Randomized comparison of primary stenting and provisional balloon angioplasty guided by flow velocity measurement.

BACKGROUND: Coronary stenting improves outcomes compared with balloon angioplasty, but it is costly and may have other disadvantages. Limiting stent use to patients with a suboptimal result after angioplasty (provisional angioplasty) may be as effective and less expensive. METHODS AND RESULTS: To analyze the cost-effectiveness of provisional angioplasty, patients scheduled for single-vessel angioplasty were first randomized to receive primary stenting (97 patients) or balloon angioplasty guided by Doppler flow velocity and angiography (523 patients). Patients in the latter group were further randomized after optimization to either additional stenting or termination of the procedure to further investigate what is "optimal." An optimal result was defined as a flow reserve >2.5 and a diameter stenosis <36%. Bailout stenting was needed in 129 patients (25%) who were randomized to balloon angioplasty, and an optimal result was obtained in 184 of the 523 patients (35%). There was no significant difference in event-free survival at 1 year between primary stenting (86.6%) and provisional angioplasty (85.6%). Costs after 1 year were significantly higher for provisional angioplasty (EUR 6573 versus EUR 5885; P:=0.014). Results after the second randomization showed that stenting was also more effective after optimal balloon angioplasty (1-year event free survival, 93.5% versus 84.1%; P:=0. 066). CONCLUSIONS: After 1 year of follow-up, provisional angioplasty was more expensive and without clinical benefit. The beneficial value of stenting is not limited to patients with a suboptimal result after balloon angioplasty

Analysis of the mechanisms underlying the changes in left ventricular filling dynamics during oral nisoldipine therapy in patients with anterior myocardial infarction.

The aim of this study was to clarify the mechanisms responsible for the increase in early filling rate observed during oral nisoldipine therapy in patients with ischaemic left ventricular (LV) dysfunction. For that purpose, the global and regional LV function was analysed before and after 2 months of double-blind monotherapy with nisoldipine (10 mg twice daily) or a placebo, in 17 patients with a previous anterior myocardial infarction. The baseline LV ejection fraction ranged from 34-51% and no patient had heart failure. Compared to the placebo, nisoldipine significantly lowered LV systolic pressure and end-diastolic pressure (-3 mmHg vs +6 with the placebo; P less than 0.01) and the LV pressure at the time of mitral opening (-2.0 +/- 3.4 mmHg vs +3.5 +/- 3.0; P less than 0.01). Despite this reduction in driving pressure, the global LV early peak filling rate improved with nisoldipine only and this improvement was related to a selective increase in expansion rate of the anterior areas, from 1010 +/- 360 to 1339 +/- 496 mm2.s-1 (P less than 0.001). The time to regional peak filling rate (-8%; P less than 0.01), the asynchrony of diastolic wall motion and the regional ejection fraction (33 +/- 10 to 38 +/- 12%; P less than 0.001) also improved in the anterior areas with nisoldipine but not with the placebo. In contrast, in the inferior, control zones, the regional ejection fraction and filling rate remained unchanged, both when compared to baseline and to the placebo.(ABSTRACT TRUNCATED AT 250 WORDS

Focus on diastolic dysfunction: A new approach to heart failure therapy

1 Although heart failure is commonly associated with depressed systolic function, there is increasing evidence that impaired diastolic performance is also universally present and might be a key determinant of symptoms, physical capacity and even survival in some subsets of patients. 2 Reduced diastolic distensibility increases cardiac filling pressure not only at rest, but even more during exercise when diastolic filling time is reduced. The increases in filling pressure and diastolic wall stress lead to pulmonary congestion and subendocardial ischaemia; it also triggers myocardial hypertrophy and a detrimental remodelling of the ventricular cavity. Perhaps even more importantly, impaired ventricular distensibility limits the use of the Frank-Starling mechanism, impairing systolic pump function and cardiac output adaptation during exercise. Therapies able to improve the distensibility of the ventricle are, therefore, desirable in heart failure. 3 Nitrates, angiotensin converting enzyme (ACE) inhibitors and diuretics may indirectly increase left ventricular chamber compliance by their effects on the right side of the heart. Cardiac glycosides do not improve myocardial relaxation and may even cause diastolic contracture at toxic doses. The new β(1)-adrenoceptor partial agonist, xamoterol, on the other hand, consistently lowers left ventricular filling pressure at rest and during exercise, and produces an increase in left ventricular dynamic compliance through the direct lusitropic effect of β(1)-adrenoceptor stimulation. These beneficial effects are maintained during prolonged therapy and also appear sufficient to slow the remodelling of the ventricular cavity. The improvement in symptoms and in exercise tolerance observed during xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587) therapy might, therefore, be related to the improvement in left ventricular diastolic distensibility induced by this drug

Effects of prolonged nisoldipine administration on the "hibernating" myocardium.

