Safety and efficacy of indigenously developed and manufactured bivalirudin in moderate/high-risk Indian patients undergoing percutaneous coronary intervention: the Bivaflo Registry.

BACKGROUND: Current treatment strategies for percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS) include concomitant use of glycoprotein IIb/IIIa inhibitors (GPI) and antithrombotic therapy such as aspirin, clopidogrel, and unfractionated or low-molecular-weight heparin. The "direct thrombin inhibitor" bivalirudin has been associated with better efficacy and safety than heparin. OBJECTIVE: The present study is performed to evaluate the safety and efficacy of an indigenously developed and manufactured bivalirudin (Bivaflo; Sun Pharmaceutical Industries Ltd., Mumbai) as the primary anticoagulation strategy during PCI in moderate-high risk patients with only provisional use of GPI. METHODS: This prospective multicentered registry enrolled 439 patients in 11 tertiary care centers across India. Patients who had ACS or other clinical/angiographic characteristics, which increase risk during PCI, were enrolled in the registry. Bivaflo was administered as a bolus dose of 0.75 mg/kg, followed by infusion at a rate of 1.75 mg/kg/h during the procedure and optionally 0.25 mg/kg/h for 4 hours after the procedure at investigator's discretion. GPI use was discouraged except as bailout. The primary endpoints were composite and individual incidences of death, myocardial infarction (MI), urgent revascularization, subacute stent thrombosis (SAT), or bleeding at day 7/hospital discharge, whichever was earlier. The secondary endpoints were 30-day composite and individual incidences of death, MI, urgent revascularization, and SAT. RESULTS: The mean age of the group was 58 +/- 10 years and 83% were males. Bivaflo was administered for a mean duration of 102 +/- 79 minutes, and 65% patients received Bivaflo infusion post-PCI. ACT values measured at 10 minutes after bolus and at the end of the PCI were found to be 339 +/- 110 and 336 +/- 104 seconds, respectively. GPI was provisionally used in only 4% (16) patients mostly due to new or suspected thrombus and obstructive dissection with decreased flow. At day 7/hospital discharge, there were no incidences of major adverse cardiac events or major bleeding. Minor bleeding occurred in only 4 patients (0.9%). The 30-day composite major adverse cardiac event rate was 0.68%. One death and two subacute thrombosis occurred during the 30-day follow-up. CONCLUSION: Bivaflo is safe and effective sole anticoagulation strategy during PCI of moderate-high risk patients. Bivaflo administration was associated with no major bleeding events and extremely low in hospital and 30-day MACE rate. These rates were lower than expected MACE rates for such a subgroup of patients based on historical controls.

WPW and preexcitation syndromes.

Wolff-Parkinson-White syndrome is a disorder characterized by presence of an accessory pathway which predisposes patients to tachyarrhythmias and sudden death. Among patients with WPW syndrome, atrioventricular reentrant tachycardia (AVRT) is the most common arrhythmia, accounting for 95% of re-entrant tachycardias. It has been estimated that one-third of patients with WPW syndrome have atrial fibrillation (AF). AF is a potentially life-threatening arrhythmia. If an accessory pathway has a short anterograde refractory period, then rapid repetitive conduction to the ventricles during AF can result in a rapid ventricular response with subsequent degeneration to ventricular fibrillation (VF). The accessory pathway may be located anywhere along the atrioventricular valve Most of the patients are young and do not have structural heart disease hence it is important to risk stratify these patients so as to prevent the sudden death. Management of asymptomatic patients with WPW syndrome has always remained controversial Catheter ablation of accessory pathways has become an established mode of therapy for symptomatic patients and asymptomatic patients employed in high-risk professions.

Coronary artery stenting for isolated proximal left anterior descending stenosis: immediate and follow-up results.

