort was relatively young (mean age 32±7 years) with good female representation (n=33, 45%). Most received tenofovir/lamivudine/dolutegravir (n=71, 97%) Half of the group smoked cigarettes. Two participants were controlled hypertensives, and two participants had metabolic syndrome. A significant decrease in PWV (with scaling factor of 0.8) was observed at 9 months of ART (5.93 ±1.0 vs. 5.69 ±1.0 m/s; p=0.01). Aortic distensibility increased significantly as well (0.20 [IQR: 0.16 to 0.26] vs. 0.21 [IQR: 0.19 to 0.27] mmHg-1; p=0.02). Conclusion Improvement in aortic stiffness was observed in a group of newly diagnosed PLWH after 9 months of ART-initiation. This provides evidence of a modifiable component of vascular dysfunction and, in turn, cardiovascular risk with the use of contemporary ART at 9 months. It is unknown if this effect will be sustained long-term. The use of aortic stiffness (alone or in combination with other parameters) as a predictor of cardiovascular outcomes in the ART era requires further study.Abstract figureAbstract table

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.

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

Body weight variability as a predictor of cardiovascular outcomes in type 1 diabetes: A nationwide cohort study.

Intraindividual body weight variability (BWV), that is, the degree of weight fluctuations over time, is associated with an increased risk of cardiovascular diseases (CVDs) in multiple settings. The impact of BWV on cardiovascular risk in type 1 diabetes (T1D) remains unclear, despite the issues relative to weight management in individuals with this condition. Using data from the Swedish National Diabetes Register, we identified individuals with T1D and without CVD at baseline with at least three measurements of body weight taken over three consecutive years. We estimated BWV as quartiles of the standard deviation of weight measures and explored its longitudinal association with the incidence of CVD during a 12.7 ± 4.6 year follow-up through adjusted Cox regression models. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke and all-cause mortality. We modelled the function of risk in relation to the magnitude of BWV, testing also whether weight trends, that is, increasing, stable or decreasing, age, sex and glycaemic control modified the association between BWV and the outcome. Among the 36 333 individuals with T1D in the register, we identified 19 373 individuals with at least three measures of body weight and without CVD at baseline. Participants with the highest BWV had a 42% increased risk of reaching the primary endpoint compared to those with the lowest BWV (hazard ratio [HR] = 1.42, 95% confidence interval [CI]: 1.24-1.62). In addition, high BWV was significantly associated with a 51% increased risk of all-cause mortality (HR = 1.51, 95% CI: 1.28-1.78), a 37% increased risk of peripheral artery disease (HR = 1.37, 95% CI: 1.06-1.77) and a 55% increased risk of hospitalization for heart failure (HR = 1.55, 95% CI: 1.20-2.01). BWV showed a quasi-linear association with the primary endpoint. No interaction was observed when comparing subgroups for weight trends, sex or degree of glycaemic control. In the subgroup of elderly individuals, the association of BWV with the primary endpoint was no longer significant. High BWV is associated with an increased risk of CVD and all-cause mortality in individuals with T1D, independently of canonical risk factors. Weight trends, sex and glycaemic control do not modify such association while older age attenuates it.

Cardiac magnetic resonance (CMR) height-based allometric scaling in Southeast Asians; implications in the diagnosis and prognosis of left ventricular hypertrophy (LVH): the REMODEL study

