Long-Term Mortality and Morbidity Related to Congestive Heart Failure with Reduced Ejection Fraction (CHFrEF) in Palestinian Patients Maintained on Submaximal Sacubitril/Valsartan Doses: A Pilot Study

Background. The efficacy of sacubitril/valsartan, a newly introduced combination drug for heart failure with reduced ejection fraction (HFrEF), was demonstrated in the PARADIGM-HF trial conducted in Western countries. However, these findings need to be verified in the Middle Eastern context, where patients may exhibit a different response due to different environmental and racial factors. Objectives. The goal of this study was to evaluate the efficacy of submaximal sacubitril/valsartan doses in terms of improving the disease symptoms, as measured by the New York Heart Association (NYHA) classification and left ventricular ejection fraction (LVEF) percentage, as well as establish long-term morbidity and mortality associated with HFrEF among Palestinian patients administered target doses of an angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs). Material and Methods. This study involved a retrospective review of charts related to patients with HFrEF maintained on sacubitril/valsartan and was conducted in a referral cardiology clinic in Palestine. The inclusion criteria were age 18+, HFrEF diagnosis, sacubitril/valsartan usage for at least six months during the period between January 1, 2016, and June 30, 2019, and LVEF < 40 % . The exclusion criteria included LVEF ≥ 40 % and drug administration duration < 6 months. The collected data included NYHA class, as well as LVEF, serum sodium (Na), potassium (K), serum creatinine (Cr), and blood urea nitrogen (BUN) levels and the mortality rate before and after the minimum treatment duration. IBM SPSS STATISTICS for Windows, version 20.0, Armonk, NY: IBM Corp. IBM Corp., released 2012, was used for data analysis, whereby T score was calculated for comparisons between numerical groups, and p < 0.05 was considered statistically significant. Results. The initial study sample comprised of 205 consecutive patients with HFrEF maintained on sacubitril/valsartan for at least six months from January 1, 2016, to June 30, 2019. Three patients were excluded due to attrition, along with further 12 patients with LVEF ≥ 40 % (based on the PARADIGM-HF trial criteria). Throughout the treatment period, most patients showed escalating improvement in terms of the LVEF and NYHA classification, as LVEF = 29.8 % and NYHA = 3 were obtained on average before initiating sacubitril/valsartan, compared to 41% and 1.7, respectively, after 6-month treatment ( p = 0.0003 and 0.046, respectively). These improvements in LVEF and NYHA class were noted across all sacubitril/valsartan doses (50−400 mg). However, 23 patients (12%) died while undergoing sacubitril/valsartan treatment. Conclusion. A significant long-term reduction in the mortality and morbidity rates was observed in Palestinian patients with HFrEF maintained on submaximal doses of sacubitril/valsartan.

Reducing the Heart Failure Burden in Romania by Predicting Congestive Heart Failure Using Artificial Intelligence: Proof of Concept

Due to population aging, we are currently confronted with an increased number of chronic heart failure patients. The primary purpose of this study was to implement a noncontact system that can predict heart failure exacerbation through vocal analysis. We designed the system to evaluate the voice characteristics of every patient, and we used the identified variations as an input for a machine-learning-based approach. We collected data from a total of 16 patients, 9 men and 7 women, aged 65–91 years old, who agreed to take part in the study, with a detailed signed informed consent. We included hospitalized patients admitted with cardiogenic acute pulmonary edema in the study, regardless of the precipitation cause or other known cardiovascular comorbidities. There were no specific exclusion criteria, except age (which had to be over 18 years old) and patients with speech inabilities. We then recorded each patient’s voice twice a day, using the same smartphone, Lenovo P780, from day one of hospitalization—when their general status was critical—until the day of discharge, when they were clinically stable. We used the New York Heart Association Functional Classification (NYHA) classification system for heart failure to include the patients in stages based on their clinical evolution. Each voice recording has been accordingly equated and subsequently introduced into the machine-learning algorithm. We used multiple machine-learning techniques for classification in order to detect which one turns out to be more appropriate for the given dataset and the one that can be the starting point for future developments. We used algorithms such as Artificial Neural Networks (ANN), Support Vector Machine (SVM) and K-Nearest Neighbors (KNN). After integrating the information from 15 patients, the algorithm correctly classified the 16th patient into the third NYHA stage at hospitalization and second NYHA stage at discharge, based only on his voice recording. The KNN algorithm proved to have the best classification accuracy, with a value of 0.945. Voice is a cheap and easy way to monitor a patient’s health status. The algorithm we have used for analyzing the voice provides highly accurate preliminary results. We aim to obtain larger datasets and compute more complex voice analyzer algorithms to certify the outcomes presented.

