Gisbert Kober

Effects of nifedipine after intravenous and intracoronary administration

Abstract A study with nifedipine, given intravenously or into the left coronary artery, was undertaken in an effort to distinguish the peripheral from the central effects of the drug in patients with stable angina. There was a significant antianginal effect 1 hour after intravenous administration of 1.0 mg of nifedipine. Intravenous administration of 0.1 mg of the drug had no antianginal effect, and did not cause hemodynamic alterations or influence coronary sinus oxygen saturation. Intracoronary infusion of 0.1 mg of nifedipine caused a significant increase in coronary sinus oxygen saturation that was abolished 5 minutes after the end of the infusion. A similar increase in oxygen saturation was found after intravenous administration of 1.0 mg of the drug; this effect, quantitatively somewhat smaller, also disappeared after 5 minutes. Infusion of 0.1 mg of nifedipine into the left coronary artery had an antianginal effect during exercise, documented by a reduction in the exercise-induced increase in left ventricular end-diastolic pressure and in the exercise-induced S-T segment depression. A similar antianginal effect, quantitatively slightly more pronounced, was achieved with intravenous administration of 1.0 mg of nifedipine. It is concluded that the antianginal potency of nifedipine cannot be related to its effect on coronary arteriolar resistance because increased flow has returned to normal when the antianginal effect persists. The mechanism of action must include a direct cardiac influence, most likely on myocardial metabolism. No serious side effects were observed after intravenous or intracoronary administration of nifedipine.

Wiktor stent implantation in patients with restenosis following balloon angioplasty of a native coronary artery

Intracoronary stenting has been introduced as an adjunct to balloon angioplasty aimed at overcoming its limitations, namely acute vessel closure and late restenosis. This study reports the first experience with the Wiktor stent implanted in the first 50 consecutive patients. All patients had restenosis of a native coronary artery lesion after prior balloon angioplasty. The target coronary artery was the left anterior descending artery in 26 patients, the circumflex artery in 7 patients and the right coronary artery in 17 patients. The implantation success rate was 98% (49 of 50 patients). There were no procedural deaths. Acute or subacute thrombotic stent occlusion occurred in 5 patients (10%). All 5 patients sustained a nonfatal acute myocardial infarction. Four of these patients underwent recanalization by means of balloon angioplasty; the remaining patient was referred for bypass surgery. A major bleeding complication occurred in 11 patients (22%): groin bleeding necessitating blood transfusion in 6, gastrointestinal bleeding in 3 and hematuria in 2. Repeat angiography was performed at a mean of 5.6 +/- 1.1 months in all but 1 patient undergoing implantation. Restenosis, defined by a reduction of greater than or equal to 0.72 mm in the minimal luminal diameter or a change in diameter stenosis from less than to greater than or equal to 50%, occurred in 20 (45%) and 13 (29%) patients, respectively. In this first experience, the easiness and high technical success rate of Wiktor stent implantation are overshadowed by a high incidence of subacute stent occlusion and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of antianginal efficacy of nifedipine to degree of coronary arterial narrowing and to presence of coronary collateral vessels.

Thirty-six patients with chronic stable angina pectoris or with stable and vasospastic components of angina pectoris were classified by coronary arteriographic findings into 4 groups. Patients in group A had a single stenotic coronary artery; patients in groups B, C and D had occluded arteries, but these arteries had been collateralized to varying degrees, and an epicardial coronary steal phenomenon was possible. All patients underwent multiple exercise tests before and after randomized, double-blind, crossover treatment with 20 mg of nifedipine, 20 mg of isosorbide dinitrate, a combination of both, and placebo. Maximal and mean ST-segment depression, occurrence of angina pectoris and heart rate were evaluated. After nifedipine treatment, mean ischemic ST-segment depression was reduced 21% in group A (p less than 0.05), but was not significantly altered in the other groups (group B, 2% decrease; group C, 10% increase; group D, 3% decrease). However, isosorbide dinitrate reduced ST-segment depression significantly in all groups (group A, 29%, p less than 0.001; group B, 18%, p less than 0.01; group C, 19%, p less than 0.05; group D, 33%, p less than 0.05). The combination with nifedipine did not further improve the effect of isosorbide dinitrate. Maximal ST-segment depression and angina pectoris paralleled the changes in mean ST depression during the different medications. Heart rate at rest was not significantly changed after nifedipine treatment in any group, but increased significantly after isosorbide dinitrate treatment in groups B and C (group B, 12%, p less than 0.01; group C, 9%, p less than 0.05); heart rate during exercise did not differ significantly in any group or after any form of medication from placebo.

