Biomedical subjects
Publications and source records attributed to H C Herrmann.
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In addition to its anticoagulant effects, heparin is known to have antiproliferative effects on vascular smooth muscle cells. Ardeparin is a partially depolymerized (low molecular weight) heparin that has a longer half-life than unfractionated heparin. Following successful coronary balloon angioplasty, 565 patients were randomized to treatment with twice-daily subcutaneous ardeparin 50 anti-Xa U/kg (low dose) or 100 anti Xa U/kg body weight (high dose), or placebo for 3 months. Follow-up angiography was performed in 415 patients at 4 months, or earlier if clinically indicated. Additionally, patients underwent treadmill exercise electrocardiography at 2 weeks and 4 months. This study was designed to test the hypothesis that 3 months of subcutaneous dosing of ardeparin would reduce angiographic restenosis after coronary balloon angioplasty. Ardeparin had no effect on the incidence of angiographic restenosis (prespecified definition: > or = 50% luminal diameter narrowing plus a loss of 50% of initial gain or absolute decrease of 20% of luminal diameter). Neither the mean luminal diameters nor mean percent diameter stenoses were different among the treatment groups before, after, or 4 months after balloon angioplasty. On exercise electrocardiography at 2 weeks and 4 months, patients in all treatment groups had similar exercise tolerance, incidence of angina, and frequency of ST depression. Thus, ardeparin treatment given subcutaneously for 3 months after successful balloon angioplasty does not reduce either angiographic or clinical measures of restenosis.
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Fifty-two patients with low gradient critical aortic stenosis who underwent aortic valve replacement were found to have a perioperative mortality of 11% and an 8-year actuarial survival of only 29%. No hemodynamic variables, including valvular resistance, predicted long-term outcome, and the only clinical variable that predicted long-term survival was the absence of coronary artery disease.
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Intracoronary stenting of de novo narrowings results in a lower restenosis rate when compared with percutaneous transluminal coronary angioplasty. We sought to determine whether intracoronary stenting for restenotic narrowings is associated with a worse outcome when compared with stenting for de novo narrowings. A total of 114 consecutive patients with 124 narrowings were retrospectively identified. Stents were deployed in 46 de novo (37%) and in 78 restenotic (63%) narrowings. The 2 groups were similar with respect to variables known to affect restenosis. Follow-up angiograms were available in 88% of patients at a mean of 6.3 +/- 3.3 months after stent implantation. At follow-up angiography, a significantly higher restenosis rate in the restenotic group was observed (p = 0.05). Restenosis risk could not be predicted from variables known at the time of stent implantation. However, the presence of angina at the time of follow-up was significantly associated with restenosis (p = 0.01). Kaplan-Meier survival curves for freedom from repeat target-site revascularization demonstrated a significant difference in the need for target-site revascularization between the de novo and restenotic groups over the first-year post-stent implantation (p = 0.01; relative risk = 1.94). Multivariate analysis identified restenosis as the indication for stenting (p <0.01), postprocedure percent stenosis (p = 0.01), and narrowing length (p = 0.01) as independent predictors for repeat target-site revascularization. When compared with de novo narrowings, restenotic narrowings have a worse outcome after stenting. A prospective, randomized trial comparing outcome after percutaneous transluminal coronary angioplasty and stents for restenotic narrowings would be useful.
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In aortic stenosis (AS), conventional indexes of severity vary with changes in transvalvular flow. It is important to determine the true severity of obstruction because AS in the presence of low cardiac output and low gradient is associated with high mortality during aortic valve replacement. This study compares 3 indexes of stenosis severity at different transvalvular flow rates in patients with low-flow, low-gradient critical AS. Eight patients with critical AS (valve area < or = 0.7 cm2), low cardiac output (< 4.0 L/min), and low mean transvalvular gradient (< or = 40 mm Hg) underwent hemodynamic assessment at baseline, after transvalvular flow was augmented with dobutamine, and after the valve opening was increased with percutaneous balloon aortic valvuloplasty. Severity of obstruction was assessed using 3 different measures: Gorlin formula calculated valve area, valvular resistance, and percentage left ventricular stroke work loss. Dobutamine infusion increased cardiac output by 35% and mean transvalvular gradient by 27%. The mean Gorlin formula calculated aortic valve area increased from 0.5 to 0.6 cm2 (p = 0.002). Percentage left ventricular stroke work loss increased from 23% to 28% (p = 0.03). Valve resistance was unchanged by dobutamine (350 to 310 dynes X sec X cm(-5); p = NS). Balloon valvuloplasty increased cardiac output 13% and decreased the gradient 31%; this resulted in an increase in the calculated valve area from 0.6 to 0.9 cm2 (p = 0.001). Percentage left ventricular stroke work loss decreased from 28% to 20% (p = 0.002), and valve resistance decreased from 310 to 181 dynes X sec X cm(-5) (p = 0.001) after valvuloplasty. We conclude that in patients with low-flow, low-gradient critical AS, valve resistance is the most flow-independent measure of severity of stenosis. All measures improve with percutaneous balloon aortic valvuloplasty.
