Prognostic Factors Research Articles

CSTB, FABP4, IBP-1 and ST2 are strong predictors of mortality after transcatheter edge-to-edge mitral valve repair

Abstract Introduction Various clinical characteristics have emerged as prognostic factors in patients undergoing transcatheter edge-to-edge mitral valve repair (M-TEER). The use of biomarkers for outcome prediction has enormous potential. The goal of this study was to identify novel biomarkers linked with adverse events after M-TEER. Methods We prospectively included 242 patients undergoing M-TEER at our center and obtained pre-procedural blood samples for biomarker analysis. Additionally, 94 follow-up samples were taken three months after M-TEER. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We analyzed differences in biomarker expression levels between patients that had died within one year after M-TEER and patients that had survived. Results 39 patients (16.3%) had died within one year after M-TEER. In these patients the most significantly upregulated biomarkers were NT-proBNP (expression 3.0-fold compared to survivors, p < 0.001), Cystatin B (CSTB; 2.0-fold, p < 0.001), fatty acid binding protein 4 (FABP4; 2.0-fold, p < 0.001), insulin-like growth factor-binding protein 1 (IBP-1; 1.9-fold, p < 0.001) and suppression of tumourigenicity 2 (ST2; 1.7-fold, p < 0.001). In non-survivors, expression levels of NT-proBNP (6.1-fold, p = 0.036), CSTB (3.2-fold, p = 0.050), FABP4 (3.7-fold, p = 0.037) and ST2 (2.1-fold, p = 0.017) were persistently elevated at the time of follow-up. Since its prognostic impact has already been described elsewhere, NT-proBNP was excluded from further analysis. Kaplan Meier analysis for 1-year mortality was carried out using tertiles of the respective biomarker expression levels. Mortality risk increased significantly with rising expression levels (CSTB: 3.4% in tertile 1, 12.2% in tertile 2, 37.9% in tertile 3; FABP4: 5.1%, 14.2% and 31.7%; IBP-1: 3.3%, 13.2% and 36.2%; ST2: 4.9%, 11.9% and 36.7%; p by log-rank-test < 0.001 for all biomarkers). Patients in which all 4 biomarkers were elevated to the highest tertile had an excessively high mortality risk of 52.9 vs. 13.5% (p by log-rank-test < 0.001). Receiver operating characteristic (ROC) analysis suggested higher predictive performances for mortality of all 4 biomarkers as compared to the EuroSCORE II (CSTB: area under the curve (AUC) 78.1%, 95% CI 70.7 – 85.5%; FABP4: AUC 71.6%, 95% CI 63.1 – 80.0%; IBP-1: AUC 73.9%, 95% CI 65.7 – 82.1%; ST2: AUC 76.2%, 95% CI 68.5 – 84.0%; EuroSCORE II: AUC 68.4%, 95% CI 59.3 – 77.5%). Conclusion This analysis has revealed novel biomarkers (CSTB, FABP4, IBP-1, ST2), which so far have not been characterized in M-TEER and suggests significant prognostic implications. Predictive performance of each of the respective biomarkers was superior to the most commonly used pre-operative risk stratification tool: the surgical EuroSCORE II. This hypothesis-generating study warrants further examination of these promising biomarkers.

Impact of global longitudinal strain and anemia for predicting cardiovascular mortality in patients hospitalized for acute heart failure with atrial fibrillation

Abstract Background Iron deficiency is a prognostic factor in heart failure (HF) with reduced ejection fraction (EF). In patients with atrial fibrillation (AF) and HF, left ventricular EF (LVEF) measurements are imprecise due to irregular tachycardia, but it is unclear whether global longitudinal strain (GLS) and anemia assessment are prognostic. Purpose We examined whether GLS and anemia predict cardiovascular death (CD) in patients with acute HF complicated by AF. Methods We retrospectively enrolled patients aged 18 years or older with acute HF complicated by AF who were consecutively admitted to our hospital from January 2014 to December 2018. Exclusion criteria were acute coronary syndromes, no transthoracic echocardiogram performed within 30 days before or after admission, and missing data. All patients were followed up from admission to CD (due to myocardial infarction, HF, stroke or sudden death), or were censored at the date of last contact or 3 years. Anemia was defined as hemoglobin < 12 g/dL in females and hemoglobin < 13 g/dL in males. Patients were divided into four groups according to median GLS and anemia status. Results A total of 320 patients (mean age 79 ± 12 years, 163 females) were included in the analysis. The median duration of AF was 1.2 years; 11% (36/320) had paroxysmal AF. The median brain natriuretic peptide value was 623 pg/ml, and 52% of the patients (165/320) were in New York Heart Association functional class 4. During a median follow-up of 528 days, 24% (77/320) patients were observed with CDs: 2 myocardial infarctions, 51 HF-related deaths, 6 strokes, and 18 sudden cardiac deaths. At the 3-year follow-up, the survival rate by the Kaplan-Meier curve was 89% (95% confidence interval (CI) 76%-95%) in the no anemia group with high GLS (< -10%) and 40% (95% CI 25%-54%) in the anemia group with low GLS (≥ -10%) (p < 0.001, log-rank test). In multivariate Cox regression analysis, GLS (adjusted hazard ratio (aHR) 1.06, 95% CI 1.01-1.14, p = 0.017) and hemoglobin (aHR 0.85, 95% CI 0.76-0.96, p = 0.009) were independent factors for CD, with a significantly increased risk in the anemia group with low GLS compared to the no anemia group with high GLS (aHR 4.11, 95% CI 1.59-10.6, p = 0.004). The results were consistent with no interaction by gender or LVEF 50%. Conclusions Anemic patients with low GLS with AF and HF may have poor prognosis. Prospective studies are needed to determine whether iron supplementation improves prognosis in such patients.

