Cases Of Idiopathic Dilated Cardiomyopathy Research Articles

Identification and in silico characterization of CSRP3 synonymous variants in dilated cardiomyopathy

Synonymous variations have always been ignored while studying the underlying genetic mechanisms for most of the human diseases. However, recent studies have suggested that these silent changes in the genome can alter the protein expression and folding. CSRP3, which is a well-known candidate gene associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), was screened for 100 idiopathic DCM cases and 100 controls. Three synonymous variations were identified viz., c.96G > A, p.K32=; c.336G > A, p.A112=; c.354G > A, p.E118=. A comprehensive in silico analysis was performed using various web based widely accepted tools, Mfold, Codon Usage, HSF3.1 and RNA22. Mfold predicted structural changes in all the variants except c.96 G > A (p.K32=), however it predicted changes in the stability of mRNA due to all the synonymous variants. Codon bias was observed as evident by the Relative Synonymous Codon Usage and Log Ratio of Codon Usage Frequencies. The Human Splicing Finder also predicted remarkable changes in the regulatory elements in the variants c.336G > A and c.354 G > A. The miRNA target prediction using varied modes available in RNA22 revealed that 70.6% of the target sites of miRNAs in CSRP3 were altered due to variant c.336G > A while 29.41% sites were completely lost. Findings of the present study suggest that synonymous variants revealed striking deviations in the structural conformation of mRNA, stability of mRNA, relative synonymous codon usage, splicing and miRNA binding sites from the wild type suggesting their possible role in the pathogenesis of DCM, either by destabilizing the mRNA structure, or codon usage bias or else altering the cis-acting regulatory elements during splicing.

Subclinical hypothyroidism and dilated cardiomyopathy (DCM) in children

Introduction: Subclinical hypothyroidism is defined by the combination of an elevated thyroid-stimulating hormone (TSH) level and a normal free thyroxine (T4L) level. Dilated cardiomyopathy is characterized by both dilation of the ventricles and hypokinesia of these ventricles. It predominantly involves the left ventricle, but the right ventricle is frequently involved.We present two cases of idiopathic dilated cardiomyopathy associated with a subclinical picture of hypothyroidism. Case report 1: An 11-year-old female patient was admitted to cardiology for congestive heart failure on CMD; she presented with New York Heart Association (NYHA) stage IV dyspnea and generalized edema. Tran’s thoracic echocardiography showed left ventricular (LV) dilatation with global hypokinesia, LV ejection fraction at 15%. The biological workup showed a subclinical hypothyroidism profile with TSH at 11.2 mIU/l, T4: 21.2 pmol/l, T3: 4.2pmol/l. Case report 2: A 9-year-old patient, without any notable history, was referred to the cardiology department for global cardiac decompensation with NYHA stage IV dyspnea and lower limb edema despite optimal medical treatment. Tran’s thoracic echocardiography showed dilated cardiomyopathy with severe impairment of LV systolic function (10%). The biological workup showed a subclinical hypothyroidism profile with TSH: 7.7 mIU/l, T4: 19.2 pmol/l. Conclusion: Dilated cardiomyopathies (DCM) represent the most common cardiomyopathies in children either of constitutional or acquired origin. Subclinical hypothyroidism is frequently observed in patients with DCM and increases the risk of mortality.

Rare variants in the FBN1 gene are associated with sporadic dilated cardiomyopathy in a Chinese Han population

