Mitral balloon valvotomy using the Inoue balloon technique for selected patients with severe pliable rheumatic mitral valve stenosis: immediate and short-term results.

We selected 40 patients with severe symptomatic rheumatic mitral stenosis for balloon valvotomy using the Inoue balloon technique. The patients' mean age was 31 +/- 14 years and there were 24 females and 16 males. The patients were selected according to the following echo/Doppler criteria; 1. Severe mitral stenosis, i. e. mitral valve area (MVA) less than 1.1 cm2; 2. pliable anterior mitral valve leaflet; 3. absence of calcification of the mitral commissures and 4. absence of significant subvalvular mitral valve disease (Block echo score less than 8). We failed to cross the mitral valve in three cases and repeat attempts in two patients with higher transeptal puncture was successful. Thirty-nine procedures were technically successful (98%). There were no complications. We used an Inoue balloon size 24-30 mm using echo/Doppler guided stepwise mitral dilatation. After mitral balloon valvotomy, the MVA increased from 0.8 +/- 0.2 to 1.7 +/- 0.5 cm2 (p less than 0.001). Five patients developed mild mitral regurgitation and in one patient the degree of mitral regurgitation increased from mild to moderate. The mean mitral valve area 48 hours after the procedure measured 1.9 +/- 0.4 cm2 (echo/Doppler); one patient (2.5%) had residual mitral stenosis (MVA less than 1.5 cm2). At six weeks follow-up study the mean mitral valve area was 1.9 +/- 0.5 cm2 (Echo/Doppler), with no restenosis. We conclude that in selected cases of severe pliable mitral stenosis, the Inoue balloon technique achieves a greater than 100% increase of the MVA, without inducing significant iatrogenic mitral regurgitation or residual stenosis.

Right atrial, right ventricular and left ventricular thrombi in (incomplete) Behçet's disease.

An 18-year-old man presented with a history of oral sores and presence of high fever, scrotal ulcerations and haemoptysis. Multiple mural cardiac masses were present in the right atrium, right ventricle and left ventricle. Furthermore, pulmonary vasculitis with aneurysm formation and venous thrombosis involving the superior sagittal sinus and right transverse sinus were found, and the diagnosis was made of (incomplete) Behçet's disease. While receiving anticoagulation and later, treatment with prednisone and cyclophosphamide, the cardiac thrombi gradually disappeared. We stress the importance of early echocardiography to evaluate cardiac abnormalities in Behçet's disease.

Effect of flecainide on regional left ventricular wall motion after acute intravenous, acute oral and chronic oral administration late after coronary artery bypass grafting.

Epicardial marker motion was measured in 14 patients before flecainide administration, immediately after an intravenous dose of 2 mg/kg over 15 minutes (maximum 150 mg) and 15 minutes thereafter. Platinum epicardial markers had been implanted more than 4 years earlier at the time of coronary artery bypass grafting. Maximal and minimal marker separation (Lmax and Lmin) during the cardiac cycle were measured and regional shortening fraction (Lmax - Lmin)/Lmax) was determined as a percentage. After intravenous flecainide, a significant increase in end-diastolic (immediately after 2.8%; after 15 minutes 2.1%) and end-systolic (3.6% and 3.2%) regional dimensions was observed, together with a decrease in regional myocardial shortening (9.3% and 9.0%). One week later, after a single oral dose of 200 mg of flecainide, Lmax and Lmin had increased 2.4% and 2.7%, while regional myocardial shortening did not differ significantly from baseline values. In 10 patients measurements were repeated after 6 weeks of chronic oral treatment with 300 mg/day. Despite plasma flecainide levels similar to those after intravenous administration, no significant changes in end-diastolic and end-systolic dimensions or regional shortening fraction were observed. Thus, acute intravenous or oral flecainide administration increases regional end-diastolic and end-systolic dimensions, but only intravenous administration decreases regional shortening fraction. Values during chronic administration indicate that regional myocardial function is more affected at the time of rising or acutely changing flecainide plasma levels than when stable plasma levels are achieved.

The haemodynamic effects of nifedipine, verapamil and diltiazem in patients with coronary artery disease. A review.