The prognostic impact of renal dysfunction and anemia in japanese heart failure patients stratified by left ventricular ejection fraction

Abstract Background Renal dysfunction and anemia have been reported to be important prognostic factors in heart failure (HF) patients, but the differences in their effects stratified by left ventricular ejection fraction (LVEF) are not clear. Therefore, we investigated the prognostic impact of renal dysfunction and anemia in Japanese HF patients stratified by LVEF. Methods We combined two registry studies of acute HF patients in Japan and examined major events and associated factors during 2-year observation period. The primary endpoint was defined as all-cause mortality or HF hospitalization. Renal dysfunction was defined as eGFR <60 mL/min/1.73 m2, and anemia was defined as hemoglobin <13 g/dl in men and 12 g/dl in women. Two groups were also analyzed by LVEF (LVEF >50% and LVEF <49%). Results A total of 2142 patients were enrolled and analyzed. The mean observation period was 623±244 days. Mean age was 78.7 years. Forty-nine percent were male. Coronary artery disease and atrial fibrillation were present in 31% and 44% of patients, respectively. Medications included beta-blockers in 61% of patients and RAS inhibitors in 53%. Renal dysfunction was present in 1676 patients (74%) and anemia in 1523 patients (67%). Combination of both was observed in 1190 patients (53%). The primary endpoint was observed in 1015 patients, with 563 deaths and 737 HF hospitalizations. Multivariate analysis in a Cox proportional hazards model showed that renal dysfunction alone (HR: 1.39, 95%CI:1.06-1.81, p=0.02) and combination of renal dysfunction and anemia (HR 1.72, 95%CI:1.34-2.21, p<0.01) were independent prognostic factors in all patients. In patients with LVEF <49%, renal dysfunction alone (HR: 1.50, 95%CI:1.04-2.16, p=0.03) and combination of renal dysfunction and anemia (HR: 1.90, 95%CI:1.34-2.68, p<0.01) were predictive factors. On the other hand, in patients with LVEF >50%, only the combination of renal dysfunction and anemia were independent predictors (HR: 1.46, 95%CI:1.01-2.10, p=0.04). Conclusion We identified differences in the prognostic impact of anemia and renal dysfunction by LVEF.

Lipoprotein (a) and lipidemic parameters in PCSK-9 inhibitor patients. Experience from a specialized centre in Greece

Abstract Background Previous studies have reported an association between Proprotein Convertase Subtilsin-kexin type 9 (PCSK-9) inhibition and levels of lipoprotein a [Lp (a)], having a possible effect on the cardiovascular benefit achieved by their use. The purpose of this study was to investigate the effect of PCSK-9 inhibitor use in Lp (a) and other lipidemic parameter levels in the population of a specialized Lipids Clinic during a follow up period of 24 months. Methods We enrolled 143 (80 males, mean age 60 years old) patients who were on PSCK-9 inhibitor treatment from the outpatient lipid clinic of our hospital. Information were obtained regarding the presence of coronary artery disease (CAD) and CAD risk factors. CAD was present in 72 patients (63%), Familial Hypercholesterolaemia (FH) in 97 patients (85%) and 20 (18%) patients suffered from statin intolerance. Patients were on triple lipid lowering therapy (statin plus ezetimibe plus PCSK-9 inhibitors) except for those with statin intolerance who were either on dual therapy (ezetimibe plus PCSK-9 inhibitors, N=8) or single PCSK-9 inhibitors therapy (N=10). Lp (a) levels and lipid parameters such as Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglycerides (TG) were measured at baseline, 3 months, 12 months and 24 months of treatment. Additionally, patients were categorized according to baseline Lp (a) levels in two groups, Group 1 (<70mg/dl) (N=62), Group 2 (≥70 mg/dl) (N=26). A comparison of the response in lipid parameters between these two groups was performed. Results Mean value for Lp (a) in the whole population was 54mg/dl, 48mg/dl, 44mg/dl, and 45mg/dl at baseline, 3, 12 and 24 months, respectively. T test analysis revealed a significant reduction in Lp (a) levels after 12 months (P<0.05) There was also a significant reduction in LDL levels at all time points (165mg/dl to 78mg/dl, 85mg/dl, 78mg/dl respectively, P<0.05), a reduction in triglyceride levels at 3 and 12 months (125mg/dl to 110mg/dl, 108mg/dl respectively, P<0.05) and an increase in HDL levels after 12 months (50mg/dl to 53mg/dl, P<0.05). Moreover, in Group 1, the response in LDL levels was higher after 12 months of treatment with PCSK-9 inhibitors (158mg/dl to 69mg/dl, P<0.05) compared to Group 2 (155mg/dl to 86mg/dl), indicating that high levels of Lp (a) seem to define the response to treatment. Colclusions Besides the detrimental effect in LDL levels, PCSK-9 inhibition has an impact on HDL and TG levels. Lp (a) was also reduced indicating an additional important effect of this inhibition. While higher levels of Lp (a) seem to correlate with poorer response to treatment, our findings enhance the already known importance of Lp (a) as a prognostic factor.

Combination therapy using low-dose anlotinib and immune checkpoint inhibitors for extensive-stage small cell lung cancer.

This study evaluated the efficacy and safety of low-dose anlotinib combined with immune checkpoint inhibitors as second-line or later treatment for extensive-stage small cell lung cancer (ES-SCLC). The study included 42 patients with ES-SCLC who were treated with low-dose anlotinib combined with programmed cell death protein 1/programmed cell death-ligand 1 inhibitors at Henan Cancer Hospital between March 2019 and August 2022. We retrospectively analyzed the efficacy and safety data for these patients. Indicators assessed included progression-free survival (PFS), overall survival (OS), the overall response rate (ORR), the disease control rate (DCR), and adverse events (AEs). Prognostic factors were identified in univariate and multivariate analyses. Median PFS was 11.0 months (95% CI: 7.868-14.132) and median OS was 17.3 months (95% CI: 11.517-23.083). The ORR was 28.5% and the DCR was 95.2%. Treatment-related AEs were noted in 27 patients (64.3%), the most common of which was thyroid dysfunction (26.2%). Grade 3/4 treatment-related AEs were observed in two patients (4.8%). A combination of low-dose anlotinib and immune checkpoint inhibitors as second-line or later treatment for ES-SCLC may achieve longer PFS and OS and have manageable AEs.

