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.

Preconditioning the human myocardium with intracoronary adenosine.

This study was designed to study the role of adenosine in ischaemic preconditioning. The clinical, electrocardiographic and metabolic parameters of ischaemia were compared before and after intracoronary adenosine during percutaneous transluminal coronary angioplasty in 15 patients with significant stenosis of the left anterior descending artery. Baseline ischaemia was demonstrated by inflating the balloon of appropriate size at its nominal pressure for 30 seconds. Intracoronary adenosine was then administered in dose of 1000 to 6000 mgm/ml. The balloon was repositioned and inflated at nominal pressure for 180 seconds. As compared to 1st balloon inflation, the 2nd balloon inflation produced less severe chest pain, less ST segment deviation on the intracoronary ECG (7.40 +/- 3.94 vs 4.30 +/- 2.15 mm; p < 0.05) and lower coronary sinus lactate levels as compared to the first (0.28 +/- 0.06 vs 0.22 +/- 0.04 mmol/lit; p < 0.05). In conclusion, this study proves that by injecting intracoronary adenosine it is possible to precondition the human myocardium.

Adenosine-induced chest pain: is it due to myocardial ischaemia? Clinical, electrocardiographic, haemodynamic and metabolic study.

Adenosine has recently been demonstrated to be a mediator of angina in human beings. The present study was undertaken to document the presence or absence of myocardial ischaemia on clinical, haemodynamic, electrocardiographic and metabolic evidences after intracoronary administration of adenosine. Fifteen patients with chronic stable angina (12 males and 3 females), positive exercise stress test and documented significant stenosis of the left anterior descending coronary artery (LAD) were included in the study. The surface and intracoronary electrocardiograms (ECGs), pulmonary artery diastolic pressure and coronary sinus lactate levels were monitored at baseline and after intracoronary administration of adenosine in all patients. Adenosine was administered intracoronary in doses of 1000-8000 microgram depending on the provocation of chest pain. Typical angina was observed in all patients. There were no signs of ischaemia on surface or intracoronary ECG. There was no statistically significant difference between the pulmonary artery diastolic pressure and coronary sins lactate levels at baseline and post-adenosine administration (p > 0.05). It is concluded that intracoronary administration of adenosine produces chest pain in patients with chronic stable angina by mechanism other than myocardial ischaemia.

Coronary artery stenting in acute myocardial infarction.

Little information is available on the use of coronary stents to treat suboptimal results during direct angioplasty in acute myocardial infarction (AMI). In this study, we report 16 cases of AMI who underwent stent implantation in infarct-related artery for suboptimal results and their 6 months angiographic follow-up. Immediate angiographic success was achieved in all patients. The minimal luminal diameter increased from 0.06 +/- 0.12 mm to 2.89 +/- 0.12 mm (p < 0.001). One patient died in the hospital on day 8 due to subacute stent thrombosis. No patient required emergency bypass surgery. Two patients required blood transfusion for groin haematoma and one required intracoronary thrombolysis. All patients underwent exercise stress test at 1 month and at 3 months and coronary angiography at 4 months or earlier it indicated. At the end of 6 months follow-up, 4 patients had a positive exercise test and coronary angiography revealed angiographic restenosis in 3 and progression of disease in other vessels in 1 patient. We conclude that stent deployment is a viable option to treat suboptimal results after direct angioplasty in AMI.

Role of percutaneous transluminal coronary angioplasty in patients of exercise induced ST segment elevation in infarct related leads.

In patients with recent myocardial infarction (MI), exercise induced ST segment elevation on infarct related leads is shown to be due to ischaemia within or around partially necrotic area. To study this hypothesis we studied 15 patients of recent MI who had ST segment elevation in infarct related leads. In 13 patients infarct related artery was patient with severe stenosis (85 +/- 8%) and in 2 patients infarct related artery was totally occluded. The patients with patent culprit artery were elected for percutaneous transluminal coronary angioplasty (PTCA). During balloon inflation 10 patients had ST segment elevation on some leads that showed ST elevation during exercise and 6 patients also had angina. There was no significant change in pulmonary artery pressure and systemic blood pressure during PTCA. Post PTCA stress test after 2 week showed decrease in ST elevation compared to previous stress tests. Therefore exercise induced ST segment elevation in infarct related leads is suggestive of ischaemia rather that left ventricular dysfunction. In such patients it may be considered as indication for revascularization.

Recovery positive exercise stress test: an indication for coronary artery disease.

The significance of ST depression occurring during exercise treadmill stress test has been well established. However, at times there may be no ST segment changes during exercise with changes occurring during the recovery phase. Out of the 1234 patients who underwent exercise stress test, 17 patients had ST segment changes confined to recovery phase. Coronary angiography performed in these 17 patients showed 11 patients had significant coronary artery disease (CAD), with nine patients having triple vessel disease and 2 having double vessel disease. Analysis showed there was no significant difference in the two groups of CAD and no CAD with respect to sex ratio, mean duration of exercise, maximal heart rate and double product achieved. Conclusion: Although, patients with recovery positive stress test may have normal coronary angiography, a large number of patients (64.7%) in our study had significant CAD. Hence, such patients should be subjected to another noninvasive test such as thallium perfusion scan or coronary angiography.

