Genetics – ABC CARDIOL

ABC

Editorial

The Thickness That Deceives: The Role of Imaging, Biopsy, and Genetics in the Evaluation of Ventricular Hypertrophy

Murillo de Oliveira Antunes

Increased ventricular wall thickness is a common finding in cardiovascular practice and is frequently attributed either to secondary myocardial hypertrophy or to sarcomeric hypertrophic cardiomyopathy (HCM). However, this phenotype may conceal a broad spectrum of genetic, infiltrative, and storage diseases, each associated with distinct prognostic implications and therapeutic strategies. Accurate differentiation between true myocardial hypertrophy and HCM phenocopies—or genocopies—remains a major diagnostic challenge and requires a multimodality approach integrating advanced cardiac imaging, endomyocardial biopsy (EMB), and genetic testing.^–

Cardiac imaging has evolved beyond morphological assessment. Cardiac magnetic resonance (CMR) with tissue characterization has become a cornerstone of noninvasive evaluation in patients with increased myocardial thickness. Parametric mapping techniques, including T1 and T2 mapping and extracellular volume (ECV) quantification, allow the detection of myocardial compositional changes such as edema, fibrosis, and infiltration, providing important diagnostic clues for conditions such as cardiac amyloidosis, Fabry disease, and glycogen storage cardiomyopathies (e.g., PRKAG2-related disease).^– In addition, specific late gadolinium enhancement patterns may further support the suspicion of non-sarcomeric etiologies.^,

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ABC

Case Report

Systemic Sclerosis Associated Pulmonary Arterial Hypertension with Venous Involvement – a Novel ABCC8 Pathogenic Variant

Daniel Inácio Cazeiro et al. João Cravo Mariana Pereira Silva João R. Inácio … Oana Moldovan Catarina Sousa Catarina Lopes Resende João Eurico Fonseca Fausto J. Pinto Rui Plácido

Discussion

PAH with venous/capillary involvement (formerly referred to as pulmonary veno-occlusive disease [PVOD] /capillary hemangiomatosis) is a rare, severe form of PH, with an incidence of 0.1-0.5 cases/million/year. This condition comprises a fibroproliferative process of pulmonary venous and capillary compartments, with small vein occlusion caused by smooth muscle hypertrophy and collagen deposition.

The diagnosis of PVOD is challenging due to its non-specific presentation, often mimicking PAH. Moreover, histological confirmation via lung biopsy is contraindicated due to the significant risk of hemorrhage. Certain clinical and imaging features can facilitate a presumptive diagnosis, which include typical findings on CCTA – centrilobular ground-glass opacities, septal lines, and mediastinal lymphadenopathy, severely reduced DLCO on PFTs, and low oxygen saturation nadir during the 6MWT. PVOD manifests in two forms: hereditary, which is associated with autosomal recessive biallelic mutations in the EIF2AK4 gene, and sporadic, which presents later in life and more frequently in males. Several risk factors are linked to sporadic PVOD, including prior exposure to chemotherapy (particularly alkylating agents),^, tobacco, and organic solvents such as trichloroethylene.^,

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ABCHF

Review Article

Reverse Remodeling and Genetics: A Review Based on a Clinical Case Description that Challenges Current Evidence and Logic

Helena Garcia Betinardi Bernardi et al. Silas Furquim Renata Lopes Hames Jorge Henrique Yoschimoto Koroishi … Jairo Alves Pinheiro Junior Stevan Krieger Martins

Abstract

Cardiac remodeling, present in heart failure (HF), is a compensatory biological process following an initial myocardial injury that gradually becomes maladaptive, leading to clinical deterioration and chronic HF. Reverse remodeling (RR), which has been increasingly addressed, occurs when the geometry and/or function of the left ventricle recover in response to treatment, approaching normal cardiac structure. RR is associated with a better prognosis. Factors associated with RR include female sex, non-ischemic etiology, mild to moderate HF, lower fibrotic burden, elevated blood pressure permitting medical optimization, shorter disease duration, and preserved renal function. However, growing knowledge of genetic factors in HF etiology has provided important insights into their role in treatment response and prognosis. To illustrate and discuss these emerging topics, we report a case of advanced HF involving RR and a genetic variant, reviewing current recommendations for management.

