Influence of treatment delay on long-term left ventricular function in patients with acute myocardial infarction successfully treated with primary angioplasty.

BACKGROUND: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of acute myocardial infarction (AMI) to reperfusion. The aim of this study was to evaluate the importance of time to reperfusion for left ventricular function recovery after primary angioplasty (percutaneous transluminal coronary angioplasty [PTCA]) for AMI. METHODS: Ninety-five patients undergoing long-term successful PTCA for AMI were studied. Echocardiography was performed before and 3, 7, 30, 90, and 180 days after PTCA. End-diastolic volume index (EDVI) and end-systolic volume index (ESVI), ejection fraction, and left ventricular wall motion score index (WMSI) were evaluated. RESULTS: Patients were divided into group A, 23 patients reperfused within 2 hours; group B, 32 patients reperfused between 2 and 4 hours; group C, 22 patients reperfused between 4 and 6 hours; and group D, 18 patients reperfused between 6 and 12 hours. Both EDVI and ESVI were reduced in groups A and B at 90 days. Groups C and D did not show any changes of EDVI and ESVI at any stage throughout the study. Ejection fraction improved only in groups A and B at 30, 90, and 180 days. At study entry, WMSI was similar in all groups. After 7 days, in group A and in group B, WMSI was improved, no changes were observed in group C, and a mild deterioration was observed in group D at 3 and 7 days. Subsequent evaluations showed progressive improvement of WMSI in all groups. CONCLUSIONS: Myocardial salvage is achieved only in patients revascularized within 4 hours from AMI onset. However, revascularization after 6 hours may be worthwhile by preventing ventricular remodeling.

Recovery of left ventricular function following early reperfusion in acute myocardial infarction: a potential role for the calcium antagonist nisoldipine.

The purpose of the present study was to test whether the administration of a vascular-selective organic calcium antagonist (nisoldipine) at the onset of early mechanical reperfusion (by coronary angioplasty) in acute myocardial infarction could prevent or attenuate postischemic stunning and enhance the recovery of left ventricular function in these patients. The study included 36 patients with anterior acute myocardial infarction who underwent an early and successful primary coronary angioplasty within 3 hours of the onset of chest pain (mean time to reperfusion = 113 +/- 37 minutes). The infarct-related artery was the left anterior descending artery in all patients. All had single-vessel disease. Baseline coronary arteriography was completed by left ventriculography. When the infarct-related artery was identified, a guidewire was placed into the target vessel and a balloon catheter was positioned in the artery. At this point all patients were administered 0.8 mg of intracoronary nitrates through the guiding catheter. Patients were then randomized. Seventeen patients (the NIT group) did not receive further treatment during the procedure, while the other 19 patients (the NIS group) received an additional 0.05 mg of intracoronary nisoldipine. Postprocedure treatment consisted of oral nitrates (80-120 mg/day) plus enalapril (10-20 mg/day) in the NIT group patients, and oral nisoldipine (20 mg/day) plus enalapril (10-20 mg/day) in the NIS group patients. The same treatment was maintained during the 6-month follow-up period. An echocardiographic study was performed at 1, 7, 30, 90, and 180 days following the procedure. Left ventriculography and coronary angiography were repeated at 1 and 180 days after the mechanical reperfusion. An exercise test was performed at 30, 90, and 180 days following primary angioplasty. Left ventriculograms and two-dimensional echocardiograms were analyzed by a computerized system that evaluated left ventricular volumes, ejection fraction, segmental wall motion, and diastolic function (from the left ventricular volume curve). Under baseline conditions, the clinical and angiographic characteristics of the patients were similar in both treatment groups. The results showed a significantly earlier recovery of left ventricular systolic and diastolic function in the NIS group patients compared with those of the NIT group. Also, exercise capacity was significantly better at 30 days in the NIS group. The findings of the present study provide further evidence that early reperfusion in acute myocardial infarction is likely to be followed by myocardial stunning. The vascular-selective organic calcium antagonist nisoldipine, administered at the onset of reperfusion, seems to attenuate postischemic stunning and to enhance the recovery of left ventricular function in this clinical subset.

Left ventricular diastolic function during adrenergic stress in essential hypertension: acute and chronic effects of ACE inhibition.