Coronary artery disease and valvular dysfunction are long-term complications of mediastinal irradiation. We describe 3 patients who underwent successful combined coronary artery bypass grafting and valve replacement for symptoms related to radiation-induced coronary artery and valvular disease.
OBJECTIVES: The objectives of this double-blind, placebo-controlled, randomized dose-ranging study were 1) to examine the safety and tolerability of tirofiban (MK-383), a new nonpeptide platelet IIb/IIIa receptor antagonist, on a background of intravenous heparin and aspirin therapy; 2) to study the pharmacodynamics and pharmacokinetics of tirofiban; and 3) to evaluate the incidence of adverse cardiac outcomes (urgent repeat revascularization, myocardial infarction and death) with tirofiban versus placebo in a high risk subset of patients undergoing coronary angioplasty. BACKGROUND: Abrupt vessel closure complicates 4% to 8% of angioplasty procedures. Recent data have suggested that agents that antagonize the platelet glycoprotein IIb/IIIa receptor may reduce the incidence of adverse ischemic outcomes after coronary angioplasty. METHODS: Seventy-three patients received tirofiban in three sequential dose panels and 20 patients received placebo. Patients within each panel were randomized to receive either tirofiban or placebo in a 3:1 randomization design. Bolus doses of 5, 10 and 10 microg/kg and continuous infusion (16 to 24 h) doses of 0.05, 0.10 and 0.15 microg/kg per min were administered in panels I, II and III, respectively. Patients received concomitant heparin and aspirin for the angioplasty procedure. Data on patients receiving placebo (heparin and aspirin only) were pooled across panels for comparisons. The pharmacodynamic effect of tirofiban on ex vivo platelet aggregation to 5 micromol/liter adenosine diphosphate (ADP) and bleeding times were measured. Clinical outcomes were assessed in all patients, but the power to detect clinically meaningful differences (a one-third reduction in clinical events) between groups was limited (5%). RESULTS: Tirofiban was associated with a dose-dependent inhibition of ex vivo ADP-mediated platelet aggregation that was sustained during intravenous infusion and resolved rapidly after drug cessation. Adverse bleeding events, largely related to vascular access site hemorrhage, were slightly increased at the highest dose. Adverse clinical outcomes were infrequent in all patients and were not different among the small number of patients within each group. CONCLUSIONS: This study establishes a rational and generally well tolerated dosing regimen for administration of tirofiban as adjunctive therapy in high risk angioplasty patients. The impact of tirofiban on adverse clinical outcomes after angioplasty awaits definition by a larger clinical trial.
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OBJECTIVES: Our goals were to examine late clinical outcome in a cohort of patients who electively received Palmaz-Schatz intracoronary stents, to identify specific predictors of outcome and to determine the time course of the development of ischemic cardiac events after stenting. BACKGROUND: Short-term results of Palmaz-Schatz intracoronary stenting have been promising, with a reduction in both angiographic restenosis and clinical cardiac events up to 1 year after stenting. METHODS: We analyzed the clinical outcomes in 65 consecutive patients who underwent stenting at least 3 years before analysis. Demographic, clinical and procedural predictors of survival and event-free survival, defined as freedom from myocardial infarction, stent-site percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery or death, were analyzed at a mean follow-up of 39 +/- 17 months. RESULTS: Absolute survival and event-free survival at 3 years were 88% and 56%, respectively. Three-year freedom from stent-site revascularization was 66%. Predictors of decreased long-term survival (p < 0.05) included diabetes and a high angina score (Canadian Cardiovascular Society class III/IV) at 6 and 12 months after stenting. Predictors of decreased event-free survival (p < 0.05) included a high angina score at 3, 6 and 12 months after stenting, smaller stent deployment balloon size and greater number of stents implanted. Freedom from adverse events by 6 months after stenting also correlated with long-term event-free survival. Eighty-five percent of stent-site revascularizations occurred within 1 year. During late follow-up (>24 months), no patients had stent-site stenoses requiring revascularization, whereas 11% of patients required revascularization in nonstented coronary segments. CONCLUSIONS: Clinical predictors of worse long-term outcome included diabetes mellitus, higher angina score at follow-up, smaller stent deployment balloon size and greater number of stents at implantation. During follow-up, the majority of adverse events and stent-site revascularizations occurred early after stenting, and disease progression in nonstented vessels accounted for the majority of late revascularization events.
