• Users Online: 252
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2017  |  Volume : 3  |  Issue : 3  |  Page : 143-149

Epidemiology of cardiomyopathy – A Clinical and Genetic Study of Restrictive Cardiomyopathy: The EPOCH-R Study

1 Department of Anthropology, University of Delhi, New Delhi, India
2 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication1-Feb-2018

Correspondence Address:
Prof. Vadlamudi Raghavendra Rao
Department of Anthropology, Laboratory of Biochemical and Molecular Anthropology, University of Delhi, New Delhi - 110 007
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcs.jpcs_23_17

Rights and Permissions

Introduction: Restrictive cardiomyopathy (RCM) is characterized by diastolic dysfunction, biatrial enlargement, and normal or near-normal systolic function. RCM is the rarest kind among cardiomyopathies with a severe outcome. Methods: Here, we present the clinical outcomes of thirty RCM patients recruited from a tertiary care unit of India, All India Institute of Medical Sciences, New Delhi. For clinical assessment, patients underwent electrocardiogram, echocardiography, and cardiac catheterization, and endomyocardial biopsy whenever required. Results: Out of 190 patients with cardiomyopathy, 100 had dilated cardiomyopathy, 60 had hypertrophic cardiomyopathy, and 30 had idiopathic RCM and were recruited for the study. Out of these thirty patients, 63.3% were males. A maximum number of patients were diagnosed in their second to third decade of life. Atrial fibrillation (73.3%) and ST-T abnormalities (76.6%) were common. Most of the patients showed the early age of onset with symptoms emerging in the first and second decades of life. Shortness of breath and fatigue were found to be common symptoms. No familial cases were found. Conclusion: RCM in India is a sporadic disease, rare, and occurs in the young. Prognosis of RCM is still worse than any other cardiomyopathy.

Keywords: Clinical phenotype, restrictive cardiomyopathy, sporadic

How to cite this article:
Kapoor M, Das S, Biswas A, Seth S, Bhargava B, Rao VR. Epidemiology of cardiomyopathy – A Clinical and Genetic Study of Restrictive Cardiomyopathy: The EPOCH-R Study. J Pract Cardiovasc Sci 2017;3:143-9

How to cite this URL:
Kapoor M, Das S, Biswas A, Seth S, Bhargava B, Rao VR. Epidemiology of cardiomyopathy – A Clinical and Genetic Study of Restrictive Cardiomyopathy: The EPOCH-R Study. J Pract Cardiovasc Sci [serial online] 2017 [cited 2023 Jan 31];3:143-9. Available from: https://www.j-pcs.org/text.asp?2017/3/3/143/224482

  Introduction Top

Restrictive cardiomyopathy (RCM) is a rare phenotype among the cardiomyopathies. It is characterized as a disorder of myocardial muscles with impaired ventricular filling with distinct impaired hemodynamic features, raised filling pressures, and impaired diastolic dysfunction.[1],[2],[3],[4] The classification of RCM is dependent on hemodynamic patterns which represents a challenge as other anatomical features may have a restrictive function as a common base.[5] A wide range of symptoms varying from patient to patient such as diminished exercise tolerance, dyspnea, edema, and palpitation has been reported.[2] Patients with idiopathic form usually lie in advanced heart failure stage, i.e., Class III and Class IV of the New York Heart Association (NYHA).[6] Nondistinctive histology can show normal findings or nonspecific degenerative changes including myocyte hypertrophy, disarray, and interstitial fibrosis.[7] In pediatric cases, RCM is the rarest phenotype with poor prognosis, accounts for 4.5% of the total cardiomyopathy cases. It has an excessively high morbidity and mortality.[8]

