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Biomedical subjects

H D White

Publications and source records attributed to H D White.

At least 55 records · Page 3Linked to original sources
PubMed2000

Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial.

BACKGROUND: New recombinant plasminogen activators have been developed to simulate the fibrinolytic action of the physiological serine protease tissue plasminogen activator (alteplase, t-PA), and have prolonged half-life features permitting bolus administration. One such activator, reteplase (r-PA), was compared with t-PA in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-III Trial. METHODS AND RESULTS: At 1-year follow-up, survival status was ascertained in 97.4% of the 15 059 patients enrolled in the GUSTO-III trial. At 1 year, the mortality rate for the t-PA-assigned group was 11.06%, and for r-PA it was 11.20% (P:=0. 77). The absolute mortality difference of 0.14% has 95% CIs of -1. 21% to 0.93%. There were no significant differences in outcome by intention-to-treat for the 2 different plasminogen activators in the prespecified groups (age, infarct location, time-to-treatment). The absolute difference in mortality rates between t-PA and r-PA progressively narrowed over the predetermined observation times after random assignment; it was 0.31% at 24 hours, 0.26% at 7 days, 0.23% at 30 days, and 0.14% at 1 year. Of note, mortality rate in the trial between 30 days and 1 year in 13 883 patients was 4.02% and did not differ between the treatment groups. However, this mortality rate was substantially greater than in GUSTO-I, in which mortality rate for t-PA versus streptokinase between 30 days and 1-year was 2.97% (heart rate 1.36, 95% CI 1.23, 1.50, P:<0.001). CONCLUSIONS: The r-PA and t-PA strategies yielded similar survival outcomes after 30 days in this trial. The increase in mortality rate during extended follow-up compared with previous trials may reflect higher-risk patients and highlights the need for improved secondary prevention strategies.

Acute Disease↗
PubMed2000

Pravastatin therapy and the risk of stroke.

BACKGROUND: Several epidemiologic studies have concluded that there is no relation between total cholesterol levels and the risk of stroke. In some studies that classified strokes according to cause, there was an association between increasing cholesterol levels and the risk of ischemic stroke and a possible association between low cholesterol levels and the risk of hemorrhagic stroke. Recent reviews of trials of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have suggested that these agents may reduce the risk of stroke. METHODS: In a double-blind trial (the Long-Term Intervention with Pravastatin in Ischaemic Disease study), we compared the effects of pravastatin on mortality due to coronary heart disease (the primary end point) with the effects of placebo among 9014 patients with a history of myocardial infarction or unstable angina and a total cholesterol level of 155 to 271 mg per deciliter (4.0 to 7.0 mmol per liter). Our goal in the present study was to assess effects on stroke from any cause and nonhemorrhagic stroke, which were secondary end points. RESULTS: There were 419 strokes among 373 patients over a follow-up period of six years. A total of 309 strokes were classified as ischemic, 31 as hemorrhagic, and 79 as of unknown type. Among the patients given placebo, the risk of stroke was 4.5 percent, as compared with 3.7 percent among those given pravastatin (relative reduction in risk, 19 percent; 95 percent confidence interval, 0 to 34 percent; P=0.05). Non-hemorrhagic stroke occurred in 4.4 percent of the patients given placebo, as compared with 3.4 percent of those given pravastatin (reduction in risk, 23 percent; 95 percent confidence interval, 5 to 38 percent; P=0.02). Pravastatin had no effect on hemorrhagic stroke (incidence, 0.2 percent in the placebo group vs. 0.4 percent in the pravastatin group; P=0.28). CONCLUSIONS: Pravastatin has a moderate effect in reducing the risk of stroke from any cause and the risk of nonhemorrhagic stroke in patients with previous myocardial infarction or unstable angina.

Adult↗
PubMed2000

ST-Segment recovery adds to the assessment of TIMI 2 and 3 flow in predicting infarct wall motion after thrombolytic therapy.