Introduction: Dilated cardiomyopathy (DCM) represents a diverse set of myocardial diseases characterized by notable genetic heterogeneity. Although over 50 genes have been associated with DCM, these collectively explain 35% of idiopathic DCM cases. Variants in the FBN1 gene encoding fibrillin-1 are primarily linked to connective tissue disorders. Considering the potential of these disorders to impact myocardial tissue, this study probes into the possible association between FBN1 variants and DCM. Aim: The objective of this study was to investigate the association between FBN1 variants and DCM in a Chinese Han population. Methods and Results: We performed whole-exome sequencing (WES) to identify rare FBN1 variants among 1,059 DCM cases and 514 controls. Utilizing a case-control strategy and the optimal sequence kernel association test (SKAT-O), we found a significant enrichment of rare deleterious FBN1 variants in DCM patients (19 of 1,059 vs. 0 of 514, PSKAT-O = 7.49E-04). Clinical characteristics analysis indicated a higher occurrence of atrial fibrillation and a higher rate of implantable cardioverter-defibrillator (ICD) implantation among DCM patients carrying FBN1 variants (FBN1+) compared to non-carriers (FBN1-). However, these FBN1 variants did not significantly affect primary endpoints, defined as cardiac mortality or heart transplantation, yet appeared to increase the risk of secondary endpoints, including all-cause mortality or heart failure recurrence. Conclusion: The findings suggest an association between rare deleterious variants in the FBN1 gene and DCM in a Chinese Han population. Our findings underline the importance of further research to validate these results and elucidate the role of FBN1 in DCM. Potential Impact of the findings: This research provides fresh insights into the potential role of FBN1 rare variants in DCM, pointing to new directions for future genetic studies and potential therapeutic strategies in DCM management.

Idiopathic dilated cardiomyopathy as cor bovinum in infancy: “A foggy road in winter”

Dilated cardiomyopathy, when diagnosed in infancy, poses an array of difficulties from reaching an etiological diagnosis to prognosticating the long-term outcome. Here, we report a case of idiopathic dilated cardiomyopathy in a 6-month-old child who responded well to beta-blocker (Carvedilol) in optimum dosage and revealed favorable cardiac remodeling over 6 months with substantial improvement in ejection fraction (EF) (EF of 22–44%) with significant amelioration of child’s symptoms. Our case has a unique message that while treating idiopathic dilated cardiomyopathy (DCM) in infancy, optimized use of the beta-blockers is most often the only way to clear the foggy road of idiopathic DCM and obtain a favorable outcome.

Frequency of Peripartum Cardiomyopathy Among Women With Idiopathic Dilated Cardiomyopathy

Among women with idiopathic dilated cardiomyopathy (IDC), the percent who develop heart failure (HF) in the peripartum period (during pregnancy or within 6 months of parturition) compared with those women who develop HF outside the peripartum period is unclear. We studied 72 women with IDC who underwent orthotopic heart transplantation for severe HF, the onset of which was in the peripartum period in 8 (11%) and outside the period in 64 (89%). Comparison of many clinical and morphologic variables between these 2 groups showed significant differences only in the ages of onset of HF, age when orthotopic heart transplantation was performed, and the frequency of the presence of diabetes mellitus. Examination of the hearts in the 2 groups disclosed no significant differences. Thus, separation of the peripartum IDC cases from the nonperipartum IDC cases by either clinical or cardiac morphologic variables is difficult.

Genetic analysis using targeted next-generation sequencing of sporadic Chinese patients with idiopathic dilated cardiomyopathy

BackgroundInherited dilated cardiomyopathy (DCM) contributes to approximately 25% of idiopathic DCM cases, and the proportion is even higher in familial DCM patients. Most studies have focused on familial DCM, whereas the genetic profile of sporadic DCM in Chinese patients remains unknown.MethodsBetween June 2018 and September 2019, 24 patients diagnosed with idiopathic DCM without a family history were included in the present study. All patients underwent genetic screening for 80 DCM-related genes using targeted next-generation sequencing.ResultsBy in silico analysis, 10 of 99 detected variants were considered pathogenic or likely-pathogenic, including seven TTN truncating variants (TTNtv), one in-frame deletion in TNNT2, one missense mutation in RBM20, and one frameshift deletion variant in FLNC. Of these variants, eight are reported for the first time.ConclusionsUsing targeted next-generation sequencing, potential genetic causes of idiopathic DCM were identified. Sarcomere mutations remained the most common genetic cause of inherited DCM in this cohort of sporadic Chinese DCM.

