Diabetes induces modifications in costameric proteins and increases cardiomyocyte stiffness.

Several studies have demonstrated that diabetes mellitus can increase the risk of cardiovascular disease and remains the principal cause of death in these patients. Costameres connect the sarcolemma with the cytoskeleton and extracellular matrix, facilitating the transmission of mechanical forces and cell signaling. They are related to cardiac physiology because individual cardiac cells are connected by intercalated discs that synchronize muscle contraction. Diabetes impacts the nanomechanical properties of cardiomyocytes, resulting in increased cellular and left ventricular stiffness, as evidenced in clinical studies of these patients. The question of whether costameric proteins are affected by diabetes in the heart has not been studied. This work analyzes whether type 1 diabetes mellitus (T1DM) modifies the costameric proteins and coincidentally changes the cellular mechanics in the same cardiomyocytes. The samples were analyzed by immunotechniques using laser confocal microscopy. Significant statistical differences were found in the spatial arrangement of the costameric proteins. However, these differences are not due to their expression. Atomic force microscopy was used to compare intrinsic cellular stiffness between diabetic and normal cardiomyocytes and obtain the first elasticity map sections of diabetic living cardiomyocytes. Data obtained demonstrated that diabetic cardiomyocytes had higher stiffness than control. The present work shows experimental evidence that intracellular changes related to cell-cell and cell-extracellular matrix communication occur, which could be related to cardiac pathogenic mechanisms. These changes could contribute to alterations in the mechanical and electrical properties of cardiomyocytes and, consequently, to diabetic cardiomyopathy.NEW & NOTEWORTHY The structural organization of cardiomyocyte proteins is critical for their efficient functioning as a contractile unit in the heart. This work shows that diabetes mellitus induces significant changes in the spatial organization of costamere proteins, t tubules, and intercalated discs. We obtained the first elasticity map sections of living diabetic cardiomyocytes. The results show statistical differences in the map sections of diabetic and control cardiomyocytes, with diabetic cardiomyocytes being stiffer than normal ones.

[Cirrhotic cardiomyopathy ­ Clinically fact or academic curiosity? Review. Part 3: treatment] / Cardiomiopatía cirrótica ­ ¿Realidad clínica o simple curiosidad académica? Revisión.

Hepatic transplantation (HT) is the standard of care of end-stage liver disease with Cirrhotic Cardiomyopathy (CCM), but medical treatment with combination of diuretics and non-selective beta blockers are important before and after that. Owing to its particular pathophysiology unlike another etiologies of heart failure, in CCM angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type I receptor blockers (ARB), and angiotensin receptor neprilysin inhibitor (ARNI) are not recommended. Transjugular intrahepatic porto-systemic shunt (TIPS) has indications in CMM but its potential benefits and risks must be considered and more researh is necessary. HT is a demanding therapy but the most effective one, and showed improvement in QTc, diastolic and systolic dysfunction; in recent decades, in spite of more severe ill patients (more severe MELD score), survival has improved significantly due to better surgical techniques, intensive care, immunosupresive drugs, and images.

El tratamiento de la enfermedad hepática terminal con Cardiomiopatía Cirrótica (CMC) es el trasplante hepático (TH), sin embargo el tratamiento médico con la combinación de diuréticos y beta bloqueantes no selectivos antes y después tienen un rol importante. A diferencia de la insuficiencia cardíaca de otras etiologías, los inhibidores de la enzima convertidora (IECA), los bloqueadores del receptor de angiotensina 2 (ARA-2) o los inhibidores del receptor de angiotensina y de neprilisina (ARNI) no se recomiendan debido a la fisiopatología particular de la CMC. El shunt porto-sistémico intrahepático transyugular (Transjugular intrahepatic porto-systemic shunt: TIPS) tiene sus indicaciones con posibles beneficios y riesgos pero más estudios son necesarios en la CMC. El TH es la opción más eficaz y puede revertir el QTc del ECG y la disfunción diastólica y sistólica; en las últimas décadas, a pesar del aumento de la complejidad en los pacientes (mayor score MELD), con la mejoría de la técnica quirúrgica, cuidados intensivos, drogas inmunosupresoras y diagnóstico por imágenes la sobrevida ha mejorado significativamente.

[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.

[Sympathetic fire and rhythm of death "Spiked Helmet" in the Takotsubo cardiomyopathy. Case report]. / Incendio simpático y ritmo de la muerte Spiked Helmet en la miocardiopatía de Takotsubo. Reporte de caso.