To assess the effects of nisoldipine on chronically underperfused myocardial areas ("hibernating myocardium"), the global and regional left ventricular (LV) function was analyzed before and after 2 months of double-blind monotherapy with nisoldipine (10 mg twice daily) or placebo in 17 patients with a previous anterior myocardial infarction. The baseline LV ejection fraction ranged from 34 to 51%, and no patient had heart failure. Compared to placebo, nisoldipine significantly lowered the LV systolic pressure and end-diastolic pressure (-3 vs. +6 mmHg with placebo; p < 0.01) and the LV pressure at the time of mitral valve opening (-2.0 +/- 3.4 vs. +3.5 +/- 3.0 mm Hg; p < 0.01). Despite this reduction in driving pressure, the global LV early peak filling rate improved only with nisoldipine and this improvement was related to a selective increase in the expansion rate of the anterior areas, from 1,010 +/- 360 to 1,339 +/- 496 mm2/s (p < 0.001). The time to regional peak filling rate (-8%; p < 0.01), the asynchrony of diastolic wall motion, and the regional ejection fraction (33 +/- 10 to 38 +/- 12%; p < 0.001) also improved in the anterior areas with nisoldipine but not with placebo. In contrast, in the inferior control zones, the regional ejection fraction and filling rate remained unchanged, both when compared to baseline and to placebo. In conclusion, prolonged nisoldipine therapy had no significant effect on the normal myocardium but improved systolic and diastolic function in hypokinetic areas.(ABSTRACT TRUNCATED AT 250 WORDS

Effects of benazeprilat on left ventricular systolic and diastolic function and neurohumoral status in patients with ischemic heart disease.

The effects of the intravenous administration of the angiotensin converting enzyme inhibitor benazeprilat on left ventricular function were examined in 18 patients with ischemic heart disease. Twenty minutes after drug infusion (0.3-10 mg), heart rate (78 +/- 17 to 71 +/- 16 beats/min, p less than 0.0003), left ventricular systolic pressure (-9 mm Hg, p less than 0.0004), and plasma norepinephrine concentration all decreased significantly. The isovolumic indexes of inotropic state also decreased slightly (-10% in dP/dtmax, p less than 0.001), whereas the ejection fraction (39 +/- 16% to 41 +/- 16%, p less than 0.08) and the end-systolic volume (-6%, p less than 0.04) tended to improve, probably because of the afterload reduction (-13% in mean systolic wall stress, p less than 0.05). After benazeprilat administration, the left ventricular end-diastolic pressure was unchanged at the group level, but there was a consistent downward shift of the diastolic pressure-volume relation during rapid filling, and the mean diastolic wall stress decreased from 99 +/- 73 to 69 +/- 42 kdyne/cm2 (p less than 0.007). These data indicate that the acute administration of benazeprilat has a dual action on left ventricular pump function, which is that the negative inotropic effect of bradycardia and reduced sympathetic drive are compensated by afterload reduction. The drug also improved left ventricular diastolic distensibility and significantly reduced wall stress during diastole. The beneficial effects on diastolic function were noted both in patients with mild left ventricular dysfunction and in patients with heart failure

Effects of intracoronary infusion of nicardipine during silent ischaemia on myocardial metabolism and function.

The effects of an intracoronary infusion of nicardipine (0.2 mg over 10 min) on myocardial substrate uptake and function were studied in 16 patients with coronary artery disease and angina pectoris. Silent ischaemia, demonstrated by myocardial lactate production, was induced twice by pacing below anginal threshold. Nicardipine or saline was randomly infused during the first or second pacing. During pacing with nicardipine, no systemic effect was noted but coronary sinus flow increased (+ 18%; P less than 0.015) and myocardial oxygen uptake decreased by 12% (P less than 0.025). Transcardiac lactate production did not improve (-8 to -10 mumol min-1; NS) but net lactate uptake, estimated from radiolabelled lactate uptake, tended to rise and the glutamine uptake increased from 1.8 to 5.5 mumol min-1 (P less than 0.04). During recovery after pacing, lactate production decreased faster and LV peak (+) dP/dt and relaxation rate were significantly better after nicardipine infusion than after saline. Thus, during silent ischaemia induced by an increased oxygen demand, intracoronary nicardipine did not prevent lactate release but allowed a faster metabolic and functional recovery. These beneficial effects of nicardipine could be explained by an improved myocardial perfusion or by an effect on intracellular calcium homeostasis

Effects of pimobendan (UD-CG 115) on the contractile function of the normal and "postischemic" canine myocardium.

