Outcomes of emergency surgical intervention for complications in the cardiac catheterization laboratory.

Background: In today's era, cardiac catheterization procedures are becoming increasingly safe, but they are still fraught with complications. We aimed to study the outcomes of patients who underwent emergency surgical intervention for complications in the cardiac catheterization laboratory. Methods: A retrospective analysis of patients who required emergency surgical management following a complication in the cardiac catheterization laboratory in our institute from July 2017 to July 2022 was done. Result: A total of 57 patients out of a total of 52,326 patients (0.1%) were included. The average age of presentation was 10.4 years. Congenital heart disease (CHD) constituted the majority of the cases (28/57-49.1%), coronary artery disease (CAD) constituted 19.3% (11/57), and rheumatic heart disease (RHD) constituted 8.8% (5/57) of the cases. Apart from this, 22.80% patients (13/57) were grouped together in the miscellaneous group. In total, 76.9% (10/13) of these patients had pericardial effusion and they developed a right ventricular (RV) rent following an attempted pigtail drainage. Also, one patient each had a RV rent following an attempted permanent pacemaker implantation for heart block and an endocardial biopsy respectively. One patient had a left bronchial rupture following thoracic endovascular aortic repair (TEVAR) for descending thoracic aorta (DTA) aneurysm. Thirty-day mortality was 7% (4/57), and the mean time of shifting the patients from the catheterization laboratory to the operating room was 8.3 h. Conclusion: Cardiac catheterization procedures have become increasingly safe, but complications can still occur, for which the cardiac surgeon should be briefed in a Heart Team meeting before taking up such cases. Even though these complications form a small percentage, the cardiologist should exercise some caution in attempting cases which could have a relatively easier surgical correction.

Pattern of Medical Device Adverse Events in a Tertiary Care Hospital in Northern India: An Ambispective Study.

BACKGROUND: Knowledge about the pattern of adverse events caused by medical devices (MDs) is limited in India. We aimed to assess the pattern of MD adverse events (MDAEs) in a tertiary hospital in Northern India. MATERIALS AND METHODS: This descriptive study was conducted ambispectively at various clinical departments of PGIMER, Chandigarh. We followed the guidelines edged by the Materiovigilance Program of India (MvPI) to conduct this study. The prospective study (PS) was done from January to December 2020, with a concurrent retrospective study (RS) proceeding to 3 years to learn more about the reporting culture, demographics, notification status, risk class of defective devices, and the type of adverse events. RESULTS: We received 224 MDAE in the PS and identified 413 MDAE in the RS. Reporting of adverse events to the national MvPI was negligible in the RS. In the PS, nurses reported the majority of MDAEs (65%), followed by doctors (30%). The occurrence of MDAE was higher in males (PS; 52%, RS; 57%) and age groups between 21 and 30 years (PS; 19.1%, RS; 23.2%) in both studies. MDAEs were frequent in low- to moderate-risk devices (class B: 66%) in the PS, while it was documented only for high-risk devices (class C: 51% and class D: 49%) in the RS. Most of the serious adverse events (SAEs) were reported among moderate to high-risk devices, and an increased frequency of SAE (60.4%) was observed among nonnotified MDs. The overall incidence of near-miss events was 14%. CONCLUSION: Knowledge of MDAEs and reporting of defective devices to regulatory authorities is essential to prevent further incidence. Adverse events caused by MDs are ubiquitous irrespective of their risk classification, notification status, and patient demographic factors. Accelerated reporting of MDAE by all cadre of healthcare professionals is urgently required to safeguard the health of Indians.

Comparison of Multisystem Inflammatory Syndrome (MIS-C) and Dengue in Hospitalized Children.

