Prognostic Parameters Research Articles

Changes in echocardiographic and analytical parameters after iron replacement in stable heart failure patients. FER-STRAIN study

Abstract Background Iron deficiency replacement with intravenous ferric carboxymaltose (FCM) has demonstrated to improve clinical and prognostic parameters in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). Improvement of myocardial contractility is proposed as possible hypothesis and strain could behave as an early and high sensitive parameter to assess this improvement in myocardial deformation due to increased iron availability after replacement of iron deficiency. Purpose Evaluate the effect of iron deficiency replacement with FCM in the strain of both ventricles in patients with stable HFrEF. Methods We performed an observational, analytical, longitudinal and prospective study that included 73 patients with stable HFrEF who presented iron deficiency without anemia defined as serum ferritin <100 ug/L or between 100 and 300 ug/L if the transferrin saturation was <20%. They were randomized 2:1 to iron replacement with FCM or control group. A central core lab, blinded to the treatment/control groups performed 3D echocardiograms and strain analysis. Analytical parameters and biomarkers were determined basal and four weeks after the randomization. Results Mean age of the study population was 70 years old, 77% were male, 75% had high blood pressure, 70% dyslipidemia and 41% diabetes. Of the total, 51 patients were assigned to the replacement group and 22 patients to the control group. Mean left ventricular ejection fraction (LVEF) was 33%, without basal differences between both groups. Four weeks after the randomization, a significant improvement of LVEF of 2.47±2.32% (p=0.018) was observed in the replacement group, as well as in the left ventricle global longitudinal strain (LV-GLS) of -0.96±2.08% (p=0.006). In blood tests, a significant improvement of ferritin (130.9±111.98mg/L, p<0.000), hemoglobin (0.3±0.7g/dL, p=0.027) and medium corpuscular volume (1.7±2.16fL, p=0.005), and also an increase of the biomarker myeloperoxidase (40.16±138.36pmol/L, p=0.02) were detected in the treatment group. Nevertheless, these changes were not observed in the control group. Conclusions In patients with stable HFrEF replacement of iron deficiency with FCM is associated with an improvement of myocardial contractility, of LVEF measured by 3D and LV-GLS.Variation of parametersLV-GLS before and after FCM

Diastolic shock index: a novel prognostic parameter unveiling insights into vasodilatory cardiogenic shock

Abstract Introduction Systemic vasodilation is an increasingly acknowledged feature in cardiogenic shock (CS), defining a subset of patients with low systemic vascular resistances and higher vasopressor requirements. While a diastolic shock index (DSI) above 2.0 predicts vasoplegia and mortality in septic shock, its cut-off and prognostic significance in CS remain unclear. Our study aimed to characterize vasoplegia in CS using the DSI and assess its impact on prognosis. Methods Single-center retrospective cohort study on Cardiac Intensive Care Unit (CICU) admissions for CS from January 2017 to October 2023. Data included patient variables, CS features, vasoactive drugs, mechanical circulatory support, and 30-day mortality. DSI (heart rate (HR) to invasive diastolic blood pressure (DBP) ratio) impact on 30-day all-cause mortality was assessed with univariate Cox regression. Optimal DSI cut-off for adverse outcomes was determined through ROC curve analysis, and survival based on this cut-off was analyzed using Kaplan-Meier curves. Results 185 patients (mean age 59 ± 12 years, 63% male) were included. Acute myocardial infarction-related CS (47%) and heart failure-related CS (29%) were predominant. According to SCAI classification, 86% were class C, 22% class D, and 4% class E, with 26% experiencing previous cardiac arrest. Median Vasoactive-Inotropic Score (VIS) was 48 (IQR 21-85), and 25% used mechanical circulatory support. At admission, median HR was 105 bpm (IQR 90-125), DBP was 60 mmHg (IQR 55-65), and DSI was 1.71 (IQR 1.31-2.18). Thirty-day all-cause mortality was 36% (n=67), with median time to death of 4 days (IQR 1-10). DSI at 30 days predicted mortality (OR 1.42, 95%CI 1.06-1.91, p=0.020). DSI showed fair discriminative power for 30-day mortality (C-Statistic 0.60, 95% CI 0.51-0.68, p=0.031) with a cut-off of 2.2. Patients with DSI >2.2 exhibited heightened likelihood of prior cardiac arrest (38% vs. 20%, p=0.032), and higher serum lactate (5.5 vs. 3.9 mmol/L, p=0.008), and serum creatinine (2.64 vs. 1.88 mg/dL, p=0.003) at admission. Despite higher VIS at 48 hours (120±136 vs. 65±93.9, p=0.04), MCS need did not significantly differ. This group had superior 30-day mortality risk (log-rank p=0.011). Conclusion In our cohort, the admission Diastolic Shock Index (DSI) emerged as a promising identifier for CS vasoplegic patients and was a predictor of a higher risk for mortality. A DSI above 2.2 identified a subset of patients with previous cardiac arrest and higher lactate levels, enlightening possible risk factors associated with vasoplegia. Further studies are warranted to establish the robustness of this novel prognostic parameter in CS patients and its therapeutic implications.

