Prognostic Impact Research Articles

First-degree family history of cancer in women with stage I endometrial carcinoma: Prevalence and prognostic impact

First-degree family history of cancer in women with stage I endometrial carcinoma: Prevalence and prognostic impact

Long-term outcome of invasive pure micropapillary breast cancer compared with invasive mixed micropapillary and invasive ductal breast cancer: a matched retrospective study.

Data on the prognostic impact of the micropapillary component in breast cancer are limited. The purpose of this study was to investigate the clinicopathological characteristics and long-term outcomes of pure and mixed invasive micropapillary breast cancer (IMPC) patients compared to invasive ductal cancer (IDC) patients. This retrospective study analysed all IMPC and IDC patients treated at the European Institute of Oncology (IEO) between 1997 and 2019. The overall cohort of IMPC patients was divided in two groups, pure and mixed IMPC. Each patient with mixed or pure IMPC was matched with one patient with IDC, based on year of surgery, age, pT, pN, and molecular subtype. A total of 30,115 IDC, 120 pure IMPC and 150 mixed IMPC patients were considered eligible. Compared to IDC, pure and mixed IMPC patients presented a higher rate of locally advanced disease (pT2-T3, pN2-N3), vascular invasion, and Luminal B subtype. After matching, pure and mixed IMPC showed a significant higher rate of vascular invasion compared to IDC patients (p < 0.001). Invasive disease-free survival was better in IDC compared to pure IMPC patients (p = 0.11). Long-term overall survival was significantly worse in pure IMPC group compared to IDC group (p = 0.004), being instead similar between mixed IMPC vs matched IDC (p = 0.07). These real-world data reported the worse prognosis of pure IMPC compared to IDC, highlighting the peculiar prognostic value of the micropapillary subtype itself in the decision-making process of IMPC management. An accurate pre-surgical diagnostic evaluation and a multidisciplinary approach are pivotal to best personalize its treatment.

Prognostic impact of a new score using lymphocyte-to-monocyte ratios in the serum and malignant body fluid in ovarian cancer patients

Prognostic impact of a new score using lymphocyte-to-monocyte ratios in the serum and malignant body fluid in ovarian cancer patients

Prognostic Value of Systemic Inflammatory Response in Lymph Node-Negative Colorectal Cancer.

The aim of this study was to investigate the prognostic value of systematic inflammatory response in patients with lymph node-negative colorectal cancer. We retrospectively investigated 245 patients with lymph node-negative colorectal cancer who underwent curative resection and evaluated the prognostic impact of systematic inflammatory response, which was represented by neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), and C-reactive protein-to-albumin ratio (CAR). Then, the prognostic significance of the systematic inflammatory response on survival was analyzed using the Kaplan-Meier method in patients selected by propensity score matching (PSM) analysis. In the multivariate analysis, CAR ≥ .081 (P = .004) was independent predictors of disease-free survival, while American Society of Anesthesiologists physical status ≥3 (P = .049) and CAR ≥ .081 (P < .001) were independent predictors of overall survival. By PSM analysis, PSM-high-CAR was significantly associated with worse disease-free survival (P = .043) and overall survival (P = .041) in patients with lymph node-negative colorectal cancer. C-reactive protein-to-albumin ratio may be a significant indicator of poor long-term outcomes in patients with lymph node-negative colorectal cancer.

Influence of Right and Left Bundle Branch Block in Patients With Cardiogenic Shock and Cardiac Arrest.

The study investigates the prognostic impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) in patients with cardiogenic shock (CS) compared with no bundle branch block (BBB). In patients with heart failure, existence of RBBB and LBBB has influence on prognosis. Prospective registry-study. ICU of a tertiary academic hospital in Germany. Adult patients with CS. None. Consecutive patients with CS were included. The prognostic impact of RBBB and LBBB on 30-day all-cause mortality was tested within the entire cohort and in the subgroup of CS patients with cardiac arrest at admission. The final study cohort comprised 248 patients. Patients with RBBB showed the highest 30-day all-cause mortality followed by LBBB and no BBB (72.5% vs. 52.9% vs. 50.0%; log-rank p = 0.015). These findings were consistent even after solely including CS patients with cardiac arrest (90.0% vs. 73.3% vs. 62.2%; log-rank p = 0.008). After adjustment for lactate, norepinephrine, troponin I, Acute Physiology Score, Society of Cardiovascular Angiography & Interventions shock stage, and heart rate in a multivariable Cox regression analysis, RBBB still revealed a negative impact on 30-day all-cause mortality (hazard ratio [HR], 1.807; 95% CI, 1.107-2.947; p = 0.018), whereas LBBB was not associated with 30-day all-cause mortality. In this multivariable Cox regression model lactate (HR, 1.065; 95% CI, 1.018-1.115; p = 0.006), troponin I (HR, 1.003; 95% CI, 1.001-1.005; p = 0.001), and Acute Physiology Score (HR, 1.033; 95% CI, 1.001-1.066; p = 0.041) were as well associated with 30-day all-cause mortality. Finally, no association of RBBB was found with the incidence of liver or severe renal failure. Besides the Acute Physiology Score, lactate, and troponin levels, RBBB was associated with an increased 30-day all-cause mortality in consecutive CS patients with and without cardiac arrest, whereas LBBB showed no prognostic impact.