BACKGROUND: Early resolution of ST-segment elevation (ST-segment recovery) is associated with an improved outcome after infarction. Whether this relation is present in patients with Thrombolysis In Myocardial Infarction (TIMI) grade 2 or 3 flow (ie, patent) infarct-related arteries is not known. METHODS AND RESULTS: To examine the associations between time to achieve stable 50% ST-segment recovery assessed by continuous ECG monitoring, infarct artery flow, and infarct zone wall motion (at 48 hours), we studied 134 patients who underwent angiography at 99 (interquartile range 92 to 110) minutes after commencing streptokinase, initiated within 12 hours of onset of symptoms of myocardial infarction. Patients with TIMI 2 or 3 flow who failed to achieve early stable ST-segment recovery (50% ST-segment recovery sustained for > or 4 hours with <100 microV change in the peak lead) by 60 or 90 minutes had a higher fraction of chords in the infarct zone >2 SD below normal wall motion (TIMI 2: 55.5% vs 15.3%, P=0.006; and 56.5% vs 26.8%, P=0.01, respectively; and TIMI 3: 48.8% vs 28.3%, P=0.07; and 51.8% vs 29.9%, P=0.03, respectively). Time to stable ST-segment recovery was a multivariate predictor of infarct zone wall motion (P=0.04) independent of TIMI flow grade and the time from symptom onset to streptokinase therapy. CONCLUSIONS: In patients with TIMI 2 or 3 flow in infarct-related artery, early stable ST-segment recovery is associated with improved infarct zone wall motion at 48 hours. ST-segment recovery may provide additional information about the degree of myocyte reperfusion achieved in patients with a patent epicardial infarct-related artery after thrombolytic therapy.

Aged↗
PubMed2000

Acute myocardial infarction complicated by systemic hypoperfusion without hypotension: report of the SHOCK trial registry.

BACKGROUND: Cardiogenic shock is usually characterized by inadequate cardiac output and sustained hypotension. However, following a large myocardial infarction, peripheral hypoperfusion can occur with relatively well maintained systolic blood pressure, a condition known as nonhypotensive cardiogenic shock. The aim of this study was to determine the characteristics of patients with this condition. METHODS: The SHOCK trial registry prospectively enrolled patients with suspected cardiogenic shock complicating acute myocardial infarction. We identified a group of 49 patients who presented with nonhypotensive shock, defined as clinical evidence of peripheral hypoperfusion with a systolic blood pressure >90 mm Hg without vasopressor circulatory support. Clinical characteristics, hemodynamic data, and outcomes in these patients were compared with a group of 943 patients with classic cardiogenic shock with hypotension. The age, gender, and distributions of coronary risk factors were similar in both groups. RESULTS: Patients with nonhypotensive shock were more likely to have an anterior wall myocardial infarction (71% versus 53%, P = 0.03). Both groups of patients had similar rates of treatment with thrombolytic therapy, angioplasty, and bypass surgery. Patients with nonhypotensive shock had an in-hospital mortality rate of 43% as compared with a rate of 66% among patients who had classic cardiogenic shock with hypotension (P = 0.001). Mortality among 76 patients who presented with a systolic blood pressure <90 mm Hg but no hypoperfusion was 26%. CONCLUSIONS: Even in the presence of normal blood pressure, clinical signs of peripheral hypoperfusion, which may be subtle, are associated with a substantial risk of in-hospital death following acute myocardial infarction.

Aged↗
PubMed2000

Cost effectiveness of early discharge after uncomplicated acute myocardial infarction.

BACKGROUND: Reducing the length of hospitalizations can reduce short-term costs, but there are few data on the long-term clinical and economic consequences of early discharge. METHODS: Using data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, we identified 22,361 patients with acute myocardial infarction who had an uncomplicated course for 72 hours after thrombolysis. Then, using a decision-analytic model, we examined the cost effectiveness of an additional day of hospitalization in this group. We defined incremental survival attributable to another day of monitored hospitalization, using Kaplan-Meier estimates to determine the rate of resuscitation after cardiac arrest between 72 and 96 hours. Lifetime survival curves for each group in the decision-analytic model were estimated from empirical one-year survival data from GUSTO-1. The costs of key hospital resources (e.g., room and monitoring) were derived from data in the GUSTO-1 cost-effectiveness analysis. RESULTS: Of the patients with an uncomplicated course within 72 hours after thrombolysis, 16 had ventricular arrhythmias during the next 24 hours; 13 of these patients (81 percent) survived for at least 24 hours. On average, another 0.006 year of life per patient could be saved by keeping patients with an uncomplicated course in the hospital another day. At a cost of $624 for hospital and physicians' services, extending the hospital stay by another day would cost $105,629 per year of life saved. In sensitivity analyses, it was found that a fourth day of hospitalization would be economically attractive only if its cost could be reduced by more than 50 percent or if a high-risk subgroup could be identified in which the estimated survival benefit would be doubled. CONCLUSIONS: Hospitalization of patients with uncomplicated myocardial infarction beyond three days after thrombolysis is economically unattractive by conventional standards.