Of the 3 most widely used calcium antagonists--nifedipine, verapamil and diltiazem--nifedipine is the most potent arterial vasodilator. Increases in cardiac output and coronary blood flow following nifedipine administration result in part from the afterload reduction. Reflex adrenergic stimulation produces an increase in heart rate and masks a direct inhibitory effect on myocardial contractility. The negative inotropic action of nifedipine is observed during intracoronary administration or may be made apparent by concurrent beta-blocker therapy. While verapamil is also a potent vasodilator, negative inotropic and dromotropic properties are more apparent in therapeutically used dosages. Reflex sympathetic activation is also triggered by verapamil, with an offsetting of the negative inotropic effects such that little change in cardiac output results. A decrease in myocardial oxygen consumption, with or without a decrease in coronary sinus blood flow, has regularly been observed following verapamil administration. Reduced oxygen demand appears to be a major mechanism of its antianginal effect. The heart rate X systolic pressure product is decreased both by the fall in arterial pressure and, particularly after oral administration, by a decrease in heart rate. Diltiazem produces similar haemodynamic and electrophysiological effects to those of verapamil but has less potency in inducing arterial dilatation and more of a tendency to slow the heart rate. Diltiazem does not appear to cause significant increases in coronary blood flow or bring about improvement in ejectional and isovolumic indices of myocardial contraction - evidence of its intrinsic negative inotropic effect.

Acute coronary hemodynamic effects of equihypotensive doses of nisoldipine and diltiazem.

The hemodynamic effects of nisoldipine and diltiazem were investigated in two groups of patients undergoing investigation for suspected coronary artery disease. Emphasis was placed on the coronary hemodynamic changes. Approximately equihypotensive doses of these two calcium channel blockers, nisoldipine (6 micrograms/kg) and diltiazem (500 micrograms/kg) were given intravenously. Although both drugs decreased peak systolic pressure by 28% and 24%, respectively, heart rate increased with nisoldipine (68 +/- 9 to 82 +/- 12 bpm) and remained unchanged with diltiazem (70 +/- 9 to 67 +/- 10 bpm). Nisoldipine increased mean coronary sinus blood flow from 146 +/- 40 to 176 +/- 35 ml/min and great cardiac vein flow from 87 +/- 20 to 109 +/- 24 ml/min, producing a significant reduction in the calculated global (from 0.79 +/- 0.2 to 0.43 +/- 0.12 mmHg min/ml) and regional (from 1.43 +/- 0.2 to 0.70 +/- 0.13 mmHg min/ml) coronary vascular resistances. There were no significant flow changes when corrected for heart rate. Global and regional myocardial oxygen consumptions were not significantly altered. Diltiazem had no significant effects on heart rate or global and regional blood flows, although the vascular resistances decreased by 32% and 35%, respectively. Diltiazem reduced global and regional arterio-coronary sinus oxygen differences, resulting in significant decreases in global (from 14.9 +/- 4.7 to 12.1 +/- 2.3 ml/min) and regional (from 5.6 +/- 0.9 to 5.2 +/- 1.2 ml/min) myocardial oxygen consumptions. The major difference between the drugs was in heart rate, despite the similar reductions in aortic pressure. The lack of a positive chronotropic response after diltiazem may explain the reduction in myocardial oxygen consumption.

Effects of short-term intravenous administration of diltiazem on left ventricular function and coronary hemodynamics in patients with coronary artery disease.

The hemodynamic effects of diltiazem were investigated in 15 patients with suspected coronary artery disease undergoing routine cardiac catheterization. Diltiazem was given in a high dose of 500 micrograms/kg over a period of 5 min and measurements made before and after drug administration during spontaneous heart rate and during matched atrial pacing. Spontaneous heart rate did not change (-5%; NS). Left ventricular (LV) systolic pressure decreased 24% (p less than 10(-6)) and LV end-diastolic pressure (LVEDP) did not change (-5%; NS). During coronary blood flow measurement, mean aortic pressure decreased 30% (p less than 10(-6)) as global (coronary sinus) and regional (great cardiac vein) coronary vascular resistance diminished with no change in coronary blood flow. Myocardial oxygen consumption decreased 19% (p less than 0.02). During matched pacing, although no change occurred in calculated systolic isovolumic indexes of contractility, end-systolic pressure-volume index decreased 15% (p less than 0.05). The time constant of isovolumic relaxation assessed by a biexponential model decreased. No net change occurred in either global or regional wall motion. In summary, high-dose diltiazem was administered safely to patients with coronary artery disease. It is concluded that, at this dose, diltiazem acted as a peripheral and coronary vasodilator. Hemodynamic changes consistent with a direct negative inotropic and chronotropic effect of the drug were observed. Myocardial oxygen consumption decreased with no change in coronary blood flow.