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ABCIC

Case Report

Long-term Follow-Up of a Patient with FLNC Gene Mutation-Related Cardiomyopathy: A Case Report

Isabela Bispo Santos da Silva Costa et al. Bruno Soares da Silva Rangel Antonio Tito Paladino Filho Bruno Normande Colombo … Thamara Carvalho Morais Ludhmila Abrahão Hajjar

Introduction

Heart Failure (HF) is estimated to affect approximately 26 million people worldwide.^, In Brazil, prevalence is high, with about 2 million diagnosed patients and an incidence of roughly 240,000 new cases every year. Between 2011 and 2021, more than 2.5 million HF-related hospitalizations were recorded in the Brazilian Unified Health System (SUS), underscoring the relevance of the disease in the national context. These figures highlight the need for early diagnostic strategies and etiological definition for the appropriate management of these patients. Establishing an etiological diagnosis is often challenging but essential to provide disease-specific treatments and improve prognosis. Diagnosis encompasses multimodality cardiac imaging, with Cardiac Magnetic Resonance imaging (CMR) being a useful tool for evaluating non-ischemic cardiomyopathy phenotypes and establishing an etiological diagnosis.

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ABC

Research Letter

Unveiling the Genetic Puzzle: Asymmetric Hypertrophy in a Heart Transplant Recipient Linked to Birt-Hogg-Dubé Syndrome

Silas Ramos Furquim et al. Lucas Vieira Lacerda Pires Nara Alves Buriti Mariana Lombardi Peres de Carvalho … Emanuelle Leonilia Marques Bianca Domit Werner Linnenkamp Luciana Sacilotto Fabiana G. Marcondes-Braga Iascara Wozniak de Campos Luis Fernando Bernal da Costa Seguro Sandrigo Mangini Monica S. Avila Fernando Bacal José Eduardo Krieger

Abstract

A case of a 54-year-old man who underwent a heart transplant with early asymmetric hypertrophy unrelated to rejection. Donor’s genetic analysis revealed a variant in folliculin gene, associated with Birt-Hogg-Dubé Syndrome. Screening of the donor’s family uncovered a similar hypertrophy and same genetic variant in the donor’s father. Although genetic evaluation of donors’ tissues is not routine, it can be crucial for understanding changes unrelated to the transplant procedure and identifying carriers of pathogenic variants.

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Research Letter

Fabry Disease and Its Different Phenotypes

Murillo Oliveira Antunes et al. Rafael Ruas Nastari Edmundo Arteaga-Fernandez Marcelle G. Henriques Lizandro … William Batah El-Feghaly Guilherme José dos Santos Ferreira Alan Silva Martins Juliana Alzira Gonzales Oliveira Leguizamon Vinicius Machado Correia Vagner Madrini Junior Fábio Fernandes

Abstract

Fabry disease (FD) is an X-linked genetic condition caused by variants in the GLA gene causing enzyme α-galactosidase A deficiency and accumulation of globotriaosylceramide (Gb3) in tissues such as the heart, kidneys, and the nervous system. This study reports a case series of patients with FD, highlighting the phenotypic diversity of the disease, which can be confused with other cardiological conditions. When properly indicated, genetic evaluation, combined with biomarker dosage and α-galactosidase enzymatic activity, is key for an accurate diagnosis. Early diagnosis of FD is fundamental for initiating treatments that can slow disease progression and prevent serious complications, reinforcing the need for greater awareness about this condition among cardiologists.