Age-predicted maximal heart rate reserve as an alternative prognostic parameter in patients with heart failure with preserved ejection fraction -insights from PURSUIT-HFpEF registry-

Abstract Background Heart rate reserve (HRR), a measure of chronotropic response, is a prognostic parameter in patients with heart failure with preserved ejection fraction (HFpEF). However, exercise testing and measuring maximum heart rate (HR) are sometimes difficult in patients with heart failure with preserved ejection fraction (HFpEF). Assessing age-predicted maximal HRR (APHRR), defined as the difference between the resting HR and the age-predicted maximum HR (220 - age), would be a simple alternative to HRR. Purpose To assess the impact of APHRR at discharge on prognosis in patients with HFpEF. Methods An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 1231 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide level ≥100 pg/ml. Excluding patients with permanent pacemakers, we enrolled 918 patients (age, 81 ± 9 years; men, 45%; atrial fibrillation, 38%) whose follow-up data after survival discharge were available. Results There was a moderate correlation between HR (median 69, interquartile range [IQR] 61-79 beats per minute [bpm]) and APHRR at discharge (71, 59-81 bpm) (r² = 0.68, p <0.001). During the median follow-up period of 23.8 months [IQR, 12.5-36.3] after discharge, 267 patients (15.4%) died, and the mortality rates incrementally decreased according to the APHRR quartiles (Q1, 44.6%; Q2, 26.6%; Q3, 26.2%; Q4, 18.4%; p <0.001). Cox regression analysis revealed that both the resting HR (hazard ratio per quartile increase, 1.16; 95% confidence interval, 1.04-1.30, p = 0.008) and APHRR (0.67; 0.60-0.75, p <0.001) were associated with mortality. However, the diagnostic accuracy was significantly superior in the APHRR than in resting HR (area under the curve; 0.628 vs. 0.552, p <0.001). Conclusions Assessment of the APHRR at discharge was a simple and useful method for risk stratification of patients with HFpEF. An incremental favorable prognosis indicated the prognostic importance of having a functional reserve during physiologic stress.

Echocardiographic left and right ventricular strain reference values and their associated characteristics in a healthy adult population from the ELSA-Brasil Study

Abstract Background/Introduction Impaired left ventricular (LV) systolic function is a well-known predictor of cardiovascular morbidity and mortality. Global longitudinal strain (GLS) analysis has been shown a robust measure to detect early systolic dysfunction and a prognostic parameter beyond traditional echocardiographic systolic parameters. Standard reference values for echocardiography measures have been established by echocardiography societies. However, these data may not accurately represent diverse world populations. Purpose We aimed to describe, from a Brazilian multiethnic population, age and sex-specific reference values for left (LV) and right ventricles (RV) GLS in a sample free of cardiovascular disease and risk factors, and to describe the impact of these risk factors according to GLS distribution. Methods ELSA-Brasil is a prospective cohort to investigate cardiovascular disease and diabetes including 15,105 participants aged 35 to 74 years. A predefined representative randomly selected sample with echocardiographic exam was included. We categorized the sample in tertiles according to severity of LV and RV systolic function measured by GLS, and applied trend tests across ordered groups to illustrate the association between GLS and demographic characteristics and echocardiographic measures of cardiac structure and function. Results In the study population (n=527), the mean age was 50.2 years and 59% were women. The overall mean value of LVGLS was -19.0 ± 2.4%, while the mean value of RVFWLS was -28.35 ± 3.06%. Women had higher absolute values of LV and RV GLS compared to men. Conclusion Our study provided the reference ranges for LV and RV GLS in a large middle-aged healthy Brazilian sample, with sex-differences reflected on these values.Central FigureTable 1:Tertiles of LVGLS and RVFWLS

Improvement of myocardial contractility after iron replacement in stable heart failure patients

