Dapagliflozin cardiovascular effects on end-stage kidney disease (DARE-ESKD-2) trial: rationale and design.

BACKGROUND: Dapagliflozin prevents myocardial dysfunction in chronic kidney disease patients regardless of residual kidney function. We hypothesized that this effect is extensible also to patients on dialysis. RESEARCH DESIGN AND METHODS: The DARE-ESKD-2 is an ongoing, single-center, open-label randomized clinical trial designed to determine the effects of adding dapagliflozin to standard treatment on myocardial function and structure. Eligible patients were adults on a regular dialysis scheme for more than 3 months. Pregnancy, liver failure, allergy to the investigational drug, and prior use of SGLT2i were exclusion criteria. Participants were randomized in a 1:1 ratio to dapagliflozin or standard treatment groups for 24-weeks. The primary goal is to compare the change in NT-proBNP levels between study arms, and secondary goals include comparing the between-group difference in left ventricle global longitudinal strain, indexed mass, ejection fraction, and E/e` ratio, and on symptoms scale and 6-minute walk test distance. An exploratory analysis will evaluate changes in body composition and bone densitometry. RESULTS: The trial has finished the enrollment of 80 patients, who are currently being followed-up. CONCLUSIONS: This trial will provide novel data on myocardial effects of SGLT2i in dialysis recipients. Results from this study may provide evidence to support SGLT2i use in ESKD.

Prognostic value of the duke activity Status Index Questionnaire in predicting mortality in patients with chronic heart failure: 36-month follow-up study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire has been the focus of numerous investigations - its discriminative and prognostic capacity has been continuously explored, supporting its use in the clinical setting, specifically during rehabilitation in patients with chronic heart failure (CHF).However, studies exploring optimal DASI questionnaire threshold scores are limited. OBJECTIVE: To investigate optimal DASI questionnaire thresholds values in predicting mortality in a CHF cohort and assess mortality rates based on the DASI questionnaire using a thresholds values obtained. METHODOLOGY: This is a prospective cohort study with a 36-month follow-up in patients with CHF. All patients completed a clinical assessment, followed by DASI questionnaire, pulmonary function, and echocardiography. The Receiver Operating Characteristic (ROC) curve analysis was used to discriminate the DASI questionnaire score in determining the risk of mortality. For survival analysis, the Kaplan-Meier model was used to explore the impact of ≤/>23 points on mortality occurring during the 36-month follow-up. RESULTS: One hundred and twenty-four patients were included, the majority being elderly men. Kaplan Meier analysis revealed that ≤/> 23 was a strong predictor of CHF mortality over a 36-month follow-up. CONCLUSION: A score of ≤/>23 presents good discriminatory capacity to predict mortality risk in 36 months in patients with CHF, especially in those with reduced or mildly reduced ejection fraction. Age, ejection fraction, DASI questionnaire score and use of digoxin are risk factors that influence mortality in this population.

[Hypertrophic cardiomyopathy with mid-ventricular phenotype and filamin C mutation, an uncommon case report]. / Cardiomiopatía hipertrófica variante medio apical con mutación de la filamina C, una variante poco común. Reporte de caso.

Hypertrophic cardiomyopathy has a different presentation spectrum, including left ventricular outflow tract obstruction. The most common phenotype is the asymmetric septal variant, with the mid-apical variant being rare. On the other hand, there are specific mutations associated with hypertrophic cardiomyopathy, with the Filamin C variant being an unusual condition in these patients. Therefore, we present the case of a 23-year-old male patient with a diagnosis of hypertrophic cardiomyopathy in whom a Filamin C variant was documented. Given the inadequate response and persistence of symptoms to medical management, a myectomy procedure was performed with a transapical approach, with subsequent improvement in clinical symptoms and outflow tract obstruction. This case illustrates a rare variant with a surgical approach different from the conventional transaortic approach, with marked improvement in symptoms.

[Prevalence of transthyretin cardiac amyloidosis in patients hospitalized for heart failure with preserved ejection fraction and septal thickness]. / Prevalencia de amiloidosis cardíaca por transtiretina en pacientes internados por insuficiencia cardíaca con fracción de eyección preservada y engrosamiento septal.