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Editorial

Sleep Duration, Genetics, and Atherosclerosis: Challenges and Opportunities

Ana Vitoria Vitoreti Martins et al. Larissa T. Krul Luciano F. Drager

Atherosclerosis, the unifying mechanism for most of the non-fatal and fatal myocardial infarction and stroke events, is a multifactorial process that has been increasing in prevalence worldwide. Traditional risk factors for atherosclerosis have been extensively studied, but recent evidence pointed out that they explained approximately only 40-50% of the variability of markers of arterial damage and atherosclerosis. Therefore, growing interest has been devoted to exploring the relative role of the “nontraditional’ risk factors. One of the promising candidates is sleep disorders. Indeed, the relationship between sleep and cardiovascular health has been increasingly explored in the literature.^, While most of the evidence relies on the impact of obstructive sleep apnea (OSA) on atherosclerosis, the potential atherogenic effects of extremes of sleep duration has been recently investigated,^, considering its positive association with poor cardiovascular outcomes. Interestingly, previous evidence consistently showed that not only short but long sleep duration (usually defined as >8 or >9hs) increased the risk for these events, confirming a U-shaped association between sleep duration and cardiovascular outcomes. This previous evidence paves the way for exploring potential mechanisms by which sleep duration extremes may increase cardiovascular risk.

In this edition of the Arquivos Brasileiros de Cardiologia, Xu et al. evaluated the association between sleep duration and the risk of atherosclerosis using a Mendelian randomization (MR) approach with data from genome-wide association studies (GWAS). Two large cohorts from Europe were included for analysis. The main results indicated that contrary to the initial hypothesis, there is no significant causal association between sleep duration and atherosclerosis. The study concluded that genetically predicted sleep duration does not affect the risk of atherosclerosis and suggested further research to explore this relationship in greater detail. Strengths of the study include the large sample size and the use of a MR study. This strategy allows for avoiding common biases observed in observational studies. However, important limitations deserve appropriate comments precluding definitive conclusions in this important research area: 1) a subjective question defined sleep duration. It is not uncommon to find misperceptions about the real sleep duration; 2) the chosen Single Nucleotide Polymorphism (SNPs) only partially explain the variability of subjective sleep duration in this investigation. This fact may contribute to lower statistical power in identifying situations with poor correlations; 3) ‘atherosclerosis’ was identified by using the International Classification of Diseases (ICD) rather than objective measurements. There is certainly an underreport of the real burden of atherosclerosis in this population; 4) other sleep disorders (highlighting the role of OSA) are consistently associated with prevalent and incident markers of atherosclerosis^– but were not studied in the present investigation; 5) the applicability of the results to non-European populations deserve further investigations.

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Review Article

Cardiomyopathy in Children and Adolescents in the Era of Precision Medicine

Ana Flávia Mallheiros Torbey et al. Raquel Germer Toja Couto Aurea Grippa Eduarda Corrêa Maia … Sara Aimée Miranda Marcos Adriano Cardoso dos Santos Elion Tavares Peres Olimpio Patrick Silva Costa Everton Mattos de Oliveira Evandro Tinoco Mesquita

Abstract

In childhood and adolescence, cardiomyopathies have their own characteristics and are an important cause of heart failure, arrhythmias, sudden death, and indication for heart transplantation. Diagnosis is a challenge in daily practice due to its varied clinical presentation, heterogeneous etiologies, and limited knowledge of tools related to clinical and molecular genetics. However, it is essential to recognize the different phenotypes and prioritize the search for the etiology. Recent advances in precision medicine have made molecular diagnosis accessible, which makes it possible to individualize therapeutic approaches, stratify the prognosis, and identify individuals in the family who are at risk of developing the disease. The objective of this review is to emphasize the particularities of cardiomyopathies in pediatrics and how the individualized approach impacts the therapy and prognosis of the patient. Through a systematized approach, the five-stage protocol used in our service is presented. These stages bring together clinical evaluation for determining the morphofunctional phenotype, identification of etiology, classification, establishment of prognosis, and the search for personalized therapies.

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Editorial

PRKAG2 Syndrome: Is Screening with Early Echocardiography Effective in Children with a Positive Genotype?

Maria Elisa Lucena Sales de Melo Assunção et al. Norma Lucena Cavalcanti Licínio da Silva Mychelle Pascoaline de Miranda Silva

Described for the first time in 2001 by Gollob et al., the syndrome determined by the mutation of the PRKAG2 gene is rare, autosomal dominant, with high penetrance and unknown prevalence in the population. It manifests with the phenotype of myocardial hypertrophy and associated ventricular pre-excitation. Tachyarrhythmias are common in this genetic syndrome, as are disturbances in the cardiac conduction system that lead, in some cases, to pacemaker implantation at an early age.