Abstract Background Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes (1). Although normalizing LV mass (LVM) to height exponents has been shown to reduce variability from body size, specific recommendations for height exponents are lacking due to the scarcity of normal cohorts to define appropriate height exponents (2). Cardiac magnetic resonance (CMR) is increasingly used in assessing LVM, and the existing body of research is based primarily on the MESA cohort (3). While the MESA cohort is ethnically diverse, the intrinsic effects of ethnicity may not fully be discerned if certain ethnic groups are under-represented. Purpose We aimed to demonstrate the diagnostic and prognostic implications of establishing height exponents specific to sex in a Southeast Asian cohort. Methods Non-overweight/obese Southeast Asian healthy volunteers (n=416) were used to establish appropriate height exponents and normal reference ranges of LVM. The impact of these height exponents was examined in a separate cohort of Southeast Asians with hypertension (n=878). All individuals underwent standardized cardiovascular magnetic resonance imaging (CMR). Primary outcome was a composite of acute coronary syndrome, heart failure hospitalization, stroke, and cardiovascular mortality. Cox regression analysis of various LVH measures were adjusted for 24-hour systolic blood pressure, diabetes, and hyperlipidemia. Results The height exponents for healthy females and males were 1.57 and 2.33, respectively. In patients with hypertension, sex-specific height exponents significantly increased the detection of LVH compared with body surface area (BSA) indexing (47% [n=409/878] versus 27% [n= 236/878], p<0.001). Most individuals re-classified to LVH with sex-specific height exponents were overweight (33.1%, n=58/175) or obese (64.6%, n=113/175). There were 37 primary events over 60 [37-73] months of follow-up. Regardless of indexing method, LVH was independently associated with increased adverse events (sex-specific height exponent hazard ratio (HR): 2.8 [1.25-6.29], P=0.013). The prediction ability of LVH diagnosis by sex-specific height exponents was similar to BSA indexing (HR: 5.43 [2.49-11.8], P<0.001). Conclusions Reference ranges specific to the ethnicity, sex and imaging modality are necessary to establish appropriate height exponents. Although utilizing sex-specific height exponents to index LVM resulted in significantly more LVH reclassification when compared with BSA indexing, this did not translate to a notable improvement in event prediction. Further research into alternative methods of LVM indexing is warranted.Abstract SummaryPredictive Ability of LVH Measures

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

Prognostic evaluation with cardiac magnetic resonance in patients with systemic sclerosis

Abstract Systemic sclerosis (SSc) is an autoimmune disease with multiorgan involvement. Cardiac involvement is common and impact in prognosis. Cardiac magnetic resonance (CMR) allows an evaluation in ventricular and atrial function and hemodynamics forces. Our study aimed to assess RVD prevalence in SSc patients and analyze its impact on cardiovascular events. Methods In this retrospective study, we included patients diagnosed with SSc and followed-up in a specialized unit. We collected clinical, hemodynamic, and imaging data, including baseline CMR studies. Pulmonary function tests were also performed. RVD was defined as a right ventricular ejection fraction ≤52% in men and ≤51% in women. Patients were monitored for a composite endpoint consisting of cardiovascular death and/or admissions due to heart failure (HF). We assessed the predictors of this endpoint using Cox regression analysis. Results The study included 74 patients with SSc, most were female (81 %) with a mean age of 60±12 years. RVD prevalence was 32 %. Patients with RVD had greater ventricular volumes (160±44.9 vs 130±36.2; p=0.003), lower right ventricular global strain (-18 % vs. -26 %; p <0.001) and lower right atria strain (19% vs 29%; p=<0.001). We don’t found differences in presence of LGE of both ventricles. In the multivariate analysis RVEF (HR 2.9.; p = 0.022), pulmonary trunk dilatation (HR 1.15; p= 0.004, pulmonary hypertension at baseline (HR 2.98; 0.09); RV GLS (HR 1.08; p = 0.03) and RA GLS (HR 0.96; p = 0.024) were predictors of composite outcome of cardiovascular death and/or heart failure hospitalization. During a mean follow-up of 46 months, patients with RVD had higher rates of heart failure admissions (38% vs. 12%; p = 0.01) and cardiovascular mortality (29% vs. 6%; p 0.01). No ventricular arrhythmias occurred. Conclusion RVD is common among SSc patients. RVEF and pulmonary hypertension are the strongest variables linked to increased adverse cardiovascular clinical events and decreased survival in these patients.

Different right ventricular mechanics in atrial and ventricular secondary tricuspid regurgitation and their prognostic role. A multicentric three-dimensional echocardiography study

