Multinational experience with next-generation sequencing: opportunity to identify transthyretin cardiac amyloidosis and Fabry disease.

Background: Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes. Methods: In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems. Results: Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in MYH7 (n=60, 11.2%) and MYBPC3 (n=41, 7.7%) were the most common HCM variants. The HCM phenocopy variants included variants in the TTR (n=7, 1.3%) and GLA (n=2, 0.4%) genes. The mean (standard deviation) ages of patients with HCM or HCM phenocopy variants, including TTR and GLA variants, were 42.8 (17.9), 54.6 (17.0), and 69.0 (1.4) years, respectively. Conclusions: The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA (TTR variants) and FD (GLA variants), which are treatable disorders, in the differential diagnosis of patients with increased LVWT of unknown etiology.

Cardiovascular Complications in Patients with Heart Failure and COVID-19: CARDIO COVID 19-20 Registry.

Since early 2020, different studies have shown an increased prevalence of COVID-19 and poorer prognosis in older adults with cardiovascular comorbidities. This study aimed to assess the impact of heart failure (HF) on cardiovascular complications, intensive care unit (ICU) admissions, and in-hospital mortality in patients hospitalized with COVID-19. The CARDIO COVID 19-20 registry includes 3260 hospitalized patients with a COVID-19 serological diagnosis between May 2020 and June 2021 from Latin American countries. A history of HF was identified in 182 patients (5.6%). In patients with and without previous HF, the incidence of supraventricular arrhythmia was 16.5% vs. 6.3%, respectively (p = 0.001), and that of acute coronary syndrome was 7.1% vs. 2.7%, respectively (p = 0.001). Patients with a history of HF had higher rates of ICU admission (61.5% vs. 53.1%, respectively; p = 0.031) and in-hospital mortality (41.8% vs. 24.5%, respectively; p = 0.001) than patients without HF. Cardiovascular mortality at discharge (42.1% vs. 18.5%, respectively; p < 0.001) and at 30 days post-discharge (66.7% vs. 18.0%, respectively) was higher for patients with a history of HF than for patients without HF. In patients hospitalized with COVID-19, previous history of HF was associated with a more severe cardiovascular profile, with increased risk of cardiovascular complications, and poor in-hospital and 30-day outcomes.

American Registry of Ambulatory or acutely decompensated heart failure (AMERICCAASS Registry): First 1000 patients.

BACKGROUND: About 80% of cardiovascular diseases (including heart failure [HF]) occur in low-income and developing countries. However, most clinical trials are conducted in developed countries. HYPOTHESIS: The American Registry of Ambulatory or Acutely Decompensated Heart Failure (AMERICCAASS) aims to describe the sociodemographic characteristics of HF, comorbidities, clinical presentation, and pharmacological management of patients with ambulatory or acutely decompensated HF in America. METHODOLOGY: Descriptive, observational, prospective, and multicenter registry, which includes patients >18 years with HF in an outpatient or hospital setting. Collected information is stored in the REDCap electronic platform. Quantitative variables are defined according to the normality of the variable using the Shapiro-Wilk test. RESULTS: This analysis includes data from the first 1000 patients recruited. 63.5% were men, the median age of 66 years (interquartile range 56.7-75.4), and 77.6% of the patients were older than 55 years old. The percentage of use of the four pharmacological pillars at the time of recruitment was 70.7% for beta-blockers (BB), 77.4% for angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB II)/angiotensin receptor-neprilysin inhibitor (ARNI), 56.8% for mineralocorticoid receptor antagonists (MRA), and 30.7% for sodium-glucose cotransporter type-2 inhibitors (SGLT2i). The main cause of decompensation in hospitalized patients was HF progression (64.4%), and the predominant hemodynamic profile was wet-warm (68.3%). CONCLUSIONS: AMERICCAASS is the first continental registry to include hospitalized or outpatient patients with HF. Regarding optimal medical therapy, approximately a quarter of the patients still need to receive BB and ACEI/ARB/ARNI, less than half do not receive MRA, and more than two-thirds do not receive SGLT2i.

Cardiovascular Disease in Latin American Women Gaps and opportunities

Abstract Cardiovascular disease (CVD) remains the leading cause of death in women. This review will address the known disparities in cardiovascular care concerning diagnosing and treating of heart disease in Latin American (LA) women. Gender-specific differences regarding the incidence, treatment, and outcomes of common cardiovascular pathology are increasingly recognized. Today, we identify that women have cardiovascular risk factors (CRFs), specifying the traditional, emerging, unique, or sex-specific determinants and the social and biological determinants that play a leading role in the prevention of CVD. The purpose of this article is to review the literature on cardiovascular disease in LA women, focusing on ischemic heart disease (IHD), valve disease (VD), heart failure, and cardiac rehabilitation (CR), where disparities continue to affect outcomes. Understanding the unique cardiovascular risk profile and barriers to optimal treatment outcomes in women is imperative to eliminate the current disparities in CVD.