The PRKAG2 gene mutation usually presents as a phenocopy of hypertrophic cardiomyopathy, differing from this in that there are no sarcomeric changes and, rather, accumulation of glycogen in cardiac myocytes. The definitive diagnosis is given by genetic study, but the presentation with left ventricular (LV) hypertrophy and conduction system disorders also form a differential diagnosis with Danon and Anderson-Fabry diseases.

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IJCS

Review Article

Genetic Testing in Cardiomyopathy: Decoding Molecular Underpinnings and Influencing Treatment Decisions

Silas Ramos Furquim et al. Layara Fernanda Vicente Pereira Lipari Fernanda Almeida Andrade Vinícius Machado Correia … Natália Quintella Sangiorgi Olivetti Lucas Vieira Lacerda Pires Luciana Sacilotto Fábio Fernandes José Eduardo Krieger

Abstract

Cardiomyopathy is characterized by structural and functional abnormalities in the heart muscle that are not influenced by coronary disease, hypertension, valve disease, or congenital heart defects. Genetic testing, which helps diagnose the molecular bases of cardiomyopathy, can affect prognostication and clinical decisions. Recent guidelines advocate classifying cardiomyopathies based on phenotypic categories, which encompass a range of clinical presentations, underlying causes, and outcomes. Beyond deepening our grasp of the disease, genetic testing can distinguish between diseases with similar presentations, known as genocopies, which can profoundly influence treatment decisions. Genetic testing is also essential for reproductive counseling and risk evaluation among family members. Combined with advanced imaging techniques such as magnetic resonance imaging, genetic investigation offers a comprehensive understanding of the disease. Thus, as the nature of cardiomyopathies continues to be unraveled, cardiologists must stay updated on advances in genetic testing and their practical applications.

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Case Report

FLNC Associated Restrictive Cardiomyopathy and Hypertrabeculation, a Rare Association

Ana M. Aristizabal et al. Carlos Alberto Guzmán-Serrano María Isabel Lizcano Walter Mosquera … Juliana Lores Harry Pachajoa Cesar Cely

Abstract

A six-year-old girl with restrictive cardiomyopathy and hypertrabeculation, due to the early onset of her disease, whole exome sequencing was conducted, revealing the presence of a novel heterozygous missense variant in the FLNC gene. The same gene variant was also identified in her father, who, at an adult age, displayed normal imaging results and was symptom-free. This variant has not been reported in population databases or current medical literature and is classified as likely pathogenic.

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ABC

Editorial

Influence of Genetics on Hypertension Development

Primary hypertension is one of the most common diseases worldwide, estimated to affect 20% of females and 25% of males. It is a risk factor for half of the ten leading causes of death globally, including the ranking leader, cardiovascular disease, and right next to it, brain, and kidney disease. For a long time, major efforts have been made to unravel the mechanisms that contribute to this – mostly – silent but devastating condition. Some advocate that hypertension is not a disease but a syndrome; a condition with multiple etiological factors which have as common sign an elevated blood pressure. Amongst intrinsic and environmental factors related to primary hypertension, some are already well established, e.g., obesity, smoking, disbalance of the renin-angiotensin-aldosterone-system (RAAS), mental stress, etc. The role of genetics in this scenario, nevertheless, has a vague and complex-to-characterize influence on hypertension development. Despite several studies dedicated to enlighten the matter, its polygenic nature makes every case unique regarding the impact of each predisposing factor. Several polymorphisms in different genes were pointed to correlate with hypertension, including the G-protein β3 subunit (GNB3) C825T polymorphism (rs5443:C>T). Guanine nucleotide-binding proteins (G proteins) are expressed in most human tissues and function as transductors in intracellular signaling pathways, regulating a wide variety of physiological processes. The 825T allele was previously associated with hypertension and obesity; however, a few studies were controversial, and the frequencies of the T allele differed amongst different ethnicities (fT≈0,8 in black Africans, fT≈0,45 in Asians, and fT≈0,3 in whites).

