Imran Hafeez

Clinical and mutation profile of children with cystic fibrosis in Jammu and Kashmir

ObjectiveTo study the clinical and mutation profiles of children with cystic fibrosis in Jammu and KashmirMethodsOne hundred consecutive patients presenting with one or more phenotypic features suggestive of cystic fibrosis (CF) were screened by quantitative sweat chloride testing. For patients with positive/equivocal test result on two occasions, CFTR gene mutation analysis was done by polymerase chain reaction.ResultsOf the 100 patients, 18 (10 females) were diagnosed to have CF at a median age of 10.5 y (IQR 4.75–15.25 y) while the median age at the onset of symptoms was 12 mo (IQR 4–63 mo) with a delay in diagnosis by 102.4±80.5 months. Clinical features at presentation included failure to thrive (94.4%), chronic cough (78%), recurrent pneumonia (61%), persistent pneumonia (11%), and chronic diarrhea (50%). Positive sweat chloride (>60 meq/L) was seen in 14 (14%) patients and 4 (4%) patients had equivocal (40–60 meq/L) value on two different occasions. Mutational analysis done in 15 patients showed DeltaF508 mutation in 20% (3/15) patients in homozygous form and in 13% (2/15) patients in heterozygous form. Intron 19 mutation 3849+10kb C>T was found in 40% (6/15) in heterozygous form. One (6.6%) patient had DeltaF508 and 3849+10kbC>T mutations in compound heterozygous form. Patients with equivocal sweat chloride and 3849+10kbC>T mutation had delayed onset of pulmonary involvement.Conclusion3849 +10kbC>T mutation appears to be common in children with cystic fibrosis in Jammu and Kashmir followed by DeltaF508, although the data are quite limited. Although presentation is delayed and sweat chloride is in the equivocal range, severe lung involvement may occur in these patients.

Complete Transcatheter Repair of Fallot’s Trilogy: A Case Report

Fallot’s trilogy is a relatively uncommon form of cyanotic congenital heart disease characterized by severe valvular pulmonary stenosis (PS), right ventricular hypertrophy and right to left interatrial shunt via an atrial septal defect (ASD) or patent foramen ovale (PFO). Historically, patients with the combination of these lesions were routinely treated by surgical correction. In recent times, transcatheter repair has become an increasingly attractive modality of treating such patients. There is limited experience with such combined transcatheter interventions, and from the scarce data available in published literature it seems that such approach has promising safety and efficacy. Herein, we describe a case of an 18 year old cyanotic male patient who was diagnosed of having severe valvular PS with supra systemic right ventricular pressures and reversed interatrial shunt via a large secundum ASD. We successfully treated him percutaneously with serial balloon pulmonary valvuloplasty, using single balloon and Inoue balloon techniques, followed by Amplatzer device closure of the ASD. The outcome was excellent with marked reduction of trans-pulmonary valvular gradient, complete cessation of shunting across the ASD, dramatic improvement of symptoms and completes disappearance of cyanosis. There were no procedure related complications and the benefits were sustained at follow up of three years. Our case demonstrates that transcatheter repair is a feasible, safe and effective alternative to surgery in selected patients with Fallot’s trilogy. With further experience, it may well become the standard of care in the management of such patients.

Clinico-angiographic profile and procedural outcomes in patients undergoing percutaneous coronary interventions: The Srinagar registry

Background This study was aimed at exploring the clinical profile, angiographic characteristics and procedural outcomes in patients undergoing PCI at our institute. Methods This prospective observational study included all consecutive patients who underwent PCI at our hospital between January 2014 and December 2015. Data including clinico-demographic profile, angiographic details and lesion characteristics were recorded in all patients. Procedural details including devices and drugs used, procedure related complications, and in-hospital outcomes of these patients were analysed. Results A total of 624 patients (mean age- 59.30 ± 11.17 years) with 84.8% males and 15.2% females were included in the study. Smoking and hypertension were the most common risk factors, present in 79.8% and 74.8% patients respectively. Diabetes mellitus, dyslipidemia, and obesity were observed in 24.5%, 26.1%, and 25.0% patients respectively. Anterior wall MI was the most common mode of presentation (32.1%). Single Vessel Disease (SVD) was most common angiographic pattern, observed in 50.3% patients; left anterior descending artery (LAD) was the most frequently involved vessel (65.9%); and type B lesions were most prevalent (52.3%). Most of the procedures were elective (61.4%) and femoral route was used in the majority (82.6%). Drug eluting stents were deployed in 99.1% of the cases. The overall procedural success rate was 93.6%. Procedural mortality was 1.0% and periprocedural complications occurred in 9.9% patients. Conclusion This first prospective PCI registry from the state of Jammu & Kashmir provides an insight into the patterns of CAD among Kashmiri population, and highlights the spectrum of PCIs performed with their outcomes.