OBJECTIVE: Multisystem inflammatory syndrome (MIS-C) in children is a febrile illness that has overlapping presentation with other locally prevalent illnesses. Clinicolaboratory profile of children admitted with MIS-C and dengue were compared to understand their presentation at the outset. METHODS: This was a retrospective study of children ≤ 12 y admitted with MIS-C (WHO definition) or laboratory-confirmed dengue between August 2020 and January 2021 at a tertiary center in North India. RESULTS: A total of 84 children (MIS-C - 40; dengue - 44) were included. The mean (SD) age [83.5 (39) vs. 91.6 (35) mo] was comparable. Rash (72.5% vs. 22.7%), conjunctival injection (60% vs. 2.3%), oral mucocutaneous changes (27.5% vs. 0) and gallop rhythm (15% vs. 0) were seen more frequently with MIS-C, while petechiae [29.5% vs. 7.5%], myalgia (38.6% vs. 10%), headache (22.7% vs. 2.5%), and hepatomegaly (68.2% vs. 27.5%) were more common with dengue. Children with MIS-C had significantly higher C-reactive protein (124 vs. 3.2 mg/L) and interleukin 6 (95.3 vs. 20.7 ng/mL), while those with dengue had higher hemoglobin (12 vs. 10.2 g/dL) lower mean platelet count (26 vs. 140 × 109/L), and greater elevation in aspartate (607 vs. 44 IU/L) and alanine (235.5 vs. 56 IU/L) aminotransferases. The hospital stay was longer with MIS-C; however, PICU stay and mortality were comparable. CONCLUSION: In hospitalized children with acute febrile illness, the presence of mucocutaneous features and highly elevated CRP could distinguish MIS-C from dengue. The presence of petechiae, hepatomegaly, and hemoconcentration may favor a diagnosis of dengue.

Cardiac MRI and Echocardiography for Early Diagnosis of Cardiomyopathy Among Boys With Duchenne Muscular Dystrophy: A Cross-Sectional Study.

Background: Cardiomyopathy is an important cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). Early diagnosis is a prerequisite for timely institution of cardioprotective therapies. Objective: We compared cardiac MRI (CMRI) with transthoracic echocardiography (TTE) including tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) for diagnosis of cardiomyopathy in early ambulatory boys with DMD. Methodology: This cross-sectional study was conducted between June 2018 and December 2020. Consecutive boys between 7 and 15 years of age with DMD were enrolled. Percentage ejection fraction (EF), fractional shortening, wall motion abnormalities, early diastolic mitral annulus velocity (Ea), medial mitral annulus ratio (E/Ea), and global strain were measured with STE. CMRI-derived EF, segmental hypokinesia, and late gadolinium enhancement (LGE) were studied and compared. Results: A total of 38 ambulatory boys with DMD were enrolled. The mean age was 8.8 ± 1.6 years, and none had clinical features suggestive of cardiac dysfunction. In the TTE, EF was ≤55% in 5 (15%), FS was ≤28% in 3 (9%), and one each had left ventricular wall thinning and wall hypokinesia. In TDI, none had diastolic dysfunction, and STE showed reduced global strain of < 18% in 3 (9%) boys. CMRI-derived EF was ≤55% in 20 (53%) boys and CMRI showed the presence of left ventricular wall hypokinesia in 9 (24%) and LGE in 4 (11%) boys. Conclusion: Cardiomyopathy remains clinically asymptomatic among early ambulatory boys with DMD. A significantly higher percentage of boys revealed early features of DMD-related cardiomyopathy in CMRI in comparison with echocardiography.

18F-NaF PET uptake characteristics of coronary artery culprit lesions in a cohort of patients of acute coronary syndrome with ST-elevation myocardial infarction and chronic stable angina: A hybrid fluoride PET/CTCA study.

BACKGROUND: 18F-NaF PET/CT identifies high-risk plaques due to active calcification in coronary arteries with potential to characterize plaques in ST-elevation myocardial infarction (MI) and chronic stable angina (CSA) patients. METHODS: Twenty-four MI and 17 CSA patients were evaluated with 18F-NaF PET/CTCA for SUVmax and TBR values of culprit and non-culprit plaques in both groups (inter-group and intra-group comparison), and pre- and post-interventional MI plaques sub-analysis. RESULTS: Culprit plaques in MI patients had significantly higher SUVmax (1.6; IQR 0.6 vs 1.3; IQR 0.3, P = 0.03) and TBR (1.4; IQR 0.6 vs 1.1; IQR 0.4, P = 0.006) than culprit plaques of CSA. Pre-interventional culprit plaques of MI group (n = 11) revealed higher SUVmax (P = 0.007) and TBR (P = 0.008) values than culprit CSA plaques. Culprit plaques showed significantly higher SUVmax (P = 0.006) and TBR (P = 0.0003) than non-culprit plaques in MI group, but without significant difference between culprit and non-culprit plaques in CSA group. With median TBR cutoff value of 1.4 in MI culprit plaques, 6/7 plaques (85.7%) among the event prone non-culprit lesions had TBR values > 1.4 in CSA group. CONCLUSION: The study shows higher SUVmax and TBR values in MI culprit plaques and comparable TBR values for event prone plaques of CSA group in identifying high-risk plaques.