Acute effects of intravenous nisoldipine on left ventricular function and coronary hemodynamics.

The hemodynamic effects of nisoldipine were investigated in 16 patients with suspected coronary artery disease who underwent routine cardiac catheterization. Nisoldipine was given intravenously in a dose of 6 micrograms/kg over 3 minutes and measurements made before and after drug administration during spontaneous and matched atrial paced heart rate. During sinus rhythm, nisoldipine produced a significant increase in heart rate (19%, p less than 10(-5]. Left ventricular systolic pressure decreased 28% (p less than 10(-6) and left ventricular end-diastolic pressure did not change significantly (5%, difference not significant). Coronary sinus and great cardiac vein blood flow increased by 21% (p less than 0.02) and 25% (p less than 0.005), respectively, after nisoldipine administration. Simultaneously, mean aortic pressure decreased 33% (p less than 10(-6]; consequently, the global and regional coronary vascular resistances decreased by 50% (p less than 10(-4]. The decreases in global (-8%) and regional (-4%) myocardial oxygen consumption did not reach statistical significance. A 6% (not significant) increase in end-diastolic volume and an 11% (p less than 0.002) decrease in end-systolic volume resulted in an increase of 21% in stroke volume (p less than 10(-4] with a consistent increase in ejection fraction (+16%, p less than 10(-5]. Total systemic vascular resistance was reduced by 30% (p less than 0.0002). During spontaneous heart rate and matched atrial pacing, the time constant of isovolumic relaxation as assessed by a biexponential model, was significantly shortened.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of long-term oral nifedipine therapy on left ventricular regional wall function at rest and during supine bicycle exercise.

15 patients, 1 to 3 year after coronary bypass surgery, underwent symptom limited supine bicycle exercise tests without nifedipine and after acute and chronic (3 months) administration of the drug. Haemodynamic variables were monitored as was epicardial marker motion, using biplane cineradiography during exercise, the markers having been implanted at the time of surgery. We found significant (P less than 0.001) reductions in end-diastolic and end-systolic regional dimensions at maximal exercise after oral nifedipine, associated with a significant reduction in exertional angina, which persisted during long-term treatment. No adverse effects of the drug were observed.

Flecainide: one-year efficacy in patients with chronic ventricular arrhythmias.

During a one-week short-term in-hospital period, 60 patients with chronic ventricular arrhythmias were treated with 200 mg flecainide twice a day. Flecainide reduced premature ventricular complexes (PVCs) by more than 85% without causing important side-effects in 47 patients, who entered a one-year follow-up period and were followed with bimonthly 24-h ECGs. Median PVC-frequency remained reduced by more than 99% during the follow-up period. Repetitive ventricular beats and ventricular tachycardia were present in 83% and 42% of patients, respectively, before flecainide. During follow-up, these arrhythmias were seen in less than 32% and less than 10% of patients, respectively, at each 24-h ECG. Furthermore, the mean number of hours with repetitive ventricular beats and ventricular tachycardia remained reduced by more than 76% and more than 79%, respectively, throughout the follow-up period. Ventricular arrhythmias remained suppressed despite a gradual reduction in flecainide dosages (to a median of 300 mg day-1) and flecainide plasma levels. In nine out of 47 patients, an increase in ventricular arrhythmias above baseline values on one or more occasions was observed. During a flecainide withdrawal period, a 65-fold increase in median PVC-frequency was observed and ventricular tachycardia reappeared in 18 patients. Subjective side-effects were acceptable except for two patients. During the follow-up period, one patient developed reversible heart failure and sinus node dysfunction. During the total study period, four patients, with either severe coronary artery disease (2) or cardiomyopathy (2) developed lethal arrhythmias (3) or ischaemic events (1). We conclude that prolonged flecainide treatment is effective in a high proportion of patients with chronic ventricular arrhythmias. In some patients an arrhythmogenic effect may occur.