Abstract Background/Introduction Secondary tricuspid regurgitation (STR) can develop from markedly different etiologies. Both progressive dilation and dysfunction of the right atrium (atrial phenotype, ASTR), and adverse right ventricular (RV) remodeling (ventricular phenotype, VSTR) may result in STR. RV function is a major determinant of outcome in patients with STR. However, data about how RV function adapts to ASTR and VSTR are scarce, and the prognostic implications of RV mechanics in ASTR and VSTR remain to be clarified. Purpose Accordingly, we aimed to investigate the RV mechanical patterns in ASTR and VSTR and to examine their prognostic role using three-dimensional (3D) echocardiography. Methods We enrolled 192 patients with STR (60% women) who underwent clinically indicated transthoracic echocardiography in a multicentric prospective observational study. The primary outcome was defined as a composite of heart failure hospitalization or cardiac death. STR etiology was assessed based on the TVARC criteria (ventricular STR n=134, atrial STR n=58). STR severity was categorized using STR effective regurgitant orifice area according to current guidelines. We assessed RV function by measuring the tricuspid annular plane systolic excursion (TAPSE) by M-mode echocardiography and RV ejection fraction (EF) by 3D echocardiography. In addition, we imported the 3D RV meshes into the ReVISION software package (Argus Cognitive, Inc, Lebanon, USA) to quantify the relative contribution of the longitudinal (LEFi), radial (REFi), and anteroposterior motion components (AEFi) to total RV EF. Results ASTR and VSTR patients had comparable TAPSE (17±5 mm vs. 18±5 mm, p=0.10), while RV EF was significantly higher in ASTR (54±7% vs. 47±10% p<0.001). Although LEFi (0.37±0.08 vs. 0.38±0.10, p=0.95) and AEFi (0.45±0.08 vs. 0.44±0.11, p=0.53) were comparable between ASTR and VSTR, REFi was significantly lower in VSTR (0.52±0.09 vs. 0.47±0.12, p<0.01). RF EF was comparable among STR severity grades (mild vs. moderate vs. severe: 50±11 vs. 49±9 vs. 50±10%, respectively, p=0.85). Conversely, LEFi was significantly higher in mild and moderate STR vs severe STR (0.39±0.08 vs. 0.39±0.09 vs. 0.35±0.10, respectively, p=0.04). Using multivariable Cox regression based on variables significant in the univariate analysis, REFi was a significant independent predictor of outcome in the entire cohort (hazard ratio: 0.978 [CI, 0.959-0.999], p= 0.037). Conclusions Using 3D echocardiographic assessment, ASTR and VSTR patients demonstrated significant differences in the RV mechanical pattern, with a lower contribution of the radial contraction in the case of ventricular STR etiology. While RV EF was comparable between STR severity grades, the relative importance of the longitudinal motion significantly differed. Notably, the relative contribution of radial motion to RV function demonstrated independent prognostic value in patients with STR.RV mechanics in STR severity stages

Validation of existing risk scores for worsening renal function in patients with newly diagnosed heart failure: a longitudinal population cohort study

Abstract Background Worsening renal function (WRF) is one of the strongest predictors of outcome in patients with heart failure (HF). The presence of WRF often influences the decision to start, up-titrate, or discontinue disease-modifying HF therapies and is one of the key determinants of suboptimal guideline-directed medical therapy. However, there are now potential cardiovascular pharmacotherapies that have favourable cardiorenal outcomes and reduce the risk of renal decline. It is therefore important to identify patients with HF early in their disease trajectory who are at risk of developing WRF. Purpose The aim of this study was to evaluate two existing WRF risk scores (the Forman risk score and the Basel risk score) in a population-based longitudinal cohort diagnosed with incident HF. Methods Data for individuals with incident HF between 2016 to 2021 were extracted and analysed from the NELSON study conducted in Tayside, Scotland. WRF was defined as a composite event of (i) having two consecutive eGFRs declined by 40% or greater; (ii) having an eGFR < 15mL/min/1.73m2; (iii) initiation of sustained dialysis; (iv) development of end-stage kidney disease; or (v) receiving kidney transplantation. The primary outcome was the occurrence of WRF within 180 days of diagnosis of HF. Among patients hospitalised with HF, in-hospital WRF was also assessed. The area under the curve (AUC) was used to assess the discrimination performance of the two risk scores in individuals with incident HF diagnosed as either in-patients or out-patients. Results 4076 individuals (mean age 72.8 ± 13.2; 58% male; 1081 HFrEF, 646 HFmrEF, 1348 HFpEF, and 1001 HF with unknown ejection fraction (EF)) who were WRF-free at incident HF diagnosis were identified. Of these, 2095 (51.4%) were diagnosed as in-patients, and 1981 (48.6%) were diagnosed as out-patients. 285 (7%) patients developed WRF within 180 days post HF diagnosis. Among the 2,095 HF in-patients, 75 (3.6%) developed WRF before discharge. The Forman risk score had an AUC of 0.618 (95% CI: 0.585 – 0.651) in predicting 180-day WRF, and an AUC of 0.650 (0.587 – 0.713) for in-hospital WRF. The Basel risk score showed similar discriminating performance with an AUC of 0.618 (0.585 – 0.651) for 180-day WRF, and 0.656 (0.593 – 0.719) for in hospital WRF. Conclusions In a contemporary population, conventional risk scores such as the Forman or Basel risk scores have limited discrimination in predicting WRF in incident HF. New models with better discrimination for WRF prediction are therefore needed.