Immediate effect of percutaneous transvenous mitral commissurotomy on atrial electromechanical delay and P-wave dispersion in patients with severe mitral stenosis.

BACKGROUND Mitral stenosis (MS) is associated with prolonged inter- and intra-atrial electromechanical delays and increased P-wave dispersion, which are markers of atrial fibrillation (AF) risk. This study was conducted to assess the immediate effect of successful percutaneous transvenous mitral commissurotomy (PTMC) on these parameters. METHODS This single center observational study included 25 patients with severe MS (aged 34.1 ± 7.1 years, with mean mitral valve area (MVA) of 0.74 ± 0.13 cm(2)), in sinus rhythm, who underwent successful PTMC at our hospital. P-wave dispersion (PWD) was calculated by subtracting minimum P-wave duration (P min) from maximum P-wave duration (Pmax), measured on a 12-lead surface ECG obtained from each patient in supine position at a paper speed of 50mm/s and 20mm/mV. Inter-atrial (AEMD), left intra-atrial (L-IAEMD), and right intra-atrial (R-IAEMD) electromechanical delays were measured on tissue Doppler imaging. PTMC was performed using the standard Inoue Balloon technique. All these parameters were evaluated and compared before and 24-48 h after PTMC. RESULTS Successful PTMC led to significant reduction in AEMD (p < 0.001), L-IAEMD (p < 0.001), and R-IAEMD (p < 0.001). There were no changes in Pmax, Pmin, and PWD immediately after PTMC. CONCLUSIONS Successful PTMC has a favorable early impact on inter- and intra-atrial electromechanical delays, which are considered as novel parameters of atrial electromechanical remodeling in MS patients. Prospective large-scale studies are required to confirm whether improvement in these markers translates into reduced long-term AF risk.

Atrial Fibrillation, Clinical Profile and Adherence to Guidelines

Background: Even in developed countries suboptimal anticoagulation and low adherence to guidelines is frequently observed in Atrial fibrillation (AF) patients. There is no data from our regional population and very scarce Indian data about the utilization patterns and adherence to guidelines for stroke prevention in AF. Aims and Objectives: To characterize clinical profile and assess adherence to guidelines in stroke prevention in AF in north Indian population. Material and Methods: It was a single centre observational study. All patients presenting to outpatient department or admitted in cardiology wards from May 2014 to April 2016 with AF were included. Detailed history, examination and relevant investigations were carried out .CHADS2 score was used for risk stratifying and prescribing oral anticoagulants in nonvalvular AF. The effectiveness of oral anticoagulant was assessed by INR. Result: Total of 446 patients were included. Mean age of our patients was 60.83±16.86 years. 48% were males and 52% were females. Rheumatic heart disease was most common (37.2%) ethology followed by hypertensive cardiovascular disease (18.2%). Mean CHADS2 score was 2.63±1.5 in non valvular AF. Out of 446 patients, 409(92%) patients were found to have indication for prescription of OAC as per guidelines, out of which only 290 (71%) patients actually received OAC. OAC prescription was significantly higher in valvular vs. non valvular AF ( p=0.0001).The rates of OAC prescription in our patients in age group, ≤65, 66-75, >75 years were 84.4%, 65% and 60.2% respectively Out of 290 patients who were eligible for OAC ,only 102(25%) patients were optimally anti-coagulated. Conclusion: Discordance between guidelines and practice was found regarding prescription of OACs and maintenance of optimal anticoagulation for stroke prevention in our population. Optimal anticoagulation needs to be emphasized on both patients as well as physicians to prevent strokes and achieve better outcomes.