Clinical features of infective endocarditis affecting cardiac implantable electronic devices

Abstract Introduction Infective endocarditis (IE) is a serious condition with high rates of serious complications and mortality. Furthermore, implantation of cardiac electronic devices (peacemakers, ICD, CRT) has been increasing in recent years, with technique-associated infections being one of the main adverse events. Our goal was to analise clinical features of IE as associated with cardiac implantable electronic devices (IE-CIED) and its prognostic impact. Methods Prospective study of a cohort of patients diagnosed with IE in our centre from 1987 to 2022. A comparative analysis was performed between patients with IE not associated with cardiac implantable electronic devices (group 1) and those who did (group 2). Clinical, microbiological, echocardiographic and therapeutic variables were analysed and the prognostic impact was evaluated in terms of mortality. Results 569 patients were analysed, of which 540 (94,9%) belonged to group 1, while 29 (5,1%) belonged to group 2. The mean age was higher in group 2 (65,1 years ±12,9 vs 55,7 years ± 18,7; p=0,011) with male predominance in both populations (67.5% overall). Patients with IE-CIED had a higher proportion of staphylococcus aureus (48.3% vs 19.7%; p&amp;lt;0.001) and staphylococcus epidermidis (34.5% vs 15.6%; p&amp;lt;0.001) infections; nosohusial endocarditis (56.5% vs 20.9%; p&amp;lt;0.001); and underlying heart disease (89.7% vs 67.3%; p=0.012). Furthermore, these patients had a higher proportion of tricuspid valve involvement (18.2% vs 81.8%; p&amp;lt;0.001). Regarding the approach, a higher percentage of surgery was performed in patients with IE-CIED (75.9% vs52.7%; p=0.015). On the other hand, patients with IE not associated to cardiac implantable electronic devices had a higher prevalence of cardiac complications (51.5%vs25.7%;p=0.003), defined as valvular rupture or perforation, pseudoaneurysm, abscess or intracardiac fistula; and central nervous system complications (17.2%vs2.9%;p=0.29). No significative differences were found in terms of echocardiographic findings compatibles with IE, nor were there any differences in severe complications or early, late or total mort ality. Conclusions Infective endocarditis affecting cardiac implantable electronic devices is associated to higher prevalence of staphylococci, underlying heart disease and less involvement of the left heart chambers. Surgery was used to a greater extent in this patients. This entity does not imply a worse prognosis in terms of severe complications or mortality.Table 1.Proportion of IE-CIEDTable 2.Microbiology, mortality

Atrial and ventricular mitral regurgitation in the general population

Abstract Background Functional mitral valve regurgitation (FMR) is the result of two concurrent pathomechanisms: (1) the dilatation of mitral valve annulus (atrial) or (2) remodelling of the left ventricle (ventricular) in the absence of relevant leaflet degeneration¹. Even though FMR has been reported to be the most common cause of relevant MR², there is no general accepted definition of the two subtypes, nor are there population-based data regarding their prevalence, distribution and risk profiles¹. Purpose We aimed to evaluate the prevalence of FMR and to provide an in-depth characterisation of the subtypes aFMR and vFMR in the general population. Methods The study included the first 10,000 participants of the population-based Hamburg City Health Study enrolled between 2016 and 2019. Of these, 8.543 echocardiographic samples were available for analysis. Mitral valve was assessed by two independent investigators. Isolated degenerative MRs as determined by valve mobility (prolapse or restrictive) were excluded. FMR was classified as ventricular when fulfilling one of the following criteria: history of myocardial infarction or coronary artery disease, left ventricular ejection fraction (LVEF) ≤ 40%, restrictive leaflet, tenting area ≥ 150 mm² or coaptation depth ≥ 10 mm. All FMR with LVEF &amp;gt; 55% were classified as atrial. Results After excluding the samples with an insufficient image quality or missing data and re-assessment by the second investigator, 216 of 282 participants with a relevant MR (i.e. moderate or severe) remained (2,6% of the total cohort, see figure 1). In the next step, 153 participants were classified as pure FMR (68.9%), the remaining were mainly functional with minor degenerative features. A total of 31 (14.4%) MRs were classified as vFMR, the remaining 185 participants had an aFMR. Female gender was significantly more common in the aFMR cohort. The remaining demographic variables (age, body mass index) as well as established cardiovascular risk factors (i.e., diabetes, smoking, hypertension) were comparable between the vFMR and aFMR cohort. However, vFMR patients had significantly higher levels of NT-proBNP or NHYA state and presented more frequently with an atrial fibrillation (see figure 2). LVEF and LV stroke volume, TAPSE, left atrial ejection fraction and E/A ratio as a parameter of diastolic dysfunction were lower in the vFMR cohort whereas tenting area and left atrial endsystolic volume was significantly increased. Conclusion In our population-based study, aFMR was found to be the predominant subtype of FMR. The established cardiovascular risk factors were comparable in the vFMR and aFMR cohort. Echocardiographic variables differed significantly and indicate more advanced heart failure and LV remodelling in the vFMR cohort. Further categorization of FMR, in particular regarding the prognostic impact and long-term outcomes, is strongly warranted to allow a clinically relevant definition of aFMR and vFMR.Figure 1:Overview of sample sizeFigure 2:Baseline characteristics

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 &amp;lt; 0.001), Cystatin B (CSTB; 2.0-fold, p &amp;lt; 0.001), fatty acid binding protein 4 (FABP4; 2.0-fold, p &amp;lt; 0.001), insulin-like growth factor-binding protein 1 (IBP-1; 1.9-fold, p &amp;lt; 0.001) and suppression of tumourigenicity 2 (ST2; 1.7-fold, p &amp;lt; 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 &amp;lt; 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 &amp;lt; 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.