Fibrosis endomiocárdica / Endomyocardial fibrosis

Resumen Las miocardiopatías son trastornos intrínsecos del músculo cardíaco. Presentan fenotipos diferenciales que determinan su clasificación; estos son: dilatada, hipertrófica, restrictiva, displasia arritmogénica del ventrículo derecho y no clasificadas. Las miocardiopatías restrictivas se caracterizan por ventrículos de tamaño normal, con grosores de pared normales o ligeramente aumentados, paredes rígidas, disfunción diastólica severa y llenado restrictivo con presiones elevadas. Una de las formas más comunes de miocardiopatía restrictiva es la fibrosis endomiocárdica la cual es endémica en algunas zonas tropicales especialmente en África (países de bajos ingresos), pero en nuestro medio hay pocos reportes de aparición. Su etiología es desconocida, aunque existen diversos mecanismos que han sido involucrados en su fisiopatología. Su diagnóstico se basa en estudios imagenológicos (ecocardiograma transtorácico y resonancia magnética nuclear cardíaca). El pronóstico es muy pobre, y usualmente se diagnostica en etapas muy avanzadas de la enfermedad. Se describe el caso de una paciente femenina, adulta media, que debutó con cardiopatía restrictiva, cuyo diagnóstico final fue fibrosis endomiocárdica.

Abstract Cardiomyopathies are intrinsic conditions of the cardiac muscle. They present differential phenotypes that determine their classification. These are: dilated, hypertrophic, restrictive, arrhythmogenic right ventricular and unclassified. Restrictive cardiomyopathies are characterised by larger than normal ventricles with normal or slightly enlarged thickness of the walls, rigid walls, severe diastolic dysfunction and restrictive filling with high pressures. One of the most common restrictive cardiomyopathies is endomyocardial fibrosis, which is endemic to some tropical areas, especially Africa (low income countries), but there are few reports of its occurrence in our environment. Its aetiology is unknown, but there are several mechanisms that have been involved in its pathophysiology. Its diagnosis is based in imaging studies (transthoracic echocardiogram, cardiac nuclear magnetic resonance). Prognosis is very poor, and it is usually diagnoses in the latest stages of the disease. The case of a female, average adult patient that debuted with restrictive cardiomyopathy with a final diagnosis of endomyocardial fibrosis is described.

Miocarditis eosinofílica como causa de disfunción ventricular izquierda reversible / Eosinophilic myocarditis as a cause of reversible left ventricular dysfunction

Resumen La miocarditis eosinofílica es una entidad poco difundida ya que su diagnóstico histopatológico se realiza en casos de mayor severidad, donde la biopsia endomiocárdica es mandatoria. No obstante, dado que esta entidad suele superponerse a muchas patologías: las infecciosas, las inmunológicas, o asociadas a la hipersensibilidad y esto se asocia con la reversibilidad, es importante tenerla presente como entidad nosológica en cuadros agudos de la disfunción ventricular izquierda. Puede o no estar asociada a la eosinofilia periférica, su ausencia no descarta la enfermedad. Se presenta un paciente joven (35 años de edad), con un cuadro clínico de la falla cardiaca aguda que progresa rápidamente a choque cardiogénico con poca respuesta al manejo inicial instaurado (inodilatadores, vasopresores), requiriendo el uso de soporte circulatorio extracorpóreo. Como antecedente: la reciente finalización del tratamiento para leishmaniasis mucocutánea, con antimoniato de meglumina (glucantime). Informe del servicio de patología: miocarditis eosinofílica. Se logra el destete del soporte circulatorio, presenta mejoría de la función sistólica del ventrículo izquierdo con recuperación total del cuadro clínico. Este caso es relevante en cuanto a diagnóstico de disfunción ventricular aguda, con una asociación previamente no descrita con antimoniato de meglumina (glucantime), nos recuerda la importancia de realizar: la biopsia endomiocárdica para definir la etiología, la toma de decisiones de terapias avanzadas, conociendo que en ciertas circunstancias puede presentarse reversibilidad de la disfunción miocárdica y mejoría del cuadro clínico.

Abstract Eosinophilic myocarditis is a little-known entity as its histopathological diagnosis is conducted in the most severe cases, where an endomyocardial biopsy is mandatory. However, because this condition is usually overlaps with many pathologies -infectious, immunological, or associated to hypersensitivity, and this is related to reversibility- it is important to keep it in mind as a nosological entity in acute presentations of left ventricular dysfunction. It may or may not be associated to peripheral eosinophilia, though its absence does not rule out the condition. A case of a young male patient (35 year-old) with clinical features of acute cardiac failure which progresses rapidly into cardiogenic shock with low response to initial management (inodilators, vasopressors) requiring the use of extracorporeal circulation support is presented. Previous history: recent completion of treatment for ucocutaneous leishmaniases with meglumine antimoniate (glucantime). Pathology service report: eosinophilic yocarditis. Weaning from circulatory support is achieved, presenting an improvement of systolic function of the left ventricle with complete recovery of the symptomatology. This case is relevant due to the diagnosis of acute ventricular dysfunction with an association with meglumine antimoniate (glucantime) that was previously not described. It reminds of the importance of carrying out an endomyocardial biopsy in order to define the aetiology and the decision-making on advances therapies, knowing that in some circumstances there can be a reversibility of the myocardial function and an improvement of the symptomatology.