Components and determinants of therapeutic delay in patients with acute ST-elevation myocardial infarction: A tertiary care hospital-based study

Background Delayed reperfusion is associated with worse outcomes in ST-segment elevation myocardial infarction (STEMI). This study was conducted to assess the components and determinants of therapeutic delay in STEMI patients of our state. Methods This study included consecutive patients of STEMI admitted to the coronary care units of two tertiary care hospitals in Srinagar, between 2012 and 2015. Various components of treatment delay including the patient’s decision to delay, referral delay, transportation delay, prehospital delay, and door-to-needle time were calculated. Factors associated with delayed treatment and clinico-demographic correlates of late presentation were identified. Results During a period of 3 years, 523 patients (mean age, 57.6 ± 10.5 years) were enrolled in this study. Thrombolysis was administered to 60.2% patients, while 39.8% of patients could not be thrombolysed because of late presentation. The median treatment delay was 250 minutes. Prehospital delay constituted about 83.8% of total treatment delay. Patient’s decision to delay, referral delay, and transport delay constituted 59%, 16%, and 25% of prehospital delay, respectively. Median door-to-needle time was 40 minutes. Residence in rural areas [odds ratio (OR), 2.35; 95% confidence interval (CI), 1.60–3.46], absence of prior coronary artery disease (OR, 1.54; 95% CI, 1.00–2.39), and negative family history of coronary artery disease (OR; 2.76; 95% CI, 1.86–4.10), were identified as independent predictors of delayed presentation (p < 0.001). Interestingly, 44.7% of the patients presented late due to misdiagnosis by local healthcare providers. Conclusion The standard of STEMI management in our state is far from ideal, and calls for a lot of improvement. Major efforts to reduce prehospital and in-hospital treatment delays are urgently needed.

Clinical profile in arrhythmogenic cardiomyopathy and a recessive plakophilin-2 gene mutation

Objective Arrhythmogenic cardiomyopathy (ACM) is not an uncommon cause of cardiac morbidity in Kashmir valley. This study was designed to document various clinical features and to sequence exons 11 and 12 of plakophilin 2 (PKP2) gene in these patients. Methods ACM patients who attended cardiology outpatient department of our institute from January 2014 to April 2015 were included in the study. Their records were reviewed. Controls were randomly selected, who had no history or family history of cardiac illness and had a normal cardiac examination. A blood sample was also taken from both the groups for sequencing of exon 11 and 12 of PKP2 gene. ACM patients were followed up until July 2016. Results Eleven ACM patients and seven controls were included in the study. Most common mode of presentation was ventricular tachycardia (VT). Two patients had left ventricular (LV) systolic dysfunction. One patient had a splice site mutation in exon 12 of PKP2 gene and one patient died during follow-up. One of the controls had an intronic variation that has no pathogenic significance vis-à-vis ACM. Conclusion Our study describes various clinical parameters in ACM patients and a recessive plakophilin 2 mutation after a limited PKP2 gene sequencing.

The effect of percutaneous coronary revascularization on plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in stable coronary artery disease

Background This study was conducted to assess the effect of percutaneous coronary revascularization (PCR) on plasma NT-proBNP concentration in patients with chronic stable angina (CSA). Methods This prospective open label interventional study included 22 patients with moderate to severe CSA, normal left ventricular (LV) systolic functions and critical (>90%) proximal stenosis in one of the three major epicardial coronary arteries. After stabilization of medications for 8 weeks, resting supine plasma NT-proBNP levels were measured and patients underwent PCR of the involved vessels. Eight weeks later, with medications unaltered; plasma NT-proBNP levels were repeated and compared with the baseline levels. LV systolic and diastolic functions were assessed before and after PCR. Results The mean age of the patients was 61.27 ± 8.87 years. Out of 22 patients, 20 were male and 2 were female. PCR was performed on left anterior descending coronary artery (LAD) in 12 patients and in a non-LAD vessel in 10 patients. After 8 weeks of successful PCR, there was a significant overall reduction in mean plasma NT-proBNP levels (from 244.36 ± 218.99 to 168.68 ± 161.61 pg/mL, p = 0.016). The patients who underwent PCR of LAD demonstrated significantly reduced NT-pro-BNP levels after PCR (p = 0.009). In the non-LAD group, NT-proBNP levels also decreased, albeit insignificantly (p = 0.432). Reduction in NT-proBNP was independent of change in LV systolic functions. Conclusion Successful PCR, by relieving myocardial ischemia, significantly reduced plasma NT-proBNP levels in majority of the patients with chronic stable angina secondary to critical epicardial coronary artery stenosis.