Cardiovascular Biomarkers and Diastolic Dysfunction in Patients With Chronic Chagas Cardiomyopathy

Background: Chronic Chagas Cardiomyopathy is a unique form of cardiomyopathy, with a significantly higher mortality risk than other heart failure etiologies. Diastolic dysfunction (DD) plays an important role in the prognosis of CCM; however, the value of serum biomarkers in identifying and stratifying DD has been poorly studied in this context. We aimed to analyze the correlation of six biochemical markers with diastolic function echocardiographic markers and DD diagnosis in patients with CCM.Methods: Cross-sectional study of 100 adults with different stages of CCM. Serum concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), neutrophil gelatinase-associated lipocalin (NGAL), high-sensitivity troponin T (hs-cTnT), soluble (sST2), and cystatin-C (Cys-c) were measured. Tissue Doppler imaging was used to measure echocardiographic parameters indicating DD. Multivariate logistic regression models adjusted by age, sex, BMI, and NYHA classification were used to evaluate the association between the biomarkers and DD.Results: From the total patients included (55% male with a median age of 62 years), 38% had a preserved LVEF, but only 14% had a normal global longitudinal strain. Moreover, 64% had a diagnosis of diastolic dysfunction, with most of the patients showing a restrictive pattern (n = 28). The median levels of all biomarkers (except for sST2) were significantly higher in the group of patients with DD. Higher levels of natural log-transformed NTproBNP (per 1-unit increase, OR = 3.41, p &lt; 0.001), Hs-cTnT (per 1-unit increase, OR = 3.24, p = 0.001), NGAL (per 1-unit increase, OR = 5.24, p =0.003), and Cys-C (per 1-unit increase, OR = 22.26, p = 0.008) were associated with increased odds of having diastolic dysfunction in the multivariate analyses. Finally, NT-proBNP had the highest AUC value (88.54) for discriminating DD presence.Conclusion: Cardiovascular biomarkers represent valuable tools for diastolic dysfunction assessment in the context of CCM. Additional studies focusing mainly on patients with HFpEF are required to validate the performance of these cardiovascular biomarkers in CCM, allowing for an optimal assessment of this unique population.

Therapeutic Effect of His-Purkinje System Pacing Proportion on Persistent Atrial Fibrillation Patients With Heart Failure

Background His-Purkinje system pacing(HPSP) combined with atrioventricular node (AVN) ablation is an effective therapy for atrial fibrillation (AF) patients with heart failure (HF).However, AVN ablation is accompanied with some limitations and disadvantages. HPSP combined with β -blocker reduces inherent heart rate and increases pacing ratio, which may be an alternative to HPSP combined with AVN ablation. This study was to assess the therapeutic effect of different His-Purkinje system pacing proportions on AF patients with HF. Methods The study enrolled 30 consecutive persistent AF patients with HF who underwent HPSP. Heart rate was controlled by medical therapy. New York Heart Association (NYHA) classification, serum NT-proBNP concentration, echocardiographic parameters were assessed at each follow-up. Results The best cut-off value of pacing proportion to predict MACE by ROC analysis was 71%. In high pacing proportion group, there were significant improvements of NYHA classification, NT-proBNP concentration, LVEF and LVEDD from the baseline in wide QRS complex patients and HFrEF patients, and there were significant improvements in NYHA classification, NT-proBNP concentration from baseline in narrow QRS complex patients and HFpEF patients, moderate but no significant improvements of LVEF and LVEDD were observed in those patients groups. In low pacing proportion group, there were no significant improvements of NT-proBNP concentration, LVEDD or LVEF regardless of baseline QRS duration or LVEF (P > 0.05). Conclusion High pacing proportion of HPSP has a beneficial effect on the prognosis of persistent AF patients with heart failure.