The electrocardiographic sign "Spiked Helmet" (SHS) has been described in critically ill patients and is associated with a high risk of death. We present the case of a young individual with Marfan syndrome, who developed a Takotsubo cardiomyopathy and the electrocardiographic manifestation of SHS, 72 hours after the postoperative period for a ruptured abdominal aorta aneurysm. In this case, the factors that may justify the presentation of this electrocardiographic pattern are the thoraco-abdominal surgical intervention and Takotsubo cardiomyopathy, which together activated the sympathetic system, triggering the clinical-electrocardiographic manifestation.

Impact of neonatal hyperoxia on adult cardiac autonomic function in rats: Role of angiotensin II type 1 receptor activation.

Individuals born preterm present altered cardiac autonomic function, a risk factor to heart diseases. Neonatal renin-angiotensin-system activation contributes to adult cardiomyopathy in rats exposed to neonatal hyperoxia, a well-established model of preterm birth-related conditions. Central angiotensin II receptor activation is a key modulator of the autonomic drive to the heart. Whether neonatal hyperoxia leads to alteration of the cardiac autonomic function through activation of the angiotensin II receptor type 1 (AT1) is unknown and was examined in the present study. Sprague-Dawley pups were exposed to hyperoxia or room air from postnatal days 3-10. AT1 antagonist losartan or water was given orally postnatal days 8-10. Blood pressure, autonomic function, left ventricular sympathetic innervation, ß-adrenergic-receptors expression, and AT1 expression in the solitary-tract-nucleus were examined in adult rats. Neonatal hyperoxia led to loss of day-night blood pressure variation, decreased heart rate variability, increased sympathovagal balance, increased AT1 expression in the solitary-tract, decreased left ventricle sympathetic innervation, and increased ß1-adrenergic-receptor protein expression. Losartan prevented the autonomic changes and AT1 expression in the solitary-tract but did not impact the loss of circadian blood pressure variation nor the changes in sympathetic innervation and in ß1-adrenergic-receptor expression. In conclusion, neonatal hyperoxia leads to both central autonomic and cardiac sympathetic changes, partly programmed by neonatal activation of the renin-angiotensin system.

Predictors of ischemic stroke in Chagas disease: Insights into mechanisms beyond cardiomyopathy severity.

BACKGROUND: Chagas disease is a risk factor for ischemic stroke, which causes high mortality rates and significant disability. This study aims to determine the incidence and risk factors for ischemic strokes in a large cohort of Chagas cardiomyopathy patients, with a particular focus on the mechanisms involved in the pathophysiology of stroke in this condition. METHODS: The study enrolled 517 patients with Chagas cardiomyopathy who were referred to our institution from March 2000 to December 2021. All patients underwent systematic cardiological and neurological assessments. The primary outcome was the occurrence of ischemic stroke during the follow-up period, classified based on the SSS-TOAST and CCS criteria. Natural cubic splines functions were applied to examine the potential nonlinear association between continuous variables and stroke risk. RESULTS: The mean age of the cohort was 52 ± 13 years, and 299 (58 %) were men. During a mean follow-up period of 4.8 years (interquartile range-IQR 1.1 to 7.1 years), a total of 72 patients (14.8 %) had an ischemic stroke, being fatal in 10. The overall incidence rate of ischemic stroke was 3.0/100 patient-years (95 % confidence interval 2.4 to 3.8). The stroke subtypes were cardioembolic (n = 41), undetermined (n = 11), and other subtypes (n = 20). The predictors of stroke were age, left atrial volume, left ventricular ejection fraction (LVEF), LV thrombus and prior stroke with thrombus. There was a nonlinear relationship between stroke risk, LVEF, and left atrial volume. A bimodal distribution of stroke occurrences was observed according to the severity of LV dysfunction, with a threshold for LVEF of 45 %. The final model for stroke risk prediction showed good discrimination, with a C statistic of 0.775. CONCLUSIONS: In a contemporary cohort of Chagas disease patients with a broad spectrum of disease severity, stroke incidence remains high despite anticoagulation. Stroke risk shows a nonlinear association with ventricular dysfunction and left atrial size, highlighting a distinct bimodal pattern of stroke occurrence in Chagas disease.

Riesgo de eventos embólicos en pacientes con miocardiopatía chagásica y fibrilación auricular a pesar de terapia antitrombótica: ¿es la anticoagulación suficiente? / Risk of Embolic Events in Patients with Chagasic Cardiomyopathy and Atrial Fibrillation Despite Antithrombotic Therapy: Is Anticoagulation Enough?

