Shantanu Pande

Therapeutic Dosing of Acenocoumarol: Proposal of a Population Specific Pharmacogenetic Dosing Algorithm and Its Validation in North Indians

Objectives To develop a population specific pharmacogenetic acenocoumarol dosing algorithm for north Indian patients and show its efficiency in dosage prediction. Methods Multiple and linear stepwise regression analyses were used to include age, sex, height, weight, body surface area, smoking status, VKORC1 -1639 G>A, CYP4F2 1347 G>A, CYP2C9*2,*3 and GGCX 12970 C>G polymorphisms as variables to generate dosing algorithms. The new dosing models were compared with already reported algorithms and also with the clinical data for various performance measures. Odds ratios for association of genotypes with drug sensitive and resistant groups were calculated. Results The pharmacogenetic dosing algorithm generated by multiple regression analysis explains 41.4% (p-value <0.001) of dosage variation. Validation of the new algorithm showed its predictive ability to be better than the already established algorithms based on similar variables. Its validity in our population is reflected by increased sensitivity, specificity, accuracy and decreased rates of over- and under- estimation in comparison to clinical data. The VKORC1-1639 G>A polymorphism was found to be strongly associated with acenocoumarol sensitivity according to recessive model. Conclusions We have proposed an efficient north India specific pharmacogenetic acenocoumarol dosing algorithm which might become a baseline for personalised medicine approach for treatment of patients in future.

Pulmonary arterial hypertension in rheumatic mitral stenosis: does it affect right ventricular function and outcome after mitral valve replacement?

Right ventricular function affects the outcome in valvular heart disease but less is known about the relation between indices of dysfunction and outcome. Seventy patients undergoing mitral valve replacement between April 2007 and April 2008 for predominant rheumatic mitral stenosis were included in the study. Two groups were formed based on right ventricular systolic pressure (RVSP), <or=40 mmHg (group I, n=16) and >41 mmHg (group II, n=54). Right ventricle (RV) function indices were studied by echocardiography. RVSP reduced significantly in group II (P=0.0001) but not in group I. Brain natriuretic peptide (BNP) was raised in all cases and reduced significantly postoperatively. Tricuspid annular plane excursion, myocardial performance index, RV descent and tricuspid valve annular shortening (TV shortening) conformed to RV dysfunction in both groups, and did not change significantly postoperatively. Regression analysis for outcome revealed TV shortening as the only significant factor (P=0.03). Receiver operating characteristic of TV shortening and adverse outcome showed worse outcome with TV shortening of <11%. RV dysfunction was observed in all cases irrespective of RVSP. TV shortening of <11% was associated with adverse outcome. Postoperative fall in BNP levels may indicate a trend towards recovery.

Valvuloplasty in the Treatment of Rheumatic Tricuspid Disease

Organic involvement of the tricuspid valve is uncommon. Valve repair is preferred over replacement as it results in a low gradient across the valve and obviates the risk of prosthesis-related complications. From October 2002 to October 2004, 37 patients who required tricuspid valve repair for organic involvement were included in this study. They were divided into 2 groups depending on the surgical procedure for valve repair: 20 patients in group 1 had tricuspid commissurotomy and De Vega annuloplasty; 17 in group 2 had tricuspid commissurotomy only. There were significant reductions in peak and mean tricuspid gradients and right ventricular systolic pressure in both groups. Annular shortening was similar in both groups (median, 23% in group 1, 21% in group 2), but the ratio of the tricuspid regurgitation jet area to right atrial area was greater in group 2 (median, 0.40 in group 2, 0.19 in group 1). There was no postoperative death. We recommend supporting the tricuspid annulus with annuloplasty in patients with organic tricuspid valve disease and no dilatation of the annulus, if annular shortening is < 30%.

A new classification of inferior vena cava thrombus in renal cell carcinoma could define the need for cardiopulmonary or venovenous bypass.

Introduction: Although the level of inferior vena cava (IVC) thrombus governs the type of surgical approach, there is no consistency in reporting the levels of IVC thrombus in the literature. This prospective study illustrates a simple three-level classification based on the need for clamping hepatoduodenal ligament and venovenous or cardiopulmonary bypass. Materials and Methods: Between January 2010 and June 2014, 30 patients of renal mass with renal vein and/or IVC thrombus were treated after classifying the IVC thrombus into three levels on the basis of need for clamping the hepatoduodenal ligament. After excluding renal vein thrombi, level I was described as thrombus located caudal to the hepatic vein. Level II included all retrohepatic, suprahepatic infradiaphragmatic or supradiaphragmatic thrombi reaching till the right atrium. Atrial thrombi were categorized as level III. Level I and II thrombi were managed without venovenous or cardiopulmonary bypass. Level III thrombus required cardiopulmonary bypass. Results: Of 26 patients with thrombus, 13 had level I thrombus. Of eight cases with level II thrombus, three were retrohepatic, three were suprahepatic infradiaphragmatic and two were supradiaphragmatic. All were removed successfully. Of five patients with level III thrombus, three were operated with cardiopulmonary bypass while the remaining two patients were too sick to be taken up for surgery. The median hepatoduodenal ligament clamp time was 10 min. One patient with level II thrombus had transient liver enzyme elevation. Conclusion: Renal vein thrombus should not be categorized as level I thrombus. Level II thrombus, irrespective of its relation to the diaphragm, could be managed without venovenous or cardiopulmonary bypass.