Does the presence of severe pulmonary hypertension affect survival at 5 years follow-up in patients who underwent TAVI for severe aortic stenosis?

Abstract Background Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS) and is associated with increased mortality after transcatheter aortic valve implantation (TAVI) as well as surgical aortic valve replacement (SAVR). Preprocedural systolic pulmonary artery pressure (sPAP) often improves after TAVI because the most common type of PH is postcapillary PH secondary to left-sided heart disease, which potentially improves after treatment for AS. However, there are limited data regarding the prognostic impact on outcomes after TAVI and their predictors. Purpose The aim of this study is to compare survival at 5 years between patients with severe PH against those who did not have severe PH who underwent TAVI. Methods Between January 2012 until December 2022, we carried out a retrospective study of all patients who underwent TAVI at our hospital. Severe PH was defined as the presence of sPAP &amp;gt;40mmHg on echocardiography. Patients with aortic regurgitation and mixed aortic valve disease were excluded. Co-morbid pulmonary disease was defined as the presence of any significant pulmonary disease including COPD and Asthma. Co-morbid neurological disease was defined as the presence of any significant neurological disease including CVA/ TIA. Diabetes mellitus was defined as per WHO and included patients who were diet, medication and insulin controlled. Survival status and date of death were ascertained from our electronic health records. Counts and incidence rates of clinical outcomes at 5-year follow-up were computed from Kaplan-Meier analysis (See Figure 1). A Cox proportional hazards model was used to compute HRs and 95% CIs for the study outcomes. Results Of the 274 patients available for analysis, 115 (14%) patients had severe PH. The mean age was 84 years in both cohorts whilst patients in the severe PH cohort were frailer by Katz Index Score. Death occurred in 67 patients out of 115 patients who had severe PH and in 87 out of 158 patients who did not have severe PH after a median follow-up time of 4.1 years (58% vs 55%; adjusted HR: 1.04; 95% CI: 0.71-1.51; P = 0.86). Conclusion Our data shows that presence of severe pulmonary hypertension in severe aortic disease patients who had undergone TAVI did not affect survival at 5 years follow up compared to patients without severe pulmonary hypertension undergoing TAVI. Determining predictors of mortality in this high-risk cohort is likely to be complex and multifactorial, owing to the severe multi-comorbidity precluding them from SAVR.

Histopathology and prognosis of new-onset atrio-ventricular block after coronary artery bypass graft surgery

Abstract Background Atrio-ventricular block (AVB) can often be seen in patients undergoing cardiac procedures. Nevertheless, little is known about the histopathological features of new-onset postoperative AVB prior to the clinical manifestation and its prognostic impact. Purpose This study explores the association of first-degree AVB in ECG and postoperative outcome of patients with either preoperative or a new-onset AVB. Furthermore, histopathological features were analyzed to distinguish the characteristics between preoperative and postoperative AVBs compared to no AVB. Methods CAREBANK is a prospective study with atrial biopsies obtained at the time of open-heart cardiac surgery and long-term follow-up focusing on the adverse events. We analyzed preoperative as well as postoperative ECGs derived after index hospitalization (1-18mo) in patients undergoing CABG. The definition of first-degree AVB was PR-interval ≥200ms. The main outcome of interest was follow-up mortality. Histopathological analysis was used to assess the amount of fibrosis, cardiomyocytes, number of nuclei and macrophages. Results Median follow up time was 4.0 (IQR 2.7 – 5.0) years. First-degree AVB was found in 84/373 (22.5%) preoperative ECGs. Altogether 25/289 (8.7%) cases where ECG was available (after excluding preop AVB, atrial fibrillation) developed first-degree AVB after index hospitalization. New-onset first-degree AVB was associated with increased mortality (aHR 4.033 (95-CI% 1.019–15.965, p=0.047). In atrial histopathological analysis, area covered by cardiomyocytes (p=0.033) as well as area covered by nuclei (p=0.047) were smaller in those with new-onset AVB after surgery, but not in those with preoperative first-degree AVB (p=0.692 and p=0.384) as compared with controls, respectively. Similarly, the total area of fibrosis was greater in those with preoperative first-degree AVB (p&amp;lt;0.001), but not in those with postoperative new-onset AVB (p=0.244). When compared with controls, share of CD68 positive macrophages was similar (p=0.073), but anti-inflammatory CD206 positive M2 macrophages were absent in patients with new-onset AVB (p=0.042). Conclusion Patients with new-onset AVB after CABG have increased mortality in the long-term compared to those without. Histopathology identifies marked differences in macrophage populations between those with and without new-onset AVB.