We studied the changes in left ventricular (LV) diastolic function induced by angiotensin-converting enzyme (ACE) inhibition at rest and during adrenergic stimulation and their relation to blood pressure (BP) variations to determine whether reductions in the renin-angiotensin system may improve diastolic function irrespective of BP reduction. Echocardiographic indices of systolic and diastolic function, plasma catecholamines as estimated by high-pressure liquid chromatography, and BP variations (Dynamap) were determined at rest and during the cold pressor test (CPT) before and 6 hours and 20 days after ACE inhibition (lisinopril), 20 mg/day by mouth in 10 subjects with uncomplicated essential hypertension. Blood Pressure was significantly reduced after both 6 hours and 20 days of therapy. The cold pressor test induced similar increases in BP in both basal conditions and after acute and chronic treatment. Catecholamine levels were unchanged by the therapy. Systolic function, evaluated by fractional shortening, ejection fraction, and systolic dV/dt, was normal and unchanged during CPT and after treatment. Diastolic function, assessed by volume curve analysis, showed a reduced percentage contribution of rapid filling to total diastolic filling, an increase in the contribution of the atrial systole, and an increase in the isovolumetric relaxation time. During CPT these parameters deteriorated further in response to increased afterload. Lisinopril therapy induced significant increases in end-diastolic volume (p < 0.005) with a progressive increase in the rapid filling dV/dt (p < 0.005 at rest; p < 0.001 during CPT) and a reduction in isovolumetric relaxation (p < 0.0001 at rest and p < 0.01 during CPT). The correlation between systolic BP (afterload) and the rapid filling dV/dt, both at rest and during CPT, was modified by treatment with the ACE inhibitor, with significantly higher rapid filling dV/dt values, and with the pressure loads equal (reduction of the slope and rightward shift of the correlation line). The improvement in diastolic function achieved by ACE inhibition at rest and during CPT appears unrelated to plasma catecholamines and only partly ascribable to the reduced pressure load. The tissue angiotensin II reduction might by itself improve the myocardial response to the pressure load and adrenergic stimulation.

Correlation between peripheral hemodynamic changes and left ventricular diastolic function in hypertensive patients treated with urapidil.

We evaluated the modifications induced by chronic treatment with an alpha 1-adrenolytic hybrid drug, urapidil, on the hemodynamic parameters in peripheral artery and left ventricle diastolic function. Fifteen mild to moderate essential hypertensive patients (13 men, 2 women; mean age 42 years, range 32-54 years) received urapidil (60 mg b.i.d.) for 6 months. Peripheral hemodynamic and cardiac parameters were evaluated by duplex scanner, coupled with a plethysmographic method, basally (T0) and after 6 weeks' (T1) and 6 months' treatment (T2). Mean blood pressure (BP) showed a reduction after 6 weeks of -9.07 mm Hg (confidence intervals [CI] 95%: -9.21; -8.92; P < 0.01), which was maintained after 6 months (-8.21 mm Hg, CI 95%: -8.97; -7.43; P < 0.01), while no significant change was seen in heart rate. Compliance showed highly significant changes after both 6 weeks (+1.073 dyn-1.cm4.10(-7), 95% CI: +0.965; +1.181, P < 0.001) and 6 months (+0.933 dyn-1.cm4. 10(-7), 95% CI: +0.903; +0.963, P < 0.001), as well as characteristic impedance (T1:-16.689 dyn.s.cm-5/10(2), 95% CI: -16.914; -16.463 P < 0.001; T2: -15.98 dyn.s.cm-5. 10(2), 95% CI: -18.186; -13.784; P < 0.001) and forearm resistances (T1: -26.153 mm Hg.ml-1.s, 95% CI: -34.553; -17.753, P < 0.01; T2: -43.587 mm Hg.ml-1.s, 95% CI: -52.711; -34.464, P < 0.01). Similarly, we have recorded a similar change in left ventricular end-diastolic posterior wall thickness (T1: -1.067 mm, 95% CI: -1.099; -1.035, P < 0.01; T2: -2.866 mm, 95% CI: -3.044; -2.688, P < 0.01), end-diastolic interventricular septum thickness (T1: -0.921 mm, 95% CI: -1.511; -0.289, P < 0.05; T2: -2.711 mm, 95% CI: -3.211; -2.199, P < 0.01), end-diastolic volume (T1: +6.4 ml, 95% CI: +6.343; +6.456, P < 0.01; T2: +19.867 ml, 95% CI: +18.564; +21.170, P < 0.01), and mass/volume index (T1: -0.11, 95% CI: -0.118; -0.101, P < 0.01; T2: -0.218, 95% CI: -0.221; -0.217, P < 0.01). Changes in arterial compliance have shown a statistically significant correlation with changes in mass/volume index (r = -0.468; P < 0.03), end diastolic volume (r = 0.501; P < 0.02), as well as left ventricle rapid filling phase (r = 0.426; P < 0.05) and left ventricle end diastolic posterior wall thickness (r = -0.478, P < 0.03). Our results suggest that the antihypertensive efficacy of urapidil coupled with the restoration of the dumping function of the large arteries, and the reduced activation of reflex sympathetic activation, may play a considerable role among the mechanisms allowing the regression of the functional modifications affecting the left ventricular diastole.