RESUMEN Introducción: La miocardiopatía chagásica (MC) difiere de otras causas de insuficiencia cardíaca en múltiples aspectos, destacándose el riesgo de embolias sistémicas. Sin embargo, pocos estudios han evaluado el riesgo de eventos embólicos en pacientes anticoagulados con MC en comparación con otras miocardiopatías. Objetivo: Nuestro objetivo fue analizar la incidencia de embolias sistémicas en una cohorte de pacientes anticoagulados con diagnóstico de fibrilación auricular (FA) con y sin MC. Material y métodos: Se realizó un estudio de cohorte retrospectivo en hospital de cuarto nivel en Colombia durante el periodo 2014-2020. Se incluyeron todos los pacientes con diagnóstico de miocardiopatía de cualquier etiología y FA que estuvieran en régimen de anticoagulación. El resultado primario fue la incidencia de eventos embólicos. Se realizó un análisis de supervivencia mediante modelos de riesgos proporcionales de Cox ajustados. Un valor de p <0,05 se consideró significativo. Todas las pruebas estadísticas fueron de dos colas. Resultados: Se evaluaron 149 pacientes anticoagulados con miocardiopatía (mediana de edad: 71 años; mujeres: 30,20%). La incidencia acumulada de eventos embólicos fue significativamente mayor en los pacientes con MC (17,50%) en comparación con aquellos con otras miocardiopatías (4,95%), a pesar de que estos últimos tenían una puntuación CHA2DS2-VASc significativamente mayor (p=0,013). Tras el análisis multivariado, los pacientes con MC tuvieron un riesgo significativamente mayor de eventos embólicos independientemente de la puntuación CHA2DS2-VASc y del tipo de anticoagulante prescrito (HR 5,65; IC 95% 1,46-21,83; p=0,012). Conclusiones: La MC se asoció con un riesgo significativamente mayor de eventos embólicos, a pesar del tratamiento anticoagulante en ambos grupos. Se requiere más investigación para comprender el origen de este riesgo observado y traducir este conocimiento en indicaciones específicas de anticoagulación para pacientes con MC.

ABSTRACT Background: Chagasic cardiomyopathy (CC) differs from other heart failure causes in multiple aspects, highlighting the risk of systemic embolisms. However, few studies have evaluated the risk of embolic events in anticoagulated patients with CC compared with other cardiomyopathies. Objective: We aimed to analyze the incidence of systemic embolisms in a cohort of anticoagulated patients diagnosed with atrial fibrillation (AF) with and without CC. Methods: A retrospective cohort study was carried out at a fourth level hospital in Colombia during the period 2014-2020. All patients diagnosed with cardiomyopathy of any etiology and AF, who were on an anticoagulation regimen were included. The primary outcome was the incidence of embolic events. A survival analysis was performed using adjusted Cox proportional hazard models. A p-value <0.05 was considered significant. All statistical tests were two-tailed. Results: A total of 149 anticoagulated patients with cardiomyopathy were evaluated (median age: 71 years; women: 30.20%). The cumulative incidence of embolic events was significantly higher in patients with CC (17.50%) compared with those presenting other cardiomyopathies (4.95%), despite that the latter had a significantly higher CHA2DS2-VASc score (p=0.013). After multivariate analysis, patients with CC had a significantly higher risk of embolic events regardless of the CHA2DS2-VASc score and the type of anticoagulant prescribed (HR 5.65; 95% CI 1.46-21.83; p=0.012). Conclusions: Chagasic cardiomyopathy was associated with a significantly higher risk of embolic events, despite anticoagulation therapy in both groups. More research is required to understand the origin of the risk observed in order to translate this knowledge into specific indications for anticoagulation in patients with CC.

Enhancing risk assessment in Chagas cardiomyopathy: Electrophysiology study stratified by Rassi score.