The prevalence and impact of changes in the severity of secondary TR during hospitalization in acute heart failure

Abstract Background Secondary tricuspid regurgitation (TR) is a prevalent entity in patients hospitalized for acute heart failure (AHF), and concomitant moderate or severe TR at admission has been demonstrated to be associated with a poor prognosis. However, no study has described the trajectories of the severity of secondary TR during admission, and the prognostic implications of changes in the severity of secondary TR. Purpose This study aimed to investigate the dynamism of secondary TR observed during hospitalization due to worsening heart failure, and its prognostic impact in patients with AHF. Methods A post-hoc analysis of 1,061 consecutive patients hospitalized with AHF was performed, enrolled in the prospective, multicenter Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure (REALITY-AHF). Patients included in the study underwent a comprehensive echocardiographic examination within 24 hours of admission and again prior to discharge. Patients were divided into four groups based on the TR severity at admission and discharge: none to mild TR at both admission and discharge (no/no group), moderate to severe TR at admission but improved to none to mild TR at discharge (resolution group), none to mild TR at admission but moderate to severe TR at discharge (worsening group), and moderate to severe TR at both admission and discharge (persistent group). The primary endpoint was the composite of 1-year all-cause mortality and HF re-hospitalization after discharge. Results The no/no, resolution, worsening, and persistent groups included 479 (45%), 275 (26%), 85 (8%), and 222 patients (21%), respectively. The no/no group and the resolution group had significantly lower tricuspid regurgitant pressure gradients prior to discharge compared to the worsening and persistent groups (P&amp;lt;0.001). Also, right ventricular dysfunction evaluated at discharge, defined by tricuspid annular plane systolic excursion &amp;lt;17 mm, was more prevalent in the worsening (65.7%) and persistent groups (66.4%) compared to the no/no (43.7%) and resolution (53.2%) groups (P&amp;lt;0.001). Compared to the no/no group, the worsening and persistent groups, but not the resolution group, were associated with a higher incidence of the primary endpoint (Log-rank: P&amp;lt;0.001). This association remained significant in an adjusted Cox regression analysis, with the worsening group (hazard ratio: 1.48, 95% confidence interval [CI]: 1.01–2.20) and persistent group (hazard ratio: 1.35, 95% CI: 1.01–1.83) independently associated with the primary endpoint, but not the resolution group (hazard ratio: 1.10, 95% CI: 0.81–1.49). Conclusions In patients hospitalized for AHF, the severity of secondary TR is dynamic, and changes in the severity of TR are significantly associated with prognosis. Our study results underscore the importance of repetitive evaluation of TR in hospitalized patients with AHF.

Prognostic significance of right ventricle to pulmonary artery coupling acute improvement after mitral transcatheter edge-to-edge repair

Abstract Background Transcatheter Edge-to-Edge Repair (TEER) of mitral valve is a valid treatment option for severe mitral regurgitation. The right ventricle is acutely affected by early hemodynamic changes following the correction of significant mitral regurgitation. Echocardiographic parameters of the right chambers could have a prognostic impact even in a periprocedural setting. In particular, right ventricle to pulmonary artery coupling improvement may be of pivotal importance, as this parameter is a validated marker of right ventricle function. Purpose To evaluate the prognostic impact of early improvement of right ventricle to pulmonary artery coupling assessed by means of the Tricuspid Annular Plane Systolic Excursion/Pulmonary Artery Systolic Pressure (TAPSE/PASP) ratio after TEER. Methods This retrospective single centre study included patients treated with TEER in our hospital from 2015 to 2023. Transthoracic echocardiography was performed before and shortly after device positioning. Acute effects of TEER on echocardiographic parameters were assessed by paired samples t-test. Diagnostic accuracy of the percent variation in the TAPSE/PASP ratio was assessed by means of receiver-operating characteristics analysis. Prognosis was evaluated by Kaplan-Meier analysis. Results The study included 95 patients (age 78 ± 10 years; 63% men; BMI 25 ± 5 kg/m2) with severe or moderate-to-severe mitral regurgitation. Mean baseline Left Ventricle (LV) ejection fraction was 45 ± 16%, LV end-diastolic volume was 157 ± 62 ml and effective regurgitant orifice area was 41 ± 25 mm2. Post-procedural echocardiographic assessment showed early improvement of LV end-diastolic diameter (p &amp;lt; 0.001), LV end-diastolic volume (p = 0.025), LV stroke volume (p &amp;lt; 0.001), LV global longitudinal strain (p &amp;lt; 0.001), right ventricle free wall longitudinal strain (p &amp;lt; 0.001) and PASP (p = 0.002). Percent improvement of TAPSE/PASP ratio showed a sufficient diagnostic accuracy in predicting a composite outcome of hospitalisation for heart failure and all cause mortality at 1 year (area under the curve 0.66, p = 0.047), with an optimal cut-off of 5.5%. An improvement of the TAPSE/PASP ratio over this threshold was associated with a reduction in the composite outcome (hazard ratio 0.38, p = 0.045). Conclusion TEER improves both left and right ventricular dynamics, which can be detected with echocardiography. In particular, an acute improvement of the TAPSE/PASP ratio is associated with an improvement in short-term prognosis. A comprehensive assessment of right ventricular function, including TAPSE/PASP ratio, should be routinely performed before and after TEER.