Role of family history and clinical screening in the identification of families with idiopathic dilated cardiomyopathy in Johannesburg, South Africa.

Familial disease is implicated in 20 - 50% of cases of idiopathic dilated cardiomyopathy (IDCM) worldwide. The contribution of familial factors to IDCM in the Johannesburg area, South Africa, is unknown. To describe the demographic details of patients with IDCM who presented at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), and to determine if there is evidence of familial disease through family history assessment and clinical screening of relatives. This was a single-centre, cohort study performed at a quaternary care centre at CMJAH. Fifty unrelated probands diagnosed with IDCM and available first- and second-degree relatives were included in the study. A three-generation family pedigree was drawn up for all 50 probands. The pedigrees were analysed to identify the presence or absence of familial disease and categorised as positive, intermediate, negative or unreliable according to the family history obtained. From the 50 proband cases, there were 21 family members available for screening for features of IDCM. Eighty-two family members (55 first-degree and 27 second-degree relatives) were screened clinically. Screening included a personal history, full physical examination, electrocardiogram (ECG) and echocardiogram. The mean age at diagnosis of IDCM in the probands was 41.7 (standard deviation (SD) 12.4) years. The majority of probands were males (n=38; 76%). Of 50 pedigrees analysed, 14 (28%) were positive and likely to be indicative of familial dilated cardiomyopathy (DCM), and 9 (18%) patients were at intermediate risk of familial disease. Eighty-two asymptomatic family members were screened, with a median age of 33 (range 11 - 76) years. No asymptomatic family members were identified with features of DCM or presymptomatic DCM. Eleven of the 21 families screened had relatives with possible presymptomatic DCM identified by abnormalities on the echocardiogram in 3 families (14.3%) (4 individuals; all first-degree relatives of the index case) or identified on the basis of a conduction defect (an arrhythmia or first-/ second-/third-degree heart block) in 8 families (72.7%) (11 individuals; 9 first-degree and 2 second-degree relatives). Screening for IDCM should include a three-generation family history and clinical screening of all first-degree family members. As IDCM has an age-related penetrance, at-risk family members should receive follow-up for screening to assess symptoms and signs of IDCM. Genetic testing would potentially identify family members at high risk, who would benefit from screening; this might be a less expensive option.

Case Study: Dilated Cardiomyopathy Evolves into Apical-Variant Hypertrophic Cardiomyopathy

Introduction Apical-variant hypertrophic cardiomyopathy (HCM) is a form of HCM in which hypertrophy is limited to the left-ventricular apex. Apical-variant HCM is rarely obstructive, though there is still an increased risk of atrial fibrillation, myocardial infarction, and sudden cardiac death (SCD). Apical-variant HCM has not previously been described in a patient with a prior diagnosis of dilated cardiomyopathy (DCM). Case A 53-year-old female with a history of hypertension and type-II diabetes mellitus presented with progressive dyspnea on exertion, fatigue and lower extremity swelling. Family history was significant for SCD of her mother at age 45. An initial transthoracic echocardiogram (TTE) showed DCM with an ejection fraction (EF) 15% and left ventricular end diastolic dimension (LVEDD) of 6.8 cm. The patient was placed on guideline-directed medical therapy (GDMT) and ultimately received cardiac resynchronization therapy with a defibrillator (CRT-D). One year later, EF was 25% with LVEDD 7.1 cm (Figure 1). A subsequent TTE two years later showed resolution of DCM with EF 55% and LVEDD of 5.1 cm. However, a new finding on this TTE was apparent: the apex demonstrated a spade-like shape on contraction consistent with apical-variant HCM (Figure 2). The patient underwent genetic testing but no genetic cause of either DCM or HCM was identified. Discussion HCM is caused by autosomal-dominant inheritance of a defective gene in sarcomere proteins. DCM and HCM are linked in that some etiologies of DCM are driven by sarcomeric protein abnormalities. DCM is also a rare phenotypical variant of HCM generally occurring very late in the disease and evolving from an initially hypertrophic myocardium. The opposite, in which DCM evolves into apical-variant HCM, to the best of our knowledge, has not been described in the literature. This relationship, as well as a family history of early SCD, suggest an inherited sarcomeric disorder manifesting as two discrete phenotypes within the same individual. This evolution may be due to treatment with GDMT, or it may be a rare expression of the disease's natural history. Only a fraction of cases of idiopathic DCM and HCM have an identifiable genetic cause and, thus, lacking an identified mutation does not preclude an inherited cardiomyopathy.