Abstract Background Iron deficiency replacement with intravenous ferric carboxymaltose (FCM) has demonstrated to improve clinical and prognostic parameters in patients with heart failure with reduced left ventricular ejection fraction (HFrEF). Improvement of myocardial contractility is proposed as possible hypothesis and strain could behave as an early and high sensitive parameter to assess this improvement in myocardial deformation due to increased iron availability after replacement of iron deficiency. Purpose Evaluate the effect of iron deficiency replacement with FCM in the strain of both ventricles in patients with stable HFrEF. Methods Observational, analytical, longitudinal and prospective study that included 73 patients with stable HFrEF who presented iron deficiency without anemia defined as serum ferritin <100 ug/L or between 100 and 300 ug/L if the transferrin saturation was <20%. They were randomized 2:1 to iron replacement with FCM or control group. A central core lab, blinded to the treatment/control groups, performed 3D echocardiograms and strain analysis basal and four weeks after the randomization. Results Mean age of the study population was 70 years old, 77% were male, 75% had high blood pressure, 70% dyslipidemia and 41% diabetes. Of the total, 51 patients were assigned to the replacement group and 22 patients to the control group. Mean left ventricular ejection fraction (LVEF) was 33%, without basal differences between both groups. Four weeks after the randomization, a significant improvement of LVEF of 2.47±2.32% (p=0.018) was observed in the replacement group, as well as in the left ventricle global longitudinal strain (LV-GLS) of -0.96±2.08% (p=0.006). Nevertheless, these changes were not observed in the control group. Conclusions In patients with stable HFrEF replacement of iron deficiency with FCM is associated with an improvement of myocardial contractility, of LVEF measured by 3D and LV-GLS.Variation of parametersLV-GLS before and after FCM

Exploring physiological determinants of ventilatory inefficiency in hypertrophic cardiomyopathy patients

Abstract Background The role of cardiopulmonary exercise test (CPET) in hypertrophic cardiomyopathy (HCM) has been previously examined, revealing two prognostic parameters: peak Vo2 and the VE/VCO2 slope. Specifically, individuals with a VE/VCO2 value above 31 (ventilator inefficiency) demonstrate a poorer prognosis. Purpose This study aims to analyze the physiological factors contributing to ventilatory inefficiency in individuals with HCM. Methods In this retrospective study, 43 patients HCM patients underwent resting transthoracic echocardiography, CPET combined with echocardiography during physical exertion, and cardiac magnetic resonance imaging. Ventilatory inefficiency was defined as a VE/VCO2 slope exceeding 31, leading to the identification of two groups: Group A (those with ventilatory inefficiency) and Group B (those without ventilatory inefficiency). Results Nine patients exhibited ventilatory inefficiency, while 34 had a normal VE/VCO2 slope. No statistically significant differences were found between the two groups concerning clinical and therapeutic characteristics. Subjects with ventilatory inefficiency showed reduced oxygen pulse (8.3 ± 2.6 vs 11.7 ± 4, p 0.013) and peak VO2 values (13 ± 5 vs 19 ± 5, p 0.005), lower left ventricle global longitudinal strain (-15±3 vs -17± 2, p 0,012), the exertional TAPSE/SPAP ratio (0.46 [0.32-0.48] vs 0.58 [0.47-0.80], p 0.001), exertional TAPSE (23 ± 3 vs 28 ± 4, p 0.001), and indexed stroke volume of the left ventricle assessed by cardiac magnetic resonance imaging (38±8 vs 48±10, p 0.011) (Table 1). The right ventricular function under physical exertion (peak TAPSE and TAPSE/sPAP) and left ventricular functional parameters (index stroke volume and global longitudinal strain) predicted the presence of ventilatory inefficiency. Conclusions This study highlights the role of exertional parameters in the origin of ventilatory inefficiency.Correlation tableFigure with scatter plot

Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension

Abstract Background The treatment of pulmonary hypertension (PH) has improved rapidly in recent years, and there is increasing evidence to support the role of early intervention. However, studies demonstrate that timely intervention is often still lagging which affects clinical outcomes in patients with PH. Purpose To assess treatment effects after escalation of specific PH treatments using continuous heart monitoring via a Reveal LINQ loop recorder. Methods The patients change in heart rate variability (HRV), heart rate (HR), and physical activity were assessed before and after treatment escalation. Treatment escalation was defined as an additional PAH drug, pulmonary endarterectomy (PEA), percutaneous balloon angioplasty (PBA), or bilateral lung transplantation (BLTX). Results In this prospective study, 41 patients (27 with PAH and 14 with chronic thromboembolic pulmonary hypertension) were enrolled. Among them, 15 patients (36.6%) underwent PH treatment escalation. Prior to escalation, patients were monitored for a median of 100 (range: 68–100) days and after therapy escalation for a median duration of 165 (range: 89–308) days. In the escalation group, a significant increase in HRV (Figure), physical activity indexed by daytime HR was observed, while a significant decrease was seen in nighttime HR assessed at baseline and after treatment escalation. These changes were found both in the PAH and CTEPH group. In parallel a significant improvement in WHO functional class, 6-minute walking distance, and N-terminal pro-b-type natriuretic peptide (NT-proBNP) was observed. Conclusions This is the first study to demonstrate a direct association between specific PH therapies and changes in HRV, HR nighttime and physical activity in patients with PAH and CTEPH. Continuous monitoring allows for an early intervention with supplementary treatment for PH. This is especially relevant considering the increasing availability of wearables that allow for a convenient measurement of relevant prognostic parameters in PH.

