Hypertrophic cardiomyopathy is the most common monogenic cardiac disorder. Clinical presentation varies widely ranging from asymptomatic to severe left ventricular outflow tract obstruction, and sudden cardiac death. Sarcomeric protein gene mutations are most common contributing to 60%, predominantly involving MYBPC3 and MYH7 genes. Some myocardial storage cardiomyopathies mimic HCM, though does not have myocyte disarray or fibrosis characteristic of HCM and are referred to as HCM phenocopies. Genetic testing is crucial to differentiate HCM phenocopies from HCM as management varies. Among the involved families there is a lot of genetic heterogeneity leading to varying phenotypic expression of disease though carrying the same genetic mutation. For better understanding we describe here the basics of human genetics, define the terminologies used in genetics, and go on to describe the genetic basis of HCM. Genetic mutation leads to altered protein structure which are incorporated in the sarcomere leading to dysregulated contractile function, myocardial disarry and fibrosis leading to various clinical manifestation of HCM . we describe the genetic screening strategies which help in identifying family members carrying the mutation and at risk of disease and help in avoiding unnecessary repeated clinical screening in family members not carrying the mutation. we emphasize Integrating genetic testing into clinical practice for proper management of HCM.
{"title":"Genetics of hypertrophic cardiomyopathy: Cardiologist’s perspective","authors":"SravanKumar Gaddamedi, Linda Koshy, Sanjay Ganapathi, Panniyammakal Jeemon, Hisham Ahmed, Ajay Bahl, PerunduraiS Dhandapany, Sivadasanpillai Harikrishnan","doi":"10.4103/hfji.hfji_21_23","DOIUrl":"https://doi.org/10.4103/hfji.hfji_21_23","url":null,"abstract":"Hypertrophic cardiomyopathy is the most common monogenic cardiac disorder. Clinical presentation varies widely ranging from asymptomatic to severe left ventricular outflow tract obstruction, and sudden cardiac death. Sarcomeric protein gene mutations are most common contributing to 60%, predominantly involving MYBPC3 and MYH7 genes. Some myocardial storage cardiomyopathies mimic HCM, though does not have myocyte disarray or fibrosis characteristic of HCM and are referred to as HCM phenocopies. Genetic testing is crucial to differentiate HCM phenocopies from HCM as management varies. Among the involved families there is a lot of genetic heterogeneity leading to varying phenotypic expression of disease though carrying the same genetic mutation. For better understanding we describe here the basics of human genetics, define the terminologies used in genetics, and go on to describe the genetic basis of HCM. Genetic mutation leads to altered protein structure which are incorporated in the sarcomere leading to dysregulated contractile function, myocardial disarry and fibrosis leading to various clinical manifestation of HCM . we describe the genetic screening strategies which help in identifying family members carrying the mutation and at risk of disease and help in avoiding unnecessary repeated clinical screening in family members not carrying the mutation. we emphasize Integrating genetic testing into clinical practice for proper management of HCM.","PeriodicalId":486649,"journal":{"name":"Heart Failure Journal of India","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134966625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cardiac amyloidosis (CA) is an infiltrative and restrictive cardiomyopathy subsequent to extracellular deposition of amyloid fibrils in cardiac tissues. CA is many a times associated with the involvement of other organs, especially the kidneys and nervous system and that may be the initial clinical manifestation. CA has two main subtypes—light‐chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). ATTR-CA is further subdivided into two, based on the presence or absence of the transthyretin gene. The wild-type transthyretin CA causes the deposition of the normal transthyretin protein, a condition previously called senile CA. The second type is now called variant transthyretin CA and is caused by transthyretin harboring mutations. This was previously referred to as familial CA. The interest in CA especially the ATTR variety has increased due to the availability of easier noninvasive diagnostic methods and therapeutic avenues. CA is relatively rare, it presents with varying symptoms, which mimic other common diseases, and this leads to missing the diagnosis early in nearly 50% of cases. Many patients spend 3–4 years to reach a diagnosis. Since the prognosis, once there is cardiac involvement is dismal, early identification and treatment becomes very important. In this issue with the theme, amyloidosis, there is a state-of-the-art review contributed by Omar Siddiqui and team from Boston University, USA—“Cardiac Amyloidosis in 2023: A Review of Pathophysiology, Diagnosis