[Glycoprotein IIB/IIIA receptor blockers as treatment of acute coronary syndromes and interventional cardiology].
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Biomedical subjects
Publications and source records attributed to B S Lewis.
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The multiple mechanisms that bring about the decompensation of the hypertrophic remodeled myocardium are synergistic and not fully understood. Our current hypothesis is that the increased stress on the ventricle is initially offset by compensatory myocardial hypertrophy. In many instances, however, progressive ventricular dilatation and heart failure occur as a result of maladaptive hypertrophy (abnormal myosin-actin production), programmed cell death (apoptosis) and/or changes in the interstitial vasculature and collagen composition. The molecular and genetic background to these processes includes changes in myocardial gene expression, activation of the local tissue renin-angiotensin and other neurohormonal systems, increased matrix metalloproteinase activity (including collagenase), and expression of certain components of the immune system, such as TNF-alpha. Future research will hopefully provide better methods for limiting the remodeling-ventricular dilatation process by novel pharmacotherapies, gene therapy and, possibly, surgical therapy, and determine the impact of such interventions on survival.
The concept of therapeutic angiogenesis is based on the premise that the potential for vascular growth inherent in vascular tissue can be utilized to promote the development of new blood vessels under the influence of the appropriate growth factors. Direct application of growth factors of the fibroblast (acidic, basic fibroblast growth factor, FGF-5), endothelial (vascular endothelial growth factor) and other series has been effective in preliminary studies. Angiogenesis by gene transfer provides an attractive alternative, with the advantage that the protein may continue to be secreted for a longer period of time and that the gene may be targeted to specific tissues to enhance efficacy and reduce systemic side effects. Angiogenesis by gene transfer is currently under investigation using a variety of growth factors and a wide array of potential delivery systems. These include application of the gene as naked DNA or by viral vector in the proximal vessel by direct intravascular injection, interventional cardiologic techniques (hydrogel coating on balloon, double balloon system, stent implantation) or by direct application to adventitia, pericardium or ischemic tissue distal to the site of arterial obstruction. As our understanding of the molecular and genetic processes underlying angiogenesis increases, and as we examine the results of preliminary animal and human protocols, we hope to develop the potential of angiogenesis by gene transfer for therapeutic use.
We conclude that there is no difference in LV wall thickness, dimensions, or functional parameters between air crew members who fly high + Gz aircraft and those who fly other types of aircraft. No differences were detected between high +Gz air crew personnel and others in development of structural and functional changes over the short-term course of a flying career.
Coronary artery bypass grafting (CABG) is being performed all over the world, with major success in the management of ischemic heart disease and angina pectoris. Complications of bypass grafting include partial or total graft reocclusion, and less common entities such as aneurysm or pseudoaneurysm formation. Noninvasive imaging procedures exist which can help include or exclude the presence of these unusual types of complications when mass-like abnormalities are seen on a chest X-ray following coronary artery bypass grafting. This case specifically illustrates the usefulness of ultrafast magnetic resonance imaging techniques in the evaluation and diagnosis of pseudoaneurysm formation at the site of coronary artery bypass graft.
BACKGROUND: This study assessed the long-term effectiveness of push enteroscopic cauterization of bleeding intestinal angiodysplasia. METHODS: We retrospectively reviewed the clinical course of patients who underwent push and sonde enteroscopy for obscure gastrointestinal bleeding and were diagnosed with intestinal angiodysplasias. RESULTS: One hundred twelve patients bleeding from small intestinal angiodysplasias were identified. After excluding those lost to follow-up (29), data were collected from 83 patients. Fifty-five patients (29 men; mean age, 73 years; mean units of packed red blood cells transfused, 21.4; average bleeding history, 22 months) were cauterized. Twenty-eight patients (12 men; mean age, 71; mean units of packed red blood cells transfused, 15.8; average bleeding history, 22 months) were not cauterized. The noncauterized group (follow-up, 26 +/- 14 months; mean +/- SD) continued to bleed, requiring 2.16 +/- 3.86 units of packed red blood cells transfused per month (units/month) before and 0.97 +/- 1.46 units/month after diagnosis (NS). The cauterized group (follow-up, 30 +/- 18 months) significantly improved, requiring 2.40 +/- 2.97 units/month before treatment and 0.32 +/- 0.91 units/month after cauterization (p < 0.0001, paired t test). CONCLUSION: Cauterization of endoscopically accessible small intestinal angiodysplasias may decrease rebleeding.