In countries like India, Africa, South, and Central America, the main cause of RCM is endomyocardial fibrosis rather than idiopathic form of RCM though the pattern is now changing.[7] Studies in the last decade have revealed that sarcomeric gene mutations are linked to cases of idiopathic RCM.[9],[10],[11],[12] RCM in adults has a prolonged course of disease as compared to pediatric cases which often have shown poor prognosis with high mortality rate.[13],[14] Females show a higher prevalence of idiopathic RCM than men (female:male ratio, 15:1). Due to the poor prognosis of pediatric cases' mean survival rate has been reported to range from months to 7.8 years.[13],[15],[16],[17],[18] Due to poor prognosis and variable response to pharmacological therapy, cardiac transplant remains the final treatment option.[19] Nearly 33%–60% of idiopathic RCM cases were reported to be caused by mutations in sarcomeric genes, with many overlapping genes and variants shared between RCM and hypertrophic cardiomyopathy (HCM). Many earlier studies reported the mixed phenotype of RCM and HCM even in the same families.[10] To study RCM as a rare entity always has its limitation with small sample sizes. Here, we represent the first clinical genetic report of a cohort of 30 RCM cases from India.

  Methods Top

From our cohort of cardiomyopathy patients, we present RCM patients as an epidemiology of cardiomyopathy study-RCM (EPOCH-R) in the third phase after dilated [20] and HCM.[21] All participants were consecutive patients [Figure 1] who underwent initial diagnostic workup, recruited from year 2012 to 2015 December. Diagnostics evaluation includes 12-lead electrocardiogram (ECG), two-dimensional echocardiography, and chest X-ray with histopathology test whenever required for diagnosis. During recruitment, family history was obtained with symptoms related to disease such as dyspnea, chest pain, palpitations, presyncope, and syncope. Patients were followed for 3 years. The study protocol was approved by Ethics Review Boards of both participating institutions of the study, and written consent forms were obtained, after explaining study details, from all the participating patients and their first-degree relatives.
Figure 1: Flowchart to identify restrictive cardiomyopathy patients through proper clinical procedures and methods on the basis of inclusion/exclusion criteria of restrictive cardiomyopathy and collection of blood samples.

Click here to view

The diagnosis of idiopathic RCM was based on fulfilling the below-given criteria: (1) biatrial enlargement, (2) markedly elevated ventricular filling pressures with characteristic restrictive hemodynamic pattern, (3) dilated inferior vena cava, and (4) restrictive Doppler flows, with preserved systolic function. Patients with ischemic heart disease, hypertension treated for 5 years, organic valvular disease, congenital or pericardial disease with any secondary RCM causing disease such as amyloidosis, and eosinophilic syndrome were excluded from the study.

Data were collected with a prescribed format for all the patients participated in the study.

For genetic analysis, 5 ml of intravenous blood was collected from patients and available family members with written informed consent. Five milliliters blood was subjected to DNA extraction from phenol–chloroform method.[22] Primers were in-house designed and are available on request. MYH7 hotspot region of cardiomyopathies, i.e., exon 23 was sequenced with the help of Sanger sequencing method (ABI 373 XL) of thirty patients. Another 100 clinically unaffected controls and family members of the patients in which variants were found also sequenced.

Sanger sequencing method is the gold standard method of determining the order of nucleotide bases (adenine, guanine, cytosine, and thymine). The method involves the synthesis of complementary DNA strand using 3' deoxynucleotide and terminates due to dideoxynucleotides. The four of the dideoxynucleotides are labeled with fluorescent dyes, and all of them emit light at different wavelengths, thus causing base-specific signaling which can be automatically recorded by a detector.

  Results Top

Demographic characterization of patients

Thirty patients from the cohort of cardiomyopathy patients met the criteria for idiopathic form of RCM and thus are included in the study. [Table 1] represents the demographic characteristics of patients. Out of thirty patients, 63.3% represent males and 36.6% were females. The mean age among patients was 31 ± 14.67, and 21.7% cases had an early age of onset. Age of onset in male (29.85 ± 14.4) was lower than female (31.6 ± 14.4) patients. Few patients showed very early age onset, i.e., 21.7% were under 20 years while one patient was only 11 years old. Most of the patients were literate and 16.6% were illiterates. Maximum percentage of patients was from upper middle class with 46.6% than lower middle class (26.6%), upper lower (23.3%), and only one patient in lower class [Table 1].
Table 1: Demographic variables of restrictive cardiomyopathy patients