Between February 1995 to August 1997, 120 patients underwent elective stent implantation for isolated proximal left anterior descending coronary artery stenosis. Their age ranged from 31 to 72 years (mean: 50.8 +/- 10.2) and the majority (89%) were males. All patients had angina, documented myocardial ischemia or both and 70 percent or more luminal diameter stenosis in the proximal left anterior descending before the origin of any branch. Majority (62.5%) of the treated lesions were type A. Successful deployment of the stent at the target site was achieved in all patients without any major in-hospital complications, including myocardial infarction, emergency bypass graft surgery or death. Clinical follow-up, ranging from 6 to 31 months (mean: 18.5 +/- 8.1, median: 20), was available in 87 out of 92 (94.5%) eligible patients who had completed at least six months after the procedure. Freedom from angina, myocardial infarction, target lesion revascularization and death was observed in 90.8, 100, 95.4 and 97.7 percent of patients, respectively. By the Kaplan-Meier estimate, an event-free survival (absence of death, myocardial infarction, recurrence of angina or revascularization) was 95.4 percent at six months, 89.5 percent at 12 and 18 months and 82.7 percent at 24 to 31 months of follow-up. Only 10 (11.5%) patients developed any event and TLR was required in 4.6 percent of patients. In conclusion, elective stenting for isolated proximal left anterior descending stenosis can be achieved safely and successfully in all patients without any adverse in-hospital events. This modality of treatment also provides long-term benefits in terms of reduction in major cardiovascular events and need for subsequent revascularization.

Elective stenting for type B and C lesions: immediate results and follow-up angiographic restenosis.

From January to December 1995, 73 out of 174 patients with coronary artery disease underwent elective stenting for type B and C lesions. The age ranged from 35 to 73 years (mean +/- SD : 52.1 +/- 12.6) and the majority (91.7%) were males. Of the 74 vessels treated, the target vessel was LAD in 49 (66.4%), LCx in 13 (17.6%), RCA in 8 (10.8%) and SVG in 4 (5.2%). Based upon the ACC/AHA task force classification, 58 (79.5%) patients had type B1, 9 (12.3%) B2 and 6 (8.2%) had type C lesions. A total of 89 stents were deployed to treat 76 lesions with a range of 1 to 3 stents per lesion. A single stent was required for 67 lesions, 2 stents for 8 and 3 stents for 2 lesions. The stents used were Wiktor (29), Palmaz-Schatz (26), Gianturco-Roubin (24), Microstent (6) and Freedom (4), depending upon the anatomical and morphological characteristics with the lesion. Using high pressure strategy, the stents were deployed successfully in all (100%) with a reduction in luminal diameter stenosis from 92 +/- 5.4 to -5 +/- 6 percent. There was no subacute stent thrombosis despite nonusability of oral anticoagulation in 95.9 percent patients. None had any major complication in the form of acute myocardial infarction, need for emergency bypass graft surgery or death. Minor complications were encountered in 9 (12.3%) patients. At a mean follow-up of 26 +/- 14 weeks, 74 percent of the patients were asymptomatic. Out of 31 patients who had completed 6 months after the procedure, repeat angiography was performed in 29 (93.5%) at a mean duration of 29 +/- 6 weeks. The angiographic restenosis was found in 6 (20.7%) patients. In conclusion, type B and C lesions can be treated successfully using elective stenting with excellent immediate results and clinical outcome. Angiographic restenosis, which develops in about one-fifth of patients, appears to be much lower than reported after balloon angioplasty for these complex lesions.

Ventricular tachycardia with left bundle branch block morphology in the absence of ischaemic heart disease--clinical and electrophysiological observations.

Clinical and electrophysiological features of 20 patients presenting with ventricular tachycardia (VT) of left bundle branch block (LBBB) morphology without evidence of coronary artery disease were studied. The mean age of the patients was 35.2 +/- 12 (range 15-57 years). The rate of VT varied between 140-240/min (182 +/- 80). Six (30%) patients experienced giddiness or syncope during palpitations. Structural heart disease was found in 10 (50%) of these patients, which included arrhythmogenic right ventricular dysplasia in five, submitral left ventricular (LV) aneurysm in one, anterolateral LV dyskinesis in one, dilated cardiomyopathy in one, endomyocardial fibrosis in one and nonobstructive hypertrophic cardiomyopathy in one case. Ten patients were free of structural heart disease. Electrophysiological study was done in all patients. VT with same morphology as spontaneous VT was inducible in only 14 patients. Seventeen patients were treated medically with total or partial amelioration of symptoms. In three patients, two with arrhythmogenic right ventricular dysplasia and one with structurally normal heart, who were unresponsive to drug therapy, the VT focus could be mapped in right ventricular outflow tract and successful electrical ablation was done. Thus in patients who present with VT with LBBB morphology, the heart is often structurally normal but organic disease is not uncommon, and should be carefully searched.

Comparative evaluation of left ventricular function in sick sinus syndrome on different long-term pacing modes.