Aged↗
PubMed2000

Can streptokinase produce beneficial effects additional to coronary recanalization? Quantitative microvascular analysis of critically injured reperfused myocardium.

The aim of this study was to evaluate whether streptokinase (SK) may produce beneficial effects at the level of microvascular circulation in addition to coronary recanalization. Twenty mongrel dogs weighing 28.4 +/- 4.6 kg were randomized to receive SK (16,000-72,000 U/kg) or 20 ml saline (control) in an open-chest anterior descending artery occlusion (3 h) and reperfusion (2 h) model. Myocardial blood flow was measured by the radioactive microsphere technique and the state of microvascular circulation (red blood cell containing capillary counts and tissue red blood cell content) was evaluated in the infarcted subendocardial zone using computerized image analysis. The percentage (mean +/- SE) of cell-containing vessels normalized to nonischemic control areas was 166.5 +/- 7.5 in SK-treated infarcts while in untreated control infarcts it was more variable (130.0 +/- 15.6%) (2P > 0.1). The red blood cell content of infarcts treated with 2.0 megaunits SK was 3.9 +/- 0.6% compared with 6.7 +/- 0.9% in untreated control infarcts (2P = 0.029). Plasma viscosity was slightly reduced in SK-treated dogs (2P = 0.05), but no significant changes in blood fibrinogen, hemoglobin, blood flow, and high energy phosphate levels between control and SK-treated infarcts were observed. SK reduces congestion and results in more even reperfusion of the microvasculature in severely ischemic myocardium to which blood flow has been restored. This effect may be beneficial in the salvage and healing of clinical infarctions.

Animals↗
PubMed2000

Redefining medical treatment in the management of unstable angina.

In 1994, the Agency for Health Care Policy and Research sponsored the development of guidelines for diagnosing and managing patients with unstable angina. Since their publication, several important developments have occurred. The prognostic value of biochemical assays for cardiac-specific troponins T and I have been shown in many studies. The possible role for C-reactive protein in determining prognosis deserves further investigation. Substantial clinical benefits have been obtained with intravenous inhibitors of the platelet glycoprotein (GP) IIb-IIIa receptor (abciximab, eptifibatide, tirofiban) and with one of the low-molecular-weight heparins (enoxaparin). The therapeutic potential of other low-molecular-weight heparins, direct thrombin inhibitors, and oral GP IIb-IIIa inhibitors remains to be clarified. On the basis of this evidence, consideration should be given to measuring serum levels of a cardiac troponin (either T or I) and using intravenous GP IIb-IIIa inhibitors and low-molecular-weight heparin in the standard management of patients with unstable angina.

Abciximab↗
PubMed2000

Relationship between corrected TIMI frame counts at three weeks and late survival after myocardial infarction.

OBJECTIVES: To evaluate the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC) as a predictor of late survival after myocardial infarction. BACKGROUND: Thrombolysis in Myocardial Infarction flow grades predict late survival after myocardial infarction. The CTFC provides a more reproducible measurement of infarct-related artery blood flow than the TIMI flow grade, and has been linked to 30-day outcomes, but it has not yet been established how the CTFC correlates with late survival. METHODS: Of 1,001 patients with acute myocardial infarction presenting within 4 h of symptom onset, 882 underwent angiography at approximately three weeks. Infarct artery flow was assessed, blinded to clinical outcomes, according to the CTFC and TIMI flow grade. Late cardiac mortality and survival were determined in 97.5% of patients. RESULTS: The mean CTFC was 40 +/- 29 in 644 patent infarct arteries (median, 34 [interquartile range, 24 to 47]). The CTFC, assessed as a continuous univariate variable, was found to be a predictor of five-year survival, as was the TIMI flow grade (both p < 0.001). On multivariate analysis, factors associated with five-year survival included the ejection fraction or end-systolic volume index (both p < 0.001); exercise duration (p = 0.005), age (p = 0.008), diabetes (p = 0.02) and CTFC (p = 0.02) or TIMI flow (p = 0.02). The same factors, except for the CTFC and TIMI flow grade, were predictors of 10-year survival. CONCLUSIONS: The CTFC three weeks after myocardial infarction was an independent predictor of five-year survival, but not 10-year survival. Although the CTFC provided additional prognostic information within TIMI flow grades, its superiority was not demonstrated.