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BACKGROUND: Pulmonary hypertension increases perioperative risk in patients having mitral valve replacement, but most studies have included patients with mixed mitral valve disease and have not examined long-term outcome. METHODS AND RESULTS: We retrospectively examined the results and predictors of outcome of cardiac surgery in 43 patients (age, 62 +/- 13 years [mean +/- SD]; 81% women) with a primary diagnosis of mitral stenosis and severe pulmonary hypertension (pulmonary artery systolic pressure > or = 60 mm Hg or mean pressure > or = 50 mm Hg). Patients with more than mild mitral regurgitation were excluded. Thirty-eight patients (88%) were in NYHA functional class III or IV, and 11 patients (26%) had an acute presentation requiring urgent surgery. Preoperative hemodynamics demonstrated a mean mitral valve area of 0.7 +/- 0.3 cm2, mean pulmonary artery pressure of 50 +/- 9 mm Hg, and pulmonary artery systolic pressure of 81 +/- 18 mm Hg. Other characteristics included right ventricular failure (18 patients), coronary artery disease (16 patients), and critical aortic stenosis (11 patients). Forty patients underwent mitral valve replacement with St Jude prostheses; 3 had open commissurotomy. Additional surgical procedures included aortic valve replacement (42%), coronary artery bypass graft surgery (26%), and tricuspid valvuloplasty (16%). There were 5 perioperative deaths (11.6%), and 7 other patients (16%) had major complications, including reoperation for hemorrhage, stroke, respiratory failure, myocardial infarction, or a > 30-day hospitalization. Univariate analysis of demographic, hemodynamic, and operative characteristics identified the following predictors of perioperative death (P < .05): acute presentation, clinical evidence of right ventricular failure, impaired left ventricular ejection fraction, and increased left ventricular diastolic pressure. Predictors of complications (P < .05) were acute presentation, ECG evidence of right ventricular hypertrophy, and elevated right ventricular systolic pressure. Multivariate analysis showed only acute presentation and right ventricular hypertrophy as predictors of perioperative death or major complications, respectively. Five- and 10-year actuarial survivals were 80% and 64%, respectively. The only predictor of long-term mortality was advanced age. Functional NYHA status was improved by one grade or more in 76% of survivors. CONCLUSIONS: Patients referred to a tertiary care hospital in the United States with mitral stenosis and severe pulmonary hypertension often have other associated cardiac diseases and comorbid conditions. Cardiac surgery can be successfully performed with an acceptable mortality, and risk factors for poor perioperative outcome can be identified by preoperative clinical characteristics. Younger patients have the best long-term survival, and most survivors experienced long-term improvement in functional status.