The study by Agostini et al. aimed to characterize a sample of 155 hypertensive Brazilian individuals in order to assess the prevalence of the C825T polymorphism and correlate it with clinical features. Unlike most of the other studies, the group found no association between the genetic variant and hypertension. The identification and selection of hypertensive subjects were based solely on interview data from medical records (use or not of anti-hypertensive medication and register or lack of register of a previous diagnosis), which might have interfered with their findings. Also, it was shown previously that the frequency of the T allele between ethnicities is often not equal, as well as hypertension prevalence. Thus, even though the idea of genetically characterizing the Brazilian population as a unity can be interesting, the Brazilian population is one of the most heterogeneous in the globe. Therefore, looking at ethnical groups separately could have enriched the analysis. The metabolic profile was also compared between groups and found positive associations of hypertensive individuals presenting the polymorphism with higher levels of triglycerides, glucose, uric acid, and obesity, similar to previous reports. The elucidation of hypertension pathways is a very complex subject, especially regarding genetics, so every effort to identify predisposing factors adds a new valuable piece to this puzzle.

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ABC

Review Article

Challenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implications

Silas Ramos Furquim et al. Bianca Linnenkamp Natália Quintella Sangiorgi Olivetti Fernando Rabioglio Giugni … Layara Fernanda Vicente Pereira Lipari Fernanda Almeida Andrade José Eduardo Krieger

Abstract

Genetic tests for dilated cardiomyopathy (DCM) have a diagnostic yield of up to 40%, but there is significant genetic heterogeneity and other challenges, such as variable expressivity and incomplete penetrance. Pedigree analysis is essential for distinguishing between sporadic and familial DCM cases by assessing family history. Familial DCM yields higher results in genetic testing, but sporadic DCM does not rule out the possibility of a genetic cause. Some genes have specific phenotypes, with the Lamin gene ( LMNA ) being associated with a phenotype of malignant arrhythmias and advanced heart failure (HF). The presence of a causal genetic variant can also aid in prognostic evaluation, identifying more severe cases with lower rates of reverse remodeling (RR) compared to individuals with a negative genotype. Current guidelines recommend genetic evaluation and counseling for individuals with DCM, along with cascade screening in first-degree relatives in cases where one or more variants are identified, offering an opportunity for early diagnosis and treatment. Relatives with a positive genotype and negative phenotype are candidates for serial evaluation, with frequency varying by age. Genotype also assists in individualized recommendations for implantable cardioverter-defibrillator (ICD) placement and advice regarding physical activity and family planning. Ongoing studies are progressively elucidating the details of genotype/phenotype relationships for a large number of variants, making molecular genetics increasingly integrated into clinical practice.

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ABCHF

Viewpoint

Clinical Reasoning and Classification of Cardiomyopathies

Vagner Madrini Junior et al. Evandro Tinoco Mesquita Diane Xavier de Avila Fabio Fernandes

Definition

Cardiomyopathies (CMPs) are a group of diseases with multiple etiologies and heterogeneous phenotypes, ranging from microscopic changes in cardiomyocytes in asymptomatic patients to cases of fulminant heart failure with fluid retention, and perfusion and heart rhythm changes. A CMP was initially defined as a heart muscle disease caused by genetic defects, myocyte injury or myocardial infiltration, and characterized by structural and functional abnormalities in the absence of congenital disease, valvular disease or hypertension. The initial approach of patients with CMP consists of clinical evaluation and complementary imaging techniques and genetic testing, in search of diagnostic evidence and the need for specific tests ().^,

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ABCHF

Review Article

Genetics in Cardiomyopathies – Genetic Tests Decoded for the Clinical Cardiologist

Arsonval Lamounier Júnior et al. Diane Xavier de Ávila Roberto Barriales-Villa

Abstract

The era of personalized medicine emphasizes the provision of health care guided by the cardiomyopathy phenotypes described, their interpretation based on genotype, and genetic counseling. The identification of high-risk cardiomyopathy subtypes and the diagnosis of rare etiologies with potential therapies cannot be neglected. Genetic sequencing of these patients, in addition to advances in cardiac imaging techniques, has indicated a new perspective for these concepts, and consequently possible new classifications of cardiomyopathies and new clinical practices. The interaction between multidisciplinary teams and cardiology genetic experts is fundamental for a more appropriate management of gene variants, especially variants of uncertain significance that may be relevant in the expression of cardiomyopathies. This article helps cardiologists in the ordering of genetic tests and their indications, provides information about pathogenicity of variants and emphasizes family screening, challenges that may be overcome in daily practice.