Mid-regional pro-adrenomedullin is an independent predictor of cardiovascular outcomes in cardiac surgery, a prospective cohort study in 500 patients

Abstract Background MR-proADM (mid-regional pro-adrenomedullin) is a stable pro-peptide of Adrenomedullin, which is expressed in various cell types such as heart, lung, and renal tissue. It is a prognostic parameter for heart failure (HF) and sepsis as well as all-cause and cardiovascular (CV) mortality. Purpose Considering the characteristics of MR-proADM as a reliable biomarker for adverse events, we aimed to investigate the prognostic impact of MR-proADM in patients undergoing elective cardiac surgery. Methods We prospectively enrolled patients undergoing elective cardiac bypass and/or valve surgery at the department of cardiac surgery between May 2013 and August 2018. Blood samples were taken one day prior to surgery. MR-proADM was measured using an automated immunofluorescence assay. Patients were followed prospectively until endpoints were reached. The primary endpoint was the composite of hospitalization for heart failure (HHF) or CV mortality, the secondary endpoint was postoperative atrial fibrillation (POAF). The multivariate regression model was adjusted for age, sex, NT-proBNP, type of surgery, and CRP-level at baseline. Results A total of 500 patients (146 female [29.2%]; median age 69.8 years [IQR 60.6-75.5]) were followed over a median of 4.6 years (IQR 3.0–5.8). Valve surgery was performed in 214 (42.8%) patients, 160 (32%) underwent a bypass operation and 126 (25.2%) a combined valve and bypass surgery. The median MR-proADM value of the entire study population was 0.58 nmol/L (IQR: 0.44-0.79 nmol/L). Patients were stratified in risk categories based on their MR-proADM values (Low Risk ≤0.63nmol/L, Intermediate Risk 0.63-0.83nmol/L, High Risk >0.84nmol/L). Patients in the highest category presented with higher rates of diabetes mellitus (p <0.001), COPD (p <0.001), HF (p=0.009) and either bypass surgery (p=0.039) or the combination of bypass and valve surgery (p=0.008), compared to patients in the lowest tertile. We observed a significant increase in 5-year’s event rates for HHF/ CV Mortality in patients in higher risk groups (Low Risk 8.6% vs High Risk 37.7%, p <0.001, Figure 1). The adjusted Cox regression model found that MR-pro ADM was independently associated with a risk increase for HHF/ CV Mortality (adjusted HR of 4.45, 95% CI 2.55-8.09; p<0.001, Figure 2) comparing the High Risk to the Low Risk Group. A comparable risk increase could be observed in POAF, with an adjusted HR of 2.61 (High Risk Group vs Low Risk Group, 95% CI 1.46-4.67, p<0.001). Conclusion Within the prospective investigation, MR-pro ADM was found to be an independent predictor for HHF and CV mortality in patients undergoing cardiac bypass and/or valve surgery. Furthermore, there was a consistent predictive potential for POAF. In the era of personalized medicine, preoperative MR-pro ADM levels could help to identify patients at risk for serious adverse events, in order to apply intensified secondary prevention and reduce mortality and morbidity.

RV-PA uncoupling is a strong predictor of 3-year all-cause mortality in transthyretin amyloid cardiomyopathy

Abstract Background Right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload which, in case of transthyretin amyloid cardiomyopathy (ATTR-CM), can result from increased left ventricular diastolic stiffness due to fibril deposition. While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unclear. This study sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM. Methods In this two-centre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with TTR stabilizer. The primary outcome was all-cause mortality. Receiver operation curves and Youden’s J analysis were applied to identify an optimal cut-off value of RV-PAc ratio. Results Within a median time of 631 (IQR 361-983) days after diagnosis, 14.4% of patients died. RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382mm/mmHg (area under the curve (AUC) 0.746, 95% CI 0.68-0.82). Patients with RV-PAc ratio ≤0.382mm/mmHg (impaired RV-PAc, n=158) exhibited significantly lower survival (HR 4.07, 95% CI 2.26-7.33, p<0.001) within 3 years of follow up than those with RV-PAc ratio > 0.382mm/mmHg. In multivariate Cox regression analysis, incorporating a range of known prognostic variables, reduced RV-PAc was a strong echocardiographic predictor of mortality (Hazard Ratio (HR) 2.99, 95% Confidence Interval (CI) 1.63-5.51, p <0.001). Conclusion Impaired adaption of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality within three years after diagnosis. Therefore, determination of RV-PAc could improve risk stratification for ATTR-CM patients.Figure_1_Kaplan-Meier curves

Prognostic value of follow-up hemodynamics after initial treatment in pulmonary arterial hypertension