INTRODUCTION: Transthyretin cardiac amyloidosis (ATTR-CM) usually presents as heart failure with preserved ejection fraction. Its diagnosis has a significant clinical impact, as specific treatment is currently available. The aim of this study is to assess the prevalence of ATTR-CM in patients hospitalized for heart failure with preserved ejection fraction and septal thickness in our region. METHODS: Cross-sectional study. Patients over 18 years old hospitalized for heart failure with preserved ejection fraction (greater than 50%) and septal thickness greater than or equal to 12 mm during the period from 8/2019 to 1/2023 were prospectively included. A pyrophosphate bone scintigraphy (PYP) was planned to assess cardiac involvement. The prevalence of ATTR-CM and its 95% confidence interval were calculated. RESULTS: A PYP was performed in 59/82 patients. The median age was 85 [IQR 78-88] years old, 54% women. On admission, 61% had atrial fibrillation/flutter rhythm and the median NT-Pro-Bnp was 3536 [IQR 1700-7748] pg/nl. The mean ejection fraction was 57% (± 5). The prevalence of ATTR-CM diagnosed by bone scintigraphy with PYP was 19% (95%CI 9.7-30.1). No differences were found compared with those patients who did not perform a PYP. CONCLUSION: In patients admitted for heart failure with preserved ejection fraction and septal thickness, the diagnosis of ATTR-CM was relatively common (1/5). We believe that it should be routinely explored.

Introducción: La amiloidosis cardíaca por transtiretina (TTR) se suele presentar como insuficiencia cardiaca (IC) con fracción de eyección preservada. Diagnosticarla tiene impacto clínico, ya que actualmente se dispone de tratamiento específico. El objetivo de este estudio fue evaluar la prevalencia en nuestro medio de TTR en pacientes hospitalizados por IC con función sistólica preservada e hipertrofia septal. Métodos: Estudio de corte transversal. Se incluyeron de forma prospectiva pacientes mayores a 18 años internados por IC con función sistólica conservada (fracción de eyección mayor a 50%) y espesor septal mayor o igual a 12 mm durante el periodo del 8/2019 a 1/2023. El compromiso cardiaco se evaluó mediante un centellograma óseo con pirofosfato (PYP) Se calculó la prevalencia de amiloidosis por TTR y su IC95%. Resultados: Se efectuó un centellograma en 59/82 pacientes. La edad fue de 85 [RIC 78-88] años, el 54% mujeres. Al ingreso, el 61% presentó ritmo de fibrilación/aleteo auricular y una mediana de NT-Pro-Bnp de 3536 pg/ml [RIC 1700-7748 pg/nl]. La media de fracción de eyección fue de 57 (± 5) %. La prevalencia de amiloidosis cardiaca por TTR diagnosticada por centellograma óseo con PYP fue del 19% (IC95% 9,7-30,1). No se detectaron diferencias con los 23 pacientes que no efectuaron centellograma. Conclusiones: En pacientes internados por IC con fracción de eyección preservada y engrosamiento septal el diagnóstico de amiloidosis cardiaca por TTR fue relativamente frecuente (1/5), por lo que consideramos que debería explorarse en forma rutinaria.

[Heart failure due to arteriovenous fistula for hemodialysis. Presentation of two clinical cases]. / Insuficiencia cardíaca por fístula arteriovenosa para hemodiálisis. Presentación de dos casos clínicos.

Arteriovenous fistulas for hemodialysis create a leftto-right shunt, resulting in an average 25% increase in cardiac output and subsequent remodeling of cardiac chambers. Some of these patients may develop highoutput heart failure. In this report, we present two cases of heart failure associated with an arteriovenous fistula for hemodialysis, each showing distinct clinical outcomes following either its occlusion or cerclage. Drawing from existing medical literature, we explore potential causes that might account for the divergent clinical courses observed in these cases.

Las fístulas arteriovenosas para hemodiálisis generan un cortocircuito de izquierda a derecha con un incremento promedio en el gasto cardíaco del 25%, asociado a remodelado de las cavidades cardíacas. Un porcentaje de estos pacientes desarrollan insuficiencia cardíaca con alto gasto cardíaco. Presentamos dos casos de insuficiencia cardíaca asociada a fístula arteriovenosa para hemodiálisis, con diferente evolución clínica luego de la oclusión o cerclaje de la misma. Basados en la literatura médica, se discuten las potenciales causas que pudieron justificar las diferencias en la evolución clínica entre ambos casos.