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ABCHF

Special Article

Cardiomyopathies: Yesterday, Today, and Tomorrow

Charles Mady et al. Diane Xavier de Ávila Vagner Madrini Junior Evandro Tinoco Mesquita

The interest in myocardial damage is very old, but only in recent decades has there been a reasonable advance in greater knowledge thereof. Ancient peoples were limited to rudimentary observations on the morphology and physiology of the circulatory system, but with special interest directed to the heart. Texts in cuneiform scripts from Sumer, considered the first civilization in human history; others from the Library of Ashurbanipal, with inscriptions on clay tiles, discovered intact under the sands at Nineveh; Egyptian hieroglyphs in stone and ink; and writings by the Mayans, the only people in the Americas to leave reports in their alphabet as well as books, of which we have only copies in some cases (the Spanish invaders took it upon themselves to destroy and burn many originals) all demonstrate an ancient interest in human anatomy and the heart. With the limitations of their times, they demonstrated curiosity about the constitution of the human body, reaching academic-level descriptions by Leonardo da Vinci’s time. Recent developments have brought us new knowledge about the etiopathogenesis and pathophysiology of the diseases that affect the heart, but they are not sufficient to generate greater therapeutic advances. There are reasons for this.

As these diseases are predominantly clinically treated, cardiology has spent the past few decades committed to understanding and disseminating themes considered more relevant in surgical areas, such as coronary, congenital, and valve diseases, which were and are subjected to highly developed treatments in the recent past, with more immediate results. The drug and equipment industries have understood the size of the doors open to their interests, actively participating in research associated with academic institutions. There is no doubt that the evolution in these fields has been enormous, with remarkable material interests, massively concentrating research, symposiums, congresses, and publications on these themes. Spaces for cardiomyopathies were very limited, due to almost total lack of interest, and therapy in these fields was limited to digitalis and diuretics, indicated for heart failure, and not for underlying diseases. It was a world apart within cardiology. It took a long time for new drugs to be studied and released on the market, but only for the treatment of dysfunction as a syndrome. There was a long delay in creating laboratories to promote understanding of the etiological factors of myocardial aggression, in an attempt to understand, reduce, or eliminate the lethality of these diseases, many of which are still little known, and to attempt to develop specific treatments for each cause. Unfortunately, we are still a long way from this goal. As an example, I cite the old and current Chagas cardiomyopathy. We treat the consequences, heart failure, thromboembolisms, and arrhythmias, but to date we do not have any truly effective specific treatment, in a society that contains a significant part of the infected population. Even prevention, which is inexpensive, given that it simply uses insecticides, is carried out on a modest scale. It has become conventional to use the terminology “disease of the poor” to justify this lack of interest. Nonetheless, this delay generates a huge social cost in the health area.

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ABCHF

Viewpoint

Genetic Counseling and Pedigree in Cardiomyopathies – the Role of the Clinical Geneticist

Diane Xavier de Ávila et al. Frank Nunes Raquel Germer Ana Flávia Malheiros Torbey

Introduction

Twenty years ago, the Human Genome Project made history by announcing the sequencing of 92% of the human genome through the development of modern genetic sequencing techniques. In 2022, the complete sequencing of human DNA was announced. This knowledge made it possible to better understand how genetics influences the functioning of the human body and, at the same time, facilitated the identification of genetic variants that can cause diseases.

In the field of cardiology, genetic study assists the assessment of aortopathy, familial hypercholesterolemia, channelopathies, and especially cardiomyopathies.

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ABCIC

Editorial

How to Perform a Diagnostic and Prognostic Analysis of Hypertrophic Cardiomyopathy in 2022: Should we Divide to Improve Treatment?

Alexandra Toste et al. Nuno Cardim

Hypertrophic cardiomyopathy (HCM), the most common genetic heart disease, has an estimated prevalence in the general population of 1:500–1:200. The diagnosis is based on the presence of left ventricular hypertrophy (LVH) that is not fully explained by loading conditions, and HCM occurs in the absence of other cardiac, systemic, or metabolic disease or in the context of a multiorgan syndrome associated with LVH.