Clinical correlates and prognostic impact of cognitive decline in patients with heart failure and preserved ejection fraction: insights from PARAGON-HF

Abstract Background Cognitive decline is common in patients with heart failure (HF), but its clinical correlates and prognostic impact are not well understood in this population. Purpose To examine the baseline variables associated with cognitive decline and the associations between cognitive decline and HF outcomes in patients with heart failure and preserved ejection fraction (HFpEF). Methods We analyzed cognitive function, as measured by the Mini-Mental State Examination (MMSE), in 2895 patients with HFpEF enrolled in a pre-specified sub-study of PARAGON-HF. Logistic regression analysis was performed to determine the factors associated with cognitive decline i.e., a decrease in MMSE score of ≥3 points by 48 weeks. Time-updated Cox proportional hazards regressions and semiparametric proportional rates models were used to examine the subsequent risk of clinical outcomes after a decline in MMSE scores of ≥1-, 2- and 3-points during follow-up respectively, adjusted for known prognostic variables including NT-proBNP and baseline MMSE. Results A total of 450 (15.5% of the population) patients experienced a decrease in MMSE score of ≥3 points from baseline, at any follow-up visit. The corresponding number for a decrease in MMSE score of ≥2 points and ≥1 point was 755 (26.1%) and 1231 (42.5%), respectively. Independent predictors of cognitive decline at 48 weeks included older age, living in Latin America or the Asia/Pacific region, ischemic etiology, prior HF hospitalization, history of stroke/TIA, and lower serum albumin level (Figure 1). There was a graded relationship between the size of the decrease in MMSE score from baseline and the subsequent risk of mortality. Notably, a decrease of ≥3 points was associated with a 50% increase in the subsequent risk of death from any cause (adjusted HR 1.53, 95% CI 1.10-2.11) and a 90% elevation in risk of death from cardiovascular causes (1.89, 1.25-2.86), respectively, after extensive adjustment for known prognostic variables and baseline MMSE score. By contrast, cognitive decline during follow-up was not associated with a higher risk of HF hospitalization or the composite of HF hospitalization or CV death (Figure 2). Conclusions In patients with HFpEF, a decline in MMSE score during follow-up is independently associated with a graded increase in the risk for mortality, but not of HF hospitalization.The predictors for cognitive declineRisk of outcomes after a decline in MMSE

Prognostic impact of left atrial reverse remodeling in patients with ADHF-HFpEF regardless of atrial fibrillation -PURSUIT-HFpEF Registry-

Abstract Background Left atrial (LA) dilatation is associated with increased mortality in patients with cardiovascular disease including heart failure (HF) and LA reverse remodeling (LARR) was reported to be associated with favorable outcomes in patients with HF. However, it remains to be clarified whether LARR could have prognostic value in patients with HF with preserved ejection fraction (HFpEF). Purpose The purpose of this study is to elucidate whether LARR is associated with clinical outcome in patients with HFpEF in relation to the presence of atrial fibrillation (AF). Methods We prospectively studied 492 patients with acute decompensated heart failure with preserved ejection fraction (ADHF-HFpEF) without the poor outcome during the first year postdischarge. Echocardiography was performed just before discharge and at 1 year after discharge. LARR was defined as the reduction of 15% or more in left atrial end-systolic volume (LAV). The primary outcome was rehospitalization for worsening heart failure. Results All study patients were divided into 2 groups according to the presence of AF at discharge (AF group, n=182 and non-AF group, n=310). During a mean follow-up period of 1.4±1.2 years, 78 patients were rehospitalized for worsening heart failure (37 patients in AF group and 41 in non-AF group). ΔLAV, the degree of reduction in LAV during the first year postdischarge, was significantly independently associated with primary outcome after multivariable adjustment both in AF group (p=0.033, HR 0.992 [0.984-0.999]) and non-AF group (p=0.021, HR 0.986 [0.974-0.998]). Kaplan-Meier analysis revealed that patients with LARR had significantly lower risk for primary outcome than those without LARR not only in the whole study patients (8% vs 20%, p=0.001) but also both in AF group (9% vs 24% p=0.013) and in non-AF group (8% vs 16% p=0.043). Among clinical characteristics during the index hospitalization, the presence of AF and prior HF hospitalization were significantly independently associated with LARR at multivariate Cox logistic regression analysis (p=0.006, OR 0.554 [0.364-0.843] and p=0.007, OR 0.491 [0.292-0.826], respectively). Conclusion(s) The left atrial reverse remodeling could have the prognostic impact in patients with ADHF-HFpEF regardless of the presence of atrial fibrillation.Kaplan-Meier curves in AF and non-AF

Mechanical right ventricular involvement is independent of right coronary arterial bed and has a prognostic impact in acute myocardial infarction complicated by cardiogenic shock

