Exercise does not influence development of phenotype in PLN p.(Arg14del) cardiomyopathy.

BACKGROUND: Endurance and frequent exercise are associated with earlier onset of arrhythmogenic right ventricular cardiomyopathy (ARVC) and ventricular arrhythmias (VA) in desmosomal gene variant carriers. Individuals with the pathogenic c.40_42del; p.(Arg14del) variant in the PLN gene are frequently diagnosed with ARVC or dilated cardiomyopathy (DCM). The aim of this study was to evaluate the effect of exercise in PLN p.(Arg14del) carriers. METHODS: In total, 207 adult PLN p.(Arg14del) carriers (39.1% male; mean age 53 ± 15 years) were interviewed on their regular physical activity since the age of 10 years. The association of exercise with diagnosis of ARVC, DCM, sustained VA and hospitalisation for heart failure (HF) was studied. RESULTS: Individuals participated in regular physical activities with a median of 1661 metabolic equivalent of task (MET) hours per year (31.9 MET-hours per week) until clinical presentation. The 50% most and least active individuals had a similar frequency of sustained VA (18.3% vs 18.4%; p = 0.974) and hospitalisation for HF (9.6% vs 8.7%; p = 0.827). There was no relationship between exercise and survival free from (incident) sustained VA (p = 0.65), hospitalisation for HF (p = 0.81), diagnosis of ARVC (p = 0.67) or DCM (p = 0.39) during follow-up. In multivariate analyses, exercise was not associated with sustained VA or HF hospitalisation during follow-up in this relatively not-active cohort. CONCLUSION: There was no association between the amount of exercise and the susceptibility to develop ARVC, DCM, VA or HF in PLN p.(Arg14del) carriers. This suggested unaffected PLN p.(Arg14del) carriers can safely perform mild-moderate exercise, in contrast to desmosomal variant carriers and ARVC patients.

Cardiomyopathy Induced by Artificial Cardiac Pacing: To Whom, When, Why, and How? Insights on Heart Failure Development.

Coordinated and harmonic (synchronous) ventricular electrical activation is essential for better left ventricular systolic function. Intraventricular conduction abnormalities, such as left bundle branch block due to artificial cardiac pacing, lead to electromechanical "dyssynchronopathy" with deleterious structural and clinical consequences. The aim of this review was to describe and improve the understanding of all the processes connecting the several mechanisms involved in the development of artificially induced ventricular dyssynchrony by cardiac pacing, most known as pacing-induced cardiomyopathy (PiCM). The chronic effect of abnormal impulse conduction and nonphysiological ectopic activation by artificial cardiac pacing is suspected to affect metabolism and myocardial perfusion, triggering regional differences in the activation/contraction processes that cause electrical and structural remodeling due to damage, inflammation, and fibrosis of the cardiac tissue. The effect of artificial cardiac pacing on ventricular function and structure can be multifactorial, and biological factors underlying PiCM could affect the time and probability of developing the condition. PiCM has not been included in the traditional classification of cardiomyopathies, which can hinder detection. This article reviews the available evidence for pacing-induced cardiovascular disease, the current understanding of its pathophysiology, and reinforces the adverse effects of right ventricular pacing, especially right ventricular pacing burden (commonly measured in percentage) and its repercussion on ventricular contraction (reflected by the impact on left ventricular systolic function). These effects might be the main defining criteria and determining mechanisms of the pathophysiology and the clinical repercussion seen on patients.

Cardiomyopathy Induced by Artificial Cardiac Pacing: To Whom, When, Why, and How? Insights on Heart Failure Development

ABSTRACT Coordinated and harmonic (synchronous) ventricular electrical activation is essential for better left ventricular systolic function. Intraventricular conduction abnormalities, such as left bundle branch block due to artificial cardiac pacing, lead to electromechanical "dyssynchronopathy" with deleterious structural and clinical consequences. The aim of this review was to describe and improve the understanding of all the processes connecting the several mechanisms involved in the development of artificially induced ventricular dyssynchrony by cardiac pacing, most known as pacing-induced cardiomyopathy (PiCM). The chronic effect of abnormal impulse conduction and nonphysiological ectopic activation by artificial cardiac pacing is suspected to affect metabolism and myocardial perfusion, triggering regional differences in the activation/contraction processes that cause electrical and structural remodeling due to damage, inflammation, and fibrosis of the cardiac tissue. The effect of artificial cardiac pacing on ventricular function and structure can be multifactorial, and biological factors underlying PiCM could affect the time and probability of developing the condition. PiCM has not been included in the traditional classification of cardiomyopathies, which can hinder detection. This article reviews the available evidence for pacing-induced cardiovascular disease, the current understanding of its pathophysiology, and reinforces the adverse effects of right ventricular pacing, especially right ventricular pacing burden (commonly measured in percentage) and its repercussion on ventricular contraction (reflected by the impact on left ventricular systolic function). These effects might be the main defining criteria and determining mechanisms of the pathophysiology and the clinical repercussion seen on patients.

