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Biomedical subjects

H K Gold

Publications and source records attributed to H K Gold.

At least 91 records · Page 5Linked to original sources
PubMed1986

Digoxin therapy and mortality after myocardial infarction. Experience in the MILIS Study.

Recent studies have led to controversy about whether long-term digoxin therapy after confirmed or suspected myocardial infarction increases mortality. We analyzed the mortality experience in 903 patients enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS). As in previous studies, the decision to treat or not to treat with digoxin was made by the patient's personal physician on the basis of the usual clinical indications. Cumulative mortality was 28 percent for the 281 digoxin-treated patients as compared with 11 percent for the 622 patients who did not receive digoxin (P less than 0.001; follow-up interval, six days to 36 months; mean, 25.1 months). However, patients treated with digoxin had more base-line characteristics predictive of mortality than did their counterparts. Adjustment for these differences with two separate applications of the Cox method yielded P values of 0.14 and 0.34 for tests of difference in mortality, providing no evidence for a significant excess mortality associated with digoxin. Thus, the findings in the MILIS population do not support the assertion that digoxin therapy is excessively hazardous after infarction, but the existence of an undetected harmful effect can only be excluded with a randomized study. Until the results of such a study are available, we recommend careful consideration of whether any treatment of ventricular dysfunction is actually needed, consideration of alternatives to digoxin therapy, and restriction of digoxin use to the subgroup of patients (with severe chronic congestive failure and a dilated left ventricle) previously shown to have a beneficial clinical response.

Clinical Trials as Topic↗
PubMed1986

Anterior ST segment depression in acute inferior myocardial infarction as a marker of greater inferior, apical, and posterolateral damage.

The clinical significance of anterior precordial ST segment depression during acute inferior myocardial infarction was evaluated in 67 consecutive patients early after onset of symptoms with gated blood pool scans, thallium-201 perfusion images, and 12-lead ECGs. Patients with anterior ST depression (n = 33) had depressed mean values for left ventricular ejection fraction (54 +/- 2% [mean +/- S.E.M.] vs 59 +/- 2%; p = 0.02), cardiac index (3.1 +/- 0.2 vs 3.6 +/- 0.2 L/m2; p = 0.03), and ratio of systolic blood pressure to end-systolic volume (2.0 +/- 0.1 vs 2.5 +/- 0.3 mm Hg/ml; p = 0.04) compared to patients with no anterior ST depression (n = 34). Patients with anterior ST depression had (1) lower mean wall motion values for the inferior, apical, and inferior posterolateral segments (p less than 0.05) and (2) greater reductions in thallium-201 uptake in the inferior and posterolateral regions (p less than 0.05). However, anterior and septal (1) wall motion and (2) thallium-201 uptake were similar in patients with and without ST depression. Thus, anterior precordial ST segment depression in patients with acute inferior wall myocardial infarction represents more than a reciprocal electrical phenomenon. It identifies patients with more severe wall motion impairment and greater hypoperfusion of the inferior and adjacent segments. The poorer global left ventricular function in these patients is a result of more extensive inferior infarction and not of remote septal or anterior injury.

Electrocardiography↗
PubMed1986

Incidence, severity and clinical course of right ventricular involvement after acute inferior myocardial infarction; assessment by sequential 99Tcm-pyrophosphate scan and gated blood pool scan.

To evaluate the incidence, severity and clinical course of right ventricular (RV) involvement after acute inferior myocardial infarction (IMI), 78 patients (pts) with IMI were investigated by both 99Tcm-pyrophosphate (PYP) scan and gated blood pool scan (GBPS). GBPS was performed at admission and 10 days, whereas 99Tcm-PYP scan was performed at 3 to 6 days. RV uptake of PYP was demonstrated in 25 (32%) pts on 99Tcm-PYP scan and RV akinesis or moderate hypokinesis by GBPS was observed in 39 (50%) pts on the acute scan; 25 pts (Group A) with positive RV uptake and 14 pts (Group B) with no RV uptake. In the remaining 39 pts (Group C) had normal RV wall motion. Severely depressed RVEF improved nearly 10 points on the tenth day in Group A (from 30.8 +/- 12.3 to 40.9 +/- 6.7%, p less than 0.01) and Group B (from 35.6 +/- 8.2 to 44.5 +/- 10.5%, p less than 0.01), respectively. Group C showed normal RVEF (from 47.4 +/- 7.6 to 50.1 +/- 10.2%). Fourteen pts of 39 (Groups A and B) who had developed shock or hypotension improved strikingly after appropriate therapy except for one death during their hospital course. Our data demonstrated: some patients with RV dysfunction in IMI do not have severe necrosis as judged by PYP scanning, those with positive RV uptake and depressed RV function show a lower degree of recovery than those with no RV uptake, but start from a lower initial value of RV function, and the combination of 99Tcm-PYP scan and GBPS offers prognostic information in IMI with RV dysfunction.