Prognostic factors and predictive models for primary pulmonary diffuse large B-cell lymphoma: a population-based analysis

ABSTRACT Background Primary pulmonary diffuse large B-cell lymphoma (PP-DLBCL) is a rare extranodal non-Hodgkin's lymphoma (EN-NHL). Its prognosis as an aggressive lymphoma is abysmal, and predictive models are still lacking. Methods We screened patients diagnosed with PP-DLBCL between 2010 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Then, univariate and multivariate COX regression analyses were used to identify independent risk factors affecting patient prognosis. Finally, a novel nomogram was constructed and the model was evaluated by looking at three dimensions. Results A total of 831 patients were included in this study. Most of the patients were elderly (526 (63.8%)) and female (428 (51.9%)). The included patients were randomized in a 7:3 ratio into a training group (577 (70%)) and a validation group (248 (30%)). We concluded that the independent risk factors of prognosis were age, extrapulmonary metastasis, radiotherapy, chemotherapy, and surgical intervention. The results of receiver operating characteristic curves, calibration curves, and decision curve analysis in the training and validation groups confirmed that the risk prediction nomogram could accurately predict the survival of PP-DLBCL. Conclusion This study is the first large population-based clinical data study on PP-DLBCL. A novel predictive model about prognosis has been developed to help clinical decision-making.

Left atrial reservoir strain as a prognostic indicator for cardiovascular events after mitral valvuloplasty

Abstract Background In patients after mitral valvuloplasty (MVP), assessing valve function and heart failure (HF) is crucial for prognostic predictions. Left ventricular diastolic function assessed by transthoracic echocardiography (TTE) plays an important role in the evaluation of HF in general practice. However, post-mitral valve surgery patients are excluded from the left ventricular diastolic function assessment guidelines proposed by the American Society of Echocardiography in 2016 due to their low correlation with left ventricular diastolic function indices. On the contrary, the left atrial reservoir strain (LARS) before MVP is considered as a prognostic factor, reflecting left atrial dysfunction caused by mitral regurgitation. Nevertheless, there are limited reports on the relationship between LARS and cardiovascular (CV) events after MVP. Purpose The study aims to investigate the utility of LARS in predicting CV events after MVP. Methods The study included 249 patients who underwent TTE between January 2011 and January 2023 after MVP at our hospital. Patient background data, including NYHA classification, medical history, medications, blood tests, and TTE data, were collected at the time of follow-up TTE. LARS, left ventricular global longitudinal strain (LV-GLS), and right ventricular free wall strain (RV-FWSL) analysis were performed using a vender-independent external strain analysis software for all patients in the cohort. The primary endpoints were cardiovascular death and HF rehospitalization. The predictor of cardiovascular events was assessed using the Cox proportional hazards model and Kaplan-Meier curve (KMC). Results The mean age was 61±14 years, and 159 patients (64%) were male. The median time from surgery to TTE was 4.8 (1.0-6.8) years, 32 patients (13%) had events within 8.5 (3.7-10.8) years after TTE. The event groups had higher age, NYHA classification, and NT-pro BNP compared to the non-event group. TTE parameters such as left ventricular mass index, left ventricular end-diastolic volume and end-systolic volume were larger, and LV-GLS and LARS were significantly lower in the event group. In multivariate Cox proportional hazards models showed that LARS was also a prognostic indicator even after adjustment for several variables (Table 1). The KMC showed that LARS was associated with events regardless of left atrial volume index (Log-rank p <0.001, chi-square:31.03) (Figure 1). Conclusion LARS was strongly associated with CV events after MVP. We consider LARS to be a useful prognostic indicator after MVP.

Prognostic factors and etiological insights in constrictive pericarditis

Abstract Constrictive pericarditis (CP) is an infrequent disease that poses a diagnostic and therapeutic challenge, with mortality often linked to underlying etiological factors. Our unicentric retrospective research aims to elucidate prognostic indicators and unravel the diverse etiological spectrum of this condition. The study is accepted by the Ethical Committee of our Center. Between January 2010 and December 2023, we have identified a total of 112 patients diagnosed with CP, with an average follow-up time of 6.42 years (IQR 1.98 - 11.45). We present the baseline variables of the patients, etiology and prescribed treatments in the table 1, comparing patients who survive with those who do not survive. 66.1% of patients were males and median age was 60.8 years old. We present two Kaplan-Meier curves (Figures 1 and 2) comparing the survival rates between CP etiologies. In Figure 1, all causes are represented separately. In Figure 2, CP related to cardiac surgery, radiotherapy, purulent pericarditis, tuberculous pericarditis, mixed and other causes are combined. Our results suggest a better prognosis in patients with idiopathic CP and worse prognosis in patients with oncological related CP. The significant predictors in the univariate Cox analysis were age, cachexia, ascites, oncology etiology, hemoglobin, sodium, Euroscore II and surgical pericardiectomy. The best predictive model (selected with a lower AIC) to predict mortality throughout follow-up, with a Harrell's C of 0.835, included the variables age, cachexia, oncological cause and hyponatremia as risk factors for mortality and surgical treatment by pericardiectomy as a protective factor (Figure 3). In conclusion, our study suggests that CP etiology has an impact on survival with oncological cause having the worst prognosis. Furthermore, other factors as hyponatremia, cachexia, shock and age at diagnosis have also resulted in indicators of poor outcome.Figure 1.Kaplan meierFigure 3.Predictive model

