Management of Long QT Syndrome: A Systematic Review.

Long QT syndrome (LQTS) is a cardiac disorder characterized by prolonged repolarization of the heart's electrical cycle, which can be observed as an extended QT interval on an electrocardiogram (ECG). The safe and effective management of LQTS often necessitates a multifaceted approach encompassing pharmacological treatment, lifestyle modifications, and, in high-risk cases, the implantation of implantable cardioverter-defibrillators (ICDs). Beta-blockers, particularly nadolol and propranolol, are foundational in treating LQTS, especially for high-risk patients, though ICDs are recommended for those with a history of cardiac arrest or recurrent arrhythmic episodes. Intermediate and low-risk patients are usually managed with medical therapy and regular monitoring. Lifestyle modifications, such as avoiding strenuous physical activities and certain medications, play a critical role. Additionally, psychological support is essential due to the anxiety and depression associated with LQTS. Left cardiac sympathetic denervation (LCSD) offers an alternative for those intolerant to beta-blockers or ICDs. For diagnosis and management, advancements in artificial intelligence (AI) are proving beneficial, enhancing early detection and risk stratification. Despite these developments, significant gaps in understanding the pathophysiology and optimal management strategies for LQTS remain. Future research should focus on refining risk stratification, developing new therapeutic approaches, and generating robust data to guide treatment decisions, ultimately aiming for a personalized medicine approach.

Pericardial Diseases Mortality Trends in Brazil From 2000 to 2022.

Background Pericardial diseases manifest in various clinical forms, including acute pericarditis, constrictive pericarditis, pericardial effusion, and cardiac tamponade, with acute pericarditis being the most prevalent. These conditions significantly contribute to mortality rates. Therefore, this article aimed to analyze mortality trends in the Brazilian population based on age and sex, shedding light on the impact of pericardial diseases on public health outcomes. Methods  This is a retrospective time-series analysis of pericardial disease mortality rates in Brazil (2000-2022). Data was obtained from the Department of Informatics of the Unified Health System (DATASUS), and the 10th edition of the International Classification of Diseases (ICD-10) codes: I30, I31, and I32 were included for analysis. We gathered population and demographic data categorized by age range and sex from the Brazilian Institute of Geography and Statistics (IBGE). Subsequently, we computed the age-standardized mortality rate per 100,000 individuals and assessed the annual percentage changes (APCs) and average annual percentage changes (AAPCs) using joinpoint regression, along with their corresponding 95% confidence intervals (CIs). Results  In terms of mortality trends based on sex, overall mortality rates remained stable for males and combined sexes over the study period. However, there was a notable increase in mortality rates among females (AAPC=1.18), particularly between 2020 and 2022, with a significant APC of 27.55. Analyzing pericardial diseases across different age groups (20 to 80 years and above), it wasobserved that mortality rates significantly increased in the 70-79 and 80 years and above age groups throughout the study period (AAPC=1.0339 and AAPC=3.4587, respectively). These two age groups experienced the highest significant rise in mortality between 2020 and 2022. Other age groups did not exhibit a significant change in AAPC. Conclusions  This comprehensive analysis spanning two decades (2000-2022), examined the mortality trends of pericardial diseases in Brazil and revealed relative stability overall. Males exhibited an overall higher mortality number due to pericardial diseases; however, females showed the most significant increase in mortality trend throughout the whole period. In the first segment (2000-2015), mortality rose across all cohorts, which was attributed to substandard healthcare facilities and infectious diseases like tuberculosis. The second segment (2016-2020) saw a decline in mortality, likely due to improved healthcare, particularly the increased availability of echocardiograms. However, the third segment (2020-2022) witnessed a sharp rise in mortality, coinciding with the COVID-19 pandemic, with post-COVID-19 symptoms, particularly pericarditis. Pericarditis-related death rates declined compared to pericardial effusion, and mortality rates correlated directly with age, with older cohorts experiencing higher mortality due to increased comorbidities, and decline in health and immunocompetency.