BACKGROUND: Chagas cardiomyopathy (CCM) is increasingly prevalent in developed countries due to migration from endemic areas. Accurate risk stratification is crucial due to the variable clinical course of CCM. OBJECTIVE: To analyze the association between Rassi score progression and electrophysiology study (EPS) changes in CCM patients. METHODS: This prospective, observational cohort study involved CCM patients from two tertiary hospitals. Patients were classified as low, intermediate, or high risk based on the Rassi score. Data collected included demographics, clinical history, and diagnostic tests. EPS assessed AH, HH, and HV intervals, and inducibility of ventricular arrhythmias. Follow-ups were at 30 days and six-month intervals, with individualized discussions for cardiac implantable electric devices (CIED) based on EPS results. RESULTS: Of 67 screened CCM patients, 59 underwent EPS. The mean Rassi score was 8.7 ± 4.5 points, with 33.8 % low, 38.9 % intermediate, and 27.1 % high risk. EPS abnormalities were found in 57.6 % of patients, mainly VT/VF (52.5 %). Most induced ventricular arrhythmias were monomorphic VT (80.7 %). A significant association was found between Rassi score risk classification and EPS changes (OR = 1.88 95 %CI: 1.15-3.06 p = 0.02). Higher Rassi scores correlated with VT presence on EPS (p = 0.0036). Syncope/pre-syncope had an OR 2.45 95 %CI:1.21-4.94; p = 0.012, independent of Rassi risk. Decreased ejection fraction was linked to EPS changes (p = 0.04). CONCLUSION: EPS changes among CCM was associated with progression of the Rassi score, indicating its utility as a stratification tool. Factors such as the presence of syncope/pre-syncope, decreased LVEF and wall motion abnormalities emerged as independent predictors within Rassi scores for changes in EPS.

Survival Analysis in Adult Heart Transplantation: Experience from a Brazilian Single Center.

INTRODUCTION: Heart transplantation is the gold standard for advanced heart failure treatment. This study examines the survival rates and risk factors for early mortality in adult heart transplant recipients at a Brazilian center. METHODS: This retrospective cohort study involved 255 adult heart transplant patients from a single center in Brazil. Data were collected from medical records and databases including three defined periods (2012-2015, 2016-2019, and 2020-2022). Statistical analysis employed Kaplan-Meier survival curves, Cox proportional hazards analysis for 30-day mortality risk factors, and Log-rank tests. RESULTS: The recipients were mostly male (74.9%), and the mean age was 46.6 years. Main causes of heart failure were idiopathic dilated cardiomyopathy (33.9%), Chagas cardiomyopathy (18%), and ischemic cardiomyopathy (14.3%). The study revealed an overall survival of 68.1% at one year, 58% at five years, and 40.8% at 10 years after heart transplantation. Survivalimproved significantly over time, combining the most recent periods (2016 to 2022) it was 73.2% in the first year and 63% in five years. The main risk factors for 30-day mortality were longer time on cardiopulmonary bypass, the initial period of transplants (2012 to 2015), older age of the donor, and nutritional status of the donor (overweight or obese). The main causes of death within 30 days post-transplant were infection and primary graft dysfunction. CONCLUSION: The survival analysis by period demonstrated that the increased surgical volume, coupled with the team's experience and modifications to the immunosuppression protocol, contributed to the improved early and mid-term outcomes.

Prevalence of Cardiomyopathy in Patients with Type 1 Diabetes Mellitus.

Background: Diabetic cardiac muscle disease or diabetic cardiomyopathy (DbCM) comprises a set of myocardial lesions that are not associated with coronary atherosclerosis or high blood pressure. It is characterized by fibrosis and hypertrophy, which ultimately results in heart failure. Diastolic dysfunction (DD) has been shown to be the first manifestation of diabetic cardiomyopathy. Currently, there are few studies on the prevalence of diabetic cardiomyopathy in adult patients diagnosed with type 1 diabetes mellitus (T1D). Methods: The study included 75 adult participants who underwent an echocardiogram. Data on their comorbidities were collected from their medical records and biochemical parameters were analyzed in blood and urine samples. Results: We found that the prevalence of DbCM in our T1D population was more than one-third (34%), which exceeded the prevalence reported in studies with adolescents and that reported in the population without diabetes. Also, we found that the probability of developing DD after 20 years of T1D diagnosis was 78%. Conclusions: Recommendations need to be issued in relation to diabetic cardiomyopathy to carry out secondary prevention in adult patients with T1D. More multicenter studies, which include a larger population, from different regions of the world need to be performed.

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.