Mechanisms behind the high mortality rate in chronic Chagas cardiomyopathy: Unmasking a three-headed monster.

Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC), the most severe form of target organ involvement in Chagas disease, is characterized by a complex pathophysiology and a unique phenotype that differentiates it from other cardiomyopathies, highlighting its worse prognosis compared to other aetiologies of heart failure. The three pathophysiological mechanisms with the largest impact on this differential mortality include rapidly progressive heart failure, a high incidence of stroke, and a high burden of ventricular arrhythmias. However, despite significant advances in understanding the unique molecular circuits underlying these mechanisms, the new knowledge acquired has not been efficiently translated into specific diagnostic and therapeutic approaches for this unique cardiomyopathy. The lack of dedicated clinical trials and the limited CCC-specific risk stratification tools available are evidence of this reality. This review aims to provide an updated perspective of the evidence and pathophysiological mechanisms associated with the higher mortality observed in CCC compared to other cardiomyopathies and highlight opportunities in the diagnostic and therapeutic approaches of the disease.

Characteristics, Treatment, and Prognosis of Heart Failure Patients with Chronic Obstructive Pulmonary Disease in the Colombian Heart Failure Registry (RECOLFACA).

The impact of chronic obstructive pulmonary disease (COPD) on heart failure (HF) has yet to be well assessed in the Latin American population. This study aimed to analyze the impact of COPD on HF patients from the Colombian Heart Failure Registry (RECOLFACA). The primary outcome was all-cause mortality. A Cox proportional-hazards regression model was used to assess the impact of COPD on mortality. From the total of 2528 patients in the registry, 2514 patients had information regarding COPD diagnosis. COPD diagnosis was associated with a worse functional class and higher use of diuretics than non-COPD patients (p < 0.001). Patients with this comorbidity had a significantly better ejection fraction (median ejection fraction 35% vs. 32% in non-COPD patients; p = 0.004), with a higher occurrence of HF with preserved ejection fraction (HFpEF) in the COPD group (p = 0.000). Finally, patients with COPD had a significantly higher risk of mortality in the multivariate regression model (HR 1.47; 95% CI 1.02, 2.11). COPD is a prevalent comorbidity among patients with HF in Colombia, showing a different clinical profile and a worse functional class than patients without this condition. Patients with COPD and HFpEF have a high mortality risk according to our results.

Health insurance and clinical outcomes in patients with chronic heart failure in Latin America: an observational study of the Colombian Heart Failure Registry (RECOLFACA).

The effect of the health insurance type on the prognosis of heart failure (HF) patients in Colombia and Latin America is poorly known. We aimed to analyze the characteristics of HF patients that participated in the Colombian Heart Failure Registry (RECOLFACA) as stated by their health insurance type and their relationship with the immediate prognosis of these patients. Patients with HF diagnosis were included in the RECOLFACA registry between 2017-2019. The registry was conducted in 60 centers in Colombia. All-cause mortality was the principal outcome. To evaluate the impact of health insurance on mortality, a Cox proportional hazards regression model was used. The Kaplan-Meier analysis was performed to compare survival probabilities according to insurance type. All statistical analyses were two-tailed and were considered significant with a p value < 0.05. Of the 2,528 participants enrolled in the registry, 99% held details about their health insurance. Of those, 897 patients (35.6%) were covered by public insurance. These patients were significantly younger, with a lower proportion of men, more frequently from rural origin, and lower prevalence of most comorbidities (omitting hypertension, chronic obstructive pulmonary disease (COPD), and Chagas disease) than those with private insurance. Furthermore, patients with public insurance had a worse functional class, as well as a poorer quality of life, and lower frequency of use of implantable devices, while exhibiting similar prescription rates of triple medical therapy for HF. Finally, no differences in short-term mortality were observed between the two groups (HR 1.09; 95% CI 0.79, 1.51). The type of health insurance represents a condition related with relevant differences in the profile of patients with HF in Colombia. Despite this, no significant differences were detected in the short-term prognosis of these patients based on the type of health insurance.

Thirst Distress Scale for Patients With Heart Failure: Cross-Cultural Adaptation and Preliminary Psychometric Assessment in Brazil.