Cerebrovascular Disease Mortality Trends in Brazil: An In-Depth Joinpoint Analysis.

Background Cerebrovascular disease is the second leading cause of death and the third leading cause of disability following heart disease. In 2019, there were over 101 million people living with a stroke and 12.2 million incidents of stroke globally. For the past three decades, stroke has remained the leading cause of death in Brazil, causing over 100,000 fatalities annually, along with numerous functional impairments among those who survive. The Brazilian healthcare system has witnessed notable advancements in the last decade, including the establishment of additional hospitals and a rise in the count of healthcare professionals specializing in cardiovascular and neurological surgery. However, there exists a gap in the research landscape for continuous comprehensive studies aimed at exploring the evolving mortality rates related to cerebrovascular diseases, of which the last one included data up to 2019. This study aimed to address this gap by meticulously analyzing the trends in cerebrovascular disease mortality in Brazil from 2000 to 2021, for the variables age, sex, state of residence, and geographic region. Methods This is a descriptive, ecological, and time series study. Nationwide data for annual cerebrovascular mortality from Brazil were used for the period 2000-2021. Age-adjusted mortality rates (AAMRs) by direct standardization, encompassing people above 20 years of age, were calculated and expressed per 100,000 persons. Mortality trends were assessed using joinpoint regression analysis by calculating the annual percentage change (APC) and its corresponding 95% confidence interval (CI) across categories of age, sex, and state and region of residence. Results The mortality rates decreased for the sex categories over the analyzed years. The AAMR for the categories decreased as follows: males and females (95 deaths/100,000 to 52 deaths/100,000 inhabitants), males (108 deaths/100,000 to 63 deaths/100,000 inhabitants), and females (83 deaths/100,000 to 44 deaths/100,000 inhabitants). The most substantial reduction in AAMR for males occurred in the 30-39-year age group (APC: -4.10), while the smallest decline was observed in the 20-29-year age group (APC: -1.44). All five macro-regions demonstrated statistically significant and downward AAPC values in mortality rates. The south and midwest regions decreased at a stable rate, as denoted by the same APC and AAPC values (-4.05 and -3.11, respectively). The north and northeast regions exhibited an increase in AAMR, followed by a decrease (APC: 0.68 to -1.42 and 2.63 to -2.35, respectively). Conclusions Our comprehensive analysis revealed a downward trend in cerebrovascular disease mortality rates across diverse demographic groups and macro-regions. Females experienced a more substantial reduction compared to males. Despite higher mortality rates among individuals aged 50 and above, all age groups displayed a marked decrease. The continuous decline can be attributed to policy interventions aimed at enhancing healthcare delivery, increased awareness, and healthier diets and lifestyles. With regard to the macro-regions, the regions in the southern zone demonstrated a more significant decrease as compared to the northern part. In Brazil, a more significant decline in cerebrovascular disease mortality rates could be achieved through increased focus on prevention measures and efforts toward mitigating disparities and inequalities between macro-regions.

Effectiveness of sacubitril-valsartan in patients with cancer therapy-related cardiac dysfunction: a systematic review of clinical and preclinical studies.

INTRODUCTION: Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. However, there are very limited data on the efficacy of sacubitril/valsartan in the prevention and treatment of cardiotoxicity. This systematic review aimed to evaluate the potential benefit of sacubitril/valsartan in patients with CTRCD. EVIDENCE ACQUISITION: The databases included MEDLINE, Embase, LILACS, Scopus and Cochrane Central up to January 20, 2022. All pre-clinical and clinical studies including observational studies (cohorts, case-control, cross-sectional and case reports) that used sacubitril/valsartan for prevention or treatment of CTRCD. The primary effectiveness endpoints was CTRCD, defined as a clinically significant change in left ventricular ejection fraction (LVEF) at the end of the follow-up. EVIDENCE SYNTHESIS: And after applying the eligibility criteria, 12 articles (9 in humans and 3 preclinical studies) were included in this systematic review. The 3 preclinical studies demonstrated beneficial effects in preventing, attenuating and/or delaying the onset of myocardial damage at the cellular level, ventricular dysfunction and remodeling. Regardind human studies, most of them were composed of case reports. The largest study consisted of a retrospective multicentric cohort with 64 patients. CONCLUSIONS: All clinical studies have demonstrated that used Sac/Val in human showed a significant increase in LVEF, and when reported, a reduction in left ventricular volume and NT-proBNP (or BNP). Randomized clinical trials are needed to confirm this hypothesis.