Real world perspective of coronary chronic total occlusion in third world countries: A tertiary care centre study from northern India.

OBJECTIVES: The aim of this study is to determine the prevalence, clinical characteristics, angiographic profile and predictors of outcome for percutaneous coronary interventions (PCI) of coronary chronic total occlusions (CTO) in a tertiary referral centre of north India. BACKGROUND: There is no data on the prevalence and very few reports on clinical characteristics, angiographic profile and outcome of PCI in CTO from India. METHODS: Retrospective analysis was done for the data of 12,020 patients undergoing coronary angiography (CAG) between January 2018 to January 2019 at our centre. Detailed baseline clinical, angiographic and revascularization data was collected. Outcome of CTO PCI was also noted. All baseline parameters were analysed for predicting the outcome of CTO PCI. RESULTS: CTO was identified in 16.3% (1968) patients undergoing CAG and in 24.4% of patients with hemodynamically significant CAD. CTO was predominantly found in LAD (48%) followed by RCA (42.9%) and LCx (25.3%) arterial distribution. Mean JCTO score was 1.93 ± 0.7. PCI as a management strategy was adopted in 456 of 1968 patients (23.1%) and was successful in 340 of 456 (74.6%) of patients. Almost all CTO PCI were attempted by an antegrade approach only. Increasing age, male sex, CTO in LCx arterial distribution and higher J CTO score were associated with poorer outcome in CTO PCI. CONCLUSIONS: CTO's are commonly encountered during CAG procedures. In patients undergoing CTO PCI, a fair success rate can be achieved in a high volume experienced centre.

Long-term outcomes of non-ischemic dilated cardiomyopathy patients with left ventricular ejection fraction ≤19% on medical therapy.

BACKGROUND: Patients with heart failure and reduced ejection fraction in low resource settings may not have access to devices and expensive therapeutic options. We followed up a cohort of patients with non-ischemic dilated cardiomyopathy (DCM) with very low left ventricle ejection fraction (LVEF≤19%) on low cost medical therapy alone. By selecting patients with such low LVEF, this study was restricted to patients with severe disease. We studied long-term transplant free survival of these patients. METHODS AND RESULTS: The study enrolled 130 patients (83 men and 47 women) of DCM cohort with LVEF≤19% from April 2003-December 2018 on medical therapy alone. Mean age was 40.35 ± 13.9 years. Mean follow-up was 45.6 ± 39 months while median follow-up was 39 months (range: 0-176 months). Patients on devices (ICD/CRT) for heart failure management were excluded. Fifty-four patients died and three underwent transplant during the study. Median survival was 86 months (S.E. 22.38). 113 patients had follow-up till end of study. In the worst case scenario, if all 17 patients who were lost to final follow-up were assumed to be dead, the median survival was still 57 (S.E.9.28) months. Higher baseline NYHA class, recurrent heart failure hospitalizations, absence of treatment with beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers and aldosterone antagonists were predictors of death on univariate analysis whereas none of these parameters were significant on multivariate analysis. CONCLUSIONS: Median survival of our DCM cohort with LVEF≤19% on medical therapy was over 7 years.

Indian Guidelines for Indications and Timing of Intervention for Common Congenital Heart Diseases: Revised and Updated Consensus Statement of the Working Group on Management of Congenital Heart Diseases. Abridged Secondary Publication.

JUSTIFICATION: A number of guidelines are available for management of congenital heart diseases from infancy to adult life. However, these guidelines are for patients living in high income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for congenital heart diseases, as often these patients present late in the course of the disease and may have co-existing morbidities and malnutrition. PROCESS: Guidelines emerged following expert deliberations at the National Consensus Meeting on Management of Congenital Heart Diseases in India, held on 10th and 11th of August 2018 at the All India Institute of Medical Sciences, New Delhi. The meeting was supported by Children's HeartLink, a non-governmental organization based in Minnesota, USA. OBJECTIVES: To frame evidence based guidelines for (i) indications and optimal timing of intervention in common congenital heart diseases; (ii) follow-up protocols for patients who have undergone cardiac surgery/catheter interventions for congenital heart diseases. RECOMMENDATIONS: Evidence based recommendations are provided for indications and timing of intervention in common congenital heart diseases, including left-to-right shunts (atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus and others), obstructive lesions (pulmonary stenosis, aortic stenosis and coarctation of aorta) and cyanotic congenital heart diseases (tetralogy of Fallot, transposition of great arteries, univentricular hearts, total anomalous pulmonary venous connection, Ebstein anomaly and others). In addition, protocols for follow-up of post surgical patients are also described, disease wise.