Haemodynamic effects of encainide, flecainide, lorcainide and tocainide.

The haemodynamic effects of encainide, flecainide, lorcainide and tocainide in man are reviewed. Most of the investigations discussed are acute intervention studies after intravenous administration of the drugs. With all four drugs, haemodynamic changes, when present, were moderate. In most studies a decrease in left ventricular maximal dp/dt is demonstrated, suggesting a negative inotropic action. Left ventricular filling pressures are unchanged or slightly increased. A small decrease in cardiac performance, as determined by measurements of cardiac output and left ventricular ejection fraction, is usually observed, while systemic vascular resistance is increased or remains unchanged. Haemodynamic deterioration and/or hypotensive reactions after intravenous administration of any of the above drugs are uncommon in patients without severe cardiac dysfunction. Conclusions relative to drug safety in frank congestive failure are not warranted, in view of the small number of patients studied. While comparative studies between the drugs discussed have not been performed, the data presented here indicate that, on the basis of haemodynamic action, no one drug can be preferred above the other.

Oral flecainide for suppression of ventricular arrhythmias.

The efficacy and safety of oral flecainide for treatment of ventricular arrhythmias were assessed during a 3-day period in patients with various cardiac diseases. Of 11 patients who received a low dose of flecainide (median daily dose 240 mg), only 4 responded with 90% or greater reduction in premature ventricular complex frequency. Ventricular tachycardia could not be suppressed. During treatment no electrocardiographic changes occurred. 14 of the 19 patients who received a high dose of flecainide (median daily dose 480 mg), demonstrated a 90% or greater reduction in premature ventricular complexes, and ventricular tachycardia did not recur during treatment in 7 out of 9 patients. However, PQ, QRS, and QTc intervals were significantly increased. In general, flecainide was well tolerated and drug administration did not have to be discontinued because of side effects. Flecainide acetate treatment, with a median dose of 480 mg daily, appears to be highly effective for suppressing complex ventricular arrhythmias.

The haemodynamic effect of intravenous flecainide acetate in patients with coronary artery disease.

Flecainide acetate has been shown to be a potent antiarrhythmic agent which is active for more than 8 h, whether given intravenously or orally. However, the negative inotropic effect demonstrated in animal studies could hamper the potential clinical utility of the drug. Ten patients with coronary artery disease but without cardiac failure were given intravenous flecainide (2 mg/kg). Stroke index (SI), left ventricular systolic pressure (LVP), end diastolic pressure (EDP) and LV contractility indices (max dP/dt, VCE 40 mm Hg, peak VCE, Vmax from total pressure (TP] were measured immediately before and 10 min after flecainide, under resting conditions and during atrial pacing with heart rates up to 133 +/- 4.2 beats/min (mean +/- s.e. mean). It is demonstrated that flecainide has a negative inotropic effect, not only under resting conditions, but also less apparently during pacing-induced tachycardia. The effect appears to be dose-related and may result in a reduction of cardiac performance.

Anti-anginal, electrophysiologic and hemodynamic effects of combined beta-blocker/calcium antagonist therapy.

Nitrates and beta-blockers have been the mainstay in the therapy of chronic stable angina pectoris for many years. Since an important number of patients remains symptomatic, new potent anti-ischemic agents like the calcium antagonists fulfil a great clinical need. Combined therapy with beta-blockers and calcium antagonists is attractive, since both classes of drugs have differing and eventually complementary modes of action. On the other hand, both have direct negative inotropic and chronotropic effects. We reviewed the anti-anginal, electrophysiologic and hemodynamic effects of combined treatment with a beta-blocker and verapamil or nifedipine. Combined therapy provides greater symptomatic relief than monotherapy with beta-blockers or slow channel blockers alone. While incidental adverse negative inotropic and chronotropic interactions have been reported, particularly when verapamil is involved, their hemodynamic interplay appears beneficial rather than detrimental in the majority of patients. Indeed, combined therapy is effective and safe, at least when a preserved or only moderately impaired left ventricular function is present. However, caution must be exercised in patients with more impaired left ventricular function, and combined therapy with verapamil must be avoided when conduction disturbances are likely to occur.