Abstract Background Hemodynamic variables such as right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2) have consistently been associated with survival in pulmonary arterial hypertension (PAH). The prognostic importance of hemodynamics after treatment initiation seems to be superior to baseline evaluation and stroke volume index (SVI) emerged as an independent prognostic parameter. New PAH treatments are, however, able to improve exercise capacity without increasing CI or SVI. Purpose The aim of this work was to define the prognostic role of follow-up hemodynamic parameters in a population of patients with idiopathic, hereditary, drug-induced PAH (I/H/D-PAH) and PAH associated with connective tissue disease (CTD-PAH) and congenital heart disease (CHD-PAH). Methods Treatment naïve PAH patients were assessed at baseline and at 1st follow-up (3-4 months after starting PAH-specific therapy; 1st F-UP) with 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC) and right heart catheterization (RHC). Collected hemodynamic parameters were: RAP, systolic, diastolic and mean pulmonary artery pressure (s/d/mPAP), CI, SVI, SvO2, pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), cardiac efficiency (CE), pulmonary arterial elastance (Ea), resistance–compliance product (RC), right ventricular (RV) power, and RV stroke work index (RVSWI). The primary outcome was all cause death. We used stepwise Cox regression to assess variables obtained at baseline and at 1st F-UP. Results 794 patients with PAH were enrolled (54% I/H/D, 28% CTD, 18% CHD). A primary outcome occurred in 54% of patients over a median follow-up duration of 5.8 (2.4–11) years. In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis but RAP. At first follow-up RHC (n=706), WHO-FC, 6-minute walk distance, RAP, and Ea were independently associated with death, adjusted for age, gender, and etiology of PAH. Because hemodynamic variables were highly correlated, we compared multivariable Cox regression models adding only variables with a correlation coefficient <0.6. In these models, RAP, Ea, PAC, CE, PVR, SvO2, CI, and SVI at follow-up RHC were independent predictors of death (Table). Conclusions Ea and right atrial pressure were the hemodynamic variables independently associated with death at 1st F-UP RHC after initial PAH treatment. These findings suggest that beyond improving RV function, RV afterload reduction can be considered a further treatment target.Table

Assessment of right ventricular ejection fraction cut-point for predicting mortality and heart failure hospitalization in asian patients with heart failure and reduced ejection fraction (HFrEF)

Abstract Background Left ventricular ejection fraction (LVEF) has been well established as a predictor of morbidity and mortality in heart failure patients (HF). Meta-analyses have confirmed that right ventricular systolic dysfunction (RVSD) identified by cardiac MR predicts adverse outcomes in HF patients. However, the cut-point and predictive value of right ventricular ejection fraction (RVEF) in Asian patients remain unknown. Objectives To evaluate the RVEF cut-point for RVSD and demonstrate the association between RVSD by cardiac MR and a composite endpoint consisting of HF hospitalisation and/or all-cause mortality in HFrEF patients (LVEF ≤40%). Materials & Methods A retrospective chart review of 370 consecutive HFrEF patients who underwent cardiac MR between 01 June 2009 and 31 December 2013 was done. The primary outcome was defined as all-cause mortality and/or HF hospitalisation. Receiver Operating Characteristic (ROC) analysis was done to explore the most accurate RVEF as a cut-point for RVSD. Multivariate Cox regression analysis was calculated. Results Patients were followed for a total of 1,989 patient-years with an average of 5.4 ± 2.9 years. The primary outcome occurred in 112 patients (30.3%). ROC analysis demonstrated that RVEF <48% provided the most accurate prognostic value (specificity 52%, sensitivity 70%) with an area under the curve of 0.62 (95% CI 0.55 – 0.69). Multivariate Cox analysis showed that RVSD was a significant independent risk factor (hazard ratio 1.71; 95% CI 1.10 – 2.66; p=0.018) for the primary outcome, in addition to age (p<0.001), New York Heart Association functional class (p<0.001), and diabetes mellitus (p=0.014), regardless of LVEF. Conclusions In Asian HFrEF patients, RVSD defined by RVEF <48% by cardiac MR can predict adverse events and provide a prognostic parameter for risk stratification.

What is the true normal: comparison of different equations for estimating peak oxygen uptake for outcome prediction in heart failure