Background and Purpose: Thirst-related distress in individuals with heart failure (HF) is associated with exacerbated symptoms. This study aimed to culturally adapt the Thirst Distress Scale for Patients with Heart Failure (TDS-HF) for Brazil and assess the content validity of the adapted version. Methods: The TDS-HF was translated, back-translated, and evaluated for linguistic equivalence, clarity, relevance, and pertinence by seven professional experts. The adapted TDS-HF was administered to 40 patients with HF, who provided feedback on its understandability. Results: The adaptation achieved satisfactory evidence of linguistic equivalence and content validity, with a total content validity coefficient of 0.95. The patients understood the translated version effectively. Conclusion: The Brazilian TDS-HF maintains linguistic equivalence to the original version and demonstrates satisfactory evidence of content validity. Further psychometric testing is deemed necessary for implementation.

Boosting the Beat: A Critical Showdown of Levosimendan and Milrinone in Surgical and Non-Surgical Scenarios: A Narrative Review.

Acute heart failure, advanced cardiac failure, cardiac surgery, and sepsis are conditions that require simultaneous treatment to stimulate contractility and/or reduce systemic vascular resistance, with levosimendan and milrinone being treatment options. This research's aim is to review the current indications and evidence for these medications across various scenarios. Evidence suggests that levosimendan is a non-inferior alternative to dobutamine and superior to milrinone in treating low cardiac output syndrome following cardiac surgery. In cases of septic shock, levosimendan has been linked to lower mortality rates compared to placebo, while milrinone's efficacy remains inconclusive. Furthermore, postoperative patients undergoing correction for congenital heart disease have shown reduced mechanical ventilation time and intensive care unit stays when treated with levosimendan, although differences exist between the populations assigned to each intervention. In conclusion, levosimendan, compared to milrinone, appears to offer better hemodynamic favorability in patients undergoing cardiac surgery. However, additional research is necessary to further understand its impact on hemodynamic outcomes, mortality, intensive care unit, and hospital stays in patients with cardiogenic shock of both ischemic and non-ischemic etiologies, as well as septic shock.

Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Cardiovascular and Renal Outcomes in Heart Failure Patients With Type 2 Diabetes: A Literature Review.

The management of heart failure (HF) in patients with type 2 diabetes has significantly evolved with the introduction of sodium-glucose cotransporter 2 (SGLT2) inhibitors. This article aims to consolidate existing knowledge on the efficacy of these inhibitors in managing HF in this patient population. Major medical databases, including PubMed, Scopus, and Web of Science, were reviewed, prioritizing research from the last decade. The results of this review highlight the mechanisms of action of SGLT2 inhibitors, their clinical benefits, challenges in patient management, and outcomes associated with their use. These medications were found to not only improve glycemic control but also offer significant cardiovascular and renal benefits, reducing cardiovascular mortality and major adverse cardiovascular events. However, challenges and knowledge gaps persist, particularly regarding long-term effects and safety in diverse populations. The conclusions of this review underscore the importance of updating clinical guidelines to incorporate these findings and propose the need for future research to address existing gaps and optimize the use of SGLT2 inhibitors in clinical practice.

The Impact of Beta-Blocker Maintenance on Decompensated Heart Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute Heart Failure (HF) is related to a significant hospital mortality rate and functional impairment in many patients. However, there is still a lack of studies that support the use of Beta-blockers (BB) in the management of decompensated HF. OBJECTIVE: This study aimed to evaluate the impact on mortality of maintaining BB in patients with decompensated HF. METHODS: A systematic review and meta-analysis was performed, using the databases PubMed, Cochrane Library, SCIELO and BVS, selecting only cohort studies and Randomized Clinical Trials (RCTs) from the last 10 years, which have been selected based on inclusion and exclusion criteria. RESULTS: An 86% reduction in the risk of in-hospital death was found (RR=0.14, 95% CI: 0.10- 0.18) in patients with HF who maintained the use of BB during hospitalization. A second analysis found a 44% (RR=0.56, 95% CI: 0.47-0.66) lower chance of in-hospital death in the group that previously used BB. Regarding the analysis of mortality after hospital discharge, only studies that have evaluated the use of BB in HF with reduced ejection fraction pointed to a reduction in mortality. Furthermore, some articles have found a relationship between the reduction in readmissions and the use of post-discharge BB. CONCLUSION: There is still no consensus regarding the use of BB in patients hospitalized with decompensated HF. In view of the limitations of the data found in the present study, the need for more RCTs that address this topic is emphasized in order to resolve this uncertainty in the management of cardiovascular patients.

