Enhanced P-selectin expression on platelet-a marker of platelet activation, in young patients with angiographically proven coronary artery disease.

P-selectin (CD62p) exposure is an established marker for platelet activation. P-selectin exposure can trigger variety of thrombotic and inflammatory reactions. In patients with coronary artery disease (CAD), platelets are activated, and hence, there is increased P-selectin exposure. The role of P-selectin exposure in patients on treatment with statins and anti-platelets is conflicting. A case-control study was performed to determine P-selectin exposure in consecutively recruited 142 patients (age ≤ 55 years) with angiographically proven CAD on treatment and 92 asymptomatic controls. P-selectin exposure was determined by flow cytometry. Data on conventional risk factors were obtained along with estimation of levels of thrombotic [fibrinogen, lipoprotein (a), tissue plasminogen activator, plasminogen activator inhibitor-1, homocysteine and von Willebrand factor] and anti-thrombotic factors (antithrombin III). The P-selectin exposure was compared among patient groups who had different modes of presentation of CAD and categories of CAD disease severity. The patients were followed up for a period of 26 months. The results indicate that P-selectin exposure was significantly elevated in patients (mean ± SD 9.24 ± 11.81) compared to controls (mean ± SD 1.48 ± 2.85) with p < 0.0001. Similarly, conventional risk factors were significantly elevated in patients. P-selectin exposure showed significant negative correlation with antithrombin III levels. P-selectin exposure was higher in patients who presented with acute coronary syndromes than those who presented with effort angina. Cardiovascular event rate was 6 % on follow-up. The study establishes that thrombotic-inflammatory pathways enhancing P-selectin exposure unrelated to treatment might be activated in patients, while the event rate remained lowered, and hence, treatment strategies should be inclusive to control these factors.

Flecainide challenge test: Predictors of unmasking of type 1 Brugada ECG pattern among those with non-type 1 Brugada ECG pattern.

BACKGROUND: Many subjects in community have non-type 1 Brugada pattern ECG with atypical symptoms, relevance of which is not clear. Provocative tests to unmask type 1 Brugada pattern in these patients would help in diagnosing Brugada Syndrome. However sensitivity and specificity of provocating drugs are variable. METHODS: We studied 29 patients referred to our institute with clinical presentation suggestive but not diagnostic of Brugada or with non-Type 1 Brugada pattern ECG. Flecainide Challenge Test (FCT) was done in these patients (IV Flecainide test in 4 patients and Oral Flecainide in 25 patients). Resting 12-lead ECG with standard precordial leads and ECG with precordial leads placed 1 Intercostal space above were performed after flecainide administration every 5 min for first 30 min and every 30 min thereafter until ECG became normal or upto 6 h. The positivity was defined as inducible Type 1 Brugada pattern in atleast 2 right sided leads. RESULT: Median age was 35(range = 5-65) years. In 16 (55%) patients the Type 1 Brugada pattern was unmasked. There were no episodes of major AV block, atrial or ventricular tachyarrhythmia. Three groups were considered for analysis: Group 1(n = 9) - FCT Positive among patients with non-type 1 Brugada ECG pattern, Group 2(n = 4) - FCT Negative among the patients with non-type 1 Brugada ECG pattern, and Group 3(n = 7) - FCT Positive among patients with no spontaneous Brugada ECG pattern. Binary logistic regression analysis found that family h/o SCD was predictive of FCT positivity in Group 1 (Odd's ratio 21, 95% Confidence interval 1.04 to 698.83, p = 0.004). CONCLUSION: Oral flecainide is useful and safe for unmasking of Type I Brugada pattern. In our study, among the many variables studied, family history of sudden cardiac death was the only predictor of flecainide test positivity among those with non-Type 1 Brugada pattern.

Circulating Thrombotic Risk Factors in Young Patients with Coronary Artery Disease Who Are on Statins and Anti-platelet Drugs.