Characterization of dyspnea in chronic diseases and heart failure in patients in a Family Health Program / Caracterización de la disnea en pacientes con enfermedades crónicas e insuficiencia cardíaca de un Programa de Salud Familiar

Abstract Background: Dyspnea is the most common symptom in heart failure. In the elderly, it is common in chronic obstructive pulmonary disease and depression. Objective: To estimate the prevalence of dyspnea on exertion, orthopnea and paroxysmal nocturnal dyspnea and its association with chronic diseases in primary care. Methods: A cross-sectional study, part of the Digitalis Study, including 633 individuals, between 45 to 99 years old, registered in a primary care program in Niteroi, Brazil. All participants underwent clinical evaluations, blood and urine collection, and responded to a questionnaire in a single day. Self-reports were used for the diagnosis of diseases. Results: Of the 633 individuals, 30% had dyspnea. In the crude analysis, chronic obstructive pulmonary disease showed the strongest associations with the three types of dyspnea, followed by depression and heart failure. Chronic obstructive pulmonary disease alone did not present any cases of paroxysmal nocturnal dyspnea, and heart failure alone showed a very strong relationship with this type of dyspnea. Conclusions: The different behavior of the associations of the types of dyspnea with major chronic diseases in patients in primary care can help in the better characterization of patients with heart failure.

Resumen Introducción: La disnea es el síntoma más común en la insuficiencia cardíaca. En los ancianos es común en la enfermedad pulmonar obstructiva crónica y la depresión. Objetivo: Estimar la prevalencia de disnea de esfuerzo, ortopnea y disnea paroxística nocturna y su asociación con enfermedades crónicas en la atención primaria. Métodos: Estudio transversal, parte del estudio Digitalis, que incluyó a 633 individuos, entre 45 y 99 años de edad, registrados en un programa de atención primaria en Niterói, Brasil. Todos los participantes se sometieron a evaluaciones clínicas, recolección de sangre y orina, y respondieron a un cuestionario en un solo día. Se usaron autorrelatos para el diagnóstico de las enfermedades. Resultados: De los 633 individuos, el 30% presentó disnea. En el análisis crudo la enfermedad pulmonar obstructiva crónica mostró las asociaciones más fuertes con los tres tipos de disnea, seguidos por la depresión y la insuficiencia cardíaca. La enfermedad pulmonar obstructiva crónica, evaluada de forma aislada, no presentó ningún caso de disnea paroxística nocturna, y la insuficiencia cardíaca por sí sola mostró una relación muy fuerte con este tipo de disnea. Conclusiones: El comportamiento diferente de las asociaciones de los tipos de disnea con las principales enfermedades crónicas en pacientes en atención primaria puede ayudar a una mejor caracterización de los pacientes con insuficiencia cardíaca.

Comparison of adipokines in a cross-sectional study with healthy overweight, insulin-sensitive and healthy lean, insulin-resistant subjects, assisted by a family doctor primary care program.