Angiographic predictors of recurrence of restenosis after Wiktor stent implantation in native coronary arteries

Intracoronary stenting has been proposed as an adjunct to balloon angioplasty to improve the immediate and long-term results. However, late luminal narrowing has been reported following the implantation of a variety of stents. One of the studies conducted with the Wiktor stent is a prospective registry designed to evaluate the feasibility, safety and efficacy of elective stent implantation in patients with documented restenosis of a native coronary artery. To identify angiographic variables predicting recurrence of restenosis, the angiograms of the first 91 patients with successful stent implantation and without clinical evidence of (sub)acute thrombotic stent occlusion were analyzed with the Computer Assisted Angiographic Analysis System using automated edge detection. The incidence of restenosis was 44% by patient and 45% by stent according to the 0.72 mm criterion, and 30% by patient and 29% by stent according to the 50% diameter stenosis criterion. The risk for restenosis for several angiographic variables was determined using an univariate analysis and is expressed as odds ratio with corresponding confidence interval. The only statistically significant predictor of restenosis was the relative gain when it exceeded 0.48 using the 0.72 mm criterion (odds ratio 2.7, 95% confidence interval 1.1-6.4). Furthermore, the relation between the relative gain (increase in minimal luminal diameter normalized to vessel size) as angiographic index of vessel wall injury and relative loss (decrease in minimal luminal diameter normalized to vessel size) as index of neointimal thickening was analyzed using a linear regression analysis. When using the categorical approach to address restenosis, there is an increased risk for recurrent restenosis when the relative gain exceeds 0.48. The continuous approach underscores this concept by indicating a weak but positive relation between the relative gain and relative loss.

Long-term follow-up after percutaneous transluminal coronary angioplasty in patients with single-vessel disease

Seven hundred ninety-eight patients with symptomatic single-vessel disease who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1977 and 1985 were reevaluated by questionnaire 78 +/- 23 months after dilatation. Indication for PTCA was stenosis of > or = 70%, anginal symptoms, and objective signs of myocardial ischemia. The immediate success rate was 81.2%, and severe complications occurred in 7.1%, which included two fatal complications (0.3%). Repeat angiograms were performed in 582 of 648 patients who underwent successful dilatation and showed restenosis in 143 cases (24.6%). Within 1 year after the first dilatation, 586 patients had been successfully revascularized by PTCA (i.e., there was no evidence of restenosis or redilatation was successful), and 113 patients had undergone bypass surgery. The remaining 99 patients were treated medically if PTCA was unsuccessful or if restenosis (> or = 70%) that was not amenable to redilatation was present. The 8-year overall survival probability was 91.7%, and cardiac survival was 95.5%. The 8-year event-free survival probability was 52.7% for all patients: 62.5% in patients who had successful PTCA and 14.5% in patients who had unsuccessful PTCA (p = 0.0000). The cardiac survival probabilities of patients with lasting PTCA success at 1 year and of surgically treated patients were significantly better than those of patients who did not have successful revascularization (at 8 years 97.2% and 98.1% vs 88.9%; p < 0.04). Late events (> or = 1 year) occurred more often in patients who did not have successful revascularization compared with patients who had successful PTCA (at 8 years 57.9% were event-free vs 74.4%; p < 0.0001); even fewer late events were observed in surgically treated patients (at 8 years 88.2% were event-free; p < 0.004). Coxs proportional hazards regression analysis revealed left ventricular ejection fraction and revascularization status at 1 year as determinants of overall, cardiac, infarct-free, and event-free survival probabilities. At the time of reevaluation significantly more patients in the successful PTCA subgroup were still free of symptoms or had experienced improvement than patients in the bypass or medical subgroups (86.8% vs 68.9% and 59.5%, respectively; p < 0.0001), and more patients in the successful PTCA subgroup were still working (75.4% vs 53.3% and 56.9%, respectively; p < 0.001). We concluded that patients with single-vessel disease who have undergone successful dilatation have an excellent long-term prognosis with regard to survival, cardiac symptoms, and vocational status.(ABSTRACT TRUNCATED AT 400 WORDS)

Direct determination of hepatic extraction of verapamil in cardiac patients

Hepatic extraction of verapamil was determined directly in cardiac patients undergoing diagnostic catheterization and receiving 10 mg verapamil intravenously or intra‐arterially. The extraction curves of verapamil concentrations in blood from the ascending aorta and hepatic vein were similar to those reported after single intravenous doses of indocyanine green. The rectilinear fall in concentration lasted 10 to 15 min. Mean hepatic extraction of verapamil in four patients who received intravenous doses was 0.86 (range 0.84 to 0.89) and in four who received intra‐arterial doses was 0.87 (range 0.83 to 0.89). These estimates are the same as those for hepatic first‐pass extraction determined by indirect methods based on areas under plasma concentration‐time curves and requiring calculation of apparent hepatic blood flow. The results are considered to be proof that the first‐pass effect of verapamil after oral doses is attributable mainly, if not entirely, to hepatic elimination.