Sion thrombolysis trial--randomised trial of intravenous thrombolysis & primary percutaneous transluminal coronary angioplasty for acute myocardial infarction [AMI]--feasibility phase data of angioplasty limb.

Reperfusion in acute myocardial Infarction [AMI] can be realised by thrombolytic therapy or percutaneous transluminal coronary angioplasty [PTCA] has theoretical advantage but hardly any randomised trials have been published till recently to compare the two modalities. We started the STAT trial with this objective. Patients of AMI were randomised to thrombolytic therapy or PTCA. In the present article we present the phase I data of the PTCA limb. The procedural success rate was 100% with no procedural mortality. In-hospital mortality was 10% [Anterior Infarction 0%, Inferior infarction 20%]. Recurrence of angina occurred in 10% patients. Direct PTCA to left anterior descending artery appeared to be more rewarding than PTCA to right coronary artery.

Percutaneous transluminal coronary angioplasty in totally occluded arteries.

Out of 321 consecutive cases of Percutaneous Transluminal Coronary Angioplasty (PTCA), 28 (8.7%) patients underwent PTCA for nonacute total occlusion with no visible antegrade flow. All patients had evidence of reversible ischaemia in the territory of totally occluded artery. Overall initial success rate was 66% and was mainly related to the duration of the occlusion (85% for occlusion of 1 month or less, 70% for 1-6 months, and nil for more than 6 months duration). In 21 (75%) cases where collateral circulation to the occluded vessel could be demonstrated before PTCA, was not visible after successful PTCA. Failure was mainly due to inability to cross the lesion with the guide wire (8 out of 10 failures). Emergency Coronary Artery Bypass Graft (CABG) surgery was required in 2 cases where dissection of nontarget vessels occurred during manipulation of the guide wire. Acute reocclusion occurred in 2 cases, both were redilated successfully. There was no death. Although the primary success rate is lower than that associated with conventional stenotic lesions, with improvement in the hardware-balloon catheters and guide wires, coronary angioplasty can be performed successfully in majority of the patients with total coronary occlusion.

Percutaneous transluminal coronary angioplasty in distal lesions.

Of 210 patients in whom percutaneous transluminal coronary angioplasties [PTCA] were performed during the period of 2 years (June 1987 to August 1989), 55 had distal lesions. These included 50 males and 5 females with the lesions in left anterior descending [LAD] artery after the origin of the second diagonal branch, circumflex [Cx] artery after the origin of the obtuse marginal [OM], and right coronary artery [RCA] after the acute marginal branch. There were a total of 71 distal lesions, involving the LAD [51%], Cx [20%], and RCA [29%]. The overall success rate with PTCA was 91%. There were 4 acute closures of vessels; all were redilated with balloon angioplasty. One of these was sent for emergency bypass surgery after balloon dilatation. There was no death. With improvement in balloon catheters and guidewires, the feasibility and success of PTCA in distal lesions have increased remarkably, thus expanding the horizon of PTCA.

Coronary arteriographic findings soon after non Q wave myocardial infarction.

We performed early coronary arteriography in 27 patients (23 males, 4 females) having non Q wave MI. Infarct related vessel (IRV) was totally blocked in 25.9%, whereas 66.7% had severe residual stenosis (greater than or equal to 70%). Left main was involved in 7.5%, and at least 2 major coronary arteries were involved in 51.8%. Visible collaterals were seen in 11%. We feel, as compared to transmural MI, where total occlusion of IRV is common, the higher incidence of subtotal occlusion of IRV with severe residual stenosis, poor collaterals and significant involvement of at least one other major coronary artery may be responsible for observation of early recurrent ischemic episodes in non Q wave MI.

Pulsed Doppler derived indices in predicting noninvasively, pulmonary arterial pressures.

The pulsed doppler (P.D.) signals obtained in RVOT just below the pulmonary leaflets were used to calculate acceleration time (AcT), pre-ejection period (PEP) and their ratios. These indices were correlated in 31 patients (2 1/2-49 yrs. age) having varying cardiac lesions to Pulmonary arterial pressure (P.A.P) measured during cardiac catheterisation. The mean values of AcT for those with normal PAP was 137 +/- 19.9ms, as compared to 105 +/- 37 ms in those in whom PAP greater than 20mm of Hg. (t = 3.0.p less than .01). The P value was less than 0.001 when comparison was between normal PAP and severe PH. The ratios of PEP upon AcT was 0.87 +/- 0.18 for normal PAP, as compared to 1.39 +/- 0.74 in those with PH (t = 0.31, p less than 0.01). The PEP/AcT predicted systolic PAP 35.49 PEP/AcT + 3.22 (r = 0.77, p less than 0.001). The mean PAP was best predicted by 23.94 PEP/AcT + 2.44 (r = 0.75, p less than 0.001). The quantitative assessment showed presence of presystolic 'a' wave in all with normal PAP; this was absent in all the 9 patients with severe PH (MAPA greater than 40mm of Hg.). We conclude that noninvasively obtained P.D. derived indices can help accurately to predict PAP.