Despite being considered a genetic disease, the initial diagnosis of HCM does not require genetic testing. The diagnostic power of current genetic panels is modest, just 46%; therefore, failure to detect a mutation does not exclude the diagnosis. Current guidelines recommend genetic testing, especially when the possibility of cascading familial genetic screening is anticipated or in cases in which the clinical presentation suggests a specific non-sarcomeric etiology potentially treatable with specific therapy, such as Anderson-Fabry disease, Danon disease, or familial amyloidosis.

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ABCHF

Case Report

Overlapping Etiologies in a Young Patient with Severe Myocarditis: A Case Report

Thaís Martins de Oliveira et al. Fernando Luis Scolari Fabiano de Oliveira Poswar Francine Hehn de Oliveira … Ricardo Stein Lívia Adams Goldraich

Introduction

Etiological identification of young patients with heart failure should always be a medical goal. In this scenario, infectious myocarditis is a possible diagnosis and, when it occurs, it has a benign course in the majority of cases. However, congenital heart diseases or familial forms of cardiomyopathy should be considered in differential diagnosis and/or concomitantly, particularly in more severe presentations of myocarditis. In these cases, in addition to specific investigation for myocarditis, which may include clinical evaluation, imaging exams, laboratory tests, and endomyocardial biopsy with viral agent testing in myocardial tissue, genetic study is also worth considering. Associated etiologies can have an impact on clinical presentation and evolution, but data are still scarce, which means that there is still a gap to be explored in the literature. In this report, we describe the case of a young man with cardiogenic shock secondary to myocarditis caused by Epstein Barr virus (EBV), which led to identification of a pathogenic mutation in the PKP2 gene.

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ABC

Editorial

Chronological Age or Biological Age, Mainly a Matter of Lifestyle

Paulo César B. Veiga Jardim et al. Thiago de Souza Veiga Jardim

Despite the significant global socioeconomic disparities, the world’s population has grown exponentially, and the average life continues to increase significantly.^–

If at the beginning of the 19th century, life expectancy in Europe was around 35 years, at present, only the African continent has populations with an average life expectancy of fewer than 60 years.^–

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IJCS

Original Article

Plasma Renin in Women Using and not Using Combined Oral Contraceptive

Sidney de Souza Oliveira et al. Jefferson Petto Diego Passos Diogo Alan Carlos Nery dos Santos … Marvyn de Santana do Sacramento Ana Marice Teixeira Ladeia

Abstract

Backgroud:

Recent studies show that women on combined oral contraceptives (COC) present abnormal fasting lipid profile, increased postprandial lipemia, plasma C-reactive protein (CRP) and blood pressure (BP) compared to women not on combined oral contraceptives. Plasma renin is one of the factors responsible for abnormal BP.

Objectives:

To assess plasma renin levels in women using or not using COC, the correlation between renin and CRP, as well as divergences in lipid profile.

Methods:

A cross-sectional study with apparently healthy women aged 20 to 30, eutrophic, irregularly active, and with fasting triglycerides < 150 mg/dL. The sample was stratified into two groups: the No Combined Oral Contraceptive Group (NCOCG), comprised of women who did not use any type of hormone contraceptive, and the Combined Oral Contraceptive Group (COCG) comprised of women on low-dose COC for at least one year. After a 12-hour fast, 5 ml of blood was collected for renin dosing and PCR. Data were analyzed by the t-Test and bidirectional Mann-Whitney Test, both with significance < 0.05.

Results:

We evaluated 44 women equally distributed between the groups, age 23 ± 1.2 years, BMI 21.0 ± 3.2 kg/m². Median and interquartile deviation of renin in the NCOCG and the COCG were, respectively, 0.5 (0.1-1.0) and 3.0 (2-6) (p < 0.01). A positive correlation between PCR and renin (p < 0.01 and r = 0.68) was found.

Conclusion:

The plasma renin levels of women using COC were higher, with a strong correlation with CRP.