Treinamento Físico Reduz a Inflamação e a Fibrose e Preserva a Função e a Perfusão Miocárdica em um Modelo de Cardiomiopatia Chagásica Crônica / Exercise Training Reduces Inflammation and Fibrosis and Preserves Myocardial Function and Perfusion in a Model of Chronic Chagas Cardiomyopathy

Resumo Fundamento: A Cardiomiopatia Chagásica Crônica (CCC) é causada por um processo inflamatório induzido pelo Trypanosoma cruzi, que leva à miocardite com fibrose reativa e reparativa. A CCC progride com alterações de perfusão miocárdica e eventos histopatológicos que afetam a Aptidão Cardiorrespiratória (ACR). Objetivos: Avaliamos os efeitos do Treinamento Físico Aeróbico (TFA) na perfusão miocárdica e nos comprometimentos morfológicos e funcionais relacionados à inflamação e fibrose em hamsters sírios com CCC. Como objetivo secundário, analisamos as áreas de secção transversa do músculo esquelético. Métodos: Hamsters com CCC e seus respectivos controles foram divididos em quatro grupos: CCC sedentário, CCC-TFA, controle sedentário e controle TFA. Sete meses após a infecção, os animais foram submetidos à ecocardiografia, à cintilografia de perfusão miocárdica e ao teste de esforço cardiopulmonar. TFA de intensidade moderada foi realizado durante cinquenta minutos, cinco vezes por semana, por oito semanas. Posteriormente, os animais foram reavaliados. A análise histopatológica foi realizada após os procedimentos acima mencionados. O nível de significância foi estabelecido em 5% em todas as análises (p<0,05). Resultados: Animais com CCC sedentários apresentaram piores Defeitos de Perfusão Miocárdica (DPM) ao longo do tempo, Fração de Ejeção do Ventrículo Esquerdo (FEVE) reduzida, e apresentaram mais inflamação e fibrose quando comparados aos demais grupos (análise ANOVA mista). Por outro lado, o TFA foi capaz de mitigar a progressão do DPM, atenuar a inflamação e a fibrose e melhorar a eficiência da ACR em animais CCC-TFA. Conclusão: Nosso estudo demonstrou que o TFA melhorou a disfunção cardíaca, DPM e reduziu a inflamação e a fibrose em modelos de hamster com CCC. Além disso, os animais CCC-SED apresentaram atrofia do músculo esquelético, enquanto os animais CCC-TFA apresentaram a AST do músculo esquelético preservada. Compreender os efeitos da TFA nas dimensões fisiopatológicas da CCC é crucial para futuras pesquisas e intervenções terapêuticas.

Abstract Background: Chronic Chagas cardiomyopathy (CCC) is caused by an inflammatory process induced by Trypanosoma cruzi, which leads to myocarditis with reactive and reparative fibrosis. CCC progresses with myocardial perfusion abnormalities and histopathological events that affect cardiorespiratory fitness (CRF). Objectives: We evaluated the effects of aerobic physical training (APT) on myocardial perfusion and on morphological and functional impairments related with inflammation and fibrosis in Syrian hamsters with CCC. As a secondary objective, we analyzed the cross-sectional areas of the skeletal muscle. Methods: Hamsters with CCC and their respective controls were divided into four groups: CCC sedentary, CCC-APT, sedentary control and APT control. Seven months after infection, the animals underwent echocardiography, myocardial perfusion scintigraphy and cardiopulmonary exercise testing. Moderate-intensity APT was performed for fifty minutes, five times a week, for eight weeks. Subsequently, the animals were reassessed. Histopathological analysis was conducted after the above-mentioned procedures. The level of significance was set at 5% in all analyses (p<0.05). Results: CCC sedentary animals presented worse myocardial perfusion defects (MPD) over time, reduced left ventricle ejection fraction (LVEF) and showed more inflammation and fibrosis when compared to other groups (mixed ANOVA analysis). Conversely, APT was able to mitigate the progression of MPD, ameliorate inflammation and fibrosis and improve CRF efficiency in CCC-APT animals. Conclusions: Our study demonstrated that APT ameliorated cardiac dysfunction, MPD, and reduced inflammation and fibrosis in CCC hamster models. Additionally, CCC-SED animals presented skeletal muscle atrophy while CCC-APT animals showed preserved skeletal muscle CSA. Understanding APT's effects on CCC's pathophysiological dimensions is crucial for future research and therapeutic interventions.