Insertion/deletion polymorphism of ACE gene in females with peripartum cardiomyopathy: A case-control study

Background The role of polymorphism of Angiotensin converting enzyme (ACE) gene and ACE activity in etiopathogenesis, prognosis, and many other clinical parameters in the various form of the cardiovascular disease has been established to some degree of certainty. The pathophysiology of Peripartum cardiomyopathy (PPCM) remains an area of active research. The main aim of our study was to see pattern of ACE- Insertion/Deletion (I/D) allele in PPCM and its implications on left ventricular performance indices. Methods This single-center case-control study included 45 cases and 70 controls. The diagnosis of PPCM was established clinically and echocardiographically. ACE genotyping was done by polymerase chain reaction (PCR) method in all subjects. Results The II, ID, and DD genotype was present in 16, 18 and 11 of subjects with PPCM and 48, 19 and 3 of controls respectively. The odds ratio for ACE-II genotype in cases vs. controls was 0.253 (95% CI = 0.114–0.558; p = 0.007), for that of II genotype was 1.93 (95% CI = 0.86–4.3; p = 0.107) and for DD genotype was 7.225 (95% CI; 1.88–27.6; p = 0.0039). Overall frequency of D allele in cases was significantly higher than controls (odds = 4.25; 95% CI = 2.01–6.7; p = 0.0001). Moreover, ejection fraction, left ventricular volume and linear dimensions were worse in patients with DD genotype. Conclusion ACE DD genotype and overall frequency of D allele is significantly higher in patients with PPCM. Also, the presence of DD genotype is associated with worse systolic performance indices measured echocardiographically.

Diagnostic utility of Gadolinium enhanced Coronary CT Angiography comparedto Conventional Invasive Coronary Angiography in detection of obstructiveCoronary Artery Disease

Background: The current gold standard for assessment of coronary artery disease, Invasive Coronary Angiography (ICA), has inherent risks of an invasive procedure including that of death. In addition use of Iodinated contrasts in ICA and Coronary CT Angiography is often contraindicated due to its renal toxicity and hypersensitivity reactions. Gadolinium, though primarily an MRI contrast, has been shown to produce vascular luminal enhancement making it an attractive alternative contrast agent for use in angiography.Objectives: To assess the possibility of use of Gd-enhanced 64-slice cardiac CT (CCT) for the diagnosis of obstructive coronary artery disease in comparison to invasive coronary angiography.Methods: A total of 25 patients of CAD underwent Gadolinium Enhanced Coronary CT Angiography followed by Invasive Coronary Angiography. The data was analyzed by comparing coronary segments with ≥ 50% stenosis detected by ICA versus detection of the same by Gd-Enhanced CTA, as well as comparison on Per-Vessel basis.Results: Mean age of patients in our study was 53.52 years (range 41-70 years). The total number of coronary segments evaluated by invasive coronary angiography was 379 of which 57 showed ≥ 50% stenosis. Gd-Enhanced CTA detected 47 of these lesions. In comparison to ICA, on Per-segment basis, Gd- Enhanced CTA showed Sensitivity of 82.46%, Specificity of 97.50%, PPV of 85.45% and NPV of 96.95%. Weighted Kappa value was 1, suggestive of strong agreement between the two modalities, excluding agreement by chance.Conclusions: Our study shows Gadolinium Enhanced Coronary CT Angiography is safer alternative for assessment of CAD in patients who have a contraindication for ICA or Iodinated Contrasts with acceptable sensitivity and specificity. Results depend on BMI and coronary calcification.