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Review Article

Genetic Evaluation, Familial Screening and Exercise

Ricardo Stein et al. Juan Pablo Trujillo Anderson Donelli da Silveira Arsonval Lamounier Júnior Lorenzo Monserrat Iglesias

Introduction

Regular physical activity practice benefits individuals of all ages, sexes and ethnicities. If on one hand the practice of moderate exercise is considered a healthy activity that favors the cardiovascular system, on the other, high-intensity exercise for a long period can increase the risk for sudden death (SD). Even considering the huge number of individuals exercising daily, SD in that context is rare. However, the prevention of SD can be difficult and it has significant repercussion, mainly among young practitioners of leisure exercise or athletes. From the epidemiological viewpoint, cardiac SD affects 200,000 to 400,000 individuals in the United States of America (USA) annually. In the sports scenario, around 200 athletes per year are estimated to have a fatal event. In Spain, the national registry of SD in athletes reported 180 cases from 1995 to 2007, suggesting an incidence of 15 to 20 cases per year.

For athletes, preparticipation evaluation (PPE) is indicated, and can be effective in preventing cardiac SD in that context. However, that type of screening has great variability between different countries and entities that perform it. In the sports context, genetic evaluation is performed only in specific cases.

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ABC

Artigo Original

Genetic factors in familial aggregation of blood pressure of portuguese nuclear families

Rogério César Fermino et al. André Seabra Rui Garganta José António Ribeiro Maia

BACKGROUND: Despite of the increase in the prevalence of hypertension in Portugal, the importance of genetic factors in blood pressure (BP) has not been studied extensively in our country. OBJECTIVES: To verify the indirect presence of vertical transmission of genetic factors between parents and children in BP values, and to estimate the magnitude of genetic factors contributing for variation in BP values in the population. METHODS: Sample size comprises 367 individuals (164 parents and 203 children) pertaining the 107 nuclear families participating in “Familias Activas” project, proceeding from different regions of North Portugal. The BP was measured with Omron® model M6 (HEM-7001-E) digital device. SPSS 15.0 was used for data analysis; PEDSTATS was used to verify the structure of each family data. Familial correlations and heritability estimates were computed in FCOR and ASSOC modules of S.A.G.E. version 5.3. RESULTS: For systolic BP (SBP), correlation values were low to moderate (0,21< r <0,35); for diastolic BP (DBP) values were found to be moderate (0,24< r <0,50). Genetic factors explain 43 and 49% of the total variation in SBP and DBP, respectively. CONCLUSION: A moderate amount of the SBP and the DBP is accounted for by genetic factors.

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Artigo Original

Genetic polymorphism, medical therapy and sequential cardiac function in patients with heart failure

Marco Antonio Romeo Cuoco et al. Alexandre Costa Pereira Glória de Fátima Alves da Mota José Eduardo Krieger Alfredo José Mansur

BACKGROUND: Functional variants of angiotensin-converting enzyme (ACE) gene may be associated with response to therapy in patients with heart failure (HF). OBJECTIVE: To test the hypothesis of differences in sequential echocardiographic evaluations of left ventricular ejection fraction in patients with HF on medical therapy, including ACE inhibitors in relation to insertion (I) / deletion (D) polymorphism of the ACE gene. METHODS: We studied 168 patients (mean age 43.3±10.1 years), 128 (76.2%) men, with HF and sequential echocardiograms. The I/D polymorphism was determined by polymerase chain reaction. Left ventricular ejection fraction (LVEF) was analyzed comparatively to genotypes. More than 90% of patients were on ACE inhibitors. RESULTS: There was a significantly greater increase in mean LVEF in patients with the D allele compared to patients with the II genotype (p=0.01) after a mean follow-up of 38.9 months. The D allele was associated with an increase of 8.8% in mean LVEF over the same period. Furthermore, there was a tendency toward a D allele “copy number” effect on the increase of mean LVEF over time: a 3.5% difference in LVEF variation between patients with the II and the ID genotypes (p = 0.03) and a 5% difference between patients with the II and DD genotypes (p=0.02). CONCLUSION: ACE gene deletion polymorphism may be operative in response to medical treatment that included ACE inhibitors in patients with HF. Further controlled studies may contribute to better understanding of genetic influences on response to therapy.

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