Calcium antagonists have a useful role in the management of patients with cardiac disease, producing coronary and systemic vasodilatation and an additional possibly beneficial effect on ventricular diastolic function. On the other hand, the myocardial depressant effect of the first-generation drugs and the abrupt changes in blood pressure, with neurohormonal activation, have been associated with worsening heart failure in certain patients. The present review summarizes the data currently available, with emphasis on the newer slow-release and long-acting calcium antagonists. Use of these drugs minimizes the peak and trough effect associated with short-acting preparations, and particularly when administered against a background of digoxin, diuretic and angiotensin converting enzyme inhibitors, may be associated with better long-term results in patients with ventricular dysfunction. The DEFIANT studies, using nisoldipine-coat core, showed that nisoldipine-CC improved diastolic ventricular function and had a significant anti-ischemic effect in patients with mild-moderate ventricular dysfunction after acute myocardial infarction. The VHeFT III trial showed that felodipine had no effect on exercise capacity or survival in patients with Class 2-3 heart failure. In the PRAISE study of Class 3-4 patients, amlodipine was neutral in patients with ischemic disease, but a strikingly beneficial effect was observed in non-ischemic heart failure (45% decrease in mortality). The precise mechanism for the beneficial effect of amlodipine in these patients is unknown. Further studies are needed to examine the issue of survival benefit in patients with non-ischemic heart failure and the mechanisms involved.
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This report describes a percutaneous, transaxillary approach for implanting permanent pacemakers in the retropectoral space. This approach was used in 17 patients; indications for the procedure included the need to find a new implantation site in patients with infections and multiple previous pacemaker pocket sites (2 patients), emaciation and absence of sufficient adipose tissue (4 patients), and cosmetic considerations (11 patients). No complications were encountered during the implantation and the results were uniformly excellent in all patients. The pacemaker was "invisible" in each case. We conclude that a percutaneous approach for implanting permanent pacemakers in the retropectoral region is safe and feasible. This approach is likely to be applicable to the implantation of transvenous antitachycardia devices.
The effects of the long-acting dihydropyridine calcium antagonist nisoldipine coat core (CC) have been investigated in > 3,500 patients with angina pectoris, hypertension, and ischemic ventricular dysfunction. In patients with angina pectoris, nisoldipine CC improved total treadmill exercise duration (p = 0.027), delayed the onset of angina pectoris (p = 0.009), and increased time to exercise-induced ST-segment depression (p = 0.061). In general, nisoldipine 20-40 mg was effective, and the dose-response curve flattened thereafter. In patients with hypertension, 10-40 mg once daily as monotherapy reduced blood pressure (p < 0.05), with a fall in diastolic pressure of > or = 10 mm Hg or a final diastolic pressure of < 90 mm Hg in 35-63% of patients. In most patients followed for a year, nisoldipine CC was continued as monotherapy. Efficacy was similar in patients < 65 and > 65 years of age. In the Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy (DEFIANT-I) study of patients recovering from myocardial infarction, nisoldipine CC had a salutary effect on diastolic ventricular function, with a higher transmitral early filling velocity and shorter isovolumic relaxation time than in patients receiving placebo. Bicycle exercise capacity was greater (by 12 W; 95% confidence interval, 0.8-23.3) and exercise-induced ischemia occurred less frequently. The nisoldipine CC data pool (3,679 patients) showed that the drug was well tolerated with a low incidence of side effects.(ABSTRACT TRUNCATED AT 250 WORDS)
We examined prospectively the hypothesis that the adequacy of initial dilatation may be a major determinant of the late result of coronary angioplasty and that a better assessment of initial dilatation can be made from a combined angiographic and perfusion study than from angiography alone. Angiographic and perfusion (thallium-201 single-photon-emission computed tomography) measurements were made very early (18 to 24 hours) after coronary angioplasty in 59 patients (67 lesions) and also immediately (37 +/- 16 minutes) after the procedures in 19 of them (23 lesions). The early measurements, singly, in combination, and as a restenosis index (restenosis index = thallium-201 ischemic score (units) - minimal luminal area (squared millimeters) were examined as predictors of the late angiographic result. At late angiography (5.5 +/- 2.2 months after angioplasty), residual stenosis was related to the immediate and very early postangioplasty minimal luminal dimension, thallium-201 ischemic score, and restenosis index, and also to day-1 loss and lesion length. The combination of a normal result in the immediate or early thallium-201 perfusion study with a large ( > or = 2 mm) angiographic luminal dimension stratified a group of patients with better long-term results after angioplasty and a lower incidence of late restenosis (p = 0.03). The findings emphasize the importance of the initial procedure as a determinant of the late result of angioplasty.