Prognostic value of neutrophil-to-lymphocyte ratio and cardiac troponin I in patients with immune checkpoint inhibitors-related myocarditis

Abstract Background Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. Purpose We executed a multicenter study aimed at characterizing ICI-related myocarditis and risk factors influencing its prognosis. Methods The study included patients with ICIs-associated myocarditis at four medical centers in China from January 28, 2019 to June 15, 2023. Logistic regression was performed to explore the risk factors for the development of severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of biomarkers to distinguish severe myocarditis, and the performance and calibration were evaluated using Hosmer-Lemeshow test. Cox regression analysis was employed to investigate the influential risk factors affecting the prognosis of ICI-related myocarditis. Kaplan-Meier survival curve analyses were conducted to assess the differences in survival times among different myocarditis groups. Results 35 ICIs-associated myocarditis patients were identified. 21 patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (P=0.013), higher N-terminal pro-B-type natriuretic peptide levels (P=0.031), higher creatine kinase (CK) levels (P=0.018), higher CK-MB levels (P=0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (P=0.016) compared to non-severe myocarditis patients. Multivariate logistic regression showed that cTnI (adjusted odds ratio: 1.021, 95% confidence interval (CI): 1.002-1.039, P=0.03) and NLR (adjusted odds ratio: 1.890, 95% CI: 1.026-3.483, P=0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.765 (95% CI: 0.601 to 0.929, P=0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, P=0.016). Multivariate COX regression showed that NLR (adjusted hazard ratio: 1.189, 95% CI: 1.028-1.376, P=0.020) and pneumonitis (adjusted hazard ratio: 8.142, 95% CI: 1.191-55.651, P=0.032) were the independent prognostic risk factor associated ICI- related myocarditis. Further Kaplan-Meier survival curve analysis showed that the survival rate among patients without pneumonitis and with low level of NLR significantly outstripped that of patients with pneumonitis (P=0.015) and high level of NLR (P=0.024). Conclusions As independent risk factors for the development of ICI-associated severe myocarditis, cTnI and NLR demonstrated a promising predictive utility for the identification of ICI-associated severe myocarditis. NLR and the presence of pneumonitis were identified as independent risk factors that significantly impacted the prognosis of ICI-related myocarditis.

Prognostic preoperative factors for recurrence of tricuspid regurgitation following annuloplasty: examining the influence of 3d echocardiography

Abstract Introduction The increasing worry revolves around the reappearance of tricuspid regurgitation (TR) following tricuspid annuloplasty (TA) among individuals dealing with functional tricuspid regurgitation (FTR). Despite TA's efficacy as a treatment, a complete understanding of the echocardiographic elements influencing the recurrence of TR is pivotal. This knowledge holds the potential to guide the development of more robust preventive strategies, aiming to ease the incidence of recurrent TR after TA. Aim The aim of this study was to examine the prognostic value of tricuspid valve (TV) and echocardiographic parameters related to both right ventricular (RV) geometry and function. Specifically, our focus is on understanding these relationships in the context of recurrent TR following TA. Methods This prospective observational cohort study aimed to investigate determinants of recurrent TR post-surgical TV repair. The focus was on patients with moderate or severe functional TR related to left heart valvular disease, primarily severe mitral regurgitation, excluding those with ischemic heart disease. The study involved 66 participants, assessed preoperatively with 2D and 3D echocardiography, examining RV and right atrial (RA) geometry, functional, and TV parameters. TR severity followed ESC guidelines. Two groups were formed: effective TA group (50 patients) and recurrent TR group (16 patients), defined by mild to moderate TR and significant moderate-severe TR one year post-surgery, respectively. Statistical analysis employed SPSS software, with adjusted univariate logistic regression considering age and gender. Results Of the patients, 54% were male, with a mean age of 68±9 years. Echocardiography parameters in Table 1 showed no significant differences in gender, left ventricular, atrial geometrical, functional parameters, or preoperative effective regurgitant TV orifice area between groups (recurrent TR vs. effective TA: 38 [33] mm2 vs. 29 [15] mm2, p=0.117). Univariate logistic regression analysis highlighted RV and RA geometry, along with TV diameter, as predictors for recurrent TR. Notably, 3D TV geometrical parameters had prognostic significance, as confirmed by univariate adjusted logistic regression analysis. Functional RV parameters did not exhibit statistical significance in this analysis. Conclusion In conclusion, the recurrence of moderate-severe functional tricuspid regurgitation following tricuspid annuloplasty is linked to the tricuspid annulus size, as well as the geometry of the right atrium and right ventricle before surgery. Notably, no correlation was identified between the recurrence of TR and alterations in RV function.

Clinical significance of echocardiographic left ventricular hypertrophy for predicting left atrial appendage thrombotic milieu in patients with atrial fibrillation and CHA2DS2-VASc scores of 0-2