Click here to view

Clinical characterization of restrictive cardiomyopathy patients

Most of the RCM patients [Table 2] were in the NYHA Class II, i.e., 63.3% while 33.3% were Class III and only 3.33% were Class IV. [Table 2] represents the clinical characters of RCM patients. RCM patients showed a wide range of clinical symptoms such as chest pain, shortness of breath, palpitation, fatigue, arrhythmias, presyncope, syncope, and edema. However, fatigue (66.4%), palpitation (53.3%), and shortness of breath (63.3%) were highest among the patients. Chest pain (40%), arrhythmia (40%), and edema (43.3%) were present in fewer patients, whereas presyncope (16.6%) and syncope (16.6%) symptoms were least present among patients.
Table 2: Clinical symptoms of restrictive cardiomyopathy cases

Click here to view

ECG was performed in all thirty patients and their family members. The most common features present were atrial fibrillation (73.3%), ST-T changes (76.6%), and abnormal sinus rhythm (60.6%). Tachycardia (60.6%) was more common than brachycardia (13.3%). Both left axis deviation (43.3%) and right axis deviation (36.6%) were present. Left bundle branch block (60%) were present in much more patients than right bundle branch block (43.3%). However, in our cohort, atrioventricular block was present in very less percentage (33.3%) among patients, and abnormal Q waves were also seen only in a few patients (36.6%).

On echocardiography examination, the mean left ventricular end-diastole diameter (LVED) was 42.8 ± 8.43 and only increased aorta thickness was 24 ± 3.7. The mean posterior wall (PW) thickness (LVED) was 10.9 ± 2.2, and interventricular septum (IVS) thickness (11.1 ± 2.33) was normal or near normal. Mean ejection fraction among RCM patients was lower than normal, i.e., 50.8 ± 11.5. Both left (76.6%) and right (80%) atria were enlarged in most of the patients. Left ventricle (40%) and right ventricle (20%) were also seen to be enlarged in some patients. Mitral valve regurgitation was absent in 40% patients, mild in 30% patients, moderate in 10%, trivial in 16.6%, and severe in 23.3%. Tricuspid regurgitation was absent in 36.6%, mild in 30%, moderate in 6%, trivial in 3.3%, and severe in 23.3%. Aortic regurgitation was absent in 93.3% patients and present as trivial in only 6.6%.

In our study, ten patients were transformed in a severe form of disease and were listed for the heart transplant, and two died at an early age of 11 years and 9 years old due to sudden cardiac death. Clinical evaluation of patients and family members revealed 100% sporadic cases.

Sanger sequencing of the hotspot region of MYH7 gene

For genetic analysis, sequencing of hot spot region of MYH7 gene, i.e., exon 23 was done on 30 RCM patients and 100 controls. Mutations were found in two patients. No cases of familial RCM were found.

Sequencing of hotspot region exon 23 of MYH7 gene revealed one rare E949K variant in one patient. This rare variant E949K was found in an 11-year-old boy who had a sporadic case of RCM with an early age of onset and severe form of disease with sudden cardiac death. This variant was earlier reported to be associated with HCM with late onset of disease.[24] On clinical screening, parents were found to be unaffected, and the mutation was absent making it a de novo variant and a sporadic case.

In another patient, a compound heterozygous variant E902k and D906N novel variant was found in a 24-year-old lady with an early age of onset and disease who progressed from Class NYHA II to NYHA IV and was registered for heart transplant. Family screening revealed all members unaffected, and the variant was also absent in the family members. These variants were found in highly conserved region of MYH7 gene. In silico assessment of rare and compound heterozygous mutations found to be deleterious.