Adult↗
PubMed1986

Acute coronary reocclusion after thrombolysis with recombinant human tissue-type plasminogen activator: prevention by a maintenance infusion.

Twenty-nine patients with acute myocardial infarction were treated with recombinant human tissue-type plasminogen activator (rt-PA). The incidence of acute coronary reocclusion and its prevention by a maintenance infusion of rt-PA were studied. Intravenous rt-PA was given at a rate of 0.4 to 0.75 mg/kg over 60 to 120 min after angiographic documentation of complete coronary occlusion. Reperfusion was accomplished within 1 hr in 24 of 29 patients (83%) and was associated with a decrease of the plasma fibrinogen level by 20%. In a first group of 13 patients, 11 of whom were successfully reperfused, prevention of reocclusion was attempted with heparin anticoagulation. However, acute reocclusion within 1 hr after cessation of rt-PA was demonstrated angiographically in five of these patients (45%). Quantitative angiographic analysis indicated that acute reocclusion only occurred in patients with 80% or greater residual stenosis. In patients with less than 80% residual stenosis, heparin anticoagulation was sufficient to maintain patency during the hospital stay in four of five patients. In a second group of patients (n = 16), 13 of whom underwent reperfusion with intravenous rt-PA, seven demonstrated a residual stenosis of 80% or greater. These patients were given heparin and, in addition, 10 mg of rt-PA per hour for 4 hr. None developed acute angiographic reocclusion or clinical signs of reocclusion during the hospital stay. Repeat angiography at 10 to 14 days confirmed persistent patency in six of the seven patients. The maintenance infusion resulted in only a moderate additional drop in fibrinogen, while a steady-state plasma rt-PA level of 750 +/- 250 ng/ml was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1986

Scintigraphic quantification of myocardial necrosis in patients after intravenous injection of myosin-specific antibody.

The Fab fragments of antimyosin antibodies, labeled with 99mTc, were used in the scintigraphic examination of 30 patients with myocardial infarction. The ability to detect necrosis and determine its extent from the antimyosin scan were compared with the results of quantitative regional wall motion analysis by contrast ventriculography at 10 to 14 days and 99mTc-pyrophosphate imaging. Antimyosin images recorded by planar and single photon-emission computed tomography (SPECT) delineated areas of myocardial necrosis in 27 of 30 patients (90%) compared with a 91% sensitivity of pyrophosphate in 21 of 23 patients. Infarct size was determined by both antimyosin and pyrophosphate SPECT images. Results by both techniques showed a significant correlation with computer-derived hypokinetic segment length (r = .79 for both, p = .002) and peak creatine kinase (r = .9 for both, p less than .01). Although sensitivity for and correlations with markers of necrosis were similar with both techniques, infarct size by pyrophosphate SPECT was 1.7 times larger than infarct size by antimyosin SPECT (p less than .01). Certain zones in the infarct area were differentially labeled; the nature and irreversibility of injury within these zones remains to be clarified.

Antibodies↗
PubMed1984

Diagnosis of acute myocardial infarction by detection of circulating cardiac myosin light chains.