Thrombotic risk factors may contribute to premature coronary artery disease (CAD), in addition to the conventional risk factors. There is paucity of data on studies evaluating the role of thrombotic factors in premature CAD in Indian patients. Thus a case-control study was performed to evaluate the role of thrombotic and atherogenic factors in young patients with angiographically proven CAD who are on treatment with statins and anti-platelet drugs. 152 patients (≤55 years) with angiographically proven CAD and 102 asymptomatic controls were recruited. Clinical and biochemical data were obtained in both groups. Blood levels of thrombotic factors-fibrinogen, antithrombin-III, tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-Willebrand factor (v-WF), lipoprotein(a) [Lp(a)] and homocysteine were analyzed. Patients had high levels of conventional CAD risk factors (diabetes mellitus, smoking, hypertension, dyslipidemia and positive family history) compared to controls. Logistic regression analysis revealed that low antithrombin-III (odds ratio/OR 11.2; 95 % confidence interval/CI 2.29-54.01), high fibrinogen (OR 6.04; 95 % CI 1.09-33.21) and high Lp(a) (OR 4.54; 95 % CI 0.92-22.56), as important, independent risk factors in patients. PAI-1(OR 0.15; 95 % CI 0.03-0.69) levels were significantly lower in patients. But other thrombotic risk factors studied (t-PA, v-WF and homocysteine) were comparable among patients and controls. The treatment using statins and anti-platelet drugs might be contributing to the control of some of the thrombotic risk factors. The strategies aiming at lowering the levels of thrombotic risk factors along with conventional risk factors may be useful in primary and secondary prevention of CAD.

A case of 'tachy-brady syndrome': What is the mechanism?

A young male presented with incessant narrow QRS tachycardia and left ventricular dysfunction. 24-Holter monitoring revealed multiple episodes of sustained and nonsustained episodes of tachycardia with prolonged sinus pauses at termination. The analysis of the electrocardiogram, followed by an invasive electrophysiological study, suggested an unusual mechanism for this tachy-brady syndrome.

Regression of pulmonary vascular disease after therapy of Abernethy malformation in visceral heterotaxy.

A 1-year-old boy who had left isomerism and corrected transposition of the great arteries (c-TGA) with moderate-sized ventricular septal defect, severe pulmonary artery hypertension (PAH), and pulmonary vascular disease with significant right-to-left shunting received a diagnosis of type 2 Abernethy malformation, which was partly responsible for disproportionate PAH in the child. The malformation was treated by plugging of the portosystemic shunt. Follow-up cardiac catheterization on sildenafil demonstrated significant left-to-right shunting (2.16:1) and a fall in pulmonary vascular resistance, making surgical correction possible. This case highlights the importance of searching for additional rare causes of PAH in patients with congenital heart diseases when the degree of pulmonary hypertension is disproportional to the defect size.

Percutaneous closure of a moderate to large tubular or elongated patent ductus arteriosus in children younger than 3 years: is the ADO II appropriate?

Protrusion of the Amplatzer duct occluder (ADO) II device into the aortic isthmus or the pulmonary artery causing obstruction and residual flow has been reported, but the same has not been widely studied in small children with a patent ductus arteriosus (PDA) anatomy not considered suitable for closure with the ADO I device. This study aimed to report the safety and efficacy of the ADO II device in children younger than 3 years with a tubular or elongated PDA and to analyze the possible reasons for residual flow in children with such a PDA. In this study, 17 children younger than 3 years (mean age, 10.3 ± 7 months; mean weight, 6 ± 3.6 kg) underwent attempted closure of a tubular or elongated PDA (mean diameter at the narrowest point, 4.1 ± 1.1 mm) with the ADO II device between July 2010 and July 2012. Of the 17 patients, 16 (2 boys and 14 girls) completed the follow-up evaluation. A complete echocardiographic evaluation was performed on all the patients before PDA closure and at the follow-up visit, and the results were compared with those of previous published studies. Of the 16 patients, the 15 who completed the follow-up evaluation had successful device closure (1 device embolization). Residual flow was present in six patients immediately after deployment, which was reduced to three patients at the last follow-up visit. Five of nine patients closed with a 6-mm-long device had residual flow compared with only one of seven patients closed with a 4-mm-long device. After device closure, significant elevations of the left and right pulmonary artery velocities occurred in three and two patients, respectively; in 12 patients, descending thoracic aortic (DTA) velocities increased mildly. There was trend toward a fall in the elevated pressures at the last follow-up visit, although one patient had an elevation in right pulmonary artery velocity at last the follow-up echocardiogram compared with the echocardiogram immediately after closure. Hence, in children younger than 3 years with or without pulmonary arterial hypertension, closure of a PDA not amenable to closure with the ADO I device is feasible using the ADO II device, with an increased incidence of clinically nonsignificant complications. Selection of device dimensions according to the manufacturer's recommendation may not be the optimal strategy.

An unusual cause for unruptured sinus of valsalva aneurysm.