Datos preliminares del registro de miocardiopatía hipertrófica en centros no especializados en Argentina. Explorando detrás de los velos de la práctica cotidiana / Preliminary Data of the Hypertrophic Cardiomyopathy Registry in Nonspecialized Centers of Argentina. Exploring Behind the Veils of Common Practice

RESUMEN Introducción. La miocardiopatía hipertrófica (MCH), es la enfermedad genética cardiovascular más común, causada por mutaciones en proteínas del sarcómero cardíaco, con una prevalencia considerable y clínica variable, desde asintomática hasta insuficiencia cardíaca y muerte súbita. Existen pacientes seguidos en centros no especializados, y es necesario conocer datos que puedan mostrar la realidad de su diagnóstico, tratamiento y pronóstico. Objetivo. Conocer las características clínicas, estrategias diagnósticas y terapéuticas al abordar la MCH en centros no especializados en la patología. Material y métodos. Estudio de corte transversal, multicéntrico, de alcance nacional, con análisis cuantitativo, de pacientes con MCH confirmada o altamente probable. Resultados. Se registraron 95 pacientes, mayormente hombres con hipertensión arterial (40 %) y dislipidemia (22 %) como principales factores de riesgo. Se observó baja proporción de comorbilidades: enfermedad pulmonar obstructiva crónica (6 %), infarto de miocardio previo (5 %), accidente cerebro vascular previo (1 %) e insuficiencia renal crónica (1 %). Los síntomas principales fueron la disnea (47 %) y el ángor (27 %), y los métodos diagnósticos más usados fueron el ecocardiograma (97 %) y la resonancia cardíaca (71 %). La localización más frecuente fue septal, con 37 % de tipo obstructivo. El test genético, realizado en un 33 %, fue positivo en más de la mitad de los pacientes. No se realizó en dos tercios de los casos principalmente por falta de cobertura. Conclusiones. Los hallazgos son concordantes con los de registros internacionales. Con base a nuestros hallazgos, se resalta la necesidad de mejorar el acceso a estudios diagnósticos más complejos y optimizar recursos en un sistema de salud fragmentado.

ABSTRACT Background . Hypertrophic cardiomyopathy (HCM) is the most common genetic disease caused by cardiac sarcomere protein mutations, with considerable prevalence and different clinical presentation, varying from asymptomatic to heart failure and sudden death. Some patients are followed-up in nonspecialized centers, and it is necessary to know data that show the reality of their diagnosis, treatment, and prognosis. Objective. The aim of this study was to know the clinical characteristics, and diagnostic and therapeutic strategies when HCM is managed in centers not specialized in this disease. Methods. This was a national, cross-sectional, multicenter study, with quantitative analysis of patients with confirmed or highly probable HCM. Results. A total of 95 patients were recruited, mostly men, with hypertension (40%) and dyslipidemia (22%) as main risk factors. A low proportion of comorbidities was observed: chronic obstructive pulmonary disease (6%), prior myocardial infarction (5%), prior stroke (1%) and chronic kidney failure (1%). The main symptoms were dyspnea (47% and angina (27%), and the most used diagnostic methods were echocardiogram (97%) and cardiac magnetic resonance imaging (71%)). The most frequent localization was septal, with 37% of hypertrophic obstructive cardiomyopathy. The genetic test, performed in 33% of patients, was positive in more than half of cases. It was not performed in the rest of the patients, mainly due to lack of health coverage. Conclusions. These findings are in agreement with international registries. Based on our findings, emphasis should be placed in improving the access to more complex diagnostic studies and optimizing the resources in a fragmented health system.

Peripartum Cardiomyopathy: A Case Report of Mortality From a Rare and Potentially Fatal Condition.

Peripartum cardiomyopathy (PPCM) poses a significant challenge in maternal health, characterized by heart failure with reduced ejection fraction during late pregnancy or early postpartum. Despite advances in understanding PPCM, it remains life-threatening with substantial maternal morbidity and mortality. This article reviews the epidemiology, etiology, diagnostic challenges, management strategies, and outcomes associated with PPCM. A case report of a 29-year-old woman with PPCM is presented, emphasizing the importance of early recognition and tailored management. The patient's presentation was marked by atypical symptoms, including dysuria, lumbar pain, persistent fever, and oral intake intolerance. Despite aggressive medical intervention, the patient experienced a tragic outcome, succumbing to cardiopulmonary arrest within 48 h of admission. This case underscores the challenges in diagnosing and managing PPCM, particularly when presenting with nonspecific symptoms and emphasizes the urgent need for improved diagnostic criteria and therapeutic interventions to mitigate adverse outcomes in affected individuals.

The effects of inflammation on connexin 43 in chronic Chagas disease cardiomyopathy.