  Discussion Top

Many classifications have come into light in the past few decades defining and classifying these cardiomyopathies according to the morphology and pathology. However, the European Heart Association defined five major types of cardiomyopathies in the classification such as HCM, dilated cardiomyopathy (DCM), RCM, arrhythmogenic right ventricular cardiomyopathy, and unclassified cardiomyopathies [Table 3].[25]
Table 3: Previous genetic studies for restrictive cardiomyopathy

Click here to view

RCM has a variable age of onset and may develop at any age. Symptoms' severity may range from asymptomatic to severe symptoms. Major complaints of patients are shortness of breath, chest pain, and fatigue, with later development of pulmonary congestion, ascites, and decreased cardiac output. The diagnosis of this condition is rare in early stages [16] and usually made at later stages of the disease only making it more severe to handle with medications,[26] and in later stages, the treatment of choice left is heart transplantation.[27] Due to its scarcity and severe form, the opportunities to define its characters and pathology make it a difficult task. Idiopathic RCM has been reported with very small number of cases.[2],[3],[28],[29]

Here, we report thirty cases of idiopathic RCM patients from a tertiary care unit of India, All India Institute of Medical Sciences, New Delhi. Idiopathic RCM was known to be more prevalent in females than males (1.5:1);[29] however, in our study, male preponderance is more with 2:1 ratio. Earlier studies reported familial occurrence in RCM as seen in HCM and DCM.[7] However, no familial case was reported in our study. Patient underwent series of clinical examinations such as ECG, echocardiography, and chest radiography, with endomyocardial biopsy whenever required. ECG abnormalities in RCM patients are usual. ST-T segment abnormalities are characteristic for RCM which reflect the abnormal diastolic function and repolarization abnormalities of the ventricular muscles.[7] Atrial fibrillation (73.3%) and ST-T abnormalities (76.6%) were the most common features present in this cohort. Abnormal sinus rhythm, left bundle branch block, and left axis deviation were present in 40%–50% patients. In the chest X-ray, appearance of mild-to-moderate cardiomegaly was the common feature seen in patients due to the presence of atrial enlargement. Echocardiography is a noninvasive method of choice for the diagnosis of cardiomyopathies. The diagnosis is based on the characteristics such as nondilated, nonhypertrophied with biatrial enlargement. Consistent with earlier reports, marked atrial enlargement was present in 76.8% of patients in our cohort and found to be prominent finding.[3],[30],[31],[32] With or without diastolic equalization, elevated diastolic pressures are a common feature present in symptomatic patients [3],[33],[34] as seen in our cohort with elevated diastolic pressures are a prominent diagnostic feature. The normal or near normal PW (LVED) and IVS thicknesses provide the basis of pure RCM without hypertrophy of heart.

RCM, as reported in earlier reports, seems to be a progressive disease over time.[3],[34] As recommended, heart transplantation remains the method of choice in the absence of effective treatment.[15],[29],[35] Sudden cardiac death has been seen in patients with stable conditions.[13],[15],[29],[35]

Latest development and advancement of molecular technologies, combining with genetic studies of cardiomyopathies in the past three decades, has revealed a genetic basis as the direct cause of many idiopathic cardiomyopathies.[36] In the past decade, all eight sarcomere genes have been associated with the cause of RCM.[37] In a recent report, we sequenced the hotspot region of MYH7 gene, i.e., exon 23 and one rare (E949K) and two novel compound heterozygous (E902K and D906N) variants were identified.[23] E949K variant was earlier reported to be associated with HCM patient with late age of onset;[24] however, we found this to be associated with a RCM phenotype without hypertrophy and early age of onset of disease.[23] In recent reports, many studies have shown the compound heterozygous and double heterozygous mutations to be associated with RCM.[38],[39] Compound heterozygote mutations were known to cause early age of onset and severe form of disease in cardiomyopathies as seen in our patient present with early age of onset and severe symptoms.[40]

However, more extensive genetic studies with a holistic approach need to be done to understand the pathophysiological mechanism of cardiomyopathies. Next-generation sequencing provides the technique to study the whole genome and exome to understand more fully the genetic basis of cardiomyopathies.