Sinus of valsalva aneurysm is considered to be one of the rarest complications of inflammatory aortitis. Herewith, we are reporting a young male patient who presented to us with severe aortic regurgitation. On evaluation, he was found to have unruptured sinus of valsalva aneurysm. CT angiography and magnetic resonance imaging have shown value in the diagnosis of sinus of valsalva aneurysm.

Pediatric cardiology in India - In search of a holistic solution.

In response to the survey among early career pediatric cardiologists from India and the accompanying editorial, we invited comments and suggestions from thought leaders and senior functionaries in the field. We have summarized the thoughts and suggestions as a mini-symposium.

Programmed ventricular stimulation in structural heart disease: Implications of patterns of ventricular arrhythmias induced to long-term outcomes.

INTRODUCTION: Currently available data gives some credence to utility of VT induction studies in patients with stable ischemic cardiomyopathy, there are some unresolved questions as to define sensitive threshold for low-risk and the prognostic relevance of ill sustained or non-specific tachycardia on induction study. We evaluated potential ability of VT inducibility to predict likelihood of SHD (Structural heart disease) patients for subsequent arrhythmic or adverse cardiac events. MATERIAL AND METHODS: All consecutive patients with syncope/documented arrhythmia who had VT induction done were included and patients with VT storm, ACS,uncontrolled HF were excluded. We studied in 4 groups-monomorphic VT, sustained polymorphicVT, ill sustainedVT/VF and no VT/VF induced. The primary-endpoints were - Sudden death, all-cause mortality and secondary-endpoints were - MACE (AICD shock, death,HF, recurrence of VT). We screened 411 patients and included 169 within inducible (n = 79) and non-inducible group (n = 90). RESULTS: There were a higher number of patients with coronary artery disease, LV dysfunction, patients on amiodarone in inducible group and no difference in usage of beta-blockers. Recurrence of VT, composite of MACE was significantly higher in inducible group (p < 0.05). Mortality was not different in 3 groups compared with no VT/VF group. We found that monomorphic VT group had significantly higher MACE as compared to others and also predicted recurrence of VT and AICD shock and showed a trend towards significance for prediction of mortality. Inducible patients on AICD had mortality similar to non-inducible group. CONCLUSION: Induction of monomorphicVT/polymorphicVT with ≤3extrastimuli is associated with a higher number of MACE events on follow up. Induction of monomorphicVT predicts recurrence of VT/ICD shock.

Crisscross pulmonary artery with double aortic arch: an unusual association.

Anomalies of pulmonary artery origin are rare. Crisscross pulmonary artery origin is a rare benign anomaly characterized by the left pulmonary artery arising superiorly and to the right side of the right pulmonary artery. The condition is usually accompanied by a conotruncal anomaly. Here, we report a child with crisscross pulmonary arteries and a complete vascular ring formed by a double aortic arch, which was confirmed by computed tomography angiography. The child underwent surgical correction for relief of stridor.

An unusual mechanism of sustained right atrial tachycardia.

Lower loop re-entry (LLR) flutter is a rare type of atypical right atrial flutter. Most of the reported cases occurred in association with typical flutter patterns as a transient arrhythmia. Our case is unique in the fact the LLR was sustained and persisted independently.

Percutaneous valvuloplasty for mitral valve restenosis: postballoon valvotomy patients fare better than postsurgical closed valvotomy patients.

AIM: To compare the results of percutaneous mitral valvuloplasty (BMV) for mitral restenosis in post-BMV versus postclosed mitral valvotomy (CMV) patients. METHODS AND RESULTS: Ninety-two patients who underwent BMV for mitral restenosis were followed up prospectively. Of these, 28 patients had undergone previous percutaneous mitral valvuloplasty (PRIOR BMV) and 64 patients had undergone previous closed mitral valvotomy (PRIOR CMV). BMV for mitral restenosis was a success in 59% patients (57.1% PRIOR BMV, 59.3% PRIOR CMV, P = 1.0). Incidence of severe mitral regurgitation was 3.25%, all in the PRIOR CMV group. In univariate analysis, the major predictor of successful BMV for mitral restenosis was Wilkins score (P = 0.004). At a follow up of 3.47 + 2.07 years, mitral valve area was similar between groups (1.45 +/- 0.22, 1.46 +/- 0.26, P = 0.35). The combined end points of mitral valve replacement (MVR), need for re-repeat BMV for mitral restenosis or death was higher in the PRIOR CMV group (31.2% PRIOR CMV, 7.1% PRIOR BMV, P = 0.027). Event-free survival at follow up was lower in the PRIOR CMV group (69% PRIOR CMV, 92.8% PRIOR BMV) mainly due to the higher need for MVR (11 vs. 0 patients, P = 0.03). CONCLUSIONS: In conclusion, following BMV for mitral restenosis, patients with PRIOR BMV are found to have lesser event rates on follow-up compared to patients with PRIOR CMV, though procedural success rates are similar.