A radioimmunoassay for human cardiac myosin light chains (CM-LC) was developed and evaluated as a selective diagnostic test for acute myocardial infarction (AMI). The assay had a sensitivity of 1.0 ng/ml (+/- 2 standard deviations) in serum. Eighty-three patients with confirmed AMI all showed an elevated plasma concentration of CM-LC at some time during the course of their illness. Of 9 patients from whom early blood samples were obtained, 7 had diagnostic concentrations within 6 hours from the onset of chest pain. Only 2 had an elevated total creatine kinase level at this time. CM-LC concentrations peaked on days 2 to 4, but remained elevated in patients with large AMIs for more than 1 week. In preinfarction syndrome, 8 of 15 patients had elevated CM-LC levels at least once. Of 15 patients with stable angina pectoris, only 1 patient, who had congestive heart failure, showed elevated light chain levels. CM-LC levels were not detectable by this method in the sera of healthy persons (n = 72), patients with recent intramuscular injection (n = 3), or those with a variety of systemic illnesses (n = 14). In initial studies using an antiserum having 25% cross-reactivity between cardiac and skeletal muscle myosin light chains, 3 patients who had extensive skeletal muscle damage appeared to have elevated concentrations. Patients with this finding have not yet been examined with a more specific antiserum (8% cross-reactivity).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Usefulness of intravenous propranolol in predicting left anterior descending blood flow during anterior myocardial infarction.

The effect of propranolol on precordial ST-segment elevation was studied in 24 patients with acute anterior myocardial infarction. The electrocardiographic response to the drug was correlated with the early angiographic appearance of the left anterior descending coronary artery (LAD). After a 30-minute observation period, intravenous propranolol (average dose 3.5 +/- 2.2 mg) was given a mean of 2.8 +/- 1.9 hours after the onset of persistent chest pain. Coronary angiography was performed 3.6 +/- 2.0 hours after the onset of symptoms. Patients were classified into 2 groups according to the angiographic findings. Group A consisted of 7 patients with a stenotic but patent LAD and 1 patient with excellent collateral blood flow to that area. Group B consisted of 16 patients with a completely occluded LAD and poor or absent collateral blood flow. Patients in group A showed a mean reduction in precordial ST-segment elevation of 77 +/- 18% and patients in group B showed a mean reduction of 13 +/- 14% (p less than 0.005). Left ventricular ejection fraction at discharge was 0.6 +/- 0.07 in group A and 0.37 +/- 0.08 in group B (p less than 0.001). Thus, the electrocardiographic response to intravenous propranolol given early in the course of acute anterior myocardial infarction predicts the presence of blood flow to the infarcting zone. The combination of residual blood flow and reduction of ST-segment elevation secondary to propranolol is associated with preservation of ventricular function.

Blood Pressure↗
PubMed1984

Effect of propranolol on myocardial-infarct size in a randomized blinded multicenter trial.

A multicenter randomized single-blind study was performed to evaluate the effects of propranolol administered during the evolution of myocardial infarction. Five centers enrolled a total of 269 patients, with 134 receiving propranolol and 135 placebo. Propranolol or placebo was given intravenously upon randomization (0.1 mg per kilogram of body weight) and then orally for nine days to keep the heart rate between 45 and 60 beats per minute. Less than 2 per cent of patients were treated within 4 hours after the onset of symptoms, but 50 per cent received therapy within 8 hours of onset of chest pain, and the remainder between 8 and 18 hours. The heart rates in the propranolol-treated group were significantly lower than those in the placebo group (P less than 0.001). Base-line characteristics, including the mean heart rate (79.6 vs. 81.3) and the left ventricular ejection fraction (49.0 vs. 49.5), were similar in the two groups. The primary end point evaluated--infarct size as estimated from plasma MB creatine kinase activity--was virtually identical in the two groups, averaging 13.3 and 13.6 gram-equivalents of MB creatine kinase per square meter of body-surface area. Peak plasma levels of the enzyme were also similar in the two groups. No significant difference was observed between the propranolol and placebo groups in the change in left ventricular ejection fraction, extent of area involved in pyrophosphate uptake, R-wave loss on electrocardiograms, or mortality (after three years). These results do not support the use of propranolol administered four or more hours after the onset of symptoms to limit infarct size.

Administration, Oral↗
PubMed1984

Combined intracoronary streptokinase infusion and coronary angioplasty during acute myocardial infarction.