Left atrioventricular coupling index: association with diastolic dysfunction and prognostic implications in heart failure patients

Abstract Background Left atrioventricular coupling index (LACI), an index coupling left atrial (LA) to left ventricular (LV) volume at end-diastole (Figure 1), showed to be associated with prognosis in different clinical settings. However, the relation between LACI and LV diastolic dysfunction (DD) remains to be established. Purpose The present study aimed to investigate the association between LACI and LV DD and to assess its prognostic value in patients with heart failure (HF). Methods We retrospectively analyzed 1158 stable HF patients (mean age 66±12 years, 75% men) on optimal medical therapy (derivation cohort). Clinical and echocardiographic features were characterized across LACI tertiles. The independent prognostic value of LACI (endpoint: all-cause death/HF-hospitalization) was assessed by Cox regression and spline curve analyses. Results were validated in an external cohort of 242 HF patients. Results In the derivation cohort, the median LACI value was 0.29 (IQR:0.19-0.42). Patients in the third tertile (LACI>0.36) were older and presented with more advanced HF symptoms. While prevalence of grade-1 DD (ASE/EACVI classification) progressively decreased across LACI tertiles, the prevalence of grade-3 DD significantly increased (8%,23%, and 46% respectively, P<0.0001). A cut-off value ³0.26 identified moderate-to-severe DD with an area-under the-curve of 0.75. During follow-up (median 28 months, IQR:11-53), 407 (35%) patients reached the endpoint. On multivariable analysis, LACI was independently associated with outcomes (HR for 1-unit-increase 2.34; 95%CI 1.35-4.03; P=0.002 – Figure 2), showing incremental predictive value over the DD grading system (net reclassification improvement=0.150, P<0.0001). The prognostic value of LACI was consistent in the external validation cohort. Conclusions LACI is associated with DD severity and is an independent predictor of outcomes in HF patients.How to assess LACIPrognostic value of LACI in HF

The effect of Trimetazidine on the left ventricular global longitudinal strain assessed by cardiac magnetic resonance in stable angina patients with previous myocardial infarction and left ventricular

Abstract Introduction Trimetazidine (TMZ) is an anti-ischemic metabolic agent that is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris (SA). Global left ventricular (LV) systolic function is an important predictor of outcomes in patients after myocardial infarction (MI). Cardiac magnetic resonance (CMR) imaging has now evolved into a major tool for the evaluation of patients with LV dysfunction, providing precise measurements of ejection fraction (EF) and viability assessment but also now allowing assessment of global longitudinal strain (GLS) from standard cine CMR images. We hypothesized that the use of TMZ 80 mg as an anti-ischemic agent in patients with SA, history of MI, reduced EF and in the presence of viable myocardium may produce an early modification of GLS. Methods TRIM-AZ - was a non-interventional, prospective Azerbaijan study to analyze the capacity of short-term therapy with TMZ 80 mg on LV GLS evaluated by CMR in patients with previous MI. Patients with a confirmed diagnosis of heart failure (HF) with impaired LV systolic function and SA in the presence of viable myocardium were included. The treatment of all patients was optimized according to the latest ESC guidelines before entry in the study. Patients were randomized into two groups, one received TMZ 80 mg on top of guidelines directed medical therapies, and the other was the control group. A CMR as well as a transthoracic echography were performed for all patients at the inclusion visit and 8 weeks later. Results 52 patients were included in the study, 30 patients in the TMZ group and 22 in the control group,. At baseline, the mean age was 62±7 years , 63% were smokers, 60% hypertensive, 60% diabetics, 48% had a family history of MI, 12% had typical symptoms of SA while 88% had atypical form (e.g. like shortness of breath). All patients received baseline therapy with ARNI/ACE-i, SGLT2 inhibitors, beta-blockers, MRA, ASA, and statin. 8 weeks after the initiation of TMZ, there were no significant changes in LVEF assessed both by Echo and CMR (29,8%±3,2% vs 30,1%±3,5% by echo in TMZ group; 31,3%±2,7% vs 31,6%±2,7% by echo in the control group; 25,9%±3,1% vs 26,9±4,1% by CMR in TMZ group; 26,9%±2,1% vs 30,1%±2,3% by CMR in the control group), however GLS was significantly improved in TMZ group (-9,9%±1,1% to -12,7%±1,2%, p=0,00), but not in control group (-9,3%±1,3% vs -10,3%±1,4% p=0,3). No adverse event related to TMZ use was reported during the study. Conclusion These findings suggest that the use of trimetazidine in patients with stable angina , previous MI and heart failure in the presence of viable myocardium could improve the left ventricular global longitudinal strain assessed by CMR.