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The present study was undertaken to determine the value of abnormal late ventricular potentials on signal-averaged electrocardiograms (ECG) in identifying patients at risk of developing ventricular tachycardia or ventricular fibrillation in the early postoperative period after coronary artery bypass grafting. Signal-averaged ECGs were recorded immediately after operation in 72 patients. Abnormal late potentials were defined as the presence of 2 or 3 of the following: (1) root-mean-square amplitude of the last 40 ms of the QRS < 20 microV; (2) duration of the terminal QRS potentials (after 40 microV) > or = 39 ms; and (3) high-frequency QRS duration > 120 ms (in patients with conduction defects, only the first 2 criteria were used). Abnormal late ventricular potentials were present on the immediate postoperative signal-averaged ECG in 26 of the 72 patients (36%). Life-threatening ventricular tachyarrhythmias occurred in 6 patients. Late potentials were present in all 6 patients, but only in 20 of 66 (30%) who did not develop ventricular tachyarrhythmias (p < 0.005) (sensitivity 100%, specificity 70%, predictive accuracy 72%). Of 12 pre- and perioperative variables examined by univariate and multivariate regression analysis, the presence of late potentials on the signal-averaged ECG and low cardiac output postoperatively were found to be independent predictors of life-threatening tachyarrhythmias.
The DEFIANT-I study (Doppler Flow and Echocardiography in Functional cardiac Insufficiency: Assessment of Nisoldipine Therapy) was a multicenter, multinational double-blind randomized study of the effects of the new calcium channel blocking drug nisoldipine on left ventricular (LV) size and function after acute myocardial infarction. Randomization to placebo or to long-acting nisoldipine core coat (20 mg once daily) was performed in 135 eligible patients with mild to moderate systolic LV dysfunction (LV ejection fraction < or = 50%) 20 days (range 7-35) after infarction, with serial clinical, echocardiographic, and Doppler cardiographic measurements during a 4 week follow-up period. At the end of the follow-up period, exercise capacity was determined by bicycle ergometry. Nisoldipine improved indices of diastolic LV function. Early diastolic transmitral blood flow velocity increased, with an increase in peak E wave of 0.06 m/sec (95% confidence intervals [CI], 0.01, 0.11) and an increase in time velocity integral of 1.2 cm (95% CI, 0.16, 2.27). Isovolumic relaxation time was reduced by 14.7 msec (95% CI, -22.5, -6.9), a change not explained by the very small (and not significant) changes in systemic arterial pressure, heart rate, or cardiac output. There was no change in systolic and diastolic LV volume, nor in LV ejection fraction. Exercise capacity was greater by 12 watts (95% CI, 0.8, 23.3) in patients receiving nisoldipine, while the incidence of > or = 1 mm ST-segment depression (relative occurrence 0.54, 95% CI, 0.30-0.97) and the incidence of angina pectoris (relative occurrence 0.67, 95% CI, 0.42-1.08) during exercise testing tended to be lower in this group. Although the relations were not exact, peak exercise workload 7 weeks after infarction correlated with resting measurements of diastolic LV function. Exercise workload was inversely related to peak late diastolic transmitral blood flow velocity (A wave, slope, -86.6; 95% CI, -120.9, -52.2) and directly to the E/A ratio (slope, 20.5, 95% CI, 6.0, 35.1). The relations between exercise workload and peak late diastolic flow velocity remained significant after correction for age, sex, resting heart rate, and usage of beta-blocking drugs or nisoldipine. Exercise capacity was not related to measurements of systolic LV function (LV end-diastolic and end-systolic volume, LV ejection fraction, stroke volume, cardiac index). In summary, the calcium channel blocker nisoldipine improved measurements of diastolic LV function in patients recovering from acute myocardial infarction. Exercise capacity was higher in patients receiving the drug, and there was less exercise induced ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