  Conclusion Top

RCM emerged as a genetic disorder in the past decade. Prognosis of RCM is still worse than any other cardiomyopathy with male preponderance. No familial cases were found and 100% are sporadic. Most of the patients showed the early age of onset as symptoms emerged in the first and second decade of life. Shortness of breath and fatigue found to be common symptoms. Genetic screening of the MYH7 exon 23 hotspot regions could only explain 6.6% of RCM cases. To understand the pathophysiological mechanism of cardiomyopathies, the combinations of thorough clinical and genetic studies are the need of the hour.[61]

Financial support and sponsorship

The present study was conducted with the financial support from Department of Biotechnology, Government of India to VRR (BT/PR5767/MED/12/563/2012).

Conflicts of interest

There are no conflicts of interest.

  References Top

Brandenburg RO, Chazov E, Cherian G, Falase AO, Grosgogeat Y, Kawai C, et al. Report of the WHO/ISFC task force on definition and classification of cardiomyopathies. Circulation 1981;64:437A-8A.  Back to cited text no. 1
Benotti JR, Grossman W, Cohn PF. Clinical profile of restrictive cardiomyopathy. Circulation 1980;61:1206-12.  Back to cited text no. 2
Siegel RJ, Shah PK, Fishbein MC. Idiopathic restrictive cardiomyopathy. Circulation 1984;70:165-9.  Back to cited text no. 3
Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology task force on the definition and classification of cardiomyopathies. Circulation 1996;93:841-2.  Back to cited text no. 4
Wood P. Chronic constrictive pericarditis. Am J Cardiol 1961;7:48-61.  Back to cited text no. 5
Nihoyannopoulos P, Dawson D. Restrictive cardiomyopathies. Eur Heart J Cardiovasc Imaging 2009;10:iii23-33.  Back to cited text no. 6
Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl J Med 1997;336:267-76.  Back to cited text no. 7
Lipshultz SE, Sleeper LA, Towbin JA, Lowe AM, Orav EJ, Cox GF, et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med 2003;348:1647-55.  Back to cited text no. 8
Kubo T, Gimeno JR, Bahl A, Steffensen U, Steffensen M, Osman E, et al. Prevalence, clinical significance, and genetic basis of hypertrophic cardiomyopathy with restrictive phenotype. J Am Coll Cardiol 2007;49:2419-26.  Back to cited text no. 9
Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, et al. Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. J Clin Invest 2003;111:209-16.  Back to cited text no. 10
Peddy SB, Vricella LA, Crosson JE, Oswald GL, Cohn RD, Cameron DE, et al. Infantile restrictive cardiomyopathy resulting from a mutation in the cardiac troponin T gene. Pediatrics 2006;117:1830-3.  Back to cited text no. 11
Rai TS, Ahmad S, Bahl A, Ahuja M, Ahluwalia TS, Singh B, et al. Genotype phenotype correlations of cardiac beta-myosin heavy chain mutations in Indian patients with hypertrophic and dilated cardiomyopathy. Mol Cell Biochem 2009;321:189-96.  Back to cited text no. 12
Weller RJ, Weintraub R, Addonizio LJ, Chrisant MR, Gersony WM, Hsu DT, et al. Outcome of idiopathic restrictive cardiomyopathy in children. Am J Cardiol 2002;90:501-6.  Back to cited text no. 13
Fenton MJ, Chubb H, McMahon AM, Rees P, Elliott MJ, Burch M, et al. Heart and heart-lung transplantation for idiopathic restrictive cardiomyopathy in children. Heart 2006;92:85-9.  Back to cited text no. 14
Kimberling MT, Balzer DT, Hirsch R, Mendeloff E, Huddleston CB, Canter CE, et al. Cardiac transplantation for pediatric restrictive cardiomyopathy: Presentation, evaluation, and short-term outcome. J Heart Lung Transplant 2002;21:455-9.  Back to cited text no. 15