Clinical and therapeutic implications of chronic left ventricular dysfunction in coronary artery disease.

In patients with myocardial ischemia, left ventricular dysfunction (LV) may arise from irreversible damage (cell death), myocardial stunning (postischemic dysfunction), or myocardial hibernation (persistent myocardial dysfunction at rest due to underperfusion). Chronic LV dysfunction usually refers to hibernating myocardium. However, stunning might also become chronic, producing persistent myocardial dysfunction. Clinical studies have demonstrated that many patients with coronary artery disease have subsequent recurring ischemic (symptomatic or silent) episodes at short intervals in the same area and that each episode may be followed by myocardial stunning. In these patients the myocardium may not recover fully between episodes and function may remain reversibly depressed for long periods or may even be clinically depressed. The recognition of both stunning and hibernation is very important clinically and therapeutically, since chronic LV dysfunction may have a negative effect on mortality and morbidity in patients with coronary artery disease. Moreover, both clinical states are potentially correctable. Pharmacologic intervention with beta blockers, angiotensin-converting enzyme inhibitors, or calcium antagonists might improve or protect hibernating myocardium. The acute hemodynamic effects of the dihydropyridine calcium antagonist nisoldipine have been investigated in patients with chronic LV dysfunction probably arising from hibernating myocardium. Nisoldipine was found to improve both left ventricular systolic and diastolic function without activating the adrenergic system. The improvement in systolic function may be due to a redistribution of coronary blood flow and to a slight reduction in afterload induced by nisoldipine. On the other hand, nisoldipine may improve diastolic function in these patients by an intrinsic mechanism, Reducing intracellular calcium overload or balancing intracellular calcium homeostasis in the ischemic areas.(ABSTRACT TRUNCATED AT 250 WORDS)

[Mechanisms of transluminal mechanical coronary recanalization]. / I meccanismi della ricanalizzazione coronarica meccanica transluminale.

Coronary angioplasty (PTCA) represents one of the most diffuse technique for myocardial revascularization in coronary artery disease patients. The principal mechanisms, responsible for the luminal increment after successful balloon dilatation are stretching of the vessel wall and splitting of the plaque and its rearrangement in an increased cross section of the vessel. Soon after balloon deflation elastic recoil of the vessel wall might occur at different grades which result in a partial loss of the result achieved by balloon PTCA. This phenomenon seems to be one of the major factors influencing the acute and long-term results of PTCA. Balloon inflation is also followed by endothelial denudation and intramural hemorrhage and intramural thrombus apposition. Then, a proliferative process takes place which is characterised by intimal and smooth muscle proliferation and migration. This process, beside the elastic recoil of the vessel wall, might also contribute to restenosis following balloon PTCA. Other devices for myocardial revascularization were introduced in the clinical practice based on different mechanisms from that of conventional PTCA. Transluminal atherectomy (directional, rotational and rotational-ablation) is based on the removal of plaque material from the vessel, increasing the lumen and creating a smooth surface. By this mechanism of action, plaque splitting and vessel wall stretching might be avoided, thus acute and long-term results are supposed to be improved as compared to balloon angioplasty. Another device for the removal of plaque material is represented by laser angioplasty which utilizes laser energy for the evaporation of the atherosclerotic material and the increase of vessel lumen without vessel wall stretching and plaque splitting.(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of direct coronary angioplasty in the course of acute myocardial infarction]. / Il ruolo dell'angioplastica coronarica diretta nell'infarto miocardico acuto in evoluzione.