Pulmonary perfusion and NYHA classification improve after cardiac resynchronization therapy

Background Evaluation of cardiac resynchronization therapy (CRT) often includes New York Heart Association (NYHA) classification, and echocardiography. However, these measures have limitations. Perfusion gradients from ventilation/perfusion single-photon emission computed tomography (V/P SPECT) are related to left-heart filling pressures and have been validated against invasive right-heart catheterization. The aim was to assess if changes in perfusion gradients are associated with improvements in heart failure (HF) symptoms after CRT, and if they correlate with currently used diagnostic methods in the follow-up of patients with HF after receiving CRT. Methods and results Nineteen patients underwent V/P SPECT, echocardiography, NYHA classification, and the quality-of-life scoring system “Minnesota living with HF” (MLWHF), before and after CRT. CRT caused improvement in perfusion gradients from V/P SPECT which were associated with improvements in NYHA classification (P = .0456), whereas improvements in end-systolic volume (LVESV) from echocardiography were not. After receiving CRT, the proportion of patients who improved was lower using LVESV (n = 7/19, 37%) than perfusion gradients (n = 13/19, 68%). Neither change in perfusion gradients nor LVESV was associated with changes in MLWHF (P = 1.0, respectively). Conclusions Measurement of perfusion gradients from V/P SPECT is a promising quantitative user-independent surrogate measure of left-sided filling pressure in the assessment of CRT response in patients with HF.

Extracting Features from Poincaré Plots to Distinguish Congestive Heart Failure Patients According to NYHA Classes

Heart-rate variability has proved a valid tool in prognosis definition of patients with congestive heart failure (CHF). Previous research has documented Poincaré plot analysis as a valuable approach to study heart-rate variability performance among different subjects. In this paper, we explored the possibility to feed machine-learning (ML) algorithms using unconventional quantitative parameters extracted from Poincaré plots (generated from 24-h electrocardiogram recordings) to classify patients with CHF belonging to different New York Heart Association (NYHA) classes. We performed in sequence the following investigations: first, a statistical analysis was carried out on 9 morphological parameters, automatically measured from Poincaré plots. Subsequently, a feature selection through a wrapper with a 10-fold cross-validation method was performed to find the best subset of features which maximized the classification accuracy for each considered ML algorithm. Finally, patient classification was assessed through a ML analysis using AdaBoost of Decision Tree, k-Nearest Neighbors and Naive Bayes algorithms. A univariate statistical analysis proved 5 out of 9 parameters presented statistically significant differences among patients of distinct NYHA classes; similarly, a multivariate logistic regression confirmed the importance of the parameter ρy in the separability between low-risk and high-risk classes. The ML analysis achieved promising results in terms of evaluation metrics (especially the Naive Bayes algorithm), with accuracies greater than 80% and Area Under the Receiver Operating Curve indices greater than 0.7 for the overall three algorithms. The study indicates the proposed features have a predictive power to discriminate the NYHA classes, to which the features seem evenly correlated. Despite the NYHA classification being subjective and easily recognized by cardiologists, the potential relevance in the clinical cardiology of the proposed features and the promising ML results implies the methodology could be a valuable approach to automatically classify CHF. Future investigations on enriched datasets may further confirm the presented evidence.