Abstract Background Even in patients with atrial fibrillation (AF) and low CHA2DS2-VASc scores, it is not always possible to completely rule out left atrial appendage (LAA) thrombus. Further stratification of the risk of LAA thrombosis in these patients remains an important yet unresolved issue. Left ventricular hypertrophy (LVH) is a prognostic risk factor in AF and has been associated with a worse prognosis, particularly in those with low CHA2DS2-VASc scores. Purpose To investigate the clinical significance of echocardiographic LVH for risk stratifying LAA thrombogenic milieu as a surrogate for cardioembolic risk in patients with AF and CHA2DS2-VASc scores of 0–2. Methods This was a single-center, retrospective study. We enrolled 707 consecutive patients with AF and CHA2DS2-VASc scores of 0–2 who underwent transesophageal echocardiography. The patients were divided into two groups based on the presence or absence of LVH. Owing to the racial differences in normative left ventricular mass index (LVMI) reference values, LVH was defined in this study using Japanese reference values. LVH was defined as LVMI ≥108 g/m2 for men and ≥98 g/m2 for women. LAA thrombogenic milieu was defined by any of the following findings: (1) thrombus, (2) severe spontaneous echo contrast or sludge, or (3) average LAA flow velocity ≤20 cm/s. Alongside conventional parameters, longitudinal strain values for the left ventricle (LV) and left atrium (LA) were obtained using transthoracic echocardiography. Results The mean age was 61 ± 10 years, and 12.2% were female. Overall, 77 (10.9%) patients were classified into the LVH group, and 41 (5.8%) of patients had LAA thrombogenic milieu. The LVH group exhibited a significantly higher prevalence of LAA thrombogenic milieu than the non-LVH (32.5% vs. 2.5%, p<0.001). Figure 1 illustrates the details of the patients with the LAA thrombogenic milieu based on LVH presence and CHA2DS2-VASc scores. The LVH group included six patients with LAA thrombus, even with CHA2DS2-VASc scores of 2, whereas the non-LVH group had no patient with LAA thrombus. Table shows the association of LAA thrombogenic milieu and clinical and echocardiographic parameters by logistic regression analysis; LVH independently associated with LAA thrombogenic milieu after adjusting for clinical factors (including CHA2DS2-VASc score, AF type, and serum brain natriuretic peptide levels) and conventional echocardiographic parameters (including LV ejection fraction, LV end-diastolic volume index, and LA volume index). Moreover, LVH provided incremental prognostic value for predicting LAA thrombogenic milieu, even when added to the longitudinal strain of the LV and LA reservoir strains (p<0.001). These findings are summarized in Figure 2. Conclusion Echocardiographic LVH significantly improves the prediction of LAA thrombogenic milieu, offering potential utility in further cardioembolic risk stratification for patients with AF and CHA2DS2-VASc scores of 0–2.

Survival benefit added by adjuvant chemotherapy in adenoid cystic carcinoma of salivary gland

The aim of this study was to investigate the potential survival advantages associated with chemoradiotherapy (CRT) compared to radiotherapy (RT) as standalone modalities in the treatment of adenoid cystic carcinoma (ACC) of the salivary glands. Patients diagnosed with resected salivary gland ACC were retrospectively enrolled and categorized into two groups based on the type of adjuvant therapy received. The overall survival outcomes between the CRT and RT cohorts were evaluated using a multivariable Cox model. Post propensity score-matching, a total of 114 patients (57 in each treatment group) were included in the analysis. In the general patient population, CRT did not confer an additional survival benefit compared to RT alone. High-grade tumors, positive surgical margins, and the presence of five or more positive lymph nodes were identified as independent prognostic factors associated with poorer overall survival. Specifically, for patients with positive surgical margins, CRT was significantly associated with improved overall survival relative to RT, displaying a hazard ratio of 0.93 (95% CI: 0.81–0.99). Furthermore, in patients with more than four metastatic lymph nodes, CRT significantly reduced the risk of mortality by 6% (95% CI: 1-24%) when compared to RT alone. Conversely, in patients with high-grade tumors, the addition of adjuvant chemotherapy to RT did not yield significant alterations in survival outcomes compared to RT alone (p = 0.437, HR: 0.95, 95% CI: 0.75–2.07). CRT may offer an overall survival benefit for patients with salivary gland ACC, particularly those characterized by positive margin or the presence of five or more metastatic lymph nodes.

The impact of QRS complex fragmentation status before and after cardiac resynchronization therapy with defibrillator implantation: Is it a predictor of arrhythmic events?

Abstract Introduction Cardiac resynchronization therapy with an implantable cardioverter defibrillator (CRT-D) has demonstrated efficacy in reducing mortality, hospitalization for heart failure (HF), and sudden cardiac death among subgroups of patients with HF with reduced ejection fraction (HFrEF). However, this population is highly heterogeneous, necessitating risk stratification. Several clinical findings, including QRS complex fragmentation (QRSf), have been identified as potential prognostic factors for arrhythmic risk. Nonetheless, evidence supporting the prognostic significance of QRSf in patients undergoing CRT-D remains limited. Purpose The aim of this study is to assess whether alterations in QRSf status, before and after CRT-D implantation, can predict arrhythmic events (AE) in patients with HFrEF. Methods This study included consecutive patients underwent CRT-D implantation at our center from October 2009 to December 2022. Demographic, clinical, electrocardiographic and echocardiographic data were obtained from electronic medical records and telephone interviews. QRSf was defined by the presence of various RSR′ patterns, including additional R waves (R′) or notching of the R and S wave in two contiguous leads corresponding to a primary coronary artery territory on a 12-lead electrocardiogram conducted before and after CRT-D implantation. An AE was characterized by appropriate ICD therapy (antitachycardia pacing or shock) for a ventricular arrhythmia or sustained ventricular arrhythmia without the need for ICD therapy. Results A total of 176 patients were included (mean age 69.9 ± 9.6 years with 80.6% male). Ischemic etiology accounted for 54.6% of cases of LV systolic dysfunction, with a mean baseline LVEF of 23.6%. CRT-D was indicated as secondary prevention in 18 patients. At baseline, 114 patients (64.8%) presented QRSf. Following CRT implantation, 17 patients (9.8%) without previous QRSf developed QRSf, while 26 patients (14.9%) resolved QRSf. The median follow-up was 43.6 months (interquartile range 19.5-81.1). During follow-up, 90 patients died and 29 AE occurred (16.5%). Among these, 23 patients had QRSf before and after CRT, whereas 6 AE occurred in patients without QRSf. Multivariate survival analysis using Cox regression demonstrated that the presence of QRSf before and after CRT-D was an independent predictor of AE (HR 3.56; 95% CI 1.00-12.70). Univariate and multivariate Cox regression analyses are presented in Table 1. Kaplan-Meier curves for AE in relation to QRSf status before and after CRT-D are illustrated in Figure 1. Conclusions Our findings suggest that the presence of QRSf and its persistence following CRT-D implantation appears to be an independent predictor of AE after CRT-D implantation in patients with HFrEF. Therefore, these patients would benefit from closer monitoring as they exhibit a heightened risk of arrhythmic events. Nevertheless, further research is warranted to validate these results.Table 1.Cox Regression Analysis.