PTCA was performed in 28 patients with acute MI immediately after intracoronary streptokinase administration. Indications were failure to obtain reflow in 16 patients and high-grade residual stenosis in 12. PTCA was successful in 11 of 16 cases of streptokinase failure, increasing the overall reflow rate from 66% to 77%. PTCA reduced residual coronary stenosis by more than 20% in 9 of 12 cases in which streptokinase infusion was successful, with 1 acute reocclusion. The frequency of recurrent ischemic events in hospital was 76% in patients with a stenosis of 90% or greater after streptokinase infusion (no PTCA), 14% when residual stenosis was less than 90%, and 6% after successful PTCA. Late restenosis or reocclusion was documented in 5 of 11 PTCA cases (45%). Immediate PTCA after streptokinase administration produces increased clinical stability in hospital, but late restenosis is frequent.

Angioplasty, Balloon↗
PubMed1984

Monoclonal antibody to cardiac myosin: imaging of experimental myocardial infarction.

Monoclonal antibody R11D10 to human cardiac myosin, which also cross-reacted with canine cardiac myosin, was used to demonstrate in vivo localization and visualization by gamma scintigraphy of experimental myocardial infarction. R11D10 Fab with a Ka of 5 X 10(8) M-1 was labeled with technetium-99m (99mTc) by the dithionite reduction method of technetium pertechnetate, via a bifunctional chelating agent, diethylene triamine pentaacetic acid (DTPA). Uptake of 99mTc R11D10 Fab in the infarct can be visualized as early as 2 h after intravenous administration. Comparison of R11D10 uptake to thallium-201, an analogue of potassium which is sequestered by normal myocardium, showed an inverse relation (r = -0.75, -0.87, -0.89), similar to that obtained with 125I labeled polyclonal antimyosin Fab. Ratios of R11D10 Fab in the infarct to normal myocardium were as high as 30:1 where access of antibody to antigen was not blood flow limited. However, with severe blood-flow restriction, the ratios were lower at about 10:1. Despite the theoretical limitation of a single epitope per myosin molecule available for binding by R11D10 Fab, the immense excess of myosin in the infarcted myocardium allowed adequate concentration of radiolabeled R11D10 for visualization of the infarct by external gamma scintiscanning.

Animals↗
PubMed1984

Coronary thrombolysis with recombinant human tissue-type plasminogen activator.

The thrombolytic potency and myocardial infarct--sparing potential of recombinant tissue-type plasminogen activator (rt-PA) were studied in electrocardiographically monitored, open-chest, anesthetized dogs. Localized coronary thrombosis was produced in the left anterior descending artery by endothelial injury and instillation of thrombin and fresh blood. After 2 hr of stable thrombotic occlusion, rt-PA was infused intravenously. At a dose of 4.3 micrograms/kg/min, time to reperfusion was greater than 40 min (n = 3). However, at higher infusion rates a linear, dose-dependent time to coronary reperfusion was obtained (r = .88): at 10 micrograms/kg/min reperfusion occurred after 31 +/- 2 min (n = 3), at 15 micrograms/kg/min it was at 26 +/- 7 min (n = 4), and at 25 micrograms/kg/min, lysis was accomplished within 13 +/- 3 min (n = 3). Thrombolysis was not associated with alterations in either plasma hemostatic factors (fibrinogen, plasminogen, and alpha 2-antiplasmin) or in systemic blood pressures. Epicardial electrographic measurements revealed a significant reduction in ST elevation in all reperfused hearts. A randomized, blinded study was also carried out with 15 micrograms/kg/min of rt-PA saline in 18 dogs with 30 min of coronary thrombosis. Reperfusion in the treated group occurred after 28 +/- 3 min. No evidence of thrombolysis was noted in the saline-treated group within 240 min. Size of myocardial infarction was determined by triphenyl tetrazolium chloride staining and planimetry. Infarction involved 2.5 +/- 0.5% of the left ventricular wall in the group receiving rt-PA, but 16 +/- 3% of the left ventricle in the saline-treated group (p = .001). It is concluded that intravenous infusion of rt-PA results in rapid, dose-dependent coronary thrombolysis without systemic fibrinolytic activation and that early lysis of coronary thrombi is associated with substantial salvage of myocardial tissue.