and Treatment.” This article gives a detailed overview of epidemiology, pathophysiology, diagnosis, and management of CA. This comprehensive review written by the cardiology team from the Amyloidosis Center from the Boston University will be very helpful to our readers. The second article is a review on the “Disease burden, management challenges and proposed approach” by Akash Batta and team from Dayanand Medical College, Ludhiana, India. They discuss the challenges faced in the detection and management of CA in a low-middle-income country (LMIC) such as India. They propose a diagnostic algorithm and suggest the development of an amyloid reference network with a central amyloid reference center with peripheral clinical sites, something like a hub and spoke model. I am sure this suggestion will be discussed in the academic circles and also in the health system management forums. Two research articles, which are related to CA, are also published in this issue. The first one is a tertiary care center experience of cardiac amyloidosis. The series from Apollo Hospitals, Chennai, which is one of the leading tertiary referral care centers in the country, describes the outcome of 31 patients with cardiac amyloidosis. Since this is one of the larger series on this rare condition from India, it will be helpful to the readers to understand the pattern of the disease and the varying modes of presentation. The challenges in genetic testing, nuclear scintigraphy, and the accessibility and aff
{"title":"Cardiac amyloidosis: Hopes and challenges","authors":"Sivadasanpillai Harikrishnan","doi":"10.4103/hfji.hfji_44_23","DOIUrl":"https://doi.org/10.4103/hfji.hfji_44_23","url":null,"abstract":"Cardiac amyloidosis (CA) is an infiltrative and restrictive cardiomyopathy subsequent to extracellular deposition of amyloid fibrils in cardiac tissues. CA is many a times associated with the involvement of other organs, especially the kidneys and nervous system and that may be the initial clinical manifestation. CA has two main subtypes—light‐chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). ATTR-CA is further subdivided into two, based on the presence or absence of the transthyretin gene. The wild-type transthyretin CA causes the deposition of the normal transthyretin protein, a condition previously called senile CA. The second type is now called variant transthyretin CA and is caused by transthyretin harboring mutations. This was previously referred to as familial CA. The interest in CA especially the ATTR variety has increased due to the availability of easier noninvasive diagnostic methods and therapeutic avenues. CA is relatively rare, it presents with varying symptoms, which mimic other common diseases, and this leads to missing the diagnosis early in nearly 50% of cases. Many patients spend 3–4 years to reach a diagnosis. Since the prognosis, once there is cardiac involvement is dismal, early identification and treatment becomes very important. In this issue with the theme, amyloidosis, there is a state-of-the-art review contributed by Omar Siddiqui and team from Boston University, USA—“Cardiac Amyloidosis in 2023: A Review of Pathophysiology, Diagnosis and Treatment.” This article gives a detailed overview of epidemiology, pathophysiology, diagnosis, and management of CA. This comprehensive review written by the cardiology team from the Amyloidosis Center from the Boston University will be very helpful to our readers. The second article is a review on the “Disease burden, management challenges and proposed approach” by Akash Batta and team from Dayanand Medical College, Ludhiana, India. They discuss the challenges faced in the detection and management of CA in a low-middle-income country (LMIC) such as India. They propose a diagnostic algorithm and suggest the development of an amyloid reference network with a central amyloid reference center with peripheral clinical sites, something like a hub and spoke model. I am sure this suggestion will be discussed in the academic circles and also in the health system management forums. Two research articles, which are related to CA, are also published in this issue. The first one is a tertiary care center experience of cardiac amyloidosis. The series from Apollo Hospitals, Chennai, which is one of the leading tertiary referral care centers in the country, describes the outcome of 31 patients with cardiac amyloidosis. Since this is one of the larger series on this rare condition from India, it will be helpful to the readers to understand the pattern of the disease and the varying modes of presentation. The challenges in genetic testing, nuclear scintigraphy, and the accessibility and aff","PeriodicalId":486649,"journal":{"name":"Heart Failure Journal of India","volume":"259 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134966628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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