Guidelines for the management of common congenital heart diseases in India: A consensus statement on indications and timing of intervention.

INTRODUCTION: A number of guidelines are available for management of congenital heart diseases from infancy to adult life. However, these guidelines are for patients living in high-income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for congenital heart diseases, as often these patients present late in the course of the disease and may have co-existing morbidities and malnutrition. PROCESS: Guidelines emerged following expert deliberations at the National Consensus Meeting on Management of Congenital Heart Diseases in India, held on the 10th and 11th of August, 2018 at the All India Institute of Medical Sciences. OBJECTIVES: The aim of the study was to frame evidence-based guidelines for (i) indications and optimal timing of intervention in common congenital heart diseases and (ii) follow-up protocols for patients who have undergone cardiac surgery/catheter interventions for congenital heart diseases. RECOMMENDATIONS: Evidence-based recommendations are provided for indications and timing of intervention in common congenital heart diseases, including left-to-right shunts, obstructive lesions, and cyanotic congenital heart diseases. In addition, protocols for follow-up of postsurgical patients are also described.

Genetic polymorphisms, Biochemical Factors, and Conventional Risk Factors in Young and Elderly North Indian Patients With Acute Myocardial Infarction.

This study compared genetic polymorphisms (factor V Leiden [FVL] 1691G/A, factor VII [FVII] 10976G/A, FVII HVR4, platelet membrane glycoproteins GP1BA 1018C/T, GP1BA VNTR, integrin ITGB3 1565T/C, ITGA2 807C/T and methylenetetrahydrofolate reductase [MTHFR] 677C/T), biochemical (fibrinogen and homocysteine), and conventional risk factors in 184 young and 166 elderly north Indian patients with acute myocardial infarction (AMI). Univariate analysis revealed higher prevalence of hypertension and obesity in elderly patients while smoking, alcohol intake, and low socioeconomic status in young patients (P < .001). Although mean fibrinogen predominated (P = .01) in elderly patients, mean homocysteine was higher (P < .001) among young patients. Prevalence of hyperhomocysteinemia was greater in young than in elderly patients (odds ratio: 2.8, 95% confidence interval: 1.8-4.4, P < .001); however, genetic polymorphisms were equally prevalent in young and elderly patients. Multiple logistic regression analysis showed smoking (P < .001), alcohol intake (P = .046), and hyperhomocysteinemia (P = .001) to be associated with AMI in the young patients while hypertension (P = .006) in elderly patients. To conclude, smoking, alcohol intake, and elevated homocysteine are the risk factors for AMI among young while hypertension among elderly patients.

Mortality in children with juvenile dermatomyositis: two decades of experience from a single tertiary care centre in North India.

Survival and outcomes have improved considerably among patients with juvenile dermatomyositis (JDM) in the west. However, mortality continues to be high in the developing world. There is paucity of literature on this aspect of JDM from developing countries. We reviewed case files of all patients with JDM registered in the Pediatric Rheumatology Clinic, Advanced Pediatrics Centre at the Post Graduate Institute of Medical Education and Research, Chandigarh, during the period 1993-2013. Seventy-six children were diagnosed to have inflammatory myopathy during this period. Of these, 63 had JDM, 3 had polymyositis while 10 had an overlap syndrome. We had reported 2 deaths out of 33 (8.3 %) patients with JDM in 2004, and over the last 9 years, we have encountered five more deaths in this group, thereby accounting for a mortality rate of 11.1 % (7/63) over two decades of follow-up. In these five children now being described, the mean duration between onset of symptoms and institution of appropriate therapy was 9.2 months. Four children (80 %) had severe muscle weakness needing nasogastric tubes at the onset, three (60 %) had cutaneous ulcers and three (60 %) had superadded infections. Two children (40 %) had gastrointestinal vasculitis and one of these developed an intestinal perforation. Three patients (60 %) had progressive pulmonary disease and air leak was identified in two of them. Although the prognosis for survival in JDM has steadily improved, in our experience the disease remains a serious illness and still carries significant mortality in the context of a developing country.