Pericardial Monocusp for Pulmonary Valve Reconstruction: A New Technique

Enhancing the pulmonary annulus renders the pulmonary valve incompetent in cases of tetralogy of Fallot. A pressure-loaded right ventricle may change to a volume-loaded ventricle, which may dilate and eventually dysfunction. This study evaluated a new technique of fashioning a monocusp valve from untreated autologous pericardium suspended on a transannular patch. It was assessed in 40 children undergoing complete repair of tetralogy of Fallot between January 2005 and December 2007. 24 patients had a transannular patch alone (group A) and 16 received a transannular patch with the autologous pericardial monocusp valve (group B). All patients were followed up for 1 year with transthoracic echocardiography to determine pulmonary insufficiency. There was no significant difference in cardiopulmonary bypass or aortic crossclamp times, postoperative chest tube drainage, duration of inotropic usage, intensive care unit or hospital stay between groups. Univariate analysis showed significantly lower grades of pulmonary insufficiency in group B. This technique for creating an autologous pericardial monocusp valve is an inexpensive, simple, and reliable procedure that effectively reduces pulmonary insufficiency at the 1-year follow-up.

Differential Release Kinetics of Cardiac Biomarkers in Patients Undergoing Valve Replacement Surgery.

Differential release kinetics of cardiac biomarkers including brain natriuretic peptide (BNP), Troponin‐I, and CK‐MB following valve replacement (VR) are not well characterized.

Off-pump coronary artery bypass in severe left ventricular dysfunction.

The outcome of multivessel off-pump coronary artery bypass grafting in cases of severe left ventricular dysfunction was studied in 58 consecutive patients with ejection fraction ≤35% who were followed up for a median of 15 months. Patients with ejection fractions ≤25% (group 1) had the largest left ventricular dimensions preoperatively, with gradual increases during follow-up; those with ejection fractions of 26%-35% (group 2) had smaller preoperative ventricular dimensions, with left ventricular regression postoperatively. There was more improvement in ejection fraction in group 2 than group 1 (33% vs. 10%). Mitral regurgitation improved from moderate to mild in group 2; whereas in group 1, mild mitral regurgitation progressed to moderate or severe during follow-up. Ejection fraction was a predictor of more frequent use of intraaortic balloon pumping, longer duration of inotropic use, a higher mean pulmonary artery-to-systemic arterial pressure ratio, and increased postoperative drainage.

Role of common sarcomeric gene polymorphisms in genetic susceptibility to left ventricular dysfunction.

Mutations in sarcomeric genes are common genetic cause of cardiomyopathies. An intronic 25-bp deletion in cardiac myosin binding protein C (MYBPC3) at 3 ′ region is associated with dilated and hypertrophic cardiomyopathies in Southeast Asia. However, the frequency of sarcomeric gene polymorphisms and associated clinical presentation have not been established with left ventricular dysfunction (LVD). Therefore, the aim of the present study was to explore the association of MYBPC3 25-bp deletion, titin (TTN) 18 bp I/D , troponin T type 2 (TNNT2) 5 bp I/D and myospryn K2906N polymorphisms with LVD. This study includes 988 consecutive patients with angiographically confirmed coronary artery disease (CAD) and 300 healthy controls. Among the 988 CAD patients, 253 with reduced left ventricle ejection fraction (LVEF ≤ 45%) were categorized as LVD. MYBPC3 25-bp deletion, TTN 18 bp I/D and TNNT2 5 bp I/D polymorphisms were determined by direct polymerase chain reaction method, while myospryn K2906N polymorphism by TaqMan assay. Our results showed that MYBPC3 25-bp deletion polymorphism was significantly associated with elevated risk of LVD (LVEF <45) (healthy controls versus LVD: OR = 3.85, P< 0.001; and nonLVD versus LVD: OR = 1.65, P = 0.035), while TTN 18 bp I/D , TNNT2 5 bp I/D and myospryn K2906N polymorphisms did not show any significant association with LVD. The results also showed that MYBPC3 25-bp deletion polymorphism was significantly associated with other parameters of LV remodelling, i.e. LV dimensions (LV end diastole dimension, LVEDD: P = 0.037 and LV end systolic dimension, LVESD: P = 0.032). Our data suggests that MYBPC3 25-bp deletion may play significant role in conferring LVD as well as CAD risk in north Indian population.

Metabolic manipulation in Dilated Cardiomyopathy: assessing the role of trimetazidine

Altered substrate metabolism plays an important role in pathophysiology of heart failure (HF). Optimization of myocardial energy metabolism with metabolic modulators like trimetazidine (TMZ) allows more efficacious energy production.

Early and mid-term results of minimally invasive coronary artery bypass grafting

INTRODUCTION Minimally invasive coronary artery bypass grafting (MICABG) is a less invasive method of performing surgical revascularization. This technique coupled with use of off pump technique of surgical revascularization makes it truly less invasive. This method is highly effective even in high-risk patients. Results of this procedure are comparable to standard off pump technique and are better than percutaneous coronary intervention utilizing drug-eluting stent. We present an early and mid-term result of the use of this technique. METHOD We enrolled 33 patients for analysis operated between 2008 and 2012. Operation was performed utilizing off-pump technique of coronary artery bypass grafting through a minimal invasive incision. Left internal mammary artery graft was done for single vessel disease and radial artery was utilized for other grafts if required. Median follow up of 2.5 years (6 months-4 years) is available. RESULTS Median age was 58.5 years (41-77) and all were male. Single vessel disease was present in 7, double vessel in 14 and triple vessel disease in 12 patients. All the patients had normal left ventricular size and function. There was no operative and 30-day mortality. Conversion to median sternotomy to complete the operation was done in 6.6% (2 out of 33 patients). One patient had acute myocardial infarction and there were no deaths during follow up. CONCLUSION MICABG is a safe and effective method of revascularization in low risk candidates for coronary artery bypass grafting.