To derive better criteria for the noninvasive localization of coronary artery disease, a 12-lead computer-averaged rest and exercise electrocardiogram was examined in 44 selected patients (34 men, 10 women) with single-vessel disease who had an exercise test positive for ischemia by established criteria. Left anterior descending disease was characterized by S-T segment elevation (> or = 0.05 mV) in lead V1 [sensitivity (S) 71%, specificity (Sp) 100%], a T wave amplitude increase in V1 (S 88%, Sp 73%) and a leftward shift or no change in mean frontal plane QRS axis (AQRS; S 92%, Sp 93%). Patients with circumflex or right coronary artery disease had no S-T segment elevation in V1 and a rightward shift in the mean frontal plane AQRS.
We compared the acute hemodynamic effects of captopril and nitrates in 11 patients with severe congestive heart failure and grade IV cardiac disability. Pressures were measured using a Swan-Ganz catheter system; cardiac output and stroke index were measured by thermodilution, and left-ventricular (LV) volumes and ejection fraction were calculated simultaneously with the hemodynamic measurements from radionuclide ventriculography. Measurements were made in each of 4 treatment states: control, sublingual isosorbide dinitrate (ISDN; 5 and 15 mg), oral captopril (50-200 mg daily) and during combined therapy with captopril and ISDN. Captopril produced a fall in mean arterial pressure (p < 0.01) from 81 +/- 14 to 72 +/- 13 mm Hg and a rise in stroke index from 30 +/- 5 to 35 +/- 91/min/m2 (p < 0.05), while LV ejection fraction increased from 18 +/- 5 to 21 +/- 7% (p < 0.05). ISDN reduced mean arterial, pulmonary arterial, right-atrial and wedge pressure. The combination of captopril and ISDN produced a greater fall in mean arterial pressure, a further rise in ejection fraction to 22 +/- 8% (p < 0.05), a fall in systemic (p < 0.05) and pulmonary vascular resistance (p < 0.01) and a rise in cardiac (p < 0.01) and stroke work index (p < 0.01), while the beneficial effects of ISDN on right-atrial, pulmonary arterial and wedge pressure were again achieved. LV contractility, assessed from end-systolic stress-shortening relations, was essentially unaltered or decreased very slightly. The study showed that combined therapy with captopril and nitrates produced acute hemodynamic benefits superior to those achieved by treatment with captopril or nitrates alone.
Incidence and pattern of myocardial ischemia during the peri-PTCA (percutaneous transluminal coronary angioplasty) period and the possible role of continuous intravenous isosorbide dinitrate in its prevention were examined prospectively in 30 patients. Holter electrocardiographic monitoring was performed for 21 +/- 3 h before PTCA and continued during and for 41 +/- 8 h after the procedure. Before PTCA, 19 ischemic episodes were present in 10 (33%) of 30 patients. PTCA produced an abrupt decrease in number (p = 0.015) and duration (p = 0.03) of spontaneous ischemic episodes. The rarity of recurrent myocardial ischemic events by Holter monitoring after PTCA negated any attempt at assessing the efficacy of intravenous isosorbide dinitrate in their prevention. Holter monitoring could not be used as an early predictor of late coronary restenosis.