Hemodynamic changes in preterm neonates with septic shock: a prospective observational study*.

OBJECTIVE: We evaluated hemodynamic changes in preterm neonates with septic shock using functional echocardiography and studied the effects of vasoactive drugs on hemodynamic variables. DESIGN: Prospective observational study. SETTING: Level III neonatal ICU. SUBJECTS AND PATIENTS: We enrolled 52 preterm neonates with septic shock (shock group) and an equal number of gestation and postnatal age-matched healthy neonates (control group). INTERVENTIONS: We measured functional hemodynamic variables (left and right ventricular output, ejection fraction, isovolumetric relaxation time, and early passive to late active peak velocity ratio) by echocardiography in the shock group during initial fluid resuscitation, before initiation of vasoactive drugs, and again 30-40 minutes after initiation of vasoactive drug infusion. Control group underwent a single assessment after enrollment. We compared various hemodynamic variables between shock group and control group using paired t test or Wilcoxon signed-rank test. MEASUREMENTS AND MAIN RESULTS: The baseline left ventricular output was significantly higher in neonates with septic shock as compared with controls (median [interquartile range], 305 mL/kg/min [204, 393] vs 233 mL/kg/min [204, 302]; p < 0.001), but ejection fraction was similar between the two groups (55% ± 12% vs 55% ± 5%, p = 0.54). Other hemodynamic variables were comparable between the two groups. After vasoactive drug infusion, there was a significant increase in heart rate (152 ± 18 to 161 ± 18 beats/min, p ≤ 0.001) and right ventricular output (median [interquartile range], 376 [286, 468] to 407 [323, 538] mL/kg/min; p = 0.018) compared with the baseline, but left ventricular output and ejection fraction did not change significantly. CONCLUSIONS: We found an elevated left ventricular output but normal ejection fraction in preterm neonates with septic shock. This suggests that septic shock in preterm neonates is predominantly due to vasoregulatory failure. Vasoactive drugs significantly increased right ventricular output, which was predominantly due to increase in heart rate.

Incomplete Kawasaki disease followed by systemic onset juvenile idiopathic arthritis- the diagnostic dilemma.

The authors report an 18-mo-old girl who presented with features of incomplete Kawasaki disease and was refractory to intravenous immunoglobulin and infliximab treatment. She subsequently responded to pulse intravenous methylprednisolone therapy. The diagnostic dilemma arose after 2 mo when she developed clinical features suggestive of systemic onset juvenile idiopathic arthritis. Since both diseases have overlapping clinical features and no specific diagnostic laboratory tests, it is difficult for the clinicians even in the best of centers to reach a definitive diagnosis as illustrated by the index case.

Association of thrombomodulin gene polymorphisms and plasma thrombomodulin levels with acute myocardial infarction in north Indian patients.

This is the first study from north India that investigated the association of thrombomodulin (TM) polymorphisms with acute myocardial infarction (AMI) in 350 patients (≤ 40 years, n = 184 and ≥ 60 years, n = 166) and 350 matched-controls. The TM polymorphisms were determined by polymerase chain reaction-single-stranded conformational polymorphism and DNA sequencing. The TM 1418TT genotype (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.3-6.4; P = .012) was independent risk predictor of young AMI as were hypertension (OR 3.3; 95% CI 1.8-5.9; P < .001), diabetes mellitus (OR 14.3; 95% CI 2.9-44.6; P = .001), smoking (OR 13.8; 95% CI 7.7-24.7; P < .001), family history (OR 1.8; 95% CI 1.1-3.3; P = .045), high body mass index (OR 2.2; 95% CI 1.3-3.6; P = .002), and high waist-hip ratio (OR 4.1; 95% CI 2.4-7.1; P < .001). Mean plasma TM also showed association with young AMI (P < .001). Smoking carriers of TM 1418CT + TT genotype had significantly higher risk of AMI (OR 12.8; 95% CI 6.0-27.3; P < .001) when compared with nonsmoking noncarriers. In conclusion, TM 1418C/T polymorphism is independent predictor of AMI and synergies with smoking.

Prothrombotic gene polymorphisms and plasma factors in young North Indian survivors of acute myocardial infarction.