Single-chamber ventricular pacing has been implicated in the development or progression of congestive heart failure in patients with sick sinus syndrome (SSS). To define the exact role of pacing modality in causation of congestive heart failure, quantitative two-dimensional echocardiographic examination was performed in 51 consecutive patients with SSS who received an initial pacemaker from January 1979 to September 1989 and were free of any structural heart disease at the time of implant. Atrial or dual chamber pacemakers were implanted in 21 patients (Group I) and ventricular pacemakers in 30 (Group II). The two groups were matched for age, gender, paced rate, blood pressure and duration of pacing. After a mean follow-up of 64 +/- 34 months, congestive heart failure developed in one patient in group I and 3 in Group II. Patients in group II, had larger left atrium (41 +/- 5 vs 37 +/- 6 mm, p < 0.05) and left ventricular end-diastolic volume (64 +/- 18 vs 54 +/- 12 ml/m2, p < 0.01) but similar left ventricular end-systolic volume (27 +/- 12 vs 24 +/- 9 ml/m2, p = NS), ejection fraction (59 +/- 10 vs 57 +/- 8%, p = NS), left ventricular mass (84.8 +/- 31 vs 85.6 +/- 29.2 gm/m2, p = NS), meridian end-systolic wall stress (48.3 +/- 22.1 vs 49.8 +/- 25 Kdynes/cm2, p = NS) and wall stress/end-systolic volume ratio (1.27 +/- 0.94 vs 1.42 +/- 0.59, p = NS). Pacing mode does not appear to influence left ventricular systolic function in patients with SSS.

Comparative clinical and electrophysiologic effects of adenosine and verapamil on termination of paroxysmal supraventricular tachycardia.

The efficacy and electrophysiologic effects of adenosine and verapamil in termination of paroxysmal supraventricular tachycardia (SVT) were compared in 18 patients (age 18-48 years, mean 33 +/- 9 years) with recurrent sustained and inducible SVT. Ten patients had atrioventricular nodal reentrant tachycardia (AVNRT) and 8 had atrioventricular reentrant tachycardia involving a retrograde accessory pathway (cycle length of SVT 280-360 msec; mean 315 +/- 20 msec). Each patient served as his own control. After induction of SVT, adenosine was administered first (6 mg i.v. bolus). If the tachycardia was not terminated, a bolus of 12 mg was given. Ten minutes later, verapamil (5 mg i.v. over 30 sec) was administered after reinduction of SVT. If the tachycardia was not terminated, a 5 mg dose was repeated every 5 minutes upto 20 mg. Adenosine terminated the SVT in 16 cases (6 mg - 7 patients, 12 mg - 9 patients). Verapamil was effective in 11 patients (5 mg - 6 patients, 10 mg - 4 patients, 15 mg - 1 patient, 20 mg - nil). The overall efficacy of adenosine (89%) was significantly greater than that of verapamil (61%; p < 0.05). Adenosine terminated the tachycardia more quickly than verapamil (mean 24 +/- 11 sec versus 142 +/- 40 sec; p < 0.01). Termination of tachycardia by both drugs was related to antegrade block of the atrioventricular node in all patients except one with AVNRT in whom adenosine blocked the retrograde fast pathway. Ventricular premature beats were seen transiently in 5 patients following adenosine. Transient side effects such as flushing, burning and chest pain were frequently observed with adenosine and correlated with the termination of tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine monotherapy in chronic stable angina.

The efficacy and safety of amlodipine was evaluated in 20 patients with stable exertional angina. Patients with > or = 3 anginal attacks per week in the placebo run-in phase were admitted into a 4 weeks active treatment phase. Amlodipine was administered at a starting dose of 5 mg once daily at bed time, which could be adjusted after 2 weeks to 10 mg once daily if the patient continued to have even a single anginal attack/week. Four weeks of treatment with amlodipine produced a significant (p < 0.05) reduction from baseline in both the mean (+/- SE) number of anginal attacks/week (from 13.3 +/- 1.5 to 1.6 +/- 0.5) and the mean (+/- SE) number of isosorbide dinitrate tablets consumed per week (12.1 +/- 1.5 to 2.6 +/- 0.8). Eighty three percent of patients required an increase in dose to 10 mg daily. No significant change in heart rate, blood pressure, ECG and laboratory results were observed. One patient was withdrawn because of deteriorating angina and sinus tachycardia secondary to beta blocker withdrawal. Worsening of ankle odema was reported in 2 (10%) patients, which was tolerated and disappeared on completing therapy. Thus amlodipine is safe and effective when used as monotherapy in the treatment of chronic stable angina.

Long term performance of atrial leads.