Animals↗
PubMed1984

Comparison of enzymatic and anatomic estimates of myocardial infarct size in man.

Enzymatic estimates of myocardial infarct size based on plasma levels of MB creatine kinase (MB-CK) were compared with anatomic infarct size in 49 human hearts obtained at autopsy. The patients studied had been enrolled in the Multicenter Investigation of Limitation of Infarct Size (MILIS) study program within 18 hr of the onset of acute infarction and were treated at one of five participating hospitals. Infarct size was estimated from serial measurements of plasma MB-CK made at the core laboratory for CK analysis. Hearts obtained at autopsy were studied independently by the core pathology laboratory without knowledge of the MB-CK levels or clinical results. Data from the two laboratories were compared at the data coordinating center. Of 49 hearts, 12 were excluded either because anatomic infarct size could not be established or because the infarct occurring at the time of enrollment in the MILIS study could not be distinguished with certainty from other infarcts. Of the remaining 37 hearts, peak MB-CK level was available in 36, but samples sufficient for estimation of infarct size were available in only 25. The overall correlation coefficient (Spearman) was .87 for these 25 hearts, indicating that enzymatic estimates of infarct size correlate closely with anatomic measurements. The results indicate that CK estimates of myocardial infarct size represent a valid clinical end point for assessing myocardial infarct size, and the effect of therapy thereon, in groups of treated and control patients.

Autopsy↗
PubMed1984

Coronary thrombolysis with recombinant human tissue-type plasminogen activator: a prospective, randomized, placebo-controlled trial.

Forty-five patients with acute transmural myocardial infarction and angiographically confirmed complete coronary occlusion were prospectively randomized, two for one, to treatment of acute coronary thrombosis with intravenous recombinant human tissue-type plasminogen activator (rt-PA) or placebo. Each of five additional consecutive patients was treated with a high dose of rt-PA for 2 hr. Twenty-five of 33 patients (75%) receiving 0.5 to 0.75 mg/kg of rt-PA over 30 to 120 min had angiographically proven recanalization within 90 min of initiation of therapy. Only one of 14 patients given placebo had spontaneous recanalization within 45 min (p less than .001). Thirteen placebo-treated patients were crossed over to the intracoronary rt-PA group. Nine (69%) exhibited subsequent recanalization within 45 min. Levels of circulating fibrinogen decreased after treatment with rt-PA by an average of only 8% of baseline values. None of the patients manifested a depletion of fibrinogen level to below 100 mg/dl. Six patients who were completely unresponsive to rt-PA were subsequently treated with intracoronary streptokinase and none responded. Thus, either intravenous or intracoronary rt-PA induced coronary thrombolysis without eliciting clinically significant fibrinogenolysis in patients with evolving myocardial infarction due to thrombotic coronary occlusion.

Arteriosclerosis↗
PubMed1983

Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients.

Over a 34.5-month period, all admissions to 5 university hospital coronary care units were screened for eligibility for the Multicenter Investigation of the Limitation of Infarct Size (MILIS), an ongoing study of the effects of hyaluronidase, propranolol and placebo on myocardial infarct (MI) size. Of 3,697 patients with greater than or equal to 30 minutes of discomfort that was thought to reflect myocardial ischemia who were assessed for the presence or absence of certain electrocardiographic abnormalities at the time of hospital admission, the electrocardiogram was considered predictive of acute MI if greater than or equal to 1 of the following abnormalities was present: new or presumably new Q waves (greater than or equal to 30 ms wide and 0.20 mV deep) in at least 2 of the 3 diaphragmatic leads (II, III, aVF), or in at least 2 of the 6 precordial leads (V1 to V6), or in I and aVL; new or presumably new ST-segment elevation or depression of greater than or equal to 0.10 mV in 1 of the same lead combinations; or complete left bundle branch block. In the screened population, the diagnostic sensitivity of the electrocardiographic criteria was 81%, whereas the overall infarct rate in the total population screened was 49%. The diagnostic specificity of these entry criteria was 69% and the predictive value 72%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Relation of segmental wall motion to global left ventricular function in acute myocardial infarction.