Pimobendan (UD-CG 115) is a long-acting positive inotropic drug with arterio- and venodilator properties. To determine to what extent this new agent is able to affect contractile function in previously ischemic areas of the left ventricle (LV), the effects of pimobendan on global and regional LV function were studied in eight conscious dogs, 2 days after a 2-h coronary occlusion followed by reperfusion. Before pimobendan, percentage of systolic shortening and mean velocity of shortening were lower in reperfused segments than in control areas (0.41 +/- 0.17 vs. 0.93 +/- 0.07 s-1 and 7 +/- 3 vs. 15 +/- 1%, respectively; both p less than 0.05). Infusion of 1 mg of pimobendan significantly improved peak + dP/dt (3202 +/- 372 to 3848 +/- 498 mm Hg/s; p less than 0.05) and ejection time (166 +/- 13 to 156 +/- 15 ms; p less than 0.05). Cumulative infusion up to 2.5 mg further improved these indexes to 5199 +/- 934 mm Hg/s and to 125 +/- 11 ms, (respectively; both p less than 0.05) without affecting mean arterial pressure (91 +/- 14 to 93 +/- 22 mm Hg; NS). Mean velocity of shortening rose to 1.18 +/- 0.09 s-1 (p less than 0.05) in control segments and to 0.62 +/- 0.18 s-1 (p less than 0.05) in reperfused segments. The ratio between end-systolic pressure and length increased by 26 +/- 9% (p less than 0.05) in the reperfused segments and by 20 +/- 8% (p less than 0.05) in control areas.(ABSTRACT TRUNCATED AT 250 WORDS

Effects of alinidine on metabolic response to high-demand myocardial ischemia.

Alinidine is a new bradycardic agent that interferes with ion channels and the if pacemaker current. To determine if alinidine had antiischemic effects unrelated to its bradycardic action, myocardial metabolism was studied during a pacing-stress test in 20 patients with coronary artery disease and angina pectoris, before and after intravenous infusion of alinidine (10 mg, n = 10; 50 mg, n = 10). When compared to the control pacing-stress test, the low dose of alinidine had no significant effect on aortic pressure, coronary sinus flow (-3%, NS), myocardial oxygen extraction, or myocardial lactate uptake. After the high dose of alinidine, aortic pressure and coronary sinus flow remained unchanged but the arteriocoronary sinus difference in oxygen content increased (12.2 +/- 1.3 to 12.7 +/- 1.4 ml/100 ml; p less than 0.0002) above the values observed during the control pacing-stress test, while both the chemical lactate extraction fraction (-19 +/- 30 to 15 +/- 21%; p less than 0.025) and the L-[1-14C]lactate extraction fraction increased. Accordingly, the net myocardial lactate uptake (corrected for production) had increased from 14 +/- 32 during the control pacing-stress test to 29 +/- 24 mumol/min during the pacing repeated after the high dose of alinidine (p less than 0.05). After the high dose of alinidine, the free fatty acid uptake also rose slightly (+23%; NS) and the alanine production was reduced in 7 of 10 patients (-3.6 +/- 1.7 to -1.4 +/- 0.6 mumol/min; NS).(ABSTRACT TRUNCATED AT 250 WORDS

Quantitative angiographic follow-up study of the free inferior epigastric coronary bypass graft

BACKGROUND: Attempts to improve late results of bypass coronary surgery have focused on the use of arterial conduits because of the high attrition rate of venous grafts. METHODS AND RESULTS: In our institution, 150 patients received an inferior epigastric artery (EPIG) as a free bypass graft, anastomosed to the right coronary artery in 73% and to a marginal branch in 20% of cases. These patients were followed prospectively by qualitative and quantitative angiography. Angiographic studies were performed in 122 patients (81%) early after surgery (11 +/- 5 days), and in 72 cases, a late evaluation (11 +/- 6 months) was also obtained. Quantative angiography (basal and after isosorbide dinitrate [ISDN]) was performed on the in situ EPIG in a large subset of these patients, as well as in 59 patients before bypass surgery. The patency rate was 98% at early control and remained high (93%) at late control. However, at late control, 14 EPIGs were occluded or threadlike, but of these 14, eight were grafted on a coronary artery with a moderate stenosis (< or = 60%) and with good anterograde perfusion. Mean basal EPIG diameter increased from 2.23 +/- 0.42 mm before surgery to 2.57 +/- 0.52 mm at 11 days (P < .01) but decreased to 2.20 +/- 0.47 mm in late study (P < .01 versus 11 days and P = NS versus before surgery). Vasodilation of EPIG with ISDN was observed before surgery (+0.34 +/- 0.20 mm, P < .001) and at late control (+0.20 +/- 0.17 mm, P < .001) but not in the early postoperative period for the whole group. Early after surgery, basal diameter was not different from native EPIG dimensions after ISDN (2.57 +/- 0.52 versus 2.56 +/- 0.39 mm), suggesting maximal dilation. However, vasodilation with ISDN was observed in a subgroup of patients at this time. These responder patients (n = 51) had a smaller basal diameter (2.47 +/- 0.49 versus 2.67 +/- 0.54 mm, P < .05) and a smaller runoff (P < .001) than nonresponder patients. CONCLUSIONS: EPIG grafts have a good early patency rate. The mid-term patency rate remains high and seems to depend, at least partially, on flow through the native coronary artery. EPIGs initially increase their lumen size, probably to meet the increased blood flow due to myocardial requirements. Over time, EPIG diameters decrease mainly as a result of a higher basal vasomotor tone. Long-term angiographic follow-up (eg, 5 to 10 years) is needed to assess late patency rate and the relation with these early findings and will define the place of this new coronary bypass conduit