BACKGROUND: In most individuals, obesity and insulin resistance coexist. However, some individuals have excessive adipose tissue mass but remain insulin sensitive. Moreover, lean individuals can develop acute inflammation-induced insulin resistance, even without excess adipose tissue mass. OBJECTIVE: Our aim was to compare inflammatory markers in overweight, insulin-sensitive and lean, insulin-resistant healthy subjects. METHODS: A cross-sectional study with 1098 participants (CAMELIA project) was conducted in family doctor primary care program at Niteroi, RJ, Brazil. In the present substudy, we have selected non-obese healthy subjects (n = 203). Insulin resistance was defined by a homeostatic model assessment (HOMA-IR) >2.6, and overweight subject BMIs were 25< BMI <30 kg/m2. Associations were estimated through binary logistic regression with generalized estimation equation models. RESULTS: We compared overweight, insulin-sensitive healthy individuals (n = 74) with a mean age of 39.2 ± 1.3 and lean, insulin-resistant healthy individuals (n = 18) with a mean age of 31.9 ± 3.6. C-reactive protein levels were positively correlated with body mass index in the lean, insulin-resistant group. In the multiple regression model, a positive association was observed with MCP-1 and IL-6 expression after adjustment for age, waist circumference, glycated hemoglobin, resistin, adiponectin, C-reactive protein and PAI-1 levels. CONCLUSION: Our findings suggest that a lean, insulin-resistant subject may have higher pro-inflammatory marker levels (MCP-1, IL-6 and resistin) than an overweight, insulin-sensitive subject. This suggest an early risk phenotype that should further be investigated for possible prognostic implications.

The Prevalence of Stages of Heart Failure in Primary Care: A Population-Based Study.

BACKGROUND: Planning strategies to prevent heart failure (HF) in developing countries require epidemiologic data in primary care. The purpose of this study was to estimate the prevalence of HF stages and their phenotypes, HF with preserved ejection fraction (HFPEF), and HF with reduced EF (HFREF) and to determine B-type natriuretic peptide (BNP) levels to identify HF in the adult population. METHODS AND RESULTS: This is a cross-sectional study including 633 individuals, aged ≥45 years, who were randomly selected and registered in a primary care program of a medium-sized city in Brazil. All participants were underwent clinical evaluations, BNP measurements, electrocardiograms, and tissue Doppler echocardiography in a single day. The participants were classified as stage 0 (healthy, 11.7%), stage A (risk factors, 36.6%), stage B (structural abnormalities, 42.7%), or stage C (symptomatic HF, 9.3%). Among patients with HF, 59% presented with HFPEF and 41% presented with HFREF. The mean BNP levels were 20 pg/mL(-1) in stage 0, 20 pg/mL(-1) in stage A, 24 pg/mL(-1) in stage B, 93 pg/mL(-1) in HFPEF, and 266 pg/mL(-1) in HFREF. The cutoff BNP level with optimal sensitivity (92%) and specificity (91%) to identify HF was 42 pg/mL(-1). CONCLUSION: The present study demonstrated a high prevalence of individuals at risk for HF and the predominance of HFPEF in a primary care setting. The clinical examination, along with BNP and tissue Doppler echocardiography, may facilitate early detection of stages A and B HF and allow implementation of interventions aimed at preventing progression to symptomatic HF.

Low quality of life as an additional criterion for the clinical diagnosis of heart failure in primary care.

OBJECTIVE: The aim of this study is to estimate the association of shortness of breath (SOB), fatigue and bilateral lower limb edema (LLE) - typical symptoms of HF - with quality of life (QOL) dimensions, measured by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). METHODS: This cross-sectional study was conducted as part of the CAMELIA study (Cardiometabolic Renal Familial Study), which involved families covered by the Family Doctor Program (FDP) in Niteroi, Rio de Janeiro, Brazil. The study included 455 patients aged 30 and over, assessed by questionnaire, medical consultation, and blood and urine tests. RESULTS: The prevalence of symptoms was: fatigue 56.9%, SOB 22.6% and LLE 16.9%. There were independent and statistically significant associations between SOB and fatigue and all SF-36 dimensions, excepting emotional performance and SOB (p<0.10). CONCLUSION: The combination of SOB and fatigue with low QOL can increase the positive predictive value for a clinical diagnosis of HF and is a possible alternative for prioritizing patients for closer investigation in a primary care setting.

Prehypertension and cardiovascular risk factors in adults enrolled in a primary care programme.