The application of coronary angioplasty (PTCA) for early mechanical reperfusion in patients with evolving acute myocardial infarction (AMI) was introduced at the beginning of the '80s. There are 5 distinct approaches to PTCA for AMI mainly based on the timing of the intervention: primary or direct PTCA refers to emergency recanalization (as soon as possible) of the "culprit" vessel by the interventional procedure without the use of thrombolytic agents; immediate or sequential PTCA is the combination of administration of intravenous thrombolytic therapy followed very closely by PTCA; rescue PTCA refers to the use of PTCA as a mechanical approach for reperfusion when thrombolytic therapy has failed (60 to 120 min after such therapy has been initiated); deferred or adjunctive PTCA implies coronary angiography and PTCA delayed by at least several days after thrombolytic therapy and reserved for patients with residual ischemia; elective PTCA refers to a delayed symptom-derived procedure after thrombolytic therapy. Immediate PTCA, in which the procedure urgently follows the thrombolytic therapy has been studied in 3 randomized trials (TAMI 1, ECoS, TIMI 2A). All 3 trials have shown that immediate PTCA does not affect positively, but can worsen, the outcome of thrombolytic therapy since it increases mortality and bleeding complication with no improvement in reocclusion rate. Rescue PTCA was evaluated by several Authors who were able to demonstrate that mechanical reperfusion after failed thrombolytic therapy improves prognosis and reduces in-hospital and long-term mortality in this subgroup of patients with AMI. Deferred or adjunctive and elective PTCA represent therapeutic approaches in patients with residual ischemia following a successful thrombolysis able, when residual or recurrent ischemia are present, to prevent major cardiac events and to improve clinical outcome. The major interest was addressed to the role of primary PTCA in evolving AMI, as alternative therapy to thrombolysis. Randomized trials have been able to demonstrate that primary PTCA could dramatically improve the clinical outcome in AMI complicated by cardiogenic shock. Moreover, this approach can be safely performed in patients with contraindications for thrombolytic therapy with excellent results. Despite other advantages, primary or direct PTCA for evolving AMI is still presenting few points which have to be furtherly evaluated: acute or subacute reocclusion rates, restenosis rates, costs and availability to majority of population. The on-going clinical evaluation of other devices for mechanical reperfusion (transluminal extraction catheter-TEC, directional atherectomy, coronary stents, thermal PTCA, prolonged autoperfusion), in order to improve acute and subacute results, could furtherly expand the use of this approach in AMI-patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Interrelation between angiographic severity of coronary artery disease and plasma levels of insulin, C-peptide and plasminogen activator inhibitor-1.

Plasma insulin, C-peptide and plasminogen activator inhibitor-1 (PAI-1) levels were measured in 64 men with coronary artery disease (CAD) documented by angiography. Coronary arteriograms were analyzed, and the severity and diffusion of coronary lesions were quantified by score systems. C-peptide and PAI-1 levels in patients with CAD were significantly higher than in 30 control subjects. Insulin, C-peptide and PAI-1 showed a highly significant correlation with the severity scores for coronary lesions (C-peptide more than insulin), but only a weak correlation with diffusion scores. Highly significant correlations were found between insulin and PAI-1, and even greater ones between C-peptide and PAI-1. It has been proposed that hyperinsulinemia may be involved in the etiology of atherosclerotic cardiovascular disease by dysregulating lipoprotein metabolism and blood pressure. These findings support that hypothesis and suggest that insulin secretion may be an index of the severity of CAD. Because a direct effect of insulin on the cells that synthesize PAI-1 has been shown, the present data further indicate that the effect of insulin on fibrinolysis may be another way by which hyperinsulinemia accelerates atherogenesis.

Left ventricular dysfunction following transient ischaemia induced by transluminal coronary angioplasty. Beneficial effects of calcium antagonists against post-ischaemic myocardial stunning.

Acute and severe ischaemia is followed by depression of myocardial contractility during reperfusion; return to full recovery might take a long time. This phenomenon, termed myocardial stunning, has been extensively demonstrated in experimental studies and in different clinical settings. The beneficial effects of calcium antagonists in preventing post-ischaemic myocardial stunning have been tested in experimental studies, showing that when administered before or during ischaemia, they inhibit post-ischaemic myocardial dysfunction. The present study was undertaken to verify the possible occurrence of myocardial stunning following transient ischaemia induced by coronary angioplasty. The aim was also to evaluate the possible protective effects of calcium antagonists (nisoldipine) and nitrates against myocardial stunning in patients with coronary artery disease undergoing routine coronary angioplasty (PCTA) with prolonged inflation. The study included 25 patients, aged between 40 and 69 years, with exercise-induced angina and single vessel disease. The stenosis was severe (80% to subtotal occlusion), localized on the left anterior descending artery, but without collaterals at coronary angiogram. All patients had normal left ventricular (LV) overall function and normal systolic thickening of the anterior wall supplied by the diseased artery. Our data suggest that post-ischaemic myocardial stunning is not only an experimental curiosity, but that it does occur in different clinical settings. Calcium antagonists (i.e. nisoldipine), when added before or during ischaemia, seem to prevent myocardial stunning. These findings confer a potential role to these agents in the treatment of post-ischaemic myocardial dysfunction.