Abstract Background In Acute Myocardial Infarction complicated by Cardiogenic Shock(AMI-CS), understanding the implications of right ventricular involvement (RVi) is crucial for refining risk stratification and optimizing management. Purpose Distinguish the prognosis in RVi at baseline(RVB) and persistent(RVP) in AMI-CS Methods 357 patients with AMI-CS+PAC serial measures at 0, 6, 12, 24h. RVi was defined as the presence of all 4 criteria PAPI&amp;lt;1; RVSWi≤4.08; RAP≥15 mmHg; and PVC/PCP≥0.86 and persistent as the presence of the 4 criteria at 4 time points. For hemodynamic measures, repeated measures ANOVA; and KM curves and Cox regression were performed. Results 300 without vs 57 with RVB. Additionally, 344 without vs 13 had RVP. Killip-Kimball classification showed a higher significant association with both RVB(P=0.042). A higher percentage of RVB received vasopressin(P=0.008), and there was a significant association with levosimendan use(P=0.009) in RVP. The higher MODS score, RVB(P=0.017) and RVP(P=0.029). The number of vasoactives was higher in RVB(P=0.031) RVP(P=0.009). Finally, the phenotypic characterization revealed a significant association with RVB(P=0.001) and RVP(P=0.032) more cardio-metabolic. The SCAI-CSWG classification indicated a higher proportion in the E category for both RVB(P=0.046) and not significant in RVP(P=0.405). Overall, mortality rates did not differ significantly between in RVB(P=0.174) or RVP(P=0.117), although there was a trend towards higher mortality in patients with RVi. Age, sex, DM, HTN, previous MI, PCI, CABG, stroke, and type of MI, primary reperfusion, LVEF, and laboratory parameters did not differ. RVB had higher heart rate(P=0.036), RAP, PASP(both P&amp;lt;0.001), lower SBP(P=0.049), cardiac output(P=0.004), index(P=0.001), power(P=0.012), power index(P=0.002), CPI(RAP), perfusion pressure, PAPi(both P&amp;lt;0.001), Stroke volume(SV, P=0.001), SVi(P&amp;lt;0.001), LVSWi(P=0.001), and RVSWi(P&amp;lt;0.001). RVP higher RAP(&amp;lt;0.001), and lower cardiac output(P=0.008), index(P=0.005), power(P=0.034), power index(P=0.029), CPI(RAP)(P=0.002), perfusion pressure(P=0.035), PAPi(P&amp;lt;0.001), SV(P=0.018), SVi(P=0.011), LVSWi(P=0.034) RVSWi(P&amp;lt;0.001). Importantly interaction between group*time was found in RVB in RAP(P&amp;lt;0.001), mPAP(P=0.038), perfusion pressure(P=0.002) and RVSWi(P&amp;lt;0.001) and in RVP in SV(P=0.014), SVi(P=0.013) and LVSWi(P=0.028) suggest that RVi had different hemodynamic response. For RVB a reduction of -4.16 days in survival time (-7.79, -0.54, P=0.024); Logrank P=0.035. Similarly, for RVP demonstrated a significant reduction of -7.27 days (-14.08, -0.47, P=0.036); Logrank P=0.017. No significant of the culprit artery in RVB, RVP (P&amp;gt;0.05) was observed. RVB and RVP was strongly associated with a higher prevalence of RVi (STe-V3/4R) on ECG (35.1 vs. 11.7%, and 61.5 vs. 13.7%, P&amp;lt;0.001). Conclusion In AMI-CS, RVi, whether baseline or persistent, is associated with distinct hemodynamic profiles and a trend toward higher mortality.Figure 1.Hemodynamics of RVB(A-C) &amp; RVP(D-F)Figure 2.Survival of RVB, RVP (A, B) &amp; HR(C)

Prognostic impact of the extent of coronary artery disease in patients with acute transmural myocardial infarction undergoing complete percutaneous revascularization

Abstract Background The management of acute myocardial infarction has been revolutionised by the introduction of early coronary angiography and the reperfusion strategies. Recent studies support the standard of care of complete myocardial revascularization in all patients with ST-elevation myocardial infarction (STEMI) without assessing the prognostic role of the extent of coronary artery disease (CAD). Purpose To evaluate whether the extent of CAD in patients with STEMI has a prognostic impact independent of complete myocardial revascularization. Methods Observational cohort study of 365 patients with STEMI who underwent complete revascularization. For each patient the extent of CAD has been quantified using Gensini Score (GS), which takes into account both the severity and location of the lesions. The primary endpoint of the study was all-cause mortality, while cardiovascular mortality and a composite of major adverse cardiovascular events (MACE: cardiovascular mortality, recurrent acute myocardial infarction or myocardial revascularization and stroke) were defined as secondary endpoints. To assess the prognostic role of GS in predicting all-cause mortality, the area under the curve (AUC) was calculated. The best cut-off was determined as the one that maximized Youden's index (sensitivity + specificity - 1). Results Patients with a GS &amp;gt;80, indicating extensive coronary disease, had significantly higher rates of both cardiovascular [4 (16.7%) vs. 12 (3.5%); p = 0.002] and all-cause mortality [5 (20.8%) vs. 24 (7%); p = 0.016], than those with a GS ≤80. A GS &amp;gt;80 was demonstrated to be an independent predictor of all-cause mortality [hazard ratio = 5; 95% confidence interval: 1.5-16.8; p = 0.01] Conclusions The Gensini Score can identify high-risk patients with STEMI who may benefit from more intensive therapies to improve prognosis, although current guidelines do not specify treatment based on the extent of coronary disease.Long-term outcomes according to GSPrognostic value of GS

Prognostic implications of guideline-directed medical therapy in functional mitral regurgitation: a meta-analysis