Chen SC, Balfour IC, Jureidini S. Clinical spectrum of restrictive cardiomyopathy in children. J Heart Lung Transplant 2001;20:90-2.  Back to cited text no. 16
Denfield SW, Rosenthal G, Gajarski RJ, Bricker JT, Schowengerdt KO, Price JK, et al. Restrictive cardiomyopathies in childhood. Etiologies and natural history. Tex Heart Inst J 1997;24:38-44.  Back to cited text no. 17
Cetta F, O'Leary PW, Seward JB, Driscoll DJ. Idiopathic restrictive cardiomyopathy in childhood: Diagnostic features and clinical course. Mayo Clin Proc 1995;70:634-40.  Back to cited text no. 18
Bograd AJ, Mital S, Schwarzenberger JC, Mosca RS, Quaegebeur JM, Addonizio LJ, et al. Twenty-year experience with heart transplantation for infants and children with restrictive cardiomyopathy: 1986-2006. Am J Transplant 2008;8:201-7.  Back to cited text no. 19
Das S, Biswas A, Kapoor M, Seth S, Bhargava B, Rao VR. Epidemiology of cardiomyopathy – A clinical and genetic study of dilated cardiomyopathy: The EPOCH-D study. J Pract Cardiovasc Sci 2015;1:30.  Back to cited text no. 20
Biswas A, Das S, Kapoor M, Seth S, Bhargava B, Rao VR. Epidemiology of cardiomyopathy – A clinical and genetic study of hypertrophic cardiomyopathy: The EPOCH-H study. J Pract Cardiovasc Sci 2015;1:143.  Back to cited text no. 21
Thangaraj K, Joshi MB, Reddy AG, Gupta NJ, Chakravarty B, Singh L, et al. CAG repeat expansion in the androgen receptor gene is not associated with male infertility in Indian populations. J Androl 2002;23:815-8.  Back to cited text no. 22
Kapoor M, Das S, Biswas A, Seth S, Bhargava B, Rao VR. Mutations in hotspot region of MYH7 gene exon 23 associated with restrictive cardiomyopathy. Cardiogenetics 2017;7,6358:1-5.  Back to cited text no. 23
Watkins H, Rosenzweig A, Hwang DS, Levi T, McKenna W, Seidman CE, et al. Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy. N Engl J Med 1992;326:1108-14.  Back to cited text no. 24
Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, et al. Classification of the cardiomyopathies: A position statement from the European Society of Cardiology working group on myocardial and pericardial diseases. Eur Heart J 2008;29:270-6.  Back to cited text no. 25
Palka P, Lange A, Donnelly JE, Nihoyannopoulos P. Differentiation between restrictive cardiomyopathy and constrictive pericarditis by early diastolic Doppler myocardial velocity gradient at the posterior wall. Circulation 2000;102:655-62.  Back to cited text no. 26
Nield LE, McCrindle BW, Bohn DJ, West LJ, Coles JG, Freedom RM, et al. Outcomes for children with cardiomyopathy awaiting transplantation. Cardiol Young 2000;10:358-66.  Back to cited text no. 27
Shabetai R. Pathophysiology and differential diagnosis of restrictive cardiomyopathy. Cardiovasc Clin 1988;19:123-32.  Back to cited text no. 28
Ammash NM, Seward JB, Bailey KR, Edwards WD, Tajik AJ. Clinical profile and outcome of idiopathic restrictive cardiomyopathy. Circulation 2000;101:2490-6.  Back to cited text no. 29
Chew CY, Ziady GM, Raphael MJ, Nellen M, Oakley CM. Primary restrictive cardiomyopathy. Non-tropical endomyocardial fibrosis and hypereosinophilic heart disease. Br Heart J 1977;39:399-413.  Back to cited text no. 30
Patton JN, Tajik AJ, Reeder GS, Edwards WD, Seward JB. Echocardiographic nondilated, nonhypertrophic (restrictive) cardiomyopathy-clinical profile and natural-history. J Am Coll Cardiol 1983;1:738.  Back to cited text no. 31