The Frankfurt experience in restenosis after coronary angioplasty

Three hundred and thirty-three of 356 patients underwent angiographic follow-up from 1 to 18 months (mean 5.6 months) after percutaneous transluminal coronary angioplasty (PTCA). This is a reangiography rate of 94%. Recurrence rate after the first PTCA was 15% (n = 289). Restenosis rate was defined as an increase from immediate post-PTCA stenosis of more than 30%, or the loss of at least half of the initial gain in luminal diameter. Patients who needed a second angioplasty due to restenosis (n = 30) had a restenosis rate of 33%. Patients with angioplasty in the aortocoronary bypass (n = 14) had a restenosis rate of 45%. All patients were treated before, during and at least 4 to 6 months after the procedure with 60 to 100 mg of isosorbide dinitrate daily plus 160 to 360 mg of verapamil or 100 to 150 mg of gallopamil and 1.5 g of acetylsalicylic acid. In a second retrospective study 111 of 399 patients had the acetylsalicylic acid therapy discontinued or decreased. Forty-two of them developed restenosis (38%), whereas only 49 of 288 patients who continued to receive 1.5 g aspirin developed restenosis (17%). The restenosis rate was 32% in those who received the reduced dose of aspirin. Thus, a large dose of acetylsalicylic acid given before, during and 4 to 6 months after the procedure seems to be necessary to achieve a low rate of restenosis after PTCA.

Ventricular Function at Rest, During Leg Raising and Physical Exercise Before and After Aortocoronary Bypass Surgery

In nine patients with coronary heart disease isometric contractility indices and ejection phase parameters were measured simultaneously using an angiographic catheter with a manometer at the tip (MILLAR). Regional wall motion at rest, after leg raising, and during physical exercise (bicycle ergometer) was analyzed applying the hemiaxis method. Five weeks after aortocoronary bypass surgery these examinations were repeated.

Noninvasive assessment of left ventricular performance following transluminal coronary angioplasty.

We studied 36 patients with successful transluminal coronary angioplasty (group 1) noninvasively using exercise electrocardiography, exercise T1-201 myocardial scintigraphy and equilibrium radionuclide ventriculography before and 3-5 days after the procedure. Six patients who underwent aortocoronary-bypass surgery (group 2) and 10 patients with stable angina pectoris (group 3) served as controls. All patients had arteriographically documented coronary artery disease at least in one major coronary vessel (stenosis greater than or equal to 70%). In group 1, average coronary stenosis was 81.1 +/- 8.4% before dilatation and 44 +/- 13.7% after the procedure (P less than 0.001). Ischemia score in the exercise electrocardiography decreased from 2.4 +/- 2.7 before dilatation to 0.4 +/- 0.8 after the procedure (P less than 0.001). Myocardial perfusion in computerized T1-201 myocardial scintigraphy 5-10 min after exercise expressed as vitality index (the ratio of T1-201 uptake in the ischemic region to the region of maximal uptake in the same image analyzed carefully in the same view in 2 studies) increased from 72.9 +/- 8.4% before dilatation to 79.9 +/- 11.7% after the procedure (P less than 0.001). Ejection fraction at rest increased from 47.2 +/- 9.2% to 51.0 +/- 9.7% (P less than 0.001) and during exercise from 39.9 +/- 10.5% to 49.4 +/- 10.9% (P less than 0.001) before and after the procedure. In group 2, noninvasive studies showed a tendency to improvement after surgery. In group 3 no significant changes were noted. We conclude that transluminal coronary angioplasty improves both coronary perfusion to ischemic areas supplied by critical coronary artery stenoses and left ventricular function, especially during exercise, if luminal diameter is dilated by greater than 20%.

Effect of balloon valvuloplasty for mitral stenosis on right ventricular function.

Abstract Percutaneous balloon mitral valvuloplasty has become a common procedure in the treatment of pliable mitral stenosis. By this method, mitral valve area can usually be doubled, thus leading to significant hemodynamic and clinical improvements. 1,2 However, because evaluation of right ventricular volumes by contrast angiography or radionuclide methods is quite cumbersome and requires greater technical efforts, only few data exist on the effects of this procedure on right ventricular performance. 3 Recently, the evaluation of right ventricular function was made easier by the introduction of a computerized thermodilution catheter, thereby enabling bedside determination of right ventricular volumes and ejection fraction. 4,5 This method showed good correlation with contrast angiography and radionuclide methods. 4,5 Aim of the following study was the investigation of balloon mitral valvuloplasty on right ventricular function at rest and during exercise.