Background: Cardiac arrhythmias are the main cause of sudden death due to Chronic Chagasic Cardiomyopathy (CCC). Here we investigated alterations in connexin 43 (Cx43) expression and phosphorylation in cardiomyocytes as well as associations with cardiac arrhythmias in CCC. Methods: C57Bl/6 mice infected with Trypanosoma cruzi underwent cardiac evaluations at 6 and 12 months after infection via treadmill testing and EKG. Histopathology, cytokine gene expression, and distribution of total Cx43 and its phosphorylated forms Cx43S368 and Cx43S325/328/330 were investigated. Human heart samples obtained from subjects with CCC were submitted to immunofluorescence analysis. In vitro simulation of a pro-inflammatory microenvironment (IL-1ß, TNF, and IFN-γ) was performed in H9c2 cells and iPSC-derived cardiomyocytes to evaluate Cx43 distribution, action potential duration, and Lucifer Yellow dye transfer. Results: Mice chronically infected with T. cruzi exhibited impaired cardiac function associated with increased inflammation, fibrosis and upregulated IL-1ß, TNF, and IFN-γ gene expression. Confocal microscopy revealed altered total Cx43, Cx43S368 and Cx43S325/328/330 localization and phosphorylation patterns in CCC, with dispersed staining outside the intercalated disc areas, i.e., in lateral membranes and the cytoplasm. Reduced co-localization of total Cx43 and N-cadherin was observed in the intercalated discs of CCC mouse hearts compared to controls. Similar results were obtained in human CCC heart samples, which showed Cx43 distribution outside the intercalated discs. Stimulation of human iPSC-derived cardiomyocytes or H9c2 cells with IL-1ß, TNF, and IFN-γ induced alterations in Cx43 localization, reduced action potential duration and dye transfer between adjacent cells. Conclusion: Heart inflammation in CCC affects the distribution and phosphorylation pattern of Cx43, which may contribute to the generation of conduction disturbances in Chagas disease.

Impact of cardiac structure and function on exercise intolerance in Chagas cardiomyopathy: Insights from CPET and echocardiography.

INTRODUCTION: Chronic Chagas cardiomyopathy (CCC), the most severe clinical condition of Chagas disease, often leads to a reduction in functional capacity and the appearance of symptoms such as fatigue and dyspnea on exertion. However, its determinant factors remain unclear. We aimed to evaluate the peak oxygen consumption (VO2peak) in patients with CCC and identify its determining factors. METHODS: An observational study with 97 CCC patients was conducted. Patients underwent clinical examination, cardiopulmonary exercise test (CPET), and echocardiography as part of the standard clinical evaluation. Multivariate linear regression was used to identify independent clinical and echocardiographic predictors of VO2peak and percentage of predicted VO2. RESULTS: Mean age of study patients was 55.9 ± 13.4 years, median left ventricle ejection fraction (LVEF) was 40 (26-61.5) % and median VO2peak was 16.1 (12.1-20.8) ml/Kg/min. 36 patients presented preserved LVEF and 61 presented reduced LVEF. There were significant differences in almost all CPET variables (p < 0.05) between these two groups. VO2peak was associated with age, male sex, NYHA functional class, LVEF, left atrium diameter, LV diastolic diameter, E wave, LV mass index, and pulmonary artery systolic pressure (PASP). Age, male sex, LVEF, and E wave remained independently associated with VO2peak in the multivariate analysis (R2 = 0.69), furthermore, only LVEF and E wave were associated with the predicted VO2 percentage (R2 = 0.53). CONCLUSION: In patients with CCC, disease severity, male sex, LV systolic and diastolic function influence the functional capacity.

Efficacy of Beta-Blockers and Angiotensin-Converting Enzyme Inhibitors in Non-Ischemic Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) is a form of heart failure with a poor prognosis and unclear optimal management. The aim of the study was to systematically review the literature and assess the efficacy and safety of beta-blockers and angiotensin-converting enzyme (ACE) inhibitors in the management of chronic heart failure secondary to NIDCM and explore their putative mechanisms of action. Methods: Studies from 1990 to 2023 were reviewed using PubMed and EMBASE, focusing on their effects on left ventricular ejection fraction (LVEF) in NIDCM patients, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Beta-blockers showed a significant beneficial effect on LVEF improvement in NIDCM, with an overall effect size of Cohen's d = 1.30, 95% confidence interval (CI) (0.76, 1.84), high heterogeneity (Tau2 = 0.90; Chi2 = 162.05, df = 13, P < 0.00001; I2 = 92%), and a significant overall effect (Z = 4.72, P < 0.00001). ACE inhibitors also showed a beneficial role, but with less heterogeneity (Tau2 = 0.02; Chi2 = 1.09, df = 1, P = 0.30; I2 = 8%) and a nonsignificant overall effect (Z = 1.36, P = 0.17), 95% CI (-0.24, 1.31). Conclusions: The study highlights the efficacy of carvedilol in improving LVEF in NIDCM patients over ACE inhibitors, recommends beta-blockers as first-line therapy, and advocates further research on ACE inhibitors.