THE TITAN OF THE HEART: A CURIOUS CASE OF TITIN MUTATION INDUCED CARDIOMYOPATHY

Titin, a giant sarcomeric protein, is a key determinant of myocardial passive stiffness and stress-sensitive signaling. Gene mutations leading to truncated titin variants (TitinTr) reportedly cause 25% of familial dilated cardiomyopathy (DCM) and 13% of idiopathic DCM cases. A 46 year old female

Toward Genetics-Driven Early Intervention in Dilated Cardiomyopathy: Design and Implementation of the DCM Precision Medicine Study.

The cause of idiopathic dilated cardiomyopathy (DCM) is unknown by definition, but its familial subtype is considered to have a genetic component. We hypothesize that most idiopathic DCM, whether familial or nonfamilial, has a genetic basis, in which case a genetics-driven approach to identifying at-risk family members for clinical screening and early intervention could reduce morbidity and mortality. On the basis of this hypothesis, we have launched the National Heart, Lung, and Blood Institute- and National Human Genome Research Institute-funded DCM Precision Medicine Study, which aims to enroll 1300 individuals (600 non-Hispanic African ancestry, 600 non-Hispanic European ancestry, and 100 Hispanic) who meet rigorous clinical criteria for idiopathic DCM along with 2600 of their relatives. Enrolled relatives will undergo clinical cardiovascular screening to identify asymptomatic disease, and all individuals with idiopathic DCM will undergo exome sequencing to identify relevant variants in genes previously implicated in DCM. Results will be returned by genetic counselors 12 to 14 months after enrollment. The data obtained will be used to describe the prevalence of familial DCM among idiopathic DCM cases and the genetic architecture of idiopathic DCM in multiple ethnicity-ancestry groups. We will also conduct a randomized controlled trial to test the effectiveness of Family Heart Talk, an intervention to aid family communication, for improving uptake of preventive screening and surveillance in at-risk first-degree relatives. We anticipate that this study will demonstrate that idiopathic DCM has a genetic basis and guide best practices for a genetics-driven approach to early intervention in at-risk relatives. URL: http://www.clinicaltrials.gov. Unique identifier: NCT03037632.

Autosomal Dominant Polycystic Kidney Patients May Be Predisposed to Various Cardiomyopathies

IntroductionMutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). Experimental evidence suggests an important role of the polycystins in cardiac development and myocardial function. To determine whether ADPKD may predispose to the development of cardiomyopathy, we have evaluated the coexistence of diagnoses of ADPKD and primary cardiomyopathy in our patients.MethodsClinical data were retrieved from medical records for patients with a coexisting diagnosis of ADPKD and cardiomyopathies evaluated at the Mayo Clinic (1984–2015).ResultsAmong the 58 of 667 patients with available echocardiography data, 39 (5.8%) had idiopathic dilated cardiomyopathy (IDCM), 17 (2.5%) had hypertrophic obstructive cardiomyopathy, and 2 (0.3%) had left ventricular noncompaction. Genetic data were available for 19, 8, and 2 cases of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction, respectively. PKD1 mutations were detected in 42.1%, 62.5%, and 100% of IDCM, hypertrophic obstructive cardiomyopathy, and left ventricular noncompaction cases, respectively. PKD2 mutations were detected only in IDCM cases and were overrepresented (36.8%) relative to the expected frequency in ADPKD (15%). In at least 1 patient from 3 IDMC families and 1 patient from a hypertrophic obstructive cardiomyopathy family, the cardiomyopathy did not segregate with ADPKD, suggesting that the PKD mutations may be predisposing factors rather than solely responsible for the development of cardiomyopathy.DiscussionCoexistence of ADPKD and cardiomyopathy in our tertiary referral center cohort appears to be higher than expected by chance. We suggest that PKD1 and PKD2 mutations may predispose to primary cardiomyopathies and that genetic interactions may account for the observed coexistence of ADPKD and cardiomyopathies.