Reassessing the NYHA classification for heart failure: a comparison between classes I and II using cardiopulmonary exercise testing

Background The New York Heart Association (NYHA) functional classification has evolved to become a major determinant of eligibility to medical interventions and clinical trials, but its reliability to discriminate patients with mild heart failure (HF) has been questioned by studies that demonstrated a major overlap in self-reported symptoms and laboratory markers between NYHA classes I and II. Purpose To assess the reliability of NYHA classification by comparing cardio-pulmonary exercise test (CPET) results and its overlap between HF patients classified as NYHA I and II. Methods We retrospectively analyzed data from HF patients who underwent CPET in 3 medical centers in Brazil. NYHA class was defined as recorded on CPET day or during the previous clinical visit. Inclusion criteria were diagnosis of HF, age ≥16, and NYHA class I or II. We analyzed overlap between kernel density estimations for the percent-predicted peak VO2, minute ventilation/carbon dioxide production (VE/VCO2) slope, and oxygen uptake efficiency slope (OUES) in patients in NYHA classes I and II. Categorical variables were compared using chi-square tests. Results We included 684 patients, of which 42% (284) were classified as NYHA I. Mean age was 56.1 years; 44% (303) were female and mean left ventricular ejection fraction was 36% (±14.2%). Regarding CPET measures, mean global percent-predicted peak VO2 was 56.6% (±26.1%), VE/VCO2 slope was 38.8 (±10.2), and OUES was 1.50 (±0.59). Kernel density overlap between NYHA classes I and II was considerable: 83% for percent-predicted peak VO2, 89% for VE/VCO2 slope, and 85% for OUES (Figure 1). There was no significant difference between NHYA I and II in CPET indicators of poor prognosis: percent-predicted peak VO2 &lt;50% was present in 53% vs. 48% of patients classified as NYHA I and II, respectively (p=0.15); VE/VCO2 slope &gt;36 in 54% vs. 57% (p=0.39); and OUES &lt;1.4 in 46% vs. 48% (p=0.51). Conclusions HF patients classified as NYHA I and II overlap substantially in objective measures of functional capacity assessed by CPET. These findings suggest that NYHA classification is a poor discriminator of cardiopulmonary capacity among patients with mild HF, and raise questions about its use as a benchmark to guide HF therapy. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Effects of Sacubitril-Valsartan in Heart Failure With Preserved Ejection Fraction in Patients Undergoing Peritoneal Dialysis

Aims: The effect of the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril-valsartan in patients with heart failure with preserved ejection fraction (HFpEF) remains unclear, and data on ARNI treatment in peritoneal dialysis (PD) patients are lacking. The present study was designed to assess the efficacy and safety of sacubitril-valsartan in patients with HFpEF undergoing peritoneal dialysis.Methods and Results: End-stage kidney disease (ESKD) patients undergoing PD for 3 months with New York Heart Association (NYHA) class II–IV heart failure, ejection fraction of 50% or higher, and elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) were assigned to receive sacubitril-valsartan. Patients were followed up regularly after medication treatment. The alterations in clinical and biochemical parameters before and after taking sacubitril-valsartan (generally 50–100 mg b.i.d) were investigated, and safety was also assessed. Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels [9769.0 (3093.5–21941.0) vs. 3034.0 (1493.2–6503.0), P = 0.002], and heart rate [80.0 (74.5–90.5) vs. 75.0 (70.3–87.0), P = 0.031] were markedly decreased after treatment with sacubitril-valsartan. Signs and symptoms of heart failure (21/21 vs. 15/21, P = 0.021) were obviously alleviated, NYHA classification and E/e' ratio showed a notable trend of improvement after 3–12 months of follow-up. None of the patients showed adverse drug reactions.Conclusions: The present data suggested that sacubitril-valsartan treatment in patients with HFpEF undergoing PD was effective and safe.

Antenatal anticoagulant therapy and neonatal hemorrhagic syndrome. Case report.