The aim of this study was to evaluate the association of prothrombotic gene polymorphisms [factor V Leiden (FVL) 1691GA, factor VII (FVII) 10976GA, FVII HVR4, platelet membrane glycoproteins GP1BA 1018CT, GP1BA VNTR, integrin ITGB3 1565TC, integrin ITGA2 807CT and methylenetetrahydrofolate reductase (MTHFR) 677C/T], plasma factors (fibrinogen and homocysteine) and traditional risk factors with acute myocardial infarction (AMI) in 184 patients ≤ 40 years of age and 350 controls (≤ 40 years) from north India. Multiple logistic-regression analysis showed that hypertension (OR 1.9, 95 % CI 1.1-3.8, p = 0.042), diabetes mellitus (OR 10.5, 95 % CI 2.0-56.7, p = 0.006), smoking (OR 7.1, 95 % CI 3.7-13.6, p < 0.001), low socio-economic status (OR 13.5, 95 % CI 2.3-78.4, p = 0.004), high waist-hip ratio (OR 35.6, 95 % CI 11.1-53.7, p < 0.001) and FVL 1691GA (OR 6.0, 95 % CI 1.2-13.4, p = 0.03) were independent risk predictors of AMI in young. Elevated plasma fibrinogen also showed association with increased AMI risk. ITGA2 807C/T polymorphism showed protection against AMI in univariate analysis only, while GP1BA VNTR-ac (OR 0.4, 95 % CI 0.2-0.9, p = 0.033) showed significant protection even after adjusting for age and sex. Multinominal logistic-regression analysis showed gene-gene (GP1BA 1018C/T with GP1BA VNTR and ITGA2 807C/T with ITGB3 1565T/C polymorphisms) and gene-environment interactions (gene polymorphisms with smoking) operating in the occurrence of AMI in young. In conclusion, the role of inherited predisposition to thrombosis in complex, polygenic and multifactorial disease like AMI is limited to certain genetic factors, in combination with environmental factor like smoking.

Synergistic effect of angiotensin II type-1 receptor 1166A/C with angiotensin-converting enzyme polymorphism on risk of acute myocardial infarction in north Indians.

INTRODUCTION: This first study from north India investigated the synergistic effect of AT1R 1166A/C with the ACE I/D polymorphism on risk of acute myocardial infarction (AMI). MATERIALS AND METHODS: Traditional coronary risk factors, ACE I/D and AT1R 1166A/C polymorphism were analyzed in 350 patients with AMI and 350 matched controls. RESULTS: In univariate analysis, hypertension (52.9% vs. 11.1%; OR=8.9; 95%CI 6.0-13.3), diabetes mellitus (16.0% vs. 0.6%; OR=33.1; 95%CI 8.0-137), smoking (43.7% vs. 20.9%; OR=2.9; 95%CI 2.1-4.1), family history of coronary artery disease (22.3% vs. 14.0%; OR=1.8; 95%CI 1.2-2.6), high body mass index (64.3% vs. 51.4%; OR=1.7; 95%CI 1.3-2.3), high waist-hip ratio (46.2% vs. 2.3%; OR=37; 95%CI 16-85.8) and AT1R 1166AC genotype (20.6% vs. 12%; OR=1.9; 95%CI 1.3-2.9) were associated with AMI. In multivariate analysis, all these factors were found to be independent risk predictors for AMI. Subjects carrying the AT1R 1166AC+CC and ACE ID+DD combined genotype showed a twofold increased association (OR=2.1; 95%CI 1.2-3.5) compared with the AT1R 1166AA-ACE II combined genotype. Patients who smoked and who carried the ACE ID+DD genotype had 2.4-fold (OR=2.4; 95%CI 1.5-3.8), and with the AT1R 1166AC+CC genotype had 15-fold (OR=14.9; 95%CI 5.2-42.8) increased risk of AMI compared with non-smoking non-carriers. CONCLUSIONS: The AT1R 1166A/C polymorphism has association with AMI among north Indian patients, particularly if integrated with ACE I/D polymorphism and smoking.

Adhesion molecule expression and ventricular remodeling in chronic rheumatic heart disease: a cause or effect in the disease progression--a pilot study.