Coronary microvascular dysfunction in patients with heart failure with reduced and mildly reduced ejection fraction: results from the PANACEA study

Abstract Aims Coronary microvascular dysfunction (CMD) is common and associated with impaired survival in patients with heart failure with preserved ejection fraction (HFpEF). In patients with heart failure with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF) the impact of CMD is not fully known. Purpose We aimed to investigate the prevalence of CMD and its association with phenotype, biomarkers, endothelial function and echocardiographic measurements in patients with HFrEF or HFmrEF. Method A prospective, exploratory bi-center study in patients with chronic stable heart failure, New York Heart Association (NYHA) Class II-IV, and ejection fraction (EF) <50% was performed. Study procedures included echocardiography, adenosine-based transthoracic Doppler echocardiography to assess coronary flow reserve (CFR), physical examination, fasting blood and urine sample, pulse wave velocity (PWV) and hemodynamic measurements. The cutoff of CFR<2.5 was used to diagnose CMD. A multivariable linear regression analysis with CFR as dependent variable, adjusted for age, sex, body mass index, smoking, atrial fibrillation and left ventricular mass, was performed to explore biomarkers, endothelial function, and echocardiographic measurements associated with CMD. Results Of 112 included patients, 87 (78%) were men, with a mean age of 73.3 (±7.5) years. Among patients with a successful CFR measurement (n=62), CMD was present in 40 (65%), mean age of 75.4 (±5.8) years (Table 1). Patients with CMD had higher N-terminal pro B-type natriuretic peptide (NTproBNP) and Troponin T (p<0.05), and more often HFrEF ( p=0.06). Patients with CMD had larger ventricles with greater left ventricular mass and larger end-diastolic volumes (p<0.05). In a linear regression analysis CMD was associated with higher NTproBNP, lower EF, PWV and global strain (table 2). Conclusion CMD was common and present in two thirds of patients with HFrEF or HFmrEF. Further CMD was associated with markers of more severe heart failure and systemic endothelial dysfunction indicating that CMD may be an important predictor of outcome in patients with HFrEF and HFmrEF.

Effect of left atrial function on cardiovascular outcome in non-dilated left ventricular cardiomyopathy

Abstract Background This study aimed to determine whether atrial function and strains can provide the greatest or joint incremental prognostic value in patients with non-dilated left ventricular cardiomyopathy (NDLVC) over a long follow-up period. Methods One hundred sixty-four NDLVC patients were included retrospectively. Comprehensive clinical evaluation and echocardiographic investigations were obtained, including measurements of strain derived left atrial (LA) reservoir, conduit, booster strain. All patients were followed up for adverse cardiac events (MACE) including all-cause mortality, hospitalization due to heart failure aggravation. The predictors of MACE were examined with univariable and multivariable Cox regression analysis. Subsequently, nested Cox regression models were built to evaluate the incremental prognostic value of strain parameters. Patient survival was illustrated by Kaplan–Meier curves and differences were evaluated by log-rank test. Results During a median follow-up of 3.8 years, MACEs were identified in 34 (21%) patients. Cox regression models showed that the predictive value of LA conduit strain was independent from and incremental to LAVi and baseline variables. Age, E/e', RASP and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.05). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, age, RASP remained associated in the multivariable model (LA conduit strain HR: 2.14 [95% CI: 1.37-3.87; P < 0.007]; age HR: 1.05 [95% CI: 1.01-1.10; P = 0.020]; and RASP HR: 1.07 [95% CI: 1.01-1.14; P = 0.021]), whereas LVEF, LAVi were not. Adding LA conduit strain to other independent predictors (age and LAVi) improved the prediction of MACEs. (p < 0.05). Also, when a Kaplan Meier graph was obtained for the occurrence of MACE based on LA conduit strain 17%, a significant difference was shown between the two groups. Conclusion LA conduit strain provided the good prognostic value and added incremental value to conventional clinical predictors for patients with NDLVC.Incremental value of LA strainKM according to LA strain 17%