Rajiv Narang

Echocardiographic Evaluation of Patients With Acute Rheumatic Fever and Rheumatic Carditis

BACKGROUND Cardiac involvement is the most important component of acute rheumatic fever. The role of echocardiography in the evaluation of rheumatic carditis has not been adequately defined. We used echocardiography in a large sample of patients with acute rheumatic fever to describe morphological abnormalities associated with rheumatic carditis and to assess its role in the diagnosis of rheumatic carditis. METHODS AND RESULTS Cross-sectional and color Doppler echocardiographic examination was performed in 108 consecutive patients with acute rheumatic fever within 24 to 48 hours of diagnosis. Twenty-eight patients had acute rheumatic fever without clinical evidence of carditis (group 1). Thirty-five patients had a presumed first episode of rheumatic carditis (group 2), and 45 patients had a recurrence of carditis (group 3). Patients in group 1 did not demonstrate any evidence of valvular regurgitation. Mitral regurgitation was the most common Doppler echocardiographic feature in groups 2 (94%) and 3 (84%). Valvular thickening with or without restriction of leaflet mobility was frequently seen in rheumatic carditis. One of every 4 patients with rheumatic carditis demonstrated echocardiographic presence of focal valvular nodules. These nodules were found on the body and the tips of the mitral valve leaflets and disappeared on follow-up. Ventricular dilatation (group 2, 54%; group 3, 74%) and restriction of leaflet mobility (group 3, 37%) were common mechanisms of mitral regurgitation in rheumatic carditis; valve prolapse (group 2, 9%; group 3, 16%) and annular dilatation (group 2, 12%; group 3, 21%) were infrequent. The majority of patients with rheumatic carditis had normal left ventricular systolic function. Congestive heart failure (group 2, 17%; group 3, 40%) was invariably associated with the presence of hemodynamically significant valve lesions. On follow-up, no patient in group 1 developed valvular regurgitation. In group 2 patients, a progressive decrease in left ventricular dimensions was observed without any change in ventricular fractional shortening. Valvular regurgitation remained unchanged in 69% of patients, decreased in 22%, and disappeared in 9%. CONCLUSIONS In patients with rheumatic carditis, the mitral valve is most often involved and mitral regurgitation is the most common finding on color flow imaging. Mitral regurgitation in rheumatic carditis is related to ventricular dilatation and/or restriction of leaflet mobility. Rheumatic carditis does not result in congestive heart failure in the absence of hemodynamically significant valve lesions. In a quarter of patients with rheumatic carditis, we observed valve nodules that may represent echocardiographic equivalents of rheumatic verrucae. Our study failed to reveal any incremental diagnostic utility of echocardiography and Doppler color flow imaging in rheumatic fever without clinical evidence of carditis.

The ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial a long-term follow-up study.

To the Editor: We reported the short-term results (6-month follow-up) of a pilot study of the role of stem cell therapy in ischemic cardiomyopathy ([1][1]). We now present the final long-term (3-year follow-up) results of the trial. The study included patients between 15 and 70 years of age with

Cardiac amyloidosis presenting as ischemic heart disease : a case report and review of literature

Cardiac amyloidosis can have varied clinical presentations, but it uncommonly leads to typical angina. The exact cause of ischaemia in this condition is not known, though various mechanisms have been postulated. We describe here a case of cardiac amyloidosis, proven by endomyocardial biopsy, which presented as ischaemic heart disease, and we also review the literature on the same.

Association of Angiotensin II Type 1 Receptor (A1166C) Gene Polymorphism and Its Increased Expression in Essential Hypertension: A Case-Control Study

Objectives Hypertension is one of the major cardiovascular diseases. It affects nearly 1.56 billion people worldwide. The present study is about a particular genetic polymorphism (A1166C), gene expression and protein expression of the angiotensin II type I receptor (AT1R) (SNP ID: rs5186) and its association with essential hypertension in a Northern Indian population. Methods We analyzed the A1166C polymorphism and expression of AT1R gene in 250 patients with essential hypertension and 250 normal healthy controls. Results A significant association was found in the AT1R genotypes (AC+CC) with essential hypertension (χ2 = 22.48, p = 0.0001). Individuals with CC genotypes were at 2.4 times higher odds (p = 0.0001) to develop essential hypertension than individuals with AC and AA genotypes. The statistically significant intergenotypic variation in the systolic blood pressure was found higher in the patients with CC (169.4±36.3 mmHg) as compared to that of AA (143.5±28.1 mmHg) and AC (153.9±30.5 mmHg) genotypes (p = 0.0001). We found a significant difference in the average delta-CT value (p = 0.0001) wherein an upregulated gene expression (approximately 16 fold) was observed in case of patients as compared to controls. Furthermore, higher expression of AT1R gene was observed in patients with CC genotype than with AC and AA genotypes. A significant difference (p = 0.0001) in the protein expression of angiotensin II Type 1 receptor was also observed in the plasma of patients (1.49±0.27) as compared to controls (0.80±0.24). Conclusion Our findings suggest that C allele of A1166C polymorphism in the angiotensin II type 1 receptor gene is associated with essential hypertension and its upregulation could play an important role in essential hypertension.