Abstract Background Randomized evidence of the role of heart failure medical therapy for patients with functional mitral regurgitation (FMR) is lacking. Purpose The present meta-analysis sought to investigate the independent long-term prognostic impact of the different medical categories recommended in heart failure, for subjects with FMR. Methods A systematic literature review was conducted in electronic databases to identify studies reporting the association of renin angiotensin system inhibitors (RASi), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) with outcomes in FMR. A random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome in each medical category. Results The final sample comprised 12 studies with 6,715 FMR patients (Picture 1). The use of RASi and BBs was associated with a significantly lower risk for all-cause mortality (HR 0.52 [0.39-0.68]; p &amp;lt;0.00001, I2 =62 % and HR 0.62 [0.49-0.77]; p &amp;lt;0.0001, I2 =44 % respectively) and for the composite outcome (HR 0.54 [0.44-0.67]; p &amp;lt;0.00001, I2 =33 % and HR 0.62 [0.52-0.75], p &amp;lt;0.00001, I2 =35% respectively) in unadjusted models (Picture 2). Both RASi (aHR 0.73 [0.56-0.95], p =0.02, I2 =52%) and BBs (aHR 0.60 [0.41-0.88], p = 0.009, I2 =55%) retained their association with the composite outcome in pooled adjusted models (Picture 2). The prognostic benefit of using RASi or BBs was retained in subgroup analysis including only patients with moderate of severe FMR. MRAs did not demonstrate a significant association with improved outcomes in FMR. Conclusions RASi and BBs appear to have a favorable prognostic impact in patients with FMR, regardless of regurgitation severity.Study flow chart for study selectionPharmacotherapy and prognosis in FMR

Mitral valve phenotypes in SMAD3-related thoracic aortic disease: insights from the Montalcino Aortic Consortium

Abstract Background SMAD3 pathogenic variants (PV) predispose to heritable thoracic aortic aneurysms and dissections (HTAD). Mitral annular disjunction (MAD) associated with mitral valve prolapse (MVP) and mitral regurgitation (MR) was identified as a potential new marker of disease severity in Marfan syndrome. The prevalence and prognostic impact of these mitral phenotypes in other forms of HTAD are less known. Purpose We hypothesize that mitral abnormalities are increased in SMAD3-related HTAD and are associated with increased risk for valve and aortic complications. Methods The Montalcino Aortic Consortium (MAC) registry has enrolled participants with PV in 15 HTAD genes. Subjects &amp;gt;16 years old with complete imaging and clinical data were included in this study. MVP was defined according to current guidelines. MR was classified as mild, moderate, or severe. MAD was defined by a &amp;gt;3-millimeter gap between the posterior mitral valve leaflet hinge point and the inferolateral myocardium as confirmed by direct measurement of echocardiogram images. Frequencies of MVP, MR, and MAD were compared between MAC participants with SMAD3 PV and other HTAD PV. Associations between clinical and echo characteristics and the composite outcome of arrhythmia, aortic surgery, aortic dissection, or congestive heart failure was evaluated with multivariable logistic regression. Results In 671 MAC participants (129 with SMAD3 PV, 36 [IQR 19-51] years, 49% female), the prevalence of MVP was 15% and the prevalence of MR was 22%. Both MVP (31/129, 24%, vs. 67/542, 12%, OR 2.2 [1.4-3.6], P&amp;lt;0.001) and MR (40/129, 31%, vs. 108/542, 20%, OR 1.8 [1.2-2.8], P&amp;lt;0.006) were more common in participants with SMAD3 PV compared to other PV and were further enriched in cases with SMAD3 missense PV compared to loss of function PV (MR or MVP: 26/48, 54% vs. 7/30, 23%, OR 3.9 [1.4-10.8], P&amp;lt;0.007). Images were available from 238 MAC participants (67 with SMAD3 PV) to assess for MAD. MAD (29/67, 43%, vs. 28/171, 16%, OR 3.9 [2.1-7.3], P&amp;lt;0.0001), or the composite of MR, MVP, or MAD (42/67, 63%, vs. 69/171, 35%, OR 3.2 [1.8-5.7], P&amp;lt;0.0001) was more common with SMAD3 PV compared to other PV (Figure 1). Twelve participants with SMAD3 PV (18%) had prominent mitral phenotypes (&amp;gt;mild MR, &amp;gt;10 mm MAD, or MAD with MVP) but no significant aortic dilation (Z&amp;lt;3). When controlling for age and sex, MR or MVP, but not MAD, was independently associated with the composite outcome (OR 16 [2.4-110], Figure 2). Conclusion Mitral valve pathology, including MVP, MR, and MAD, is increased in individuals with SMAD3 PV compared to other HTAD PV. Prominent mitral phenotypes related to SMAD3 missense PV may identify a high-risk subgroup with adverse cardiovascular outcomes. Because congenital mitral disease may be the primary presenting feature of SMAD3 PV, genetic testing for HTAD should be considered for such patients, especially if they also have a family history of thoracic aortic disease.