Abstract Background and Objectives One of the strongest prognostic parameters obtained during Cardiopulmonary exercise testing (CPET) in patients with heart failure (HF) is the peak oxygen uptake (pVO2), as a standalone or as a percentage of the predicted peak oxygen uptake (ppVO2) reached. However, traditional standards by which ppVO2 is calculated have limitations, having been derived from small cohorts, lacking portability and poorly represented by women. Thus, we aim to compare the FRIEND Registry equation to previously used methods of calculating ppVO2 as it relates to prognostic value imparted by the percentage of ppVO2 (%ppVO2) reached during CPET and portability to the Portuguese HF population. Methods Single centre retrospective study of patients with HF with LVEF < 50% who underwent CPET between 2015-2021. Patients who did not reach RER≥ 1.05 were excluded from our analysis. All tests were evaluated and ventilatory thresholds determined by 3 independent, experienced operators. ppVO2 was calculated according to 1) the Wasserman equation; 2) the Wasserman equation using ideal body weight; 3) the Neder equation, 4) the SHIP equation and 5) the FRIEND equation. Our primary endpoint was a composite of CV death, urgent transplant or left ventricular assist device implantation and HF hospitalization. Results We included 238 patients (mean age 59 ± 11 years, 83% males). The HF aetiology was mostly ischemic in nature (68%), with LVEF of 34 ± 9% and median NTproBNP of 776 (2566 – 2342) pg/mL. Most patients (67%) were in class NYHA I-II and with high prevalence of GDMT (93% ACEi/ARB; 97% beta-blockers and 64% on MRA). Mean BMI in this group was 27.3 ± 4.7 kg/min. Patients performed CPET on a treadmill with a protocol adjusted to their predicted exercise capacity. Mean pVO2 was 18.1 ± 6.2mL/kg/min, corresponding to a median %ppVO2 that ranges from 51 ± 16% to 71 ± 22%, depending on the equation that is used. Mean VE/VCO2 Slope was 42 ± 13 and 48 % (n = 98) of patients showed exercise oscillatory ventilation (EOV). Mean ppVO2 as per the FRIEND and Wasserman equations was 18.9 ± 6.6 and 21.2 ± 4.5 mL/kg/min, with no statistically significant difference between both. %ppVO2 as calculated through all equations was an independent predictor of prognosis on multivariate analysis adjusted for LVEF, NTproBNP and VE/VCO2 Slope (p < 0.001 for values derived from all equations). However, the FRIEND and Wasserman equations showed a slight advantage over the remaining 2 equations, with higher AUC on ROC curve analysis (see figure). Conclusions In our population of Portuguese patients with HF, both the FRIEND registry and Wasserman equations for predicting pVO2 yielded strong prognostic power. However, these equations provide different absolute predicted VO2 values for the same patients and thus should not be used interchangeably. Standardisation of the type ppVO2 equation used should be recommended by local scientific societies.

Expression of CD44 in Triple Negative Breast Cancer and its Correlation with Prognostic Parameters

Background: The study aims to evaluate CD44 expression as a cancer stem cell marker in Triple-negative breast cancer (TNBC) and its correlation with prognostic parameters. Evaluation of CD44 immunoexpression in TNBC is vital for understanding tumour aggressiveness and determining its prognostic value. Methods: A hospital based cross sectional study of 50 cases of primary triple negative breast cancer patients. The tissue sections were subjected to immunohistochemical examination using CD44 antigen marker. The proportion and intensity of CD44 immunostaining was assessed and correlation with prognostic markers such as histological grade, tumor size and nodal status. Results: CD44 expression was observed in 40% of the total cases with a statistically significant association with histological grade (p-value= 0.002). Higher CD44 expression was noticed with increasing tumour grade. However, no statistical significance was observed with respect to tumour size and nodal status. Conclusion: The study suggests that CD44 immunoexpression may serve as a surrogate marker of BCSCs and may hold prognostic value in TNBC patients. However, further studies on larger samples are required to fully understand its role.

The combination of CDX2 expression status and tumor-infiltrating lymphocyte density as a prognostic factor in adjuvant FOLFOX-treated patients with stage III colorectal cancers.

Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050-5.100) and 0.378 (0.175-0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023-0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939-63.230]). Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Correlation of tumor budding with a novel and other established prognostic parameters in patients with invasive breast carcinoma.

Breast cancer is the most common malignancy among women. Established prognostic markers in breast carcinomas include tumor size, histologic grade, nodal status, lymphovascular invasion, perineural invasion, hormone receptor status, HER-2 status, and age. To correlate peripheral tumor budding (pTB) with stromal tumor-infiltrating lymphocytes (sTILs) and established prognostic factors in invasive breast carcinoma. It is a retrospective study conducted at multiple centers including a tertiary care center. 100 cases were included over a period of 2.5 years. All cases of invasive breast carcinoma (IBC) in which excision specimens with lymph node dissection were available were studied. Slides were reviewed for pTB and sTILs. Tumor budding of ≤20/10 hpf was considered low tumor budding, and >20 buds/10 hpf was considered high tumor budding. Tumor budding was correlated with age, tumor size, lymphovascular invasion, perineural invasion, tumor stage (pT, pN), stromal tumor-infiltrating lymphocytes, tumor grade, ductal carcinoma in situ, hormonal receptors, and HER2neu. Fisher exact test and Chi-square test were used. We found that high tumor budding was seen in 34 cases and low tumor budding in 66 cases. There was a statistically significant association between high tumor budding and tumor size (P = 0.007), lymphovascular invasion (P < 0.001), perineural invasion (P = 0.004), tumor staging/pT (P = 0.006), nodal staging/pN (P = 0.001), and low sTILs (P < 0.001). However, the association of high tumor budding with parameters like age (P = 0.979), histological type (P = 0.243), tumor grade (P = 0.052), DCIS (P = 0.478), and ER (P = 0.633), and PR (P = 0.544), HER2Neu status (P = 0.171) was not significant. This study suggests tumor budding score can be used as a prognostic indicator for breast cancer.