BACKGROUND: Rheumatic fever and chronic rheumatic heart disease (RHD) remains one of the most important causes of cardiovascular morbidity leading to a major public health problem, especially in developing countries. This was a pilot study to assess the presence of inflammation and expression of adhesion molecules by immunohistochemistry (IHC) in endomyocardial biopsy specimens of patients with chronic RHD. METHODS: Endomyocardial biopsy was obtained from 14 patients of chronic RHD with no features of activity clinically. Biopsies were processed for histology and IHC. IHC was carried using monoclonal antibodies against CD3, CD4, CD8, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. RESULTS: Histomorphologically, varying degree of interstitial and perivascular fibrosis was seen in all the 13 patients (100%). Mild fibrosis (1+) was seen in five patients (38.5%); moderate interstitial fibrosis (2+) was present in four patients (30.8%).There was no Aschoff nodule or evidence of active myocarditis in any of the biopsy specimens. IMMUNOHISTOCHEMISTRY: Moderate positivity of (2+) and intense positivity of (3+) for intercellular adhesion molecule-1 was seen in 11 and 2 patients, respectively. With vascular cell adhesion molecule-1, four showed mild positivity (1+), and three showed intense positivity (3+). The phenotypic analysis of the inflammatory cells in our study revealed CD8(+) cells in 77%, CD4(+) in 23.1%, and CD3(+) in 38.5% of total patients, which suggests chronicity. CONCLUSION: The nonspecific histomorphological changes and increased adhesion molecules expression could be a part of the ventricular remodeling due to the hemodynamic stress by the stenotic or regurgitant lesions of RHD itself.

Clinical pearls in pediatric cardiology.

In this section, the authors present four interesting clinical cases that presented with common symptoms, but required careful clinical examination and investigations to arrive at a correct diagnosis and institute appropriate management. The first case is a 3-month-old infant who presented with hypertonia, bulging anterior fontanelle and tachycardia. ECG revealed supraventricular tachycardia which was managed appropriately. The clinical suspicion of meningitis was not borne out by the CSF findings. The second is a pre-school girl who presented with recurrent, episodic wheezing that did not respond to standard asthma therapy. The authors discuss the management approach in such cases; careful examination of radiographs and clinical course led to the correct diagnosis of dilated cardiomyopathy. The next two cases are older children; one of them presented with massive bilateral pleural effusion; this was found to be caused by congestive cardiac failure. The last case is a 10-year-old child presenting with features of right sided heart failure without obvious cardiac abnormality on clinical examination. Advanced investigations confirmed a rare diagnosis of arrhythmogenic right ventricular dysplasia; retrospective ECG examination showed the characteristic findings of this condition.

Decreased myocardial expression of dystrophin and titin mRNA and protein in dilated cardiomyopathy: possibly an adverse effect of TNF-alpha.

BACKGROUND AND AIMS: While the molecular basis of dilated cardiomyopathy (DCM) remains uncertain, concrete evidence is emerging that sarcomeric and cytoskeleton gene expression of myocardium isolated from failing versus non-failing patients differ dramatically. The central aim to this work was to find out the possible role of dystrophin and titin along with the TNF-alpha in the pathogenesis of cardiomyopathy. PATIENTS AND METHODS: mRNA levels and protein expression of a cytoskeletal protein, dystrophin and a sarcomeric protein, titin in endomyocardial biopsies of DCM patients were examined using RT-PCR and immunohistochemistry, respectively. Further, we examined the effect of TNF-alpha on myocardial expression of titin and dystrophin in vitro in rat cardiac myoblast cell line (H9c2). RESULTS: We observed significantly decreased mRNA and protein levels of dystrophin and titin in endomyocardial biopsy of DCM patients as compared to control group. The decreased levels of these proteins correlated with the severity of the disease. Plasma levels of both TNF-alpha and its soluble receptors TNFR1 and TNFR2 were found to be significantly higher in patients as compared to control group. Treatment of H9c2 cells with TNF-alpha resulted in a dose- and time-dependent decrease in mRNA levels of dystrophin and titin. Pretreatment of these cells with MG132, an inhibitor of nuclear factor kappa B (NF-kappaB) pathway, abolished TNF-alpha-induced reduction in mRNA levels of dystrophin and titin. CONCLUSION: Our results suggest that reduced expression of dystrophin and titin is associated with the pathophysiology of DCM, and TNF-alpha may modulate the expression of these proteins via NF-kappaB pathway.