Long term performance of 163 atrial leads implanted in 158 patients between July 1981 and June 1993 was evaluated. There were 122 DDD and 36 AAI units, with 125 (77%) polyurethane and 38 (23%) silicone leads. One hundred and nine (67%) unipolar and 54 (33%) bipolar leads were used. Patients were followed in the Pacemaker Clinic for 6 to 124 months (mean 50 +/- 39 months). Five patients were lost to follow up. Transient malfunction was observed in 18 cases (sensing 13, pacing 5) within the first 2 weeks. In 13 cases failure to sense subsided spontaneously and in 4 pacing malfunction could be corrected by reprogramming. Lead dislodgement occurred in 4 patients (2.5%), all within the first week. After the 1st month malfunction was uncommon. Between 1 and 12 months undersensing occurred in 4 (2.5%). In 3 cases it could be corrected by reprogramming. In the first year, reoperation was performed in 5 cases for lead related problems (3 dislodgements, 2 insulation failures). Beyond 12 months complications were as follows: failure to sense-8 (5%), failure to pace-3 (2%), insulation break -1 (0.6%). Majority of these problems could be managed by reprogramming. Reoperation was performed in 1 case with insulation break. The pacing mode had to be changed in 5 (3%) patients with dual chamber units who had loss of P wave sensing. During follow-up 98%, 98%, 96%, 95% and 83% of the leads were working satisfactorily at 1,2,3,4 and 9 years respectively. Thus atrial leads have excellent long term performance and an acceptable rate of late malfunction.

Amlodipine monotherapy in mild to moderate hypertension.

The efficacy and safety of amlodipine was evaluated in 20 patients of mild to moderate hypertension in a single blind, placebo controlled, noncomparative study. Patients with a baseline diastolic blood pressure of > 90 and < 115 mmHg while on placebo were admitted to a 4 week active treatment phase. Amlodipine produced a significant (p < 0.05) reduction in mean systolic (177 mmHg to 145 mmHg) and diastolic blood pressure (106 mmHg to 84 mmHg) after 4 weeks treatment in all patients. 95% of the patients had their diastolic blood pressure reduced to < or = 90 mmHg by the end of the study period. There was no significant change in heart rate or in the laboratory parameters with amlodipine therapy. Seven patients reported mild to moderate adverse events which did not require discontinuation of therapy. This combination of efficacy and tolerability, together with convenience of once daily dosing, should ensure the usefulness of amlodipine in the treatment of hypertension.

Dual exposure and repair technique for ruptured aneurysms of aortic sinus of Valsalva.

Thirteen patients with ruptured sinus of Valsalva aneurysm have been operated over a 3-1/2 year period. Right coronary sinus was predominantly involved and right ventricle was the most common site of rupture. Early surgery was performed in all cases. Both aorta and chamber of entry were explored for effective repair. Main repair was always done in the chamber of rupture either with a patch or interrupted pledgeted sutures followed by assessment at either end. Subannular ventricular septal defects in three cases were closed with a common patch with additional fixation in the middle at the aortic annulus to prevent aortic leak into the left ventricle. Three patients needed aortic valve replacement for gross aortic incompetence. Postoperative echocardiographic study revealed uniformly excellent results with good aortic valve or prosthetic function. One patient developed fatal pulmonary embolism two weeks following surgery. All other surviving patients are doing well and are in NYHA class I. We recommend dual exposure and repair technique for the repair of ruptured sinus of Valsalva aneurysms for optimal results.

Transcatheter ablation of ventricular tachycardia arising from right ventricular outflow tract.

Two patients with recurrent episodes of symptomatic, sustained monomorphic ventricular tachycardia (VT) resistant to medical therapy underwent catheter ablation for the relief of VT. One patient had arrhythmogenic right ventricular dysplasia while the other had no structural heart disease. The VT had left bundle branch block morphology with normal axis in both the patients. The cycle length during VT was 260 msec and 270 msec respectively. Site for ablation was guided by pacemapping and the target site was identified in the right ventricular outflow tract in both the patients. Two cathodal shocks of 200 J in the first patient and one shock of 200 J in the second patient resulted in abolition of the arrhythmia. At repeat electrophysiologic testing at 7 days in the first patient and at 8 months in the second, VT was not inducible despite three extrastimuli from two right ventricular sites. Over a follow up of 24 and 26 months respectively, there has been no recurrence without any antiarrhythmic therapy. There were no acute or long term complications. In conclusion, catheter ablation offers a cure in patients with right ventricular tachycardia resistant to antiarrhythmic drugs.