Neonatal hemorrhagic syndrome, which affects several principal organs during the early neonatal period, denotes a deficiency of vitamin K and coagulation factors, respectively.This article presents the case of a patient that gave birth at term, who had congenital heart disease and required several prior surgical interventions including corrected transposition of the great vessels via ventricular septal defect (VSD) repair, atrial septal defect (in childhood) and tricuspid valve replacement (6 years ago), mitral regurgitation (MR), grade I pulmonary regurgitation (PR), grade II mitral and tricuspid valve regurgitation, and grade II heart failure based on the New York Health Association (NYHA) classification. Throughout the pregnancy the patient administered large doses of anticoagulant, specifically Acenocumarolum, until the moment she gave birth. The vaginal delivery was spontaneous, contrary to the recommendations given to the pregnant woman in a secondary healthcare institution. At birth, the newborn was in satisfactory condition, with 8/9 on the Apgar score. However, the newborn’s condition worsened over time, suspected of having neonatal hemorrhagic syndrome caused by medications administered by the mother. Forty-eight hours after birth the newborn died.Anticoagulant therapy cannot be considered absolutely safe during pregnancy because it presents risks for the development of hemodynamic disorders, not only for the mother, but also for the newborn. In such cases, it is recommended that a multidisciplinary team work together to inform the mother about possible complications, collaboratively establish the duration of treatment with vitamin K antagonists (VKAs), establish a plan for monitoring the pregnancy and determining in which institution the mother and newborn can benefit from qualified medical assistance, taking into consideration the higher incidence of perinatal mortality in such cases (10-30%).

Risk Stratification for Atrial Fibrillation and Outcomes in Tachycardia-Bradycardia Syndrome: Ablation vs. Pacing

Background: Catheter ablation of atrial fibrillation is an alternative treatment for patients with tachycardia-bradycardia syndrome (TBS) to avoid pacemaker implantation. The risk stratification for atrial fibrillation and outcomes between ablation and pacing has not been fully evaluated.Methods: This retrospective study involved 306 TBS patients, including 141 patients who received catheter ablation (Ablation group, age: 62.2 ± 9.0 months, mean longest pauses: 5.2 ± 2.2 s) and 165 patients who received pacemaker implement (Pacing group, age: 62.3 ± 9.1 months, mean longest pauses: 6.0 ± 2.3 s). The primary endpoint was a composite of call cause mortality, cardiovascular-related hospitalization or thrombosis events (stroke, or peripheral thrombosis). The second endpoint was progress of atrial fibrillation and heart failure.Results: After a median follow-up of 75.4 months, the primary endpoint occurred in significantly higher patients in the pacing group than in the ablation group (59.4 vs.15.6%, OR 6.05, 95% CI: 3.73–9.80, P &lt; 0.001). None of deaths was occurred in ablation group, and 1 death occurred due to cancer. Cardiovascular-related hospitalization occurred in 50.9% of the pacing group compared with 14.2% in the ablation group (OR: 4.87, 95% CI: 2.99–7.95, P &lt; 0.001). More thrombosis events occurred in the pacing group than in the ablation group (12.7 vs. 2.1%, OR 6.06, 95% CI: 1.81–20.35, P = 0.004). Significant more patients progressed to persistent atrial fibrillation in pacing group than in ablation group (23.6 vs. 2.1%, P &lt; 0.001). The NYHA classification of the pacing group was significantly higher than that of the ablation group (2.11 ± 0.83 vs. 1.50 ± 0.74, P &lt; 0.001). The proportion of antiarrhythmic drugs and anticoagulants used in the pacing group was significantly higher than that in the ablation group (41.2 vs. 7.1%, P &lt; 0.001; 16.4 vs. 2.1%, P = 0.009).Conclusion: Catheter ablation for patients with TBS was associated with a significantly lower rate of a composite end point of cardiovascular related hospitalization and thromboembolic events. Furthermore, catheter ablation reduced the progression of atrial fibrillation and heart failure.