Mehta AV, Ferrer PL, Pickoff AS, Singh SS, Wolff GS, Tamer DS, et al. M-mode echocardiographic findings in children with idiopathic restrictive cardiomyopathy. Pediatr Cardiol 1984;5:273-9.  Back to cited text no. 32
Janos GG, Arjunan K, Meyer RA, Engel P, Kaplan S. Differentiation of constrictive pericarditis and restrictive cardiomyopathy using digitized echocardiography. J Am Coll Cardiol 1983;1:541-9.  Back to cited text no. 33
Hosenpud JD, Niles NR. Clinical, hemodynamic and endomyocardial biopsy findings in idiopathic restrictive cardiomyopathy. West J Med 1986;144:303-6.  Back to cited text no. 34
Russo LM, Webber SA. Idiopathic restrictive cardiomyopathy in children. Heart 2005;91:1199-202.  Back to cited text no. 35
Arimura T, Hayashi T, Matsumoto Y, Shibata H, Hiroi S, Nakamura T, et al. Structural analysis of four and half LIM protein-2 in dilated cardiomyopathy. Biochem Biophys Res Commun 2007;357:162-7.  Back to cited text no. 36
Caleshu C, Sakhuja R, Nussbaum RL, Schiller NB, Ursell PC, Eng C, et al. Furthering the link between the sarcomere and primary cardiomyopathies: Restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy. Am J Med Genet A 2011;155A: 2229-35.  Back to cited text no. 37
Blok R, van den Wijngaard A, Merckx D. Two Novel TNNI3 Mutations in Restrictive Cardiomyopathy [Poster P0135]. In Poster Presented at: European Human Genetics Conference; May, 2005. p. 7-10.  Back to cited text no. 38
Kelly M, Semsarian C. Multiple mutations in genetic cardiovascular disease: A marker of disease severity? Circ Cardiovasc Genet 2009;2:182-90.  Back to cited text no. 39
Zhang J, Kumar A, Kaplan L, Fricker FJ, Wallace MR. Genetic linkage of a novel autosomal dominant restrictive cardiomyopathy locus. J Med Genet 2005;42:663-5.  Back to cited text no. 40
Cubero GI, Larraya GL, Reguero JR. Familial restrictive cardiomyopathy with atrioventricular block without skeletal myopathy. Exp Clin Cardiol 2007;12:54.  Back to cited text no. 41
Kaski JP, Syrris P, Burch M, Tomé-Esteban MT, Fenton M, Christiansen M, et al. Idiopathic restrictive cardiomyopathy in children is caused by mutations in cardiac sarcomere protein genes. Heart 2008;94:1478-84.  Back to cited text no. 42
Karam S, Raboisson MJ, Ducreux C, Chalabreysse L, Millat G, Bozio A, et al. A de novo mutation of the beta cardiac myosin heavy chain gene in an infantile restrictive cardiomyopathy. Congenit Heart Dis 2008;3:138-43.  Back to cited text no. 43
Ware SM, Quinn ME, Ballard ET, Miller E, Uzark K, Spicer RL, et al. Pediatric restrictive cardiomyopathy associated with a mutation in beta-myosin heavy chain. Clin Genet 2008;73:165-70.  Back to cited text no. 44
Menon SC, Michels VV, Pellikka PA, Ballew JD, Karst ML, Herron KJ, et al. Cardiac troponin T mutation in familial cardiomyopathy with variable remodeling and restrictive physiology. Clin Genet 2008;74:445-54.  Back to cited text no. 45
Kostareva A, Gudkova A, Sjöberg G, Mörner S, Semernin E, Krutikov A, et al. Deletion in TNNI3 gene is associated with restrictive cardiomyopathy. Int J Cardiol 2009;131:410-2.  Back to cited text no. 46
Rai TS, Ahmad S, Ahluwalia TS, Ahuja M, Bahl A, Saikia UN, et al. Genetic and clinical profile of Indian patients of idiopathic restrictive cardiomyopathy with and without hypertrophy. Mol Cell Biochem 2009;331:187-92.  Back to cited text no. 47
Yang SW, Hitz MP, Andelfinger G. Ventricular septal defect and restrictive cardiomyopathy in a paediatric TNNI3 mutation carrier. Cardiol Young 2010;20:574-6.  Back to cited text no. 48