Congestive heart failure associated with itraconazole in a patient with paracoccidioidomycosis.

Itraconazole (ITZ) is widely prescribed for the treatment of mycosis such as Paracoccidioidomycosis (PCM). However, it's related to toxicity and serious adverse events, such as Congestive Heart Failure (CHF). The objective is to describe a patient with PCM and CHF secondary to ITZ. Male, 50-years old, was diagnosed with chronic adult PCM and started ITZ 200 mg 12/12 h. After 2-months, acute CHF began without previous-heart disease. The electrocardiogram showed changes in ventricular repolarization and left anterior superior divisional block. Echocardiogram: slight reduction in left ventricular systolic function and ejection fraction of 51%. ITZ was replaced by trimethoprim-sulfamethoxazole. After a week, there was remission of symptoms. Despite thousands of patients around the world received ITZ, few cases of CHF were reported. It's dose dependent and improves when the drug is discontinuing. ITZ has negative inotropic effect and probably causes mitochondrial dysfunction. However, the intrinsic mechanisms are not yet completely understood.

Heart Failure in Rheumatoid Arthritis: Clinical Implications.

PURPOSE OF REVIEW: This review focuses on the association between RA and heart failure, highlighting the role of inflammation and the prevalence of heart failure with preserved ejection fraction (HFpEF) in this population. RECENT FINDINGS: The incidence of heart failure in RA patients is two to three times higher than in the general population, with inflammation playing a significant role independent of traditional cardiovascular risk factors. HFpEF accounts for about half of heart failure cases and is increasingly recognized in RA patients, although it remains underdiagnosed. Atypical presentations and non-specific symptoms further complicate diagnosis. Early control of inflammation has been shown to reduce the risk of heart failure development and progression, improving both morbidity and mortality outcomes. Rheumatoid arthritis (RA) is a systemic inflammatory disease affecting approximately 1% of the population, with cardiovascular disease being the leading cause of premature death in these patients.

Heart Failure Care Facilitators and Barriers in Rural Haiti: A Qualitative Study.

Background: Heart failure (HF) is a leading cause of hospitalizations in Haiti. However, few patients return for outpatient care. The factors contributing to chronic HF care access are poorly understood. Objective: The purpose of this study is to investigate the facilitators and barriers to accessing care for chronic HF from the patients' perspectives. Methods: We conducted a qualitative descriptive study of 13 patients with HF participating in three group interviews and one individual interview. We recruited patients after discharge from a nongovernmental organization-supported academic hospital in rural Haiti. We employed thematic analysis using emergent coding and categorized themes using the socioecological model. Findings: Facilitators of chronic care included participants' knowledge about the importance of treatment for HF and engagement with health systems to manage symptoms. Social support networks helped participants access clinics. Participants reported low cost of care at this subsidized hospital, good medication accessibility, and trust in the healthcare system. Participants expressedstrong spiritual beliefs, with the view that the healthcare system is an extension of God's influence. Barriers to chronic care included misconceptions about the importance of adherence to medications when symptoms improve and remembering follow-up appointments. Unexpectedly, participants believed they should take their HF medications with food and that food insecurity resulted in missed doses. Lack of social support networks limited clinic access. The nonhealthcare costs associated with clinic visits were prohibitive for many participants. Participants expressed low satisfaction regarding the clinic experience. A barrier to healthcare was the belief that heart disease caused by mystical and supernatural spirits is incurable. Conclusions: We identified several facilitators and barriers to chronic HF care with meaningful implications for HF management in rural Haiti. Future interventions to improve chronic HF care should emphasize addressing misconceptions about HF management and fostering patient support systems for visit and medication adherence. Leveraging local spiritual beliefs may also promote care engagement.

Differential impacts of body composition on oxygen kinetics and exercise tolerance of HFrEF and HFpEF patients.