Natural history of aortic valve disease following intervention for rheumatic mitral valve disease.

BACKGROUND AND AIM OF THE STUDY: A significant proportion of patients who require interventions for rheumatic mitral valve (MV) disease have coexisting aortic valve (AV) disease. To date, little is known of the natural history of AV disease in these patients. METHODS: The details of a cohort of 200 patients (146 females, 54 males; mean age at MV intervention 30.3 +/- 9.9 years) with rheumatic heart disease were retrospectively reviewed. The patients had undergone an index MV intervention (either closed or balloon mitral valvotomy) or MV replacement between 1994 and 1996, and received long-term regular follow up examinations. The clinical and echocardiographic data at entry and at follow up were noted. Patients were allocated to two groups, based on whether the AV disease was absent (group I, n=98) or present (group II, n=102) at baseline. The AV disease was categorized as thickening only (group IIA), isolated aortic regurgitation (AR) (group IIB), or combined aortic stenosis (AS) and AR (group IIC). No patient had isolated AS at baseline. RESULTS: The mean follow up period was 9.3 +/- 1.07 years; during which 10 patients in group I developed new AV disease, which included AV thickening only (n=2), trivial-mild AR (n=7) and mild AS with trivial AR (n=1). Of 16 patients in group IIA, 11 developed isolated AR, and one patient progressed to have mild AS and AR. Among 69 patients in group IIB, 22 (31.9%) developed AS, and all had either mild (n=8) or moderate (n=14) AR with mild AS. Group IIC included 17 patients with mild combined AV disease at baseline, except for moderate AS and moderate AR in one patient each. Among 16 patients with mild AS in group IIC, six progressed to moderate AS and two to severe AS. AR became moderate in 10 patients and severe in one patient. The two patients who progressed to severe AS requiring AV replacement had mild AS at baseline. No patient who developed new combined AV disease had lesions with severity more than mild AS or moderate AR. On logistic regression analysis of the variables predisposing to progression of AV disease, such as age, gender, history of rheumatic fever (RF) and recurrence, and interval from RF episode to symptom onset, only the initial AV gradient was identified as being statistically significant (beta coefficient 0.528, SE = 0.17, p < 0.0001). CONCLUSION: Patients with no or mild AV disease at the time of MV intervention rarely develop severe AV disease, and seldom require AV surgery over the long-term follow up. The presence of mild AS at baseline is predictive in the minority of cases where AV disease will progress relatively more rapidly.

Doppler echocardiographic assessment of TTK Chitra prosthetic heart valve in the mitral position.

AIMS: TTK Chitra heart valve prosthesis (CHVP), a tilting disc mechanical heart valve of low cost and proven efficacy, has been in use for the last 15 years. Although various studies substantiating its long-term safety and efficacy are available, no study had assessed its echocardiographic characteristics. The purpose of this study was to determine the normal Doppler parameters of CHVP in the mitral position and to assess whether derivation of mitral valve area (MVA) using the continuity equation (CE) and more commonly used pressure half-time (PHT) method is comparable in the functional assessment of this tilting disc mitral prosthesis. METHODS AND RESULTS: Doppler echocardiography was performed in 40 consecutive patients with CHVP in the mitral position. All patients were clinically stable, without evidence of prosthetic valve dysfunction such as significant obstruction or regurgitation, endocarditis, left ventricular dysfunction (ejection fraction <40%), or significant aortic regurgitation. Valve sizes studied included 25, 27, and 29 mm. Mitral valve area was derived both by the PHT method and by the CE, using the stroke volume measured in the ventricular outflow tract divided by the time-velocity integral of CHVP jet. The peak Doppler gradient ranged from 5 to 21 (mean 11.0) mmHg, and the mean gradient ranged from 1.7 to 9.2 (mean 4.1) mmHg. Mean gradient negatively correlated with an increase in the actual orifice area (AOA) derived from the valve orifice diameter given by the manufacturer (r = -0.45, P = 0.004). Mitral valve area calculated by both PHT and CE increased significantly with an increase in the AOA (r = 0.42, P = 0.007 and r = 0.32, P = 0.046, respectively). Mitral valve area by the CE averaged 1.55 +/- 0.36 cm(2) (range 0.85 cm(2) for a 25 mm valve to 2.41 cm(2) for a 29 mm valve) and was smaller than by PHT (mean 2.04 +/- 0.41 cm(2), range 1.40-3.14 cm(2); P = 0.0001; t-test), irrespective of whether PHT is less than or >110 ms. CONCLUSION: The Doppler parameters obtained with CHVP in the mitral position are comparable with those obtained with the different prosthetic valves in common use. In the selected group of patients with CHVP, assessment of MVA by the PHT method is comparable with that by the CE. Areas by both methods were smaller than the AOA provided by the manufacturer, as seen in other similar design valves.

