Consensus guidelines for interventional cardiology services delivery during covid-19 pandemic in Australia and new Zealand.

The global coronavirus disease (COVID-19) pandemic poses an unprecedented stress on healthcare systems internationally. These Health system-wide demands call for efficient utilisation of resources at this time in a fair, consistent, ethical and efficient manner would improve our ability to treat patients. Excellent co-operation between hospital units (especially intensive care unit [ICU], emergency department [ED] and cardiology) is critical in ensuring optimal patient outcomes. The purpose of this document is to provide practical guidelines for the effective use of interventional cardiology services in Australia and New Zealand. The document will be updated regularly as new evidence and knowledge is gained with time. Goals Considerations.

Long-term outcomes in patients with restrictive filling following ST-segment elevation myocardial infarction.

This study evaluated the effect of restrictive filling pattern (RFP) on 5-year outcomes in patients following ST-segment elevation myocardial infarction (STEMI). A hundred STEMI patients treated either by rescue or primary percutaneous coronary intervention with an echocardiogram performed within 6 weeks of STEMI comprised the study group. Creatinine kinase (CK) and left ventricular ejection fraction were independent determinants of RFP, and RFP was an independent predictor of cardiac and all-cause mortality at median follow up of 5 years.

Nephrotoxic effects of iodixanol and iopromide in patients with abnormal renal function receiving N-acetylcysteine and hydration before coronary angiography and intervention: a randomized trial.

BACKGROUND: The use of contrast agents during coronary intervention can result in nephropathy, particularly in patients with renal dysfunction. We aimed to determine whether the use of iso-osmolar iodixanol is less nephrotoxic than that of low-osmolar iopromide when patients are adequately prehydrated and have received N-acetylcysteine. METHODS: We conducted a randomized, double-blind, multicentre study of patients with impaired renal function undergoing a coronary interventional procedure. Primary end-point was the incidence of contrast-induced nephropathy (CIN) on day 2, defined as an increase in serum creatinine concentration of > or =44 micromol/L (0.5 mg/dL) or by a relative increase of > or =25% from baseline. Secondary end-points included peak increase in serum creatinine between baseline and day 7. RESULTS: Of 191 patients recruited, 15% (95% CI: 8-22) of the patients receiving iopromide and 12% (95% CI: 5-19) of the patients receiving iodixanol developed CIN (95% CI of the difference: 13 to -7, P = 0.56). When including peak serum creatinine on day 7, CIN developed in 23% of patients receiving iopromide and in 27% of patients receiving iodixanol (95% CI of the difference: 8 to -16, P = 0.48). The peak increase in serum creatinine concentration at day 7 was similar in both groups (patients receiving iopromide, 18.4 +/- 24.4 micromol/L, vs patients receiving iodixanol, 21.9 +/- 24.2 micromol/L; P = 0.33). CONCLUSION: There remains a high incidence of CIN despite prehydration and routine use of N-acetylcysteine in patients with pre-existing renal dysfunction undergoing coronary interventional procedures. Although our study is underpowered, iodixanol was not associated with a statistically significant lower incidence of CIN when compared with iopromide.

The pharmaco-invasive approach to STEMI: when should fibrinolytic-treated patients go to the "cath lab"?

Although primary percutaneous coronary intervention (PCI) in clinical trials has lower rates of reinfarction, stroke and mortality than fibrinolytic therapy, because of system delays in routine practice, field triage and prehospital administration of fibrinolytic therapy may lead to similar clinical outcomes, especially in those patients who present in the first 2 h after symptom onset. Necessary for these outcomes is the liberal use of both rescue PCI and in-hospital revascularisation. Non-invasive prediction of failed reperfusion may be enhanced by the use of ST recovery, patient characteristics and troponin T levels, measured by point-of-care assays. This review focuses on the timing of, and indications for, an invasive strategy after fibrinolytic therapy, including that for failed pharmacological reperfusion.

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.

Early noninvasive identification of failed reperfusion after intravenous thrombolytic therapy in acute myocardial infarction.

OBJECTIVES: This study sought to evaluate a biochemical approach to the early noninvasive assessment of reperfusion. BACKGROUND: In patients with an acute myocardial infarction, a rapid noninvasive method of detecting failure of intravenous thrombolytic therapy to restore early Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery (IRA) is needed. METHODS: Serial blood samples were collected to assay creatine kinase-MB fraction (CKMB mass), cardiac troponin T and myoglobin concentrations in 105 patients with a myocardial infarction who underwent early angiography after intravenous streptokinase. The ratios of the 60- and 90-min concentrations to prethrombolytic values were used to determine an index that could identify failure to achieve TIMI grade 3 flow in the IRA at 90 min. RESULTS: Significant increases in serum concentrations of markers at 60 min were more likely with TIMI grade 3 flow (59 patients) than with TIMI grade 0 to 2 flow (46 patients). Ratios < or = 5 at 60 min after thrombolysis detected failure to achieve 90-min TIMI grade 3 flow with 92% to 97% sensitivity, 43% to 60% specificity and 63% to 76% positive and 86% to 94% negative predictive values. Ratios < or = 10 at 90 min showed 88% to 95% sensitivity, 49% to 65% specificity and 61% to 69% positive and 86% to 94% negative predictive values for TIMI flow grade < 3. The overall predictive values were thus similar for all three markers. CONCLUSIONS: In acute myocardial infarction treated with intravenous streptokinase, a simple measurement of increased serum concentrations of CKMB mass, cardiac troponin T or myoglobin at 60 and 90 min can accurately predict failure to achieve TIMI grade 3 flow in the IRA at 90 min.

Survival 12 years after randomization to streptokinase: the influence of thrombolysis in myocardial infarction flow at three to four weeks.

OBJECTIVES: The purpose of this study was to determine whether the mortality benefit of intravenous streptokinase administered within 4 h of the onset of acute myocardial infarction is maintained at 12 years, and whether Thrombolysis in Myocardial Infarction (TIMI) flow grades independently influence late survival. BACKGROUND: Treatment with reperfusion therapies and achievement of TIMI 3 flow are associated with increased short- and medium-term survival after infarction. Whether infarct artery flow independently influences survival more than five years after infarction is unknown. METHODS: The late survival of patients randomized to receive either streptokinase (1,500,000 IU over 30 to 60 min) or a matching placebo within 4 h of symptom onset in 1984-1986 was determined. Angiography was performed in surviving patients at three to four weeks, and TIMI flow grades were assessed blind to randomization and outcomes. The late vital status was determined in 99% of patients. RESULTS: Patients randomized to receive streptokinase (n = 107) had improved survival compared with those randomized to placebo (n = 112) at five years (84% vs. 70%; p = 0.023) and 12 years (66% vs. 51%; p = 0.022). At five years 94% of patients with TIMI grade 3 flow, 81% of those with TIMI grade 2 flow and 72% of those with TIMI grade 0-1 flow survived (p = 