Left ventricular systolic dysfunction in two patients with ankylosing spondylitis: What is the role of corticosteroids?

Ankylosing spondylitis (AS) is a chronic inflammatory condition that most commonly affects the axial skeleton. The most common cardiac manifestation in patients with AS is the aortic root and valve disease, followed by conduction and rhythm abnormalities, decreased coronary flow reserve, myocardial infarction, and diastolic dysfunction. However, the presence of systolic dysfunction has been less described in patients with AS. Herein we present two cases of idiopathic dilated cardiomyopathy in patients with AS. These patients were noted to have an improvement of their ejection fraction following treatment of AS. Clinical and echocardiographic improvement on anti-inflammatory treatment might be a clue to the inflammatory nature of this myocardial problem, and further investigations to study the issue is required.

Acute Fulminant Giant Cell Myocarditis Presenting with Syncopal Events Treated Successfully with Orthotopic Heart Transplant

ABSTRACT Myocarditis is a major cause of end-stage heart failure and is responsible for up to 10% of cases of idiopathic dilated cardiomyopathy. Giant cell myocarditis is a particularly fulminant disease that has a poor response to immunosuppressive therapy. Cardiac transplantation is the definitive treatment.

Modified Batista Procedure for Idiopathic Dilated Cardiomyopathy: Report of a Case

The surgical indications for dilated cardiomyopathy (DCM) remain controversial, not including cardiac transplantation and mechanical circulatory support. We describe a case of idiopathic DCM that underwent successful surgical treatment using a modified left ventriculectomy, modification of the Batista procedure. The patient was a 63-year-old man who suffered from heart failure, New York Heart Association (NYHA) Class IV. Heart failure was derived from idiopathic DCM with a severely compromised left ventricular function complicated by left ventricular thrombosis. He underwent successful surgical treatment, specifically partial left ventriculectomy combined with the papillary muscle approximation, and the postoperative course was uneventful. He has been well with NYHA Class I for 3 years after the operation without heart failure.

BRCA1 Reflects Myocardial Adverse Remodeling in Idiopathic Dilated Cardiomyopathy

BackgroundThe role of BRCA1 in chronic ischemic episodes seems to be pivotal for adverse remodeling and development of ischemic cardiomyopathy, because of its role in DNA repair and apoptosis. The aim of this study was to investigate the role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM). Material and MethodsThe study group (IDCM) comprised myocardial samples from hearts explanted before transplantation owing to IDCM in 10 males (age 44 ± 5.3 years) without clinical symptoms of ischemic heart disease. The control group consisted myocardial fragments taken from 10 male heart valve and pulmonary artery donors with diagnosed cerebral death (age 40 ± 2.3 years). BRCA1 was detected immunohistochemically with rabbit anti-BRCA1 polyclonal antibody. The intensity of BRCA1 expression was semiquantitatively assessed for cardiocytes, small vessels including capillaries, and interstitial cells. The significances between groups were estimated using the Mann-Whitney U test. ResultsAll IDCM cases were positive and presented nonuniform BRCA1 expression: hypertrophied cardiocytes showed very intense staining and typical cardiomyopathic cardiocytes were stained weakly forming mosaic. Control cases showed weak-to-moderate uniform staining. Intensity of staining was significantly higher in IDCM cardiocytes, whereas small vessels and interstitial were stained similarly in both groups. ConclusionsIDCM adverse remodeling results in more intense but nonuniform BRCA1 expression. This phenomenon seems to reflect IDCM biology: lower BRCA1 expression in myocytes with lower anti-apoptotic and DNA damage repair activity, with the opposite in hypertrophied myofibers.