Immunomodulatory, Antioxidant, and Potential Anticancer Activity of the Polysaccharides of the Fungus Fomitiporia chilensis.

Fomitiporia species have aroused the interest of numerous investigations that reveal their biological activity and medicinal potential. The present investigation shows the antioxidant, anticancer, and immunomodulatory activity of acidic polysaccharides obtained from the fungus Fomitiporia chilensis. The acidic polysaccharides were obtained for acidic precipitation with 2% O-N-cetylpyridinium bromide. Chemical analysis was performed using FT-IR and GC-MS methods. The antioxidant capacity of acidic polysaccharides from F. chilensis was evaluated by scavenging free radicals with an ABTS assay. Macrophage proliferation and cytokine production assays were used to determine the immunomodulatory capacity of the polysaccharides. Anti-tumor and cytotoxicity activity was evaluated with an MTT assay in the U-937, HTC-116, and HGF-1 cell lines. The effect of polysaccharides on the cell cycle of the HCT-116 cell line was determined for flow cytometry. Fourier Transform-infrared characterization revealed characteristic absorption peaks for polysaccharides, whereas the GC-MS analysis detected three peaks corresponding to D-galactose, galacturonic acid, and D-glucose. The secreted TNF-α concentration was increased when the cell was treated with 2 mg mL-1 polysaccharides, whereas the IL-6 concentration was increased with all of the evaluated polysaccharide concentrations. A cell cycle analysis of HTC-116 treated with polysaccharides evidenced that the acidic polysaccharides from F. chilensis induce an increase in the G0/G1 cell cycle phase, increasing the apoptotic cell percentage. Results from a proteomic analysis suggest that some of the molecular mechanisms involved in their antioxidant and cellular detoxifying effects and justify their traditional use in heart diseases. Proteomic data are available through ProteomeXchange under identifier PXD048361. The study on acidic polysaccharides from F. chilensis has unveiled their diverse biological activities, including antioxidant, anticancer, and immunomodulatory effects. These findings underscore the promising therapeutic applications of acidic polysaccharides from F. chilensis, warranting further pharmaceutical and medicinal research exploration.

Unraveling the rationale and conducting a comprehensive assessment of AdipoRon (adiponectin receptor agonist) as a candidate drug for diabetic nephropathy and cardiomyopathy prevention and intervention-a systematic review.

Type 2 diabetes mellitus (T2DM) is a widespread chronic disease characterized by persistent hyperglycemia, leading to severe complications such as diabetic cardiomyopathy and nephropathy, significantly affecting patient health and quality of life. The complex mechanisms underlying these complications include chronic inflammation, oxidative stress, and metabolic dysregulation. Diabetic cardiomyopathy, marked by structural and functional heart abnormalities, and diabetic nephropathy, characterized by progressive kidney damage, are major contributors to the increased morbidity and mortality associated with T2DM. AdipoRon, a synthetic adiponectin receptor agonist, has shown potential in preclinical studies for mimicking the beneficial effects of endogenous adiponectin, reducing inflammation and oxidative stress, and improving lipid metabolism and mitochondrial function. This systematic review evaluates the therapeutic potential of AdipoRon, focusing on its impact on diabetic cardiomyopathy and nephropathy. Through a comprehensive literature search and analysis, we highlight AdipoRon's role in ameliorating cardiovascular and renal complications in various animal models and cellular systems. The findings underscore the urgent need for translational clinical studies to validate AdipoRon's efficacy and safety in human populations, aiming to advance this promising therapeutic approach from experimental models to clinical application, potentially offering new hope for improved management of diabetic complications.

Coincident Thyrotoxic Hypokalemic Periodic Paralysis and Cardiomyopathy.

Thyrotoxic periodic paralysis (TPP) and thyrotoxic cardiomyopathy (TCMP) are potentially lethal complications of thyrotoxicosis that require emergent recognition and management to attenuate significant morbidity and mortality. We present the case of a 23-year-old Asian male with no prior medical history who developed TPP with coincident TCMP, which was successfully managed with antithyroid and heart failure therapies. The clinician should be aware of the diagnosis and treatment of these 2 life-threatening conditions in a hyperthyroid state.