Adult↗
PubMed2000

Prevalence of factor V Leiden and prothrombin variant G20210A in patients age <50 years with no significant stenoses at angiography three to four weeks after myocardial infarction.

OBJECTIVES: We sought to determine the frequencies of factor V Leiden and prothrombin variant G20210A in patients age <50 years with no significant coronary stenoses three to four weeks after myocardial infarction (MI). BACKGROUND: Factor V Leiden and prothrombin variant G20210A occur frequently in patients with venous thromboembolism. However, the contribution of these mutations to the development of MI requires clarification. METHODS: The frequencies of factor V Leiden and prothrombin variant G20210A were determined in 41 patients age <50 years who had "normal" or "near normal" coronary arteries (no stenosis >50%) at angiography three to four weeks after MI (the study group) and compared with those in 114 patients who had at least one angiographic stenosis >50% after MI (the control group). Patients age > or =50 years with, or without, stenoses were also studied. RESULTS: The frequency of factor V Leiden was 14.6% in patients age <50 years in the study group compared with 3.6% in patients in the control group (odds ratio [OR] 4.7 [95% confidence interval (CI) 1.3-17.7], p = 0.02). The frequency of the prothrombin variant G20210A was 7.3% in the study group compared with 1.8% in the control group (OR 4.4 [95% CI 0.7-27.5], p = 0.12). One or both mutations were present in 8 of the 41 patients (19.5%) age <50 years in the study group compared with 6 of the 114 patients (5.5%) in the control group (OR 4.4 [95% CI 1.4-13.5], p = 0.01). In all 271 patients (irrespective of age) with normal arteries, the frequency of factor V Leiden was 11.7% (7/60) compared with 4.3% (9/211) in patients with at least one >50% stenosis (OR 2.9 [95% CI 1.1-8.3], p = 0.04), and the frequency of prothrombin variant G20210A was 6.7% (4/60) compared with 1.4% (3/211) (OR 4.9 [95% CI 1.1-22.8], p = 0.04), respectively. CONCLUSIONS: The frequencies of factor V Leiden and/or prothrombin variant G20210A are increased in patients age <50 years with normal or near normal coronary arteries after MI.

Aged↗
PubMed2000

Implications of the timing of onset of cardiogenic shock after acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to examine the implications of the timing of onset of cardiogenic shock (CS) after acute myocardial infarction (MI). BACKGROUND: Little information is available about the relationships between timing, clinical substrate, management and outcomes of shock. METHODS: The multinational SHOCK Trial Registry enrolled MI patients with CS from 1993 to 1997. Cardiogenic shock was predominantly attributable to left ventricular (LV) failure in 815 Registry patients for whom temporal data were available. We examined factors related to the timing of shock onset and the relation of temporal onset to in-hospital outcomes. RESULTS: Overall, shock developed a median of 6.2 h after MI symptom onset. Shock onset varied by culprit artery: left main, median 1.7 h; right, 3.5 h; circumflex, 3.9 h; left anterior descending (LAD), 11.0 h; saphenous vein graft, 10.9 h (p = 0.025). Early shock (< 24 h) occurred in 74.1% and was associated with chest pain at shock onset, ST-segment elevation in two or more leads, multiple infarct locations, inferior MI, left main disease and smoking. Late shock (> or = 24 h) was associated with recurrent ischemia, Q waves in two or more leads and LAD culprit vessel. Mortality was higher in patients with early versus late shock (62.6% vs. 53.6%, p = 0.022). CONCLUSIONS: Shock onset after acute MI occurred within 24 h in 74% of the patients with predominant LV failure. Mortality was slightly higher in patients developing shock early rather than later. Many factors influence when shock develops, which has implications for its management.