This study aims to (1) compare the kinetics of pulmonary oxygen uptake (VO2p), skeletal muscle deoxygenation ([HHb]), and microvascular O2 delivery (QO2mv) between heart failure (HF) patients with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF), and (2) explore the correlation between body composition, kinetic parameters, and exercise performance. Twenty-one patients (10 HFpEF and 11 HFrEF) underwent cardiopulmonary exercise testing to assess VO2 kinetics, with near-infrared spectroscopy (NIRS) employed to measure [HHb]. Microvascular O2 delivery (QO2mv) was calculated using the Fick principle. Dual-energy X-ray absorptiometry (DEXA) was performed to evaluate body composition. HFrEF patients exhibited significantly slower VO2 kinetics (time constant [t]: 63 ± 10.8 s vs. 45.4 ± 7.9 s; P < 0.05) and quicker [HHb] response (t: 12.4 ± 9.9 s vs. 25 ± 11.6 s; P < 0.05). Microvascular O2 delivery (QO2mv) was higher in HFrEF patients (3.6 ± 1.2 vs. 1.7 ± 0.8; P < 0.05), who also experienced shorter time to exercise intolerance (281.6 ± 84 s vs. 405.3 ± 96 s; P < 0.05). Correlation analyses revealed a significant negative relationship between time to exercise and both QO2mv (ρ= -0.51; P < 0.05) and VO2 kinetics (ρ= -0.63). Body adiposity was negatively correlated with [HHb] amplitude (ρ= -0.78) and peak VO2 (ρ= -0.54), while a positive correlation was observed between lean muscle percentage, [HHb] amplitude, and tau (ρ= 0.74 and 0.57; P < 0.05), respectively. HFrEF patients demonstrate more severely impaired VO2p kinetics, skeletal muscle deoxygenation, and microvascular O2 delivery compared to HFpEF patients, indicating compromised peripheral function. Additionally, increased adiposity and reduced lean mass are linked to decreased oxygen diffusion capacity and impaired oxygen uptake kinetics in HFrEF patients.

Clinical outcomes of patients with heart failure and atrial fibrillation: Experience from an outpatient heart failure clinic in Colombia.

BACKGROUND: Heart failure (HF) can coexist with atrial fibrillation in up to 60 % of cases, increasing rates of hospitalizations and death. This study analyzed the clinical characteristics, treatment, hospitalization, and mortality of patients with HF and atrial fibrillation based on left ventricular ejection fraction (LVEF). METHODS: A retrospective cohort study included patients from an outpatient HF clinic at Medellín (Colombia) between 2020-2022. Patients were classified into two groups according to LVEF: reduced (LVEF≤40 %) and mildly reduced or preserved ejection fraction (LVEF>40 %). The evaluated outcomes were hospitalization and mortality during follow-up. Values for B-type natriuretic peptide (BNP), LVEF and functional class according to the New York Heart Association (NYHA) were also analyzed at admission and during the last follow-up visit. RESULTS: The study included 185 patients, with 51.9% being male. The median age of the participants was 80 years (interquartile range [IQR] 74 - 86). There was an overall improvement in the NYHA functional class, BNP levels, and LVEF compared with the baseline values, irrespective of left systolic function. Atrial fibrillation ablation was performed in 3.2 % of patients, and cardiac device implantation with atrioventricular node ablation in 29 %. No statistically significant differences were found in terms of hospitalization and mortality regarding left systolic function. CONCLUSION: Compressive optimal treatment for patients with HF and atrial fibrillation requires pharmacological treatment, ablation strategies, cardiac devices, cardiovascular rehabilitation and close follow-up. In this cohort, hospitalization and mortality rates were similar according to LVEF categories and there was improvement in NYHA functional class and BNP level.

Cardioprotection of Canagliflozin, Dapagliflozin, and Empagliflozin: Lessons from preclinical studies.

Clinical and preclinical studies have elucidated the favorable effects of Inhibitors of Sodium-Glucose Cotransporter-2 (iSGLT2) in patients and animal models with type 2 diabetes. Notably, these inhibitors have shown significant benefits in reducing hospitalizations and mortality among patients with heart failure. However, despite their incorporation into clinical practice for indications beyond diabetes, the decision-making process regarding their use often lacks a systematic approach. The selection of iSGLT2 remains arbitrary, with only a limited number of studies simultaneously exploring the different classes of them. Currently, no unique guideline establishes their application in both clinical and basic research. This review delves into the prevalent use of iSGLT2 in animal models previously subjected to induced cardiac stress. We have compiled key findings related to cardioprotection across various animal models, encompassing diverse dosages and routes of administration. Beyond their established role in diabetes management, iSGLT2 has demonstrated utility as agents for safeguarding heart health and cardioprotection can be class-dependent among the iSGLT2. These findings may serve as valuable references for other researchers. Preclinical studies play a pivotal role in ensuring the safety of novel compounds or treatments for potential human use. By assessing side effects, toxicity, and optimal dosages, these studies offer a robust foundation for informed decisions, identifying interventions with the highest likelihood of success and minimal risk to patients. The insights gleaned from preclinical studies, which play a crucial role in highlighting areas of knowledge deficiency, can guide the exploration of novel mechanisms and strategies involving iSGLT2.