Myocardial stunning following coronary angioplasty: protective effects of calcium-channel blockers.

The beneficial effects of calcium-channel blockers against myocardial stunning have been tested in experimental studies, showing that, when added before or during ischemia, a protective effect against postischemia stunning is achieved. The present study was undertaken to test and compare the protective effect of calcium antagonists [nisoldipine (NIS) and nifedipine (NIF)] and nitrates (NIT) against myocardial stunning in patients with coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA) with prolonged inflation as PTCA represents a model of induced acute and severe ischemia for a brief period and might cause myocardial stunning. The study included 30 patients between the ages of 42 and 67 years, all with exercise-induced angina and single-vessel disease, with severe stenosis (80% to subtotal occlusion) localized on the left anterior descending artery and with the absence of collaterals on the coronary angiograms. Moreover, all patients had normal left ventricular (LV) overall function, as well as normal systolic thickening of the anterior wall, supplied by the diseased artery. Patients were randomized to a pre-PTCA treatment with NIT, 80-120 mg/day (10 patients), NIF, 40-60 mg/day (10 patients), and NIS, 10-20 mg/day (10 patients). Pre-PTCA treatment was initiated 7 days before the procedure and continued after. During the PTCA, at the first balloon inflation, an additional dose of 300 micrograms of NIT was injected into the left anterior descending artery through the balloon catheter in the patients in the NIT group, as well as 0.2 mg of NIF in NIF group patients and 0.05 mg of NIS in NIS group patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Remodeling of left ventricular geometry and function induced by lacidipine and nifedipine SR in mild-to-moderate hypertension.

The effects of nifedipine SR and lacidipine on blood pressure, left ventricular (LV) hypertrophy, and diastolic function were evaluated in 15 male patients (mean age of 45 +/- 8 years) with mild-to-moderate hypertension. Clinical evaluation and complete echocardiography were performed at baseline (after 15 days of washout). Seven patients received nifedipine SR (20-40 mg twice daily) and eight lacidipine (4-6 mg once daily). Clinical evaluation and complete echocardiography studies were repeated after 1 and 6 months of active treatment. In addition, full echocardiographic evaluations were carried out in 10 normotensive subjects (for comparison). Results were similar with either drug. After 1 month of therapy, systolic and diastolic blood pressures were significantly decreased (p less than 0.05); after 6 months of therapy, further changes were observed, confirming their significance. Analysis of our data suggests that (a) mild essential hypertension induces early modifications of LV geometry with consequent LV diastolic function characterized by a prolonged and incomplete diastolic filling; thus, LV wall thickness may be increased with a simultaneous reduction in LV end-diastolic short-axis diameter and volume; and (b) antihypertensive treatment with calcium antagonists such as nifedipine SR and lacidipine leads to early normalization of LV geometry and diastolic function without a significant change in total LV mass.

Early regression of left ventricular diastolic abnormalities in hypertensive patients treated with nifedipine.

The effects of nifedipine on blood pressure (BP), left ventricular hypertrophy, and diastolic function were evaluated in 14 patients with essential hypertension (EH). All males with a mean age of 44 +/- 6 years (range 35-58 years), and in ten normotensive subjects (control group) aged 32-42 years (mean age 36 +/- 4). A complete echocardiogram (ECHO) was performed in basal conditions after 1 and 6 months of therapy with nifedipine (20-40 mg/day). Left ventricular echocardiograms (LV ECHO, M-mode, two-dimensional guided) were plotted with a simultaneous ECG tracing by means of a computerized system that allows evaluation of the following parameters: LV end-diastolic and systolic diameters (EDD, ESD); variations in LV diameter and volume during the entire cardiac cycle, and the velocities of such variations; end-diastolic thicknesses of the interventricular septum and posterior wall (ST, PWT); LV mass, mass/volume (M/V) index, end-diastolic diameter/thickness (D/Th) index, and LV ejection fraction (EF). Left ventricular volume curves were obtained and the contributions of rapid filling (RF) and atrial systole (AS) to EDV were evaluated. Filling velocities during RF (vRF) and AS (vAS) were estimated, as well as the isovolumic relaxation period (IR). No significant changes were observed in the heart rate. After 1 month of therapy, systolic and diastolic BP were significantly decreased (p less than 0.05). ST and PWT were reduced, with a simultaneous increase in EDD and EDV (p less than 0.01). LV mass was slightly reduced, as was the M/V index. The D/Th index was increased (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)