The prognostic impact of tricuspid regurgitation improvement after left-sided valvular interventions

Abstract Background Tricuspid regurgitation is a common bystander in patients with left-sided valvular heart disease such as mitral regurgitation (MR) or aortic stenosis (AS). Data on the prognostic impact of potential TR improvement after interventions for left sided valvar disease is scarce. Objectives This study aimed to assess incidence and prognostic value of TR improvement after left-sided valvular interventions (M-TEER and TAVI) using merged data from two prospective single-center registries. Methods The merged database included all consecutive patients with symptomatic left-sided valvular heart disease (MR or AS) undergoing either M-TEER or TAVI from 2008 until 2023. The prognostic impact of baseline TR severity and TR improvement was assessed using Kaplan-Meier estimates and stepwise Cox regression. TR improvement was defined as a reduction in TR severity at discharge by at least one grade compared to baseline in patients with ≥moderate TR at baseline. Results A total of 4,461 patients undergoing left-sided valvular interventions (M-TEER: N=663; TAVI: N=3,798) were eligible for study inclusion (age 81.0 years [IQR 76.2-84.7], 52.7% male). TR severity at baseline was none or mild in 70.9% (N=3,161), moderate in 19.4% (N=864), and severe in 9.8% (N=436). Patients with ≥moderate TR at baseline showed significantly higher rates of all-cause mortality (p&amp;lt;0.001) and of the combined endpoint after 3 years (p&amp;lt;0.001), compared to patients with none or mild TR. This finding was consistent for the M-TEER and TAVI subgroups. Among patients with ≥moderate TR at baseline (N=1,300), 499 patients (38.4%) showed TR improvement by at least one grade following left-sided valvular intervention, while TR did not improve in 801 patients (61.6%). In the overall study population, patients with TR improvement showed lower rates of all-cause mortality (p&amp;lt;0.001) and the combined endpoint after 3 years (p=0.006) (Figure 1A, 1B). This finding was consistent only in the subgroup of patients undergoing M-TEER (p=0.013 and p=0.003), but not for patients undergoing TAVI (p=0.12 and 0.62) (Figure 2A, 2B). Following stepwise Cox regression (incl. adjustment for treatment), TR ≥moderate at baseline was independently associated with death (p=0.0019) and combined death or HF rehospitalization (p=0.0068) 3 years after intervention (Figure 3A,3B). TR improvement was independently associated with survival (p=0.015) and combined survival or absent HF rehospitalization (p=0.032) 3 years after intervention (Figure 4A, 4B). Conclusions Patients with TR improvement after left sided valvular interventions showed significantly better clinical outcomes compared to those without. These results reinforce the need for assessment for TR assessment before and after left-sided valvular interventions and may identify patients that qualify for subsequent TR intervention.

Albuminuria is associated with progression of diastolic dysfunction in patients at risk for cardiovascular disease

Abstract Background The number of the patients with heart failure with preserved ejection fraction (HFpEF) is increasing as society ages, which indicates that the number of pre-HFpEF patients is increasing even more. To combat this sociomedical burden, it is critical to establish cost-effective and simple biomarkers to identify the high-risk population at early phase of the disease. Recent studies demonstrated the association between albuminuria and incident heart failure, but the prognostic impact of albuminuria on diastolic dysfunction, an early phenotype of HFpEF, has not been elucidated. Purpose To examine the impact of albuminuria on the diastolic function over time in the patients with cardiovascular risks. Methods One hundred and fifty-eight patients with at least one cardiovascular risk factor without history of heart failure were followed up for 5 years. Echocardiogram was conducted at baseline, year 3, and year 5. Diastolic dysfunction was defined as E/e’ &amp;gt;14. Albuminuria was defined as urine albumin-to-creatinine ratio (UACR) 30 ≧mg/gCre. The patients with ejection fraction &amp;lt;40% and those had diastolic dysfunction at baseline were excluded from the study. The relationship between albuminuria at baseline and diastolic function at year 3 and 5 were investigated. Results Among 158 subjects, 27 showed albuminuria at baseline and the prevalence of hypertension, dyslipidemia, and diabetes was not significantly different between patients with and without albuminuria. The baseline E/e’ tended to be higher in patients with albuminuria, although the difference was not statistically significant (Fig1: E/e’ = 10.0±2.4 vs. 9.4±2.2, p = 0.08) . However, the patients with albuminuria showed a steeper increase in E/e’ than those without albuminuria, and the significant difference was observed at year 3, that was even greater at year 5 (Fig1: E/e’ = 11.1±2.8 vs 10.0±2.6, p = 0.04 in year 3, E/e’ = 12.5±4.1 vs 10.3±2.9, p = 0.002 in year 5, respectively). Furthermore, log UACR at baseline showed significant correlation with E/e’ at year 5 (p = 0.02, r = 0.21) and normo-, micro-, and macroalbuminuria (UACR&amp;lt;30, 30-300, and &amp;gt;300mg/gCre, respectively) at baseline showed elevated E/e’ at year 5 in this order ( p = 0.01 for UACR&amp;lt;30 vs. 30-300mg/gCre, and p = 0.04 for UACR&amp;lt;30 vs. &amp;gt;300mg/gCre, reapectively ). The prevalence of incident diastolic dysfunction increased greater in patients with albuminuria throughout the follow-up period and the difference reached statistical significance at year 5 (Fig2: 18.5% vs. 9.2%, p = 0.28 for year 3, and 25.9% vs. 8.4%, p = 0.009 for year 5, respectively). Conclusion In the patients with cardiovascular risk factors, albuminuria was associated with development and progression of diastolic dysfunction over subsequent 5 years. Future prospective study is warranted to investigate the effectiveness of albuminuria-directed care to prevent development of HFpEF.