Association of Angiotensin Converting Enzyme (Insertion/Deletion) Gene Polymorphism with Essential Hypertension in Northern Indian Subjects

OBJECTIVE Essential hypertension is a multifactorial disease in which genetic and environmental factors play an important role. The renin-angiotensin system (RAS) is known to play a critical role in the homeostasis of blood pressure. Angiotensin-I converting enzyme (ACE) is a significant component of RAS, and an insertion/deletion (I/D) polymorphism in its gene has been implicated in predisposition to hypertension. The purpose of the current study is to investigate the association of I/D polymorphism of the ACE gene with essential hypertension in northern Indians. METHOD Two hundred twenty-two patients with essential hypertension and 252 controls were recruited for the study. DNA samples were isolated from peripheral blood by using a kit. Polymerase chain reaction was used for genotyping. RESULT All the genotypes and allele distribution in study subjects were in the Hardy-Weinberg equilibrium. There was a significant difference in the distribution of DD, II, and ID genotypes of ACE polymorphism in patients and controls. In the subjects having an I allele, the odds ratio is 2.08 [1.6-2.58] at 95% confidence interval, thus suggesting an association of ACE I/D gene polymorphism with essential hypertension. CONCLUSION Our findings suggest that the I allele of ACE I/D polymorphism is associated with essential hypertension in our population.

Apolipoprotein C3 SstI polymorphism in the risk assessment of CAD

Various population studies have reported the association of rare S2 allele of apolipoprotein C3 (APOC3) SstI polymorphism with hypertriglyceridemia (HTG) and coronary artery disease (CAD). We were the first to report an association of S2 allele with high triglyceride (TG) levels in healthy volunteers from Northern India. Since HTG is suggested to be a predominant risk factor for CAD among Indians, we have elucidated the relationship of APOC3 SstI polymorphism with the lipid profile and CAD. A total of 158 patients with ≥ 70% stenosis in one or more coronary artery (angiographically proven CAD patients), 35 subjects with < 70% stenosis (NCAD) and 151 normal controls (free of heart disease) from Northern plains of India were recruited in the study. DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Lipid profile was estimated by enzymatic kit. We found a strong association of S2 allele with high TG levels, which was more significant in patients. Prevalence of S2 allele in normal controls and CAD patients were comparable, despite the fact that mean TG level was significantly higher in patients. A greater insight into this observation revealed that the prevalence of high TG, if not coupled with other risk factors (like high total cholesterol, low HDL), was comparable in patients and controls. Thus, our study reveals that rare S2 allele may be employed as a susceptibility marker for high TG. However, high TG or S2 allele alone may not contribute to the etiology of CAD.

Development and characterization of ligand-appended liposomes for multiple drug therapy for pulmonary tuberculosis

Abstract Tuberculosis (TB) remains one of the oldest and deadliest diseases in the current scenario. The intracellular organism Mycobacterium tuberculosis, which mainly resides in mononuclear phagocytes, is responsible for tuberculosis in humans. A few therapies are available for the treatment of tuberculosis but they have many hurdles. To overcome these hurdles, a combination of chemotherapeutic agent-loaded vesicular systems have been prepared to overcome tuberculosis. To investigate the role of novel drug delivery systems for the treatment of pulmonary tuberculosis, ligand appended liposomals have been developed. In the present study, drug-loaded, ligand-appended liposomes and their DPI (Dry Powder Inhaler) forms have been prepared and characterized using various in vitro and in vivo parameters. The prepared ligand-appended liposomal formulation showed good entrapment efficiency, prolonged drug release, improved recovery of drugs from the target site, and proved to be more suitable for use as DPI, justifying their potential for improved drug delivery. Thus we tried our best by our project to reduce the national burden of tuberculosis, which is still a global health challenge.

Two- and three-locus haplotypes of the paraoxonase (PON1) gene are associated with coronary artery disease in Asian Indians.