Outcome of autologous bone marrow transplant in patients with relapsed and refractory diffuse large B-cell lymphoma in relation with prognostic factor: A single-center experience

Abstract: BACKGROUND Currently, about 50% of diffuse large B-cell lymphoma patients are relapsed following their complete response to first-line therapy. The treatment strategy for fit patients with relapsed refractory diffuse large B-cell lymphoma (R/R DLBCL) has been done with salvage therapy with non-cross resistant combination chemo-immunotherapy regimens followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). OBJECTIVES: The aim of study was to evaluate the outcome of ASCT for R/R DLBCL in relation to certain prognostic parameters. PATIENTS, MATERIALS AND METHODS: This is retrospective study, conducted from May 2014 to December 2022, at Hematology and BMT Center of Medical City Complex in Baghdad. Thirty-six patients with R/R DLBCL were investigated pre- and post-ASCT; the recorded data included patient disease status pre-transplant, early mortality rate, and type of response at day 100 post-transplant and, survival rate, relapsed rate, and mortality at the end of the study were documented accordingly. RESULTS: The mean age of DLBCL patients in this study was 41.3 (14–65) years, post-ASCT at day 100; there were 33 (91.6%), 2 (5.5%), and 1 (2.7%) patients in complete remission, relapsed progressive disease, and death, respectively, At 3-year posttransplant, the overall survival (OS) was 71%, whereas the event-free survival (EFS) was 59%. According to disease status pre-ASCT, the OS was 62%, 80%, and 66% with P = 0.7, whereas the EFS was 66%, 60%, and 50% with P = 0.5 for CR, UCR, and PR, respectively. CONCLUSION: Iraqi bone marrow transplant center data showed acceptable OS and EFS results in the treatment of R/R DLBCL patients in areas where there is no more option in terms of better OS and EFS but with insignificant relation to the available prognostic factor.

Immunohistochemical Expression of Cyclin D1 in Invasive Breast Carcinoma

Objective: This study was conducted to determine the immunohistochemical expression of cyclin D1 in invasive breast carcinoma and its association with already established prognostic parameters like estrogen receptor (ER), progesterone receptor (PR), HER2/Neu, and Ki67 status. Study Design &amp; Setting: Cross sectional Observational. Department of Pathology, Armed Forces Institute of Pathology, Rawalpindi Methodology: The study included 350 cases of invasive breast cancer diagnosed between January 2023 and December 2023. Data collected included patient age, histological subtype, molecular subtypes, tumor size, and the presence of estrogen (ER) and progesterone (PR) receptors, as well as HER2/Neu and Ki67 status. Patients who had undergone chemotherapy, received radiation to the breasts, or experienced relapse were excluded from the study. Immunohistochemistry was conducted using a Cyclin D1 antibody to assess Cyclin D1 expression in tissue samples. The expression levels were categorized as negative, weak, moderate, strong staining in tumor cells. Data analysis was performed using SPSS 29.0, and statistical comparisons were made between Cyclin D1 staining and ER, PR, HER2/Neu, and Ki67 status. Results: Cyclin D1 moderate to strong staining was seen in 173/352 (49.14%) cases of invasive BC. Cyclin D1 expression was slightly statistically significantly associated with ER (x2 = 7.78, P value &lt;0.051) and Ki67 positivity (÷2 = 7.27, P value &lt;0.064). Conclusion: Cyclin D1 has the potential to serve as a prognostic marker. Incorporating it into the routine IHC workup for breast cancer could enhance patient management, especially with the development of new targeted therapies that inhibit the Cyclin D-CDK4/6 axis.

Clinical cases of verruciform epidermodysplasia of Lewandovski—Luts

Data from the medical literature and own observations of veruciform epidermodysplasia of Lewandovski — Luts (VEDLL) indicate that there are many issues that need to be resolved or clarified. They relate, in particular, to carrying out genetic research — in order to prove the phenomenon and regularities of heredity of dermatosis. The detection of a benign neoplastic formation in one of our patients — esophageal leiomyoma — obliges doctors to carefully examine patients with VEDLL, even without complaints about disorders of one or another body system. Does such a case not suggest the possibility of neoplastic transformation of a benign nature and not only from the side of the skin (papillomas and warts)? Can HPV for VEDLL cause, in addition to skin carcinoma, the occurrence of internal organ tumors? An important task of dermatologists is the early detection of patients among children, who often have common forms of wart-like efflorescences. It can be assumed that in some patients, the disease is latent for some time and manifests itself only under the influence of adverse factors (inadequate insolation, stress, etc.). The issues of VEDLL require practicing dermatovenereologists not only to conduct clinical and differential diagnosis of wart-like dermatoses but also to carry out laboratory tests to identify dermatosis (biopsy, cytology, PCR), which will allow for more frequent detection of VDLL. Since the rarity of VEDLL does not contribute to the accumulation of a sufficient amount of results on the detection of pathogenetic factors of dermatosis, particularly immunological ones, the treatment problem remains relevant. It is necessary to conduct permanent monitoring of the development of VEDLL to identify early signs of neoplastic transformation and determine predictors, that is, prognostic parameters, and introduce methods for their determination.