Pharmacogenomics and Cardiovascular Disease: Where are We and Where do We go from Here? / Farmacogenômica e Doença Cardiovascular: Onde Estamos e Para Onde Vamos.

A farmacogenômica (FGx) investiga a interação entre genes e medicamentos. Através da análise de regiões específicas do DNA, informações sobre o perfil de metabolização do paciente para um determinado fármaco podem ser descritas, assim como o perfil esperado de resposta ao tratamento. Objetivamente, esse tipo de teste pode ter impacto no tratamento de pacientes que não estão respondendo adequadamente a um determinado medicamento, seja pela ausência dos efeitos esperados ou em virtude do aparecimento de efeitos adversos. Neste cenário, o objetivo desta revisão é o de informar o cardiologista clínico sobre esta importante área do conhecimento e atualizá-lo sobre o tema, procurando preencher as lacunas no que diz respeito à relação custo-benefício da aplicação da FGx nas doenças cardiovasculares, além de fornecer informações para a implementação da terapia guiada pela FGx na prática clínica.

Farmacogenômica e Doença Cardiovascular: Onde Estamos e Para Onde Vamos / Pharmacogenomics and Cardiovascular Disease: Where are We and Where do We go from Here?

Resumo A farmacogenômica (FGx) investiga a interação entre genes e medicamentos. Através da análise de regiões específicas do DNA, informações sobre o perfil de metabolização do paciente para um determinado fármaco podem ser descritas, assim como o perfil esperado de resposta ao tratamento. Objetivamente, esse tipo de teste pode ter impacto no tratamento de pacientes que não estão respondendo adequadamente a um determinado medicamento, seja pela ausência dos efeitos esperados ou em virtude do aparecimento de efeitos adversos. Neste cenário, o objetivo desta revisão é o de informar o cardiologista clínico sobre esta importante área do conhecimento e atualizá-lo sobre o tema, procurando preencher as lacunas no que diz respeito à relação custo-benefício da aplicação da FGx nas doenças cardiovasculares, além de fornecer informações para a implementação da terapia guiada pela FGx na prática clínica.

Torpor-arousal cycles in Syrian hamster heart are associated with transient activation of the protein quality control system.

Hibernation consists of torpor, with marked suppression of metabolism and physiological functions, alternated with arousal periods featuring their full restoration. The heart is particularly challenged, exemplified by its rate reduction from 400 to 5-10 beats per minute during torpor in Syrian hamsters. In addition, during arousals, the heart needs to accommodate the very rapid return to normal function, which lead to our hypothesis that cardiac function during hibernation is supported by maintenance of protein homeostasis through adaptations in the protein quality control (PQC) system. Hereto, we examined autophagy, the endoplasmic reticulum (ER) unfolded protein (UPRER) response and the heat shock response (HSR) in Syrian hamster hearts during torpor and arousal. Transition from torpor to arousal (1.5 h) was associated with stimulation of the PQC system during early arousal, demonstrated by induction of autophagosomes, as shown by an increase in LC3B-II protein abundance, likely related to the activation of the UPRER during late torpor in response to proteotoxic stress. The HSR was not activated during torpor or arousal. Our results demonstrate activation of the cardiac PQC system - particularly autophagosomal degradation - in early arousal in response to cardiac stress, to clear excess aberrant or damaged proteins, being gradually formed during the torpor bout and/or the rapid increase in heart rate during the transition from torpor to arousal. This mechanism may enable the large gain in cardiac function during the transition from torpor to arousal, which may hold promise to further understand 'hibernation' of cardiomyocytes in human heart disease.

Abordagem inicial da taquicardia na emergência / Tachycardia first approach in the emergency room

A taquicardia, comumente causadora de sintomas que levam o paciente a buscar setores de emergência, necessita de avaliação e manejo adequados por qualquer profissional de medicina pelo seu potencial risco iminente à vida.

Tachycardia, a common cause of symptoms that encourage patients to search for emergency sectors, needs to be properly evaluated and managed by any physician considering its imminent life threat potential.

Atualização do tratamento da hipertensão arterial sistêmica em adultos / Updating the treatment of high blood pressure

A Hipertensão Arterial Sistêmica é uma das situações mais frequentes na prática clínica, sendo obrigatório para o médico o conhecimento a respeito da sua apresentação e tratamento, independente da especialidade. Este artigo irá revisar as últimas diretrizes de tratamento Hipertensão Arterial Sistêmica em adultos (18 anos ou mais).

High Blood pressure is one of the most frequently situations in the clinical practice, so that it is mandatory to the physician having the knowledge about the presentation and treatment of this pathology irrespective of the medical specialization. This article will review the latest guidelines about the treatment of High Blood Pressure in adults.