Impact of QRS complex fragmentation on all-cause mortality before and after cardiac resynchronization therapy

Abstract Introduction Cardiac resynchronization therapy (CRT) have demonstrated to reduce all-cause mortality in selected patients with HFrEF. However, there is still a high rate of non-responders, so risk stratification is crucial. Fragmentation of the QRS complex (QRSf) has been suggested as a valuable prognostic factor in different cardiac diseases, but the evidence in patients undergoing CRT is controversial and limited. Purpose To evaluate if changes in QRSf status before and after CRT implantation has a prognostic role in patients undergoing CRT in terms all-cause mortality. Methods Consecutive patients undergoing CRT were prospectively included from October 2009 to December 2022. Demographic clinical, electrocardiographic and echocardiographic variables were recorded. Prospective follow-up variables were collected from electronic clinical records and telephone interview. QRSf complex was defined by the presence of different RSR′ patterns including additional R-waves (R′) and notches of the R-wave and S-wave in two contiguous leads corresponding to a main coronary artery territory in a 12-lead electrocardiogram performed before and after CRT. Results A total of 244 patients (mean age 71.8 ± 9.8 years, 79.5% male) were included. The etiology of LV systolic disfunction was ischemic in 50.0%. Mean LVEF before implantation was 25 ± 9%. A CRT-D was implanted in 176 patients (72.2%). The mean width of the paced QRS was 141 ± 23 ms. At baseline, 150 patients had a QRSf. After CRT implantation, 69 (28.4%) patients experimented a change in QRSf status: 29 patients (11.9%) without prior QRSf developed QRSf, whereas 40 patients (16.5%) resolved QRSf after CRT. Median follow-up time was 36.0 months (interquartile range 18.2-75.7). During the follow-up period, 90 patients died. In the multivariate Cox regression survival analysis, the presence of QRSf before the implantation with or without paced QRSf after CRT were independently associated with all-cause mortality (HR 4.43; 95% CI 1.53-12.80 and HR 3.69; 95% CI 1.16-11.80 respectively). Those without QRSf prior implantation who developed QRSf after CRT did not present significantly higher risk of all-cause mortality. Univariate and multivariate Cox regression analyses for all-cause mortality are presented in Table 1. Figure 1 presents Kaplan-Meier curves for all-cause mortality according to QRSf status before and after CRT implantation. Conclusions According to our results, preimplantation QRSf is an independent predictor of all-cause mortality regardless the resolution or maintenance of QRSf after CRT in patients with HFrEF undergoing CRT. Therefore, patients with QRSf before CRT implantation regardless the paced QRSf status, should be followed more strictly because they are at higher mortality risk.Table 1.Cox Regression Analyses

Hip fracture in elderly: malnutrition and health outcomes. A systematic review and meta-analysis

Abstract Background Hip fracture is a common condition among elderly and one of the leading causes of disability. Malnutrition is widely present in older patients and has been identified in several studies as an important and modifiable prognostic factor for several medical conditions, including hip fracture. The aim of the present study is to evaluate the association between malnutrition, assessed by validated tools, and selected health outcomes for different follow-up intervals from hip fracture, in particular: mortality, changes in mobility/living arrangements and postoperative delirium. Methods A literature search on PubMed, Web of Science and Scopus databases up to September 2023, was conducted to identify all studies involving older subjects that reported an association between MNA/GNRI/PNI/CONUT score and health outcome after hip fracture. Meta-analysis was performed by a random-effects model using risk values (RR/OR/HR) extracted from 14 eligible selected studies. Results Malnutrition significantly increased the risk of any adverse outcome by 70% at 1 month, and up to 250% at 1 year, showing an increasing trend with longer follow-up periods. One month after hip fracture, malnutrition significantly increased the risk of postoperative delirium by 275% (OR = 2.75; 95% CI 1.80-4.18; p ≤ 0.05), mortality by 342% (OR = 3.42; 95% CI 2.14-5.48; p ≤ 0.05) and mortality hazard risk by 351% (HR = 3.51; 95% CI 1.63-7.55; p ≤ 0.05). One year after hip fracture, malnutrition significantly increased the risk of transfer to more supported living arrangements by 218% (OR = 2.18; 95% CI 1.58-3.01; p ≤ 0.05), declined mobility by 41% (OR = 1.41; 95% CI 1.14-1.75; p ≤ 0.05), mortality by 368% (OR = 3.68; 95% CI 3.00-4.52; p ≤ 0.05) and mortality hazard risk by 234% (HR = 2.34; 95% CI 1.91-2.87; p ≤ 0.05). Conclusions These findings underscore that malnutrition worsens outcomes after hip fracture in elderly, emphasizing the importance of nutritional assessment to mitigate potential adverse consequences. Key messages • The results of the present study underscore that malnutrition increases the risk of death and worsens mobility and independence after hip fracture in older adults. • Routine nutritional status evaluation could prove beneficial in the management of hip fracture older patients in order to prevent potential adverse outcomes.