The relation of left ventricular regional wall motion to global ventricular function was evaluated by radionuclide ventriculography in 127 patients within 18 hours of acute myocardial infarction. No patient had evidence of previous myocardial infarction. The following parameters were measured: (1) wall motion index; (2) percent of abnormally contracting segment; (3) ejection fraction (EF); (4) end-diastolic volume (EDV) and end-systolic volume (ESV); and (5) peak systolic cuff pressure/end-systolic volume ratio (PSP/ESV). The measurements of global function correlated well with wall motion index (r = 0.83, p less than 0.001 for EF; r = -0.69, p less than 0.001 for ESV; and r = 0.061, p less than 0.001 for PSP/ESV), but EDV correlated less well (r = -0.35, p less than 0.001). Multiple linear regression analysis revealed that EF correlated best with wall motion index, and no other parameters of global left ventricular function added significantly to the regression. The correlation of motion in each segment with EF was determined by multiple linear regression analysis. Ejection fraction correlated best with motion in the anterobasal, then in order of correlation, in the apical-septal, inferoapical, anterolateral, and superlateral walls. The relation of EDV, ESV, and degree of percent abnormally contracting segments was as follows: EDV did not increase with a mild regional wall motion abnormality; however, ESV did increase and reduced stroke volume. As percent abnormally contracting segments worsened, enlargement of both EDV and ESV was seen and was associated with further reduction in systolic volume. These data suggest that EF is the best global left ventricular function correlate of the severity of the regional wall motion abnormality, and that abnormal motion in the territory of the left anterior descending coronary best predicts reduction in global left ventricular function. Radionuclide ventriculography is useful in characterizing global and regional left ventricular function in the early hours of acute myocardial infarction.

Aged↗
PubMed1983

Enzymatic estimation of myocardial infarct size when early creatine kinase values are not available.

Estimates of myocardial infarct (MI) size based on plasma creatine kinase (CK) are used widely for prognosis and in the assessment of therapy designed to salvage ischemic myocardium. However, if the initial plasma CK activity is elevated, MI size will be underestimated. To determine the impact of loss of early CK values on estimates of MI size and to develop a procedure to compensate for it, estimates of MI size based on complete and incomplete MB and total CK time-activity curves from 120 patients (experimental group) were compared. Estimates of MI size based on data inclusion intervals beginning at 24, 12, 8, and 4 hours before peak CK were 11, 14, 23, and 47% smaller than values based on complete CK curves, but the correlation was good between complete and incomplete estimates of MI size at any given interval, with r values ranging from 0.91 to 0.98. The derived correction factors were then prospectively applied to a new population (n = 25) with complete CK curves to compensate for purposely omitted early CK values. The corrected estimates of MI size were within 7% of those based on the complete CK curves. Similar results were obtained for transmural and nontransmural and anterior or inferior MI. Thus, if peak plasma CK is known, underestimation of MI size can be compensated for despite the unavailability of early CK values. Since greater than 90% of patients present before plasma CK has reached its peak (24 hours), MI size can be obtained in nearly all patients. Thus, being able to correct for unavailable early CK values makes MI size a more widely applicable endpoint for use in clinical trials and patient management.

Aged↗
PubMed1983

Coronary reocclusion after selective administration of streptokinase.

Intracoronary streptokinase was given to 40 patients with acute transmural myocardial infarction. In 34 of the patients (85%), it resulted in reflow or improved flow. Six patients showed no reflow and six reocclusion within 2 hours. No consistent explanation was found for this resistance to therapy. Five other patients developed reocclusion after 6 days to 11 months, when heparin or warfarin anticoagulation had been stopped. Percutaneous angioplasty at the time of streptokinase infusion was performed in seven, with six successes. Bypass surgery was performed after successful streptokinase administration in eight. Follow-up revealed recurrent ischemia in patients successfully treated with streptokinase alone, but not in patients with successful angioplasty or bypass surgery. Long-term coronary patency after thrombolysis may require careful anticoagulation or a procedure that modifies or bypasses the residual stenosis.

Angioplasty, Balloon↗