Low Thyroid Hormones Level Attenuates Mitochondrial Dysfunction and Right Ventricular Failure in Pulmonary Hypertensive Rats.

PURPOSE: This study is to investigate the repercussions of hypothyroidism in the pathophysiological progression of pulmonary arterial hypertension (PAH). METHODS: While the control (CTL, n = 5) male Wistar rats received vehicle, PAH was induced with monocrotaline (MCT group, n = 15). Hypothyroidism was induced in a subset of rats by methimazole 3 weeks prior to the MCT injection (MMZ + MCT group, n = 15). Plasma thyroid hormones were measured by radioimmunoassay. Electrocardiographic, echocardiographic, and hemodynamic analyses were performed to evaluate the progression of PAH. Gene expression of antioxidant enzymes and cardiac hypertrophy markers were assessed by qPCR. Mitochondrial respiration, ATP levels, and ROS production were measured in right ventricular (RV) samples. RESULTS: Plasma T3 and T4 decreased in both MCT and MMZ + MCT groups (p < 0.05). Right ventricular systolic pressure (RVSP) increased, and RV - dP/dt, + dP/dt, and contractility index decreased in the MCT versus the CTL group and remained within control levels in the MMZ + MCT group (p < 0.05). Relative RV weight, RV wall thickness, RV diastolic area, and relative lung weight were augmented in the MCT versus the CTL group, whereas all parameters were improved to the CTL levels in the MMZ + MCT group (p < 0.05). Only the MCT group exhibited an increased duration of QTc interval compared to the baseline period (p < 0.05). ADP-induced mitochondrial respiration and ATP levels were decreased, and ROS production was increased in MCT versus the CTL group (p < 0.05), while the MMZ + MCT group exhibited increased mitochondrial respiration versus the MCT group (p < 0.05). CONCLUSION: Hypothyroidism attenuated the RV mitochondrial dysfunction and the pathophysiological progression of MCT-induced PAH.

External validation of the natriuretic response prediction equation to discriminate diuretic response in heart failure.

AIMS: Incomplete decongestion due to lack of titration of diuretics to effective doses is a common reason for readmission in patients with acute decompensated heart failure (ADHF). The natriuretic response prediction equation (NRPE) is a novel tool that proved to be rapid and accurate to predict natriuretic response and does not need urine collection. However, the NRPE has not been externally validated. The goal of this study was to externally validate the discrimination capacity of the NRPE in patients with ADHF and fluid overload. METHODS AND RESULTS: Patients admitted with ADHF who required intravenous loop diuretics were included. A spot urine sample was obtained ~2 h following diuretic administration, and a timed 6-h urine collection by study staff was carried out. Urine sodium and urine creatinine from the spot urine sample were used to predict the 6-h natriuretic response using the NRPE. The primary goal was to validate the NRPE to discriminate poor loop diuretic natriuretic response (sodium output <50 mmol in the 6 h following diuretic administration). The NRPE was compared with urine sodium and measured urine output which are the methods currently recommended by international guidelines to assess diuretic response. Eighty-seven diuretic administrations from 49 patients were analysed. Mean age of patients was 57 ± 17 years and 67% were male. Mean estimated glomerular filtration rate was 65 ± 28 mL/min/1.73 m2, and ejection fraction was 35 ± 15%. Median dose of intravenous furosemide equivalents administered the day of the study was 80 mg (IQR 40 - 160). Poor natriuretic response occurred in 39% of the visits. The AUC of the NRPE to predict poor natriuretic response during the 6-h urine collection was 0.91 (95% CI 0.85-0.98). Compared with the NRPE, spot urine sodium concentration (AUC 0.75) and urine output during the corresponding nursing shift (AUC 0.74) showed lower discrimination capacity. CONCLUSIONS: In this cohort of patients with ADHF, the NRPE outperformed spot urine sodium concentration and all other metrics related to diuretic response to predict poor natriuretic response. Our findings support the use of this equation at other settings to allow rapid and accurate prediction of natriuretic response.