Aged↗
PubMed2000

Cardiogenic shock complicating acute myocardial infarction--etiologies, management and outcome: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: This SHOCK Study report seeks to provide an overview of patients with cardiogenic shock (CS) complicating acute myocardial infarction (MI) and the outcome with various treatments. The outcome of patients undergoing revascularization in the SHOCK Trial Registry and SHOCK Trial are compared. BACKGROUND: Cardiogenic shock is the leading cause of death in patients hospitalized for acute MI. The randomized SHOCK Trial reported improved six-month survival with early revascularization. METHODS: Patients with CS complicating acute MI who were not enrolled in the concurrent randomized trial were registered. Patient characteristics were recorded as were procedures and vital status at hospital discharge. RESULTS: Between April 1993 and August 1997, 1,190 patients with CS were registered and 232 were randomized in the SHOCK Trial. Predominant left ventricular failure (78.5%) was most common, with isolated right ventricular shock in 2.8%, severe mitral regurgitation in 6.9%, ventricular septal rupture in 3.9% and tamponade in 1.4%. In-hospital Registry mortality was 60%, with ventricular septal rupture associated with a significantly higher mortality (87.3%) than all other categories (p < 0.01). The risk profile and mortality were lower for Registry patients who were managed with thrombolytic therapy and/or intra-aortic balloon counter-pulsation, coronary angiography, angioplasty and/or coronary artery bypass surgery. After adjusting for these differences, the extent to which survival was improved with early revascularization was similar to that observed in the randomized SHOCK Trial. CONCLUSIONS: In this prospective Registry the etiology of CS was a mechanical complication in 12%. The similarity of the beneficial treatment effect in patients undergoing early revascularization in the SHOCK Trial Registry and SHOCK Trial provides strong support for the generalizability of the SHOCK Trial results.

Aged↗
PubMed2000

Serum troponins T and I after elective cardioversion.

AIMS: To describe the pattern of release of five myocardial proteins after elective cardioversion. METHODS AND RESULTS: We measured serum levels of the myocardial proteins creatine kinase, creatine kinase MB mass, myoglobin, troponin T and troponin I serially from baseline to 24 h after 72 elective cardioversion attempts. The total energy used for attempted cardioversion was 408+/-318 J (range 50 to 1280 J). Maximal creatine kinase levels (median 232 IU x l(-1), interquartile range 91 to 1152 IU x l(-1)) occurred at 24 h and correlated with the total energy delivered (r=0.75, P<0.0001). The peak creatine kinase MB mass levels exceeded the discrimination level for myocardial injury (>/=5 microg x l(-1)) in seven patients (10%). The peak myoglobin levels were elevated (>85 microg x l(-1)) in 40 patients (56%) and correlated with the peak creatine kinase levels (r=0.83, P<0.0001). Troponin T reached the discrimination level (0.10 microg x l(-1)) in one patient with a serum creatinine level of 0.16 mmol x l(-1)and severe left ventricular impairment. Twelve patients had baseline troponin I levels above our prespecified discrimination level of 0.4 microg x l(-1)(range 0.4 to 3.1 microg x l(-1)), which did not increase after cardioversion. In two patients the levels rose from <0.4 microg x l(-1) to 0.5 microg x l(-1) and 0.6 microg x l(-1) respectively. CONCLUSIONS: Troponin T levels do not rise after elective cardioversion. The minor increases in troponin I may reflect our choice of discrimination level. Cardiac troponins are useful in determining whether arrhythmias requiring emergency cardioversion are primary or secondary to myocardial infarction.

Atrial Fibrillation↗
PubMed2000

New Q waves on the presenting electrocardiogram independently predict increased cardiac mortality following a first ST-elevation myocardial infarction.

AIMS: The prognostic significance of pathological Q waves appearing in the acute phase of myocardial infarction has not been determined. We investigated whether new Q waves on the presenting electrocardiogram of patients with acute ST-segment elevation were independently associated with a worse outcome after a first myocardial infarction. METHODS AND RESULTS: The presence or absence of new Q waves on the presenting electrocardiogram was assessed in 481 patients who presented within 4 h of symptom onset and were randomized to receive either captopril or placebo within 2 h of streptokinase therapy for myocardial infarction. Ventriculography was performed at 22+/-6 days and mortality status was obtained at a median follow-up of 5.6 years. New Q waves were associated with a lower ejection fraction (51+/-13% vs 61+/-12%, P<0.0001), a larger end-systolic volume index (37 ml vs 28 ml, P<0.001), and increased cardiac mortality at 30 days (7% vs 2%, P=0.01) and at follow-up (17% vs 7%, P=0.002). On multivariate analysis, age (P<0.01), new Q waves at presentation (P<0.01) and a history of angina (P=0.046) were independent predictors of cardiac mortality, whereas randomization to captopril and the time from symptom onset to streptokinase administration were not. CONCLUSION: New Q waves at presentation are independently associated with a worse outcome after a first myocardial infarction. The presence of new Q waves on the presenting electrocardiogram allows very early identification of patients at risk of increased cardiac mortality.

Aged↗