van den Wijngaard A, Volders P, Van Tintelen JP, Jongbloed JD, van den Berg MP, Lekanne Deprez RH, et al. Recurrent and founder mutations in the Netherlands: Cardiac troponin I (TNNI3) gene mutations as a cause of severe forms of hypertrophic and restrictive cardiomyopathy. Neth Heart J 2011;19:344-51.  Back to cited text no. 49
Peled Y, Gramlich M, Yoskovitz G, Feinberg MS, Afek A, Polak-Charcon S, et al. Titin mutation in familial restrictive cardiomyopathy. Int J Cardiol 2014;171:24-30.  Back to cited text no. 50
Wu W, Lu CX, Wang YN, Liu F, Chen W, Liu YT, et al. Novel phenotype-genotype correlations of restrictive cardiomyopathy with myosin-binding protein C (MYBPC3) gene mutations tested by next-generation sequencing. J Am Heart Assoc 2015;4. pii: e001879.  Back to cited text no. 51
Brodehl A, Ferrier RA, Hamilton SJ, Greenway SC, Brundler MA, Yu W, et al. Mutations in FLNC are associated with familial restrictive cardiomyopathy. Hum Mutat 2016;37:269-79.  Back to cited text no. 52
Mouton JM, Pellizzon AS, Goosen A, Kinnear CJ, Herbst PG, Brink PA, et al. Diagnostic disparity and identification of two TNNI3 gene mutations, one novel and one arising de novo, in South African patients with restrictive cardiomyopathy and focal ventricular hypertrophy: Cardiovascular topic. Cardiovasc J Afr 2015;26:63-9.  Back to cited text no. 53
Yu HC, Coughlin CR, Geiger EA, Salvador BJ, Elias ER, Cavanaugh JL, et al. Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy. Cold Spring Harb Mol Case Stud 2016;2:a000844.  Back to cited text no. 54
Ruan YP, Lu CX, Zhao XY, Liang RJ, Lian H, Routledge M, et al. Restrictive cardiomyopathy resulting from a troponin I type 3 mutation in a Chinese family. Chin Med Sci J 2016;31:1-7.  Back to cited text no. 55
Kostareva A, Kiselev A, Gudkova A, Frishman G, Ruepp A, Frishman D, et al. Genetic spectrum of idiopathic restrictive cardiomyopathy uncovered by next-generation sequencing. PLoS One 2016;11:e0163362.  Back to cited text no. 56
Ploski R, Rydzanicz M, Ksiazczyk TM, Franaszczyk M, Pollak A, Kosinska J, et al. Evidence for troponin C (TNNC1) as a gene for autosomal recessive restrictive cardiomyopathy with fatal outcome in infancy. Am J Med Genet A 2016;170:3241-8.  Back to cited text no. 57
Ouellette AC, Mathew J, Manickaraj AK, Manase G, Zahavich L, Wilson J, et al. Clinical genetic testing in pediatric cardiomyopathy: Is bigger better? Clin Genet 2018;93:33-40.  Back to cited text no. 58
JurcuŢ RO, Bastian AE, Militaru S, Popa A, Manole E, Popescu BA, et al. Discovery of a new mutation in the desmin gene in a young patient with cardiomyopathy and muscular weakness. Rom J Morphol Embryol 2017;58:225-30.  Back to cited text no. 59
Hwang JW, Jang MA, Jang SY, Seo SH, Seong MW, Park SS, et al. Diverse phenotypic expression of cardiomyopathies in a family with TNNI3 p. Arg145Trp mutation. Korean Circ J 2017;47:270-7.  Back to cited text no. 60
Brodehl A, Gaertner-Rommel A, Klauke B, Grewe SA, Schirmer I, Peterschröder A, et al. The novel αB-crystallin (CRYAB) mutation p.D109G causes restrictive cardiomyopathy. Hum Mutat 2017;38:947-52.  Back to cited text no. 61


  [Figure 1]

  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 Unusual case of restrictive cardiomyopathy in young
Archit Dahiya, Deepesh Agarwal, Naveen Gupta, Harsh Wardhan, Jai Chowdhary
IHJ Cardiovascular Case Reports (CVCR). 2021;
[Pubmed] | [DOI]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
   Article Figures
   Article Tables

 Article Access Statistics
    PDF Downloaded371    
    Comments [Add]    
    Cited by others 1    

Recommend this journal