Variants of resistin gene and the risk of idiopathic dilated cardiomyopathy in Pakistan

BackgroundIn cardiovascular disease phenotypes, a genetic factor is an important determinant of both familial and non-familial dilated cardiomyopathies. Resistin is a novel adipocyte derived peptide, associated with inflammation and suggested to be involved in contractile abnormalities of cardiomyocytes. MethodsIn this study, we examined the association of the RETN SNPs in −420 and +299 in patients with idiopathic dilated cardiomyopathy (IDCM). Patients with IDCM (n=250) and healthy controls (n=250) were enrolled in this study. RETN genotyping was performed by using PCR-RFLP method. ResultsRETN −420C>G and +299G>A polymorphisms were significantly more prevalent in patient group vs. controls (P<0.0001 and P=0.0007, respectively). GG genotype at −420 and AA genotype at +299 were higher in the patient group compared with healthy controls (OR=11.4, P<0.0001, and OR=2.3, P=0.030, respectively). We found that the −420G allele increased the risk of developing IDCM in patients (P<0.0001). Moreover, there was a significant difference between G and A alleles at RETN +299 from IDCM cases and controls (P=0.0032). The RETN −420G and +299A haplotypes were more prevalent in the patient vs. control group (P<0.0001). ConclusionThe results suggest that the RETN −420C>G and +299G>A polymorphisms may have a role in the pathogenesis of IDCM.

Comparative study of peripartum cardiomyopathy and idiopathic dilated cardiomyopathy MRI

Objective To characterize the cardiac magnetic resonance (CMR) features of peripartum cardiomyopathy(PPCM) and idiopathic dilated cardiomyopathy (IDCM) , and to explore the value of MRI in the diagnosis of PPCM. Methods Ten cases of PPCM and 10 cases of Idiopathic dilated cardiomyopathy (IDCM) were included in this study. With 1.5 T MRI scanner, the heart shape (atrioventricular size, hypertrabeculation, thickness of the thinnest ventricular wall), function (ventricular wall movement and the overall function), cardiomyopathy perfusion were comprehensively evaluated. Paired samplest-test andFisher exact probability method were used for statistical analysis. Results Between PPCM and IDCM group, there was no statistical significant difference in the atrioventricular size, cardiac output(CO), end diastolic volume(EDV), ejection fraction (EF), end systolic volume (ESV) and stroke volume (SV) (P> 0.05). IDCM and PPCM group both showed ventricular wall thinning on MRI, with 4 cases of PPCM and 3 cases of IDCM presenting hypertrabeculation in the left ventricular apex. Seven cases of PPCM and 4 cases of IDCM depicted left ventricular local dysfunction, while 3 cases of PPCM and 6 cases of IDCM had abnormal integral movement. Two cases of PPCM appeared local delayed enhancement, while 4 cases of IDCM showed intramural delayed enhancement. After one year of follow-up, heart function recovered in 10 cases of PPCM and 4 cases of IDCM. Conclusions MRI diagnosis using multiple sequences is an ideal method in the evaluation of PPCM. Although there were no differences in cardiac morphology and function between PPCM and IDCM, the prognosis of PPCM is better than IDCM. Key words: Magnetic resonance imaging; Cardiomyopathies; Diagnosis

Functional Amyloid Signaling via the Inflammasome, Necrosome, and Signalosome: New Therapeutic Targets in Heart Failure.