BACKGROUND: An increase in cardiovascular (CV) disease has been observed in prehypertensive subjects who frequently carry other cardiovascular risk factors. In Brazil, little is known about prehypertension and its association with cardiovascular risk factors. OBJECTIVE: To estimate the association between prehypertension and cardiovascular risk factors in a public primary healthcare programme. METHODS: Associations in this cross-sectional study were estimated on the basis of generalized estimating equations. Results are expressed as odds ratio (OR) or adjusted odds ratio (OR(a)) with 95% confidence interval (CI). RESULTS: The 357 participants were classified as normotensive (64.4%) or prehypertensive (35.6%). In a univariate analysis, prehypertension was statistically associated with male gender, age, table salt use, diabetes, body mass index (BMI), uric acid, and all lipids except high-density lipoprotein cholesterol. When analysis was performed adjusting for gender, age, and table salt use, the association of each metabolic parameter with prehypertension, remained significant for BMI (OR(a) = 1.097; 95% CI 1.035-1.162), triglycerides (OR(a) = 1.008; 95% CI 1.003-1.013), and uric acid (OR(a) = 1.269; 95% CI 1.023- .576). To check for their independence of obesity, associations of triglycerides and uric acid with prehypertension were reanalysed after adjustment for BMI. The association of triglycerides remained statistically significant. A trend of association was present for uric acid. The prevalence of prehypertension paralleled the increase of the number of risk factors. CONCLUSION: Prehypertension in Brazil is associated with well-recognized cardiovascular risk factors even in a continuously monitored population such the one under study. Prehypertension can be a valuable clue to alert health professionals to treat underlying perturbations to prevent overt cardiovascular disease.

Noninvasive ventilation with continuous positive airway pressure acutely improves 6-minute walk distance in chronic heart failure.

BACKGROUND: Noninvasive ventilation with continuous positive airway pressure (CPAP) has been used in patients with chronic heart failure (CHF), although its effect on exercise tolerance in these patients is unknown. The aim of this study was to determine the effects of CPAP on exercise tolerance in outpatients with CHF. METHODS: Following a double-blind, randomized, crossover, and placebo-controlled protocol, 12 patients with CHF (8 male; 4 female; age 54 +/- 12 years; body mass index 27.3 +/- 1.8 kg/m2, New York Heart Association Class II, III) underwent CPAP via nasal mask for 30 minutes in a recumbent position. Mask pressure was 3 cm H2O for 10 minutes, followed by individual progression up to 4 to 6 cm H2O, whereas placebo was fixed 0 to 1 cm H2O. A 6-minute walk test was performed after placebo and CPAP. RESULTS: Continuous positive airway pressure decreased the resting heart rate (pre: 80 +/- 17 bpm; post: 71 +/- 15 bpm; P = .001) and mean arterial pressure (pre: 103 +/- 14 mm Hg; post: 97 +/- 13 mm Hg; P = .008). During exercise test, CPAP increased the distance covered (CPAP: 538 +/- 78 m; placebo: 479 +/- 83 m; P < .001) and the peak heart rate (CPAP: 98 +/- 17; placebo: 89 +/- 12 bpm; P = .049) but did not change the peak mean arterial pressure (P = .161). CONCLUSION: Noninvasive ventilation with CPAP increased exercise tolerance in patients with stable CHF. Future clinical trials should investigate whether this effect is associated with improved clinical outcome.

Cholinergic stimulation with pyridostigmine prevents the impairment in ventricular function during mental stress in coronary artery disease patients.