INTRODUCTION In view of the reported association of SNPs in the paraoxonase (PON1) gene with coronary artery disease (CAD), and the absence of conclusive data from India, we investigated the relationship of three SNPs at different loci (-108C/T, L55M and Q192R) of the PON1 gene and their haplotypes with CAD among people residing in the northern plains of India. MATERIALS AND METHODS One hundred and seventy-eight healthy controls and two hundred and four angiographically-proven CAD patients were genotyped using PCR-RFLP. RESULTS Of the three SNPs, only the R allele of Q192R polymorphism was associated with CAD (p<0.05). Two locus haplotypes QT (OR 0.55, p=0.0004, 95% CI 0.39-0.77, significant) and LQ (odds ratio 0.73, p=0.03, 95% CI 0.55-0.97, trend) showed protective effects, while haplotypes MR (OR=5.36, p=0.0001, 95% CI 2.045-14.049) and MC (OR=2.71, p=0.011, 95% CI 1.221-6.046) were associated with increased risk of CAD. MRT, a minor three-locus haplotype also displayed significant association (OR 4.93, 95% CI 1.7-13.5) with the disease. Significance was assessed after applying Bonferronis correction. CONCLUSIONS Our study revealed that only one SNP at a single locus but several haplotype combinations of PON1 coding and promoter-region polymorphisms were associated with the risk of or protection against CAD. Thus, haplotype analysis brought better insights into the association of PON1 gene polymorphisms with CAD in Asian Indians.

In vivo cardioprotection by pitavastatin from ischemic-reperfusion injury through suppression of IKK/NF-κB and upregulation of pAkt-e-NOS.

Recent studies have uncovered the beneficial effects of statin in cardiovascular diseases; however, the role of pitavastatin in ischemia-reperfusion (IR)-induced apoptosis and myocardial damage is not established. Therefore, in this study, we aim to investigate whether pitavastatin treatment attenuates myocardial IR injury via regulating oxidative stress, inflammation, apoptosis, and phosphorylated protein kinase B (pAkt) endothelial nitric oxide synthase (e-NOS) pathways. After the 14-day treatment with pitavastatin (0.16-0.64 mg·kg−1·d−1, po) or saline, rats were subjected to 45 minutes of ischemia by occluding the left anterior descending coronary artery and to 60 minutes of reperfusion to induce myocardial damage. Pitavastatin at a dose of 0.32 and 0.64 mg/kg significantly improved cardiac function as evidenced by the normalization of the mean arterial pressure, heart rate, ±LVdP/dtmax, and left ventricular end-diastolic pressure as compared with the IR control. Additionally, pitavastatin dose-dependently normalized myocardial antioxidants, lactate dehydrogenase, and thiobarbituric acid reactive substances along with decreased serum tumor necrosis factor-α level and creatine kinase isoenzyme-MB activity. Furthermore, pitavastatin enhanced pAkt, (p) e-NOS, Bcl-2, and suppressed IκB kinase/nuclear factor-kappa B, nitrotyrosine (NO inactivation product), Bax, and capases-3 protein expression in the heart. Morphological assessments of the IR-challenged myocardium showed that 0.32 and 0.64 mg/kg of pitavastatin decrease myocardial necrosis and inflammatory changes. Thus, pitavastatin reduced IR-induced infarction and dysfunction via the augmentation of endogenous antioxidant, suppression of IκB kinase/nuclear factor-kappa B, activation of pAkt-e-NOS, and/or decreased NO inactivation and apoptosis.

Transient, Subclinical Atrial Fibrillation and Risk of Systemic Embolism in Patients With Rheumatic Mitral Stenosis in Sinus Rhythm

Stroke and systemic embolism occur frequently in patients with rheumatic mitral stenosis (MS) in sinus rhythm (SR), but the risk and predictors of embolic events in this population are not well studied. The aim of this study was to determine if transient, subclinical atrial fibrillation (AF) increases the risk of systemic embolism in patients with MS in SR. A single-center, prospective observational study of patients with rheumatic MS in SR was performed. The rate of the composite primary outcome of stroke, transient ischemic attack, or non-central nervous system embolism was determined, as well as the predictive value of Holter-detected episodes of transient (<30 seconds), subclinical AF for this outcome. Hazard ratios were derived for subclinical AF, after adjustment for clinical and echocardiographic predictors of systemic embolism, using Cox regression. The sensitivity, specificity, and area under the receiver-operating characteristic curve of subclinical AF were determined for the primary outcome. Among 179 patients (mean follow-up 10.2 months), the rate of the primary outcome was 5.3/100 patient-years (95% confidence interval [CI] 2.6 to 10.5). In univariate analysis, subclinical AF (hazard ratio 4.54, 95% CI 1.08 to 19.0, p = 0.038) and dense spontaneous echocardiographic contrast (hazard ratio 4.32, 95% CI 1.03 to 18.09, p = 0.045) were predictors of the primary outcome. In multivariate analysis, subclinical AF remained the only significant predictor (hazard ratio 5.02, 95% CI 1.15 to 22.0, p = 0.032). Subclinical AF had an area under the receiver-operating characteristic curve of 0.68 and high negative predictive value (97.7%) for the primary outcome. In conclusion, Holter-detected, transient (<30 seconds), subclinical AF is a predictor of stroke and systemic embolism in patients with rheumatic MS in SR. Considering the high risk for embolism, randomized trials of oral anticoagulation are needed in this population.