Evaluation of Multiple Tissue Levels Frequently Upstages Patients With Clinically Localized Thin Primary Cutaneous Melanoma.

Breslow thickness (BT), ulceration, and microsatellitosis are critical prognostic parameters for cutaneous melanoma staging. These parameters can vary depending on the number of tissue levels examined from individual paraffin blocks. We sought to evaluate all prognostic histopathologic parameters in melanoma for their variations between levels, taken at regular intervals, in a single study. We analyzed 40 consecutive cases of primary cutaneous (nonacral) melanoma through five hematoxylin and eosin sections, taken at 100 μm intervals, for staging and prognostic parameters. Examination of additional levels resulted in (a) an increase in BT in 47.5% (19 out of 40) of cases and (b) detection of ulceration in a further 5% (2/40). This resulted in upstaging for 20% (8 out of 40) of patients (15% because of BT, 2.5% because of ulceration, and 2.5% because of BT and ulceration). The upstaging effect was incremental, with approximately 5% of patients upstaged with each additional 100 μm interval (up to 400 μm). Incipient ulceration and epidermal consumption were infrequent (10% of cases); however, when present, ulceration was subsequently observed in half of cases. We encountered no cases where microsatellitosis was detected at deeper levels. The performance of additional tissue levels is a simple and inexpensive procedure that can improve the accuracy of staging for patients with thin (pT1) primary cutaneous melanomas. It may be pertinent for pathologists to consider additional levels for thin melanomas when a BT measurement is close to a staging threshold (e.g., within 0.1-0.3 mm for pT1a vs. pT1b, or pT1b vs. pT2a), or when incipient ulceration is encountered.

Fetal Fraction of Cell-Free DNA in the Prediction of Adverse Pregnancy Outcomes: A Nationwide Retrospective Cohort Study.

To assess the added value of fetal fraction of cell-free DNA in the maternal circulation in the prediction of adverse pregnancy outcomes. Retrospective cohort study. Nationwide implementation study on non-invasive prenatal testing (NIPT; TRIDENT-2 study). Pregnant women in the Netherlands opting for NIPT between June 2018 and June 2019. Two logistic regression prediction models were constructed for each adverse pregnancy outcome. The first model (base model) included prognostic clinical parameters that were selected from existing first-trimester prediction models for adverse pregnancy outcomes. The second model (fetal fraction model) included fetal fraction as a predictor on top of the prognostic clinical parameters included in the base model. The added prognostic value of fetal fraction was assessed by comparing the base and fetal fraction models in terms of goodness of fit and predictive performance. Likelihood ratio test (LRT), area under the curve (AUC) and Integrated Discrimination Improvement (IDI) index. The study cohort consisted of 56 110 pregnancies. The incidence of adverse pregnancy outcomes was 5.7% for hypertensive disorders of pregnancy (HDP; n = 3207), 10.2% for birthweight < p10 (n = 5726), 3.2% for birthweight < p2.3 (n = 1796), 3.4% for spontaneous preterm birth (sPTB; n = 1891), 3.4% for diabetes (n = 1902) and 1.3% for congenital anomalies (n = 741). Adding fetal fraction to the base model improved model fit for HDP, birthweight < p10, birthweight < p2.3, all sPTB, and diabetes, but not for congenital anomalies (LRT p < 0.05). For HDP, the AUC improved from 0.67 to 0.68 by adding fetal fraction to the base model (p = 0.14) with an IDI of 0.0018 (p < 0.0001). For birthweight < p10, the AUC improved from 0.65 to 0.66 (p < 0.0001) with an IDI of 0.0023 (p < 0.0001). For birthweight < p2.3, the AUC improved from 0.67 to 0.69 (p < 0.0001) with an IDI of 0.0011 (p < 0.0001). For all sPTB, the AUC was similar for both models (AUC 0.63, p = 0.021) with an IDI of 0.00028 (p = 0.0023). For diabetes, the AUC was similar (AUC 0.72, p = 0.35) with an IDI of 0.00055 (p = 0.00015). Fetal fraction has statistically significant but limited prognostic value in the prediction of adverse pregnancy outcomes in addition to known prognostic clinical parameters.