As the most common cause of death and disability, globally, heart disease remains an incompletely understood enigma. A growing number of cardiac diseases are being characterized by the presence of misfolded proteins underlying their pathophysiology, including cardiac amyloidosis and dilated cardiomyopathy (DCM). At least nine precursor proteins have been implicated in the development of cardiac amyloidosis, most commonly caused by multiple myeloma light chain disease and disease-causing mutant or wildtype transthyretin (TTR). Similarly, aggregates with PSEN1 and COFILIN-2 have been identified in up to one-third of idiopathic DCM cases studied, indicating the potential predominance of misfolded proteins in heart failure. In this review, we present recent evidence linking misfolded proteins mechanistically with heart failure and present multiple lines of new therapeutic approaches that target the prevention of misfolded proteins in cardiac TTR amyloid disease. These include multiple small molecule pharmacological chaperones now in clinical trials designed specifically to support TTR folding by rational design, such as tafamidis, and chaperones previously developed for other purposes, such as doxycycline and tauroursodeoxycholic acid. Last, we present newly discovered non-pathological “functional” amyloid structures, such as the inflammasome and necrosome signaling complexes, which can be activated directly by amyloid. These may represent future targets to successfully attenuate amyloid-induced proteotoxicity in heart failure, as the inflammasome, for example, is being therapeutically inhibited experimentally in autoimmune disease. Together, these studies demonstrate multiple novel points in which new therapies may be used to primarily prevent misfolded proteins or to inhibit their downstream amyloid-mediated effectors, such as the inflammasome, to prevent proteotoxicity in heart failure.

Morphological changes in mitochondria during mechanical unloading observed on electron microscopy: a case report of a bridge to complete recovery in a patient with idiopathic dilated cardiomyopathy

The recovery of the cardiac function under mechanical support has not been well documented from a histopathological point of view. We herein report a case of idiopathic dilated cardiomyopathy in which the patient showed a complete recovery of the systolic function following treatment with a left ventricular assist device (LVAD) for deteriorated heart failure. A light microscopic observation showed marked regression of hypertrophic myocytes with significant intracellular vacuolization and scarcity at the time of LVAD implantation after the administration of mechanical support. Furthermore, an electron microscopic observation revealed that these findings were regulated primarily by volumetric regression and morphometric improvements in cardiomyocytic mitochondria.

The tumor necrosis factor-α -238G/A and IL-6 -572G/C gene polymorphisms and the risk of idiopathic dilated cardiomyopathy: a meta-analysis of 25 studies including 9493 cases and 13,971 controls.

Inflammation plays an imperative role in the etiology of cardiovascular diseases (CVD). The role of cytokines in the development and progression of idiopathic dilated cardiomyopathy (IDCM) is still uncertain. The current study was conducted to evaluate the association of tumor necrosis factor-α (TNF-α) -238G/A and IL-6 -572G/C gene polymorphism with IDCM in a Pakistani population. IDCM cases (n=250) and healthy controls (n=300) were genotyped using PCR-RFLP. The variant genotypes of both the loci showed significant differences between patients and controls (p<0.05). However, -238G/A polymorphism did not show association with the disease in the presence of covariates. We also conducted a meta-analysis of both the loci with regards to CVD in accordance with the Prisma checklist. No significant relation of the TNF-α -238G/A polymorphism with CVD was found; however, this single nucleotide polymorphism (SNP) showed an association with the disease in the Asian population after subgroup analysis (p=0.01). Whereas, the IL-6 -572G/C polymorphism showed that the variant genotype (GC+CC) was associated with higher risk of CVD in contrast to the GG genotype. Furthermore, subgroup meta-analysis demonstrated a significant association of the -572 polymorphism with CVD in Asians, but no association was observed among Western populations with this SNP. Our findings support an association between the IL-6 -572G/C polymorphism and IDCM risk. The role of the TNF-α -238G/A polymorphism in IDCM is still unclear. Further studies are warranted to determine the serum cytokine levels in relation to the cytokines' SNP in diverse ethnic groups to ascertain the molecular basis of the disease pathology.