Mental stress causes physiological autonomic adjustments that may trigger myocardial ischemia and ventricular dysfunction in patients with coronary artery disease. Thus, it was hypothetized that cholinergic stimulation may counteract the ventricular dysfunction provoked by mental stress in coronary disease. Six patients with coronary disease underwent a randomized, double-blind, cross-over, and placebo-controlled protocol in which they received placebo or a single dose of pyridostigmine bromide (45 mg p.o.), a reversible cholinesterase inhibitor, and thus, a cholinomimetic agent 2 h before a standard mental stress task (Stroop color-word test), while hemodynamic and echocardiographic variables were continuously monitored. There were no signs of myocardial ischemia on ECG during mental stress under PYR or placebo. Heart rate and blood pressure increased during mental stress (P<0.01) similarly with placebo and PYR (P>0.05). There were no ventricular wall motion abnormalities during mental stress with either placebo or PYR, but mental stress decreased ejection fraction (pre 63+/-2%, stress 57+/-2%; P=0.004) and impaired the indices of diastolic ventricular function. On the other hand, PYR prevented the fall in ejection fraction (pre 62+/-2%, stress 64+/-2%; P=0.13) and in the indices of diastolic function (P>0.05). In conclusion, cholinergic stimulation with pyridostigmine prevented the impairment in myocardial function during mental stress in patients with coronary artery disease.

Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure.

BACKGROUND: This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility. METHODS AND RESULTS: Twenty-one patients were enrolled in this prospective, nonrandomized, open-label study (first 14 patients, treatment; last 7 patients, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring. Bone marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cc). Electromechanical mapping was used to identify viable myocardium (unipolar voltage > or =6.9 mV) for treatment. Treated and control patients underwent 2-month noninvasive follow-up, and treated patients alone underwent a 4-month invasive follow-up according to standard protocols and with the same procedures used as at baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up, being relatively higher in control patients. At 2 months, there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups (P=0.02) on quantitative single-photon emission computed tomography analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% (P=0.003) and a reduction in end-systolic volume (P=0.03) in the treated patients. Electromechanical mapping revealed significant mechanical improvement of the injected segments (P<0.0005) at 4 months after treatment. CONCLUSIONS: Thus, the present study demonstrates the relative safety of intramyocardial injections of bone marrow-derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function.

Taquicardia ventricular polimórfica: análise do início dos surtos / Polymorphous ventricular tachycardia. Analysis of the onset of the episodes

Objetivo - Analisar o início de surtos de taquicardias ventriculares polimórficas, com a finalidade de determinar a importância deste parâmetro no contexto clínico-eletrofisiológico. Métodos - Foram analisados um total de 124 inícios de episódios, em gravaçöes de Holter, em 6 pacientes. Quatro faziam uso de quinidina e diuréticos e 2 somente diuréticos. Determinaram-se os valores em ms, dos dois ciclos imediatamente precedentes ao início dos surtos e dos ciclos indutores (ciclos A, B e C). Analisaram-se as características da repolarizaçäo ventricular e os intervalos QT ou QTU desses ciclos, bem como os valores de QT fora dos episódios. Resultados - Em 105 ocasiöes (84%), os inícios de surtos foram pausas-dependentes; em 12 ocasiöes (10%) ocorreram sem pausas e a partir de uma fusäo ventricular e em 7 momentos (6%) sem pausas e a partir de um encurtamento súbito dos ciclos C (fenômeno R + T). Os surtos pausas-dependentes somente foram observados nos pacientes em uso de sulfato de quindina e diuréticos e os näo dependentes de pausas nos pacientes em uso somente de duréticos. Todos apresentavam intervalos QTU prolongados fora dos surtos, havendo uma relaçäo linear entre a amplitude das ondas U dos ciclos C e a duraçäo dos ciclos A e B. Conclusäo - Frente aos resultados, os seguintes aspectos foram acentuados, a partir da análise do início de surtos de taquicardias ventriculares polimórficas; pode-se diferenciar formas típicas de torsades de pointers (pausa-dependente) e atípicas. As primeiras ocorrem provavelmente em funçäo da presença de atividade de disparo (pós-potenciais precoces). As formas atípicas melhor se enquadrariam a presença de mecanismos reentrantes ou hiperautomáticos. Somente nas formas típicas, haveria benefício no uso de MP artificial provisório para tratamento, pela regularizaçäo dos ciclos cardíacos que este procedimento produz