Efficacy and safety of combination of extended release niacin and atorvastatin in patients with low levels of high density lipoprotein cholesterol.

OBJECTIVE: We investigated the safety and efficacy of combination therapy of extended release (ER) niacin and atorvastatin in patients with low HDL-C and compared the results with atorvastatin monotherapy. METHODS: This open label study recruited consecutive men and women who had coronary artery disease with HDL-C levels <35 mg/dL. These patients were already on atorvastatin therapy targeted to lower low density lipoprotein cholesterol (LDL-C), for a minimum period of 6 months. Group 1, n = 104 (mean age 52.7 years) received ER niacin in addition to atorvastatin and group 2 (n = 106) continued on atorvastatin (mean age 52.3 years). ER niacin dose was built up to a maximum of 1.5 g and atorvastatin dose titrated according to LDL levels in both the groups. The lipoprotein levels at baseline were similar (p = NS). RESULTS: At 9 +/- 1.8 months of follow-up, the mean dose of ER niacin was 1.3 g and atorvastatin 13.2 mg in group 1. In comparison, group 2 patients had mean atorvastatin dose of 15.9 mg. Patients in group 1 had significant elevation in HDL-C cholesterol (39.5 +/- 5.5 vs 35.7 +/- 4.5 mg/dL), reduction in total cholesterol (156.4 +/- 31 vs 164.5 +/- 39.3 mg/dL) and also LDL-C (88.9 +/- 28.3 vs 99.8 +/- 35.4 mg/dL) compared to group 2 (all p < 0.05). The magnitude of reduction in triglyceride levels was not significant between the groups (140.1 +/- 40.4 vs 145.2 +/- 46.5 mg/dL) (p = NS). No major adverse events or clinical myopathy occurred in either groups. Four patients (4%) discontinued ER niacin (2 due to gastro-intestinal symptoms and 2 due to worsening of diabetes). Flushing occurred in 3% patients, but none felt it to be troublesome. CONCLUSION: Adding ER niacin to atorvastatin exhibited beneficial effects on lipid profile with significant elevation of HDL-C cholesterol and further lowering of LDL-C compared to monotherapy. This treatment offered better targeted therapy and was well tolerated with proper monitoring in Indian patients.

Acute phase reactants predict mitral regurgitation following mitral valvuloplasty.

This report evaluated whether acute phase reactants can predict the development of mitral regurgitation following percutaneous mitral valvotomy. 58 patients who developed significant mitral regurgitation following valvotomy were retrospectively compared with 58 age, sex and procedure technique matched control patients, who had valvotomy without mitral regurgitation. ESR and total leucocyte count were significantly higher in the group who developed mitral regurgitation, than in the control group. Higher ESR and total leucocyte count may be indicative of ongoing low grade sub-clinical inflammatory process, which makes the valve tissue friable which can give way during balloon stretch and lead onto mitral regurgitation.

Acquired Fontan paradox in isolated right ventricular cardiomyopathy.

A 44-year-old woman presented with features of congestive heart failure. Echocardiography revealed severe right ventricular dysfunction along with passive minimally pulsatile pulmonary blood flow suggesting very high systemic venous pressures. This was confirmed with cardiac catheterization in which the pressures of superior vena cava and inferior vena cava (19 mmHg) were higher than the pulmonary artery pressures (17 mmHg). Elevation of systemic venous pressures above the pulmonary venous pressures, Fontan paradox, to drive the forward flow, is a specific feature of artificially created cavopulmonary shunts. Late stage of isolated right ventricular cardiomyopathy resulted in the spontaneous evolution of Fontan circulation with a nonfunctional right ventricle in this patient.