Left atrial strain predicts adverse events in hypertrophic cardiomyopathy: preliminary results from a CMR study

Abstract Background Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of major adverse cardiovascular events (MACE), however, current risk stratification methods are imperfect. Left atrial global longitudinal strain (LA GLS) is an increasingly acknowledged predictive parameter, yet its potential role in HCM is not well defined. Purpose This study aims to investigate the prognostic role of cardiac magnetic resonance (CMR)-derived LA GLS for the occurrence of MACE in patients with HCM. Methods A retrospective, single-centre, CMR study of HCM patients was conducted. Clinical data was collected from electronic medical record and CMR images were analysed by two blinded investigators. LA GLS was derived from CMR two-chamber cine images by a semiautomatic method, and was categorized according to its median value. The endpoint was a composite of MACE, including all-cause death, sudden cardiac death (SCD), sustained and non-sustained ventricular tachycardias (VT), appropriate implantable cardiac defibrillator (ICD) shocks, heart failure (HF) hospitalization, and new-onset atrial fibrillation (AF). Cox regression analysis was performed. The preliminary results of the study are now reported. Results A total of 54 HCM patients were included, mean age was 58.5 years ± 15.9 and 38.9% were female. Average maximal wall thickness (MWT) was 18.0 mm ± 3.9, 37% had left ventricular outflow obstruction (LVOTO) and 45.1% had positive late gadolinium enhancement (LGE). After a mean follow-up of 6.9 ± 3.0 years, 26 patients (48.1%) experienced the composite endpoint. Figure 1 shows the clinical and CMR differences according to the occurrence of MACE. LA GLS was significantly lower in patients with MACE compared to those without (26.5 ± 19% vs 36.7 ± 13%, p=0.026), with a moderate predictive value (AUC = 0.68, Figure 2A). Multivariate Cox regression analysis revealed that a decrease in LA GLS (HR 1.09 per each 1% decrease, 95% CI 1.03-1.15, p=0.002), the presence of LGE (HR 6.9, 95% CI 1.7-28, p=0.007), the presence of LVOTO (HR 3.4, 95% CI 1.12-10.2, p=0.031) and an increase in MWT (HR 1.23 per each 1mm increase, 95% CI 1.05-1.45, p=0.011) were independently associated with MACE. Among low-risk HCM patients (absence of LGE or LVOTO, or MWT below our median value), LA GLS had an additional prognostic role, and those with an LA GLS above the median value (LA GLS>29.7%) presented a remarkably favourable prognosis (Figure 2B-D). Conclusions CMR-derived LA GLS is a predictor of outcomes in HCM beyond established imaging prognostic factors. Particularly, LA GLS appears to be useful in risk-stratifying low-risk HCM patients: those with normal LA GLS show an excellent prognosis. If confirmed in larger studies, LA GLS could be used to individualise HCM management.Figure 2

Genetic and phenotypic architecture of biventricular trabeculation

Abstract Introduction Cardiac trabeculae form a network of muscular strands that line the inner surfaces of the heart, and their development involves molecular pathways that regulate structural complexity. Excessive or hypertrabeculation occurs as part of normal variation in apparently healthy individuals, as an adaptation to altered loading conditions, and is observed in patients with cardiomyopathies (CMs) and heart failure (HF). Purpose In adults, trabeculation is not a prognostic factor independent of the underlying myocardial disease but may play a role in the natural history of ventricular remodelling. We sought to (i) understand the genetic and non-genetic determinants of trabeculation, (ii) understand its role in the causality of disease, and (iii) evaluate trabeculation as a biomarker for diagnosis and stratification. Methods We report genes with a burden of rare variants and novel common variant associations across the allele frequency spectrum for biventricular trabecular morphology in 47,803 participants of the UK Biobank using fractal dimension analysis of cardiac imaging (Figure 1). We assessed environmental modifiers of trabecular morphology, correlation with cardiac traits, phenome-wide association studies, and the relationship with the progression of CMs and HF. Results We identified a burden of trabeculation-associated rare variants in genes that regulate myocardial contractility and cardiac development and GWAS identified novel loci near genes implicated in CMs, conduction traits, and signalling pathways that define the early development of trabeculation. For example, we identified 56 genes with a burden of rare variants and 68 novel loci from GWAS (e.g., CASQ2, CACNA1C, MYBPC3, MYH7, NKX2-5, NOTCH1, TBX20) for the left ventricle. The strongest imaging relationships with trabeculation were with measures of volume and strain. Modifiers of trabeculation included African ancestry, alcohol intake, and physical activity. Carriers of CM-associated pathogenic variants had increased trabeculation. Of participants with CM reported after imaging, 25% had hypertrabeculation on imaging and hypertrabeculation was a risk factor for a subsequent diagnosis of HF (HR=1.3), mitral valve disorders (HR=1.4), bundle branch block (HR=1.2). Comparisons of biventricular trabeculation showed similarities in trabeculation across the ventricles in CM. Reduced right ventricular trabeculation and end-diastolic volume associated with Type-2 diabetes. Conclusions These data provide new insights into the mechanisms that regulate structural complexity in the heart. Changes in trabeculation may occur early in the pathogenesis of heart disease, can be modified by genes regulating pathways outside the sarcomere, and causality depends on the underlying cardiomyopathic substrate. Trabeculation progresses with cardiovascular disease, is a useful marker of remodelling, and identifies novel genetic modifiers of ventricular complexity.Figure 1