A comparison of consecutive initial and later patients receiving emergent coronary artery stents to salvage failed PTCA procedures was made to determine whether experience with this procedure can improve patient outcome. Twenty-six consecutive patients underwent emergent, unplanned implantation of one or more Palmaz-Schatz coronary stents at our institution over a 3-1/2 year period. Indications for stent insertion included impending vessel closure (decrease in TIMI flow grade and clinical evidence of ischemia) or acute occlusion (TIMI flow grade 0 or 1 and > or = 99% stenosis) after PTCA. Immediate and final success (30 day) were determined, and the results in the first (Initial) 13 patients were compared to the remaining (Later) 13 patients. Baseline characteristics of the study population included a male predominance (69%) with a mean (+/- SD) age of 57 +/- 10 years. Conventional balloon PTCA was performed in all three native coronary arteries with an increase in mean percentage stenosis from 76 +/- 13 to 85 +/- 14% (P < 0.05). Twelve patients developed acute occlusion and 14 patients impending closure after PTCA due to the appearance of thrombus (12%), dissection (46%), or both (35%). Palmaz-Schatz stents were successfully inserted in all patients restoring TIMI grade 3 antegrade flow; however, major complications developed in almost 50% of patients. Comparison of initial and later patients showed no differences in demographic or pre-PTCA angiographic characteristics. Later patients had less severe stenoses post-PTCA (before stenting) and were less likely to have thrombus present at the angioplasty site (15% vs. 77%, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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OBJECTIVES: This study evaluated the immediate and long-term results of percutaneous Inoue balloon mitral valvotomy in patients with severe valvular and subvalvular deformity. METHODS: We reviewed the prevalvotomy transthoracic echocardiograms of patients from the North American multicenter Inoue registry with total Massachusetts General Hospital (MGH) echocardiographic scores > or = 10. The echocardiograms were rescored by two investigators to assess valvular and subvalvular morphology to eliminate interinstitutional variability. Ninety patients were originally assigned scores > or = 10. After rescoring, 18 patients (20%) were eliminated, leaving 72 study patients. RESULTS: Balloon mitral valvotomy was technically successful in 69 (96%) of the 72 patients. Mean (+/- SD) mitral valve area increased from 0.9 +/- 0.3 to 1.5 +/- 0.5 cm2. An immediate optimal result, defined as > or = 50% increase in mitral valve area or a final area > or = 1.5 cm2 with no major complications, was achieved in 46 patients (64%). End points for clinical follow-up (events) included mitral valve replacement, repeat valvotomy or death. At a mean follow-up of 22.9 +/- 11.0 months, 22 patients (31%) required mitral valve replacement or a second valvotomy, 9 patients (13%) died, and 32 patients (45%) were in New York Heart Association functional class I or II. Univariate predictors of an immediate optimal result included sinus rhythm, male gender and a lower University of Southern California commissural calcium score. Only sinus rhythm predicted an optimal result by multivariate analysis. Actuarial 3-year event-free survival was 42%. Univariate predictors of event-free survival were a lower grade of mitral regurgitation, lower MGH total echocardiographic score, lower MGH leaflet thickness subscore and lower prevalvotomy left ventricular systolic pressure. Only grade of mitral regurgitation after valvotomy predicted event-free survival by multivariate analysis. CONCLUSIONS: Inoue mitral valvotomy in patients with severe valvular and subvalvular deformity has a high technical success rate and good immediate hemodynamic result but a high cardiovascular event rate in follow-up. Mitral valve replacement should be considered in surgical candidates with an MGH total echocardiographic score > or = 10 because it may be able to provide better long-term event-free survival. Balloon valvotomy remains a reasonable palliative therapeutic option for some patients with severe valvular deformity and high surgical risk.
OBJECTIVE: To discuss the diagnosis and treatment of malignant pericardial effusion and focus on quantitating the success and complication rates of the many treatment modalities and updating recent advances in the field. DATA SOURCES: English-language publications were identified by a computerized search (MEDLINE) of these key words: cancer, tumor, malignancy, pericardium, and pericardial effusion. This computerized search was supplemented by a manual search of the bibliographies of original research articles and textbooks. STUDY SELECTION: Studies were included if the outcome of patients undergoing treatment for malignant pericardial effusion was reported separately from the outcome of patients with other causes of pericardial effusions. Studies that only reported the combined results of patients with malignant and nonmalignant effusions were excluded. DATA EXTRACTION: To determine success rates for the various treatment modalities, we examined freedom from symptomatic recurrence of pericardial effusion requiring reintervention as the key end point. Where appropriate, we also examined procedural mortality rates. RESULTS: Initial relief of symptoms is achieved in most cases with percutaneous pericardiocentesis that, with echocardiographic guidance, can be performed with low morbidity and mortality. In many cases, drainage for several days with an indwelling catheter alleviates the effusion without subsequent recurrence. Systemic antitumor therapy with chemotherapy or radiation therapy is effective in controlling malignant effusions in cases of sensitive tumors such as lymphomas, leukemias, and breast cancer. Local sclerotherapy with tetracycline hydrochloride or bleomycin sulfate is also effective and associated with low morbidity. Sclerotherapy with other agents or radionuclides offers no advantages. Of the several surgical options, subxiphoid pericardiotomy has the advantage of low morbidity and mortality, can often be performed under local anesthesia, and is highly effective in preventing recurrence. Percutaneous balloon pericardiotomy has recently been described. This intervention is performed with local anesthesia, is effective in preventing reaccumulation, and has a low morbidity. CONCLUSIONS: Treatment of malignant pericardial effusions must be individualized with consideration given to the patient's condition and tumor type, the success rates and risks of the various modalities, and local availability and expertise.