Improving prognostic accuracy in ischemic cardiomyopathy: the CMR-LGE score

Abstract Background There is a need for accurate prognostic stratification tools in patients with ischemic cardiomyopathy (ICM). Several studies have shown the considerable impact of cardiac magnetic resonance (CMR) imaging findings notably late gadolinium enhancement (LGE) but an easy interpretable score to guide clinical practice is lacking. Purpose To determine the CMR parameters most predictive of mortality in a cohort of ICM patients with left ventricular ejection fraction (LVEF) less than 50%, and then to develop a readily interpretable score based on these parameters. Methods Between 2008 and 2022, all consecutive patients with a history of ICM with LVEF<50% and presence of ischemic LGE on viability CMR examination, were recruited by two independent centers. The primary outcome was all-cause death using French National Registry of Death. The first center (N=2,900) was designated as the derivation cohort for variable selection and score development, and the second center (N=691) was used as the validation cohort to evaluate the performance of the final score. Thirty-two variables (17 clinical and 15 CMR) were initially assessed. Automatic feature selection was performed using a machine-learning approach with a Random Survival Forest (RSF) algorithm. Using the selected variables, our proposed score, the CMR-LGE score, was derived from coefficients of the Cox regression. Performance evaluation on the validation cohort was conducted using Harrel’s C index compared with traditional prognostic factors associated with poor outcomes in ICM. Categories for the prognostic score were identified using a survival conditional inference tree analysis on the derivation cohort, aiming to maximize the log-rank score. Results Among the 3,591 patients included (mean age 65±12 years; 75% male; mean LVEF 44±6%), 549 (15.3%) died over a median follow-up of 9 (interquartile range: 7–12) years. Feature selection with RSF highlighted that the most important variables to predict death were LGE variables: the extent, the location (septal and anterior) and the transmurality of ischemic LGE as well as the extent of additional midwall LGE (Figure 1). Following these findings, we developed the CMR-LGE score by rounding the coefficient of a Cox regression (Figure 2A). Harrel’s C index of CMR-LGE score outperformed traditional prognostic factors, including LVEF (0.88 vs 0.69). Finally, based on our CMR-LGE score, we identified a low-risk population (CMR-LGE score below 6) and a high-risk population (CMR-LGE above 8), validated using survival curves in the validation cohort (Figure 2B). Conclusion Using RSF, we identified that the 5 most important CMR variables to predict mortality in ICM were all LGE features. Our CMR-LGE score showed excellent performance to stratify patient risk compared to traditional prognostic factors including LVEF.Variable selectionModel building and evaluation

Incidence and predictors of 2-year mortality following percutaneous left atrial appendage occlusion in the EWOLUTION tria

Abstract Background and aims Sufficient survival time following left atrial appendage occlusion (LAAO) is essential for ensuring the efficacy and cost-effectiveness of this strategy for stroke prevention. Understanding prognostic factors for early mortality after LAAO could optimize patient selection. In the current study we perform an in-depth analysis of 2-year mortality after LAAO, focusing particularly on potential predictors. Methods The EWOLUTION registry is a real-world cohort comprising 1020 patients that underwent LAAO. Endpoint definitions were prespecified and death was categorized as cardiovascular, non-cardiovascular, or of unknown origin. Mortality rates were calculated from Kaplan-Meier estimates. Patient characteristics and event rates were compared between deceased and alive patients by unpaired T-tests or Chi-squared test, as appropriate. Baseline characteristics significantly associated with death in univariate Cox regression analysis were incorporated into the multivariate analysis. All multivariate predictors were included in a risk model. Results 2-year mortality rate was 16.4% (CI: 14.0-18.7%), with 50% of patients dying from a noncardiovascular cause. Deceased patients had more comorbities and more often had a major bleeding after LAAO (20.6% vs 3.3%, p<0.001). Multivariate baseline predictors of 2-year mortality included age (HR 1.05, CI: 1.03-1.08, per year increase), heart failure (HR 1.73, CI: 1.24-2.41), vascular disease(HR 1.47, CI: 1.05-2.05), valvular disease (HR 1.63 CI: 1.15-2.33), abnormal liver function (HR 1.80 CI: 1.02-3.17) and abnormal renal function (HR 1.58, CI: 1.10-2.27). Mortality rate exhibited a gradual rise as the number of risk factors increased, reaching 46.1% in patients presenting with five or six risk factors. Conclusion One in six patients died within 2 years after LAAO. We were able to identify six independent predictors of mortality. When combined, this model showed a gradual increase in mortality rate with a growing number of risk factors, which may guide appropriate patient selection for LAAO.

Identifying prognostic factors in patients with cardiogenic shock undergoing VA-ECMO treatment: insights from ECLS-SHOCK using machine learning

Abstract Background/Introduction Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has not been shown to reduce short-term mortality in patients with acute myocardial infarction complicated by cardiogenic shock. However, whether some patients might benefit from VA-ECMO remains to be cleared. Purpose To identify the impact of VA-ECMO therapy on outcomes by leveraging the potential of machine learning. Methods The ECLS-SHOCK trial is a randomized controlled trial where patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early VA-ECMO plus usual medical treatment or usual medical treatment alone. The primary outcome was death from any cause at 30 days. Extreme gradient boosting (XGBoost) was used to develop a model for the prediction of 30-day all-cause mortality and to assess the influence of VA-ECMO on outcomes. Results Overall, 209 patients were randomized to the VA-ECMO and 208 to control. Baseline characteristics between groups were well balanced (median age 63 years, 81% male, 67% presenting with ST-segment elevation myocardial infarction). At 30-days 100 patients in the VA-ECMO and 102 in the control group were dead. The final XGBoost model contained 27 variables and the 10 most influential variables are shown in Fig. 1. On derivation the model predicted mortality with an AUC of 1.00 and on validation with an AUC of 0.80 (95% CI 0.71 to 0.89), with a sensitivity of 95% (95% CI 88% to 100%) and a specificity of 55% (40% to 69%), resulting in a positive predictive value of 65% and a negative predictive value of 92% at a Youden-derived cut-off. Importantly, neither the VA-ECMO therapy nor its complications were among the most influential factors of the model with a relative importance of 1.1% for VA-ECMO therapy and 0.25% for peripheral vascular complications and bleeding complications even being discarded by the model. Conclusion In patients with acute myocardial infarction complicated by cardiogenic shock the influence of VA-ECMO therapy on 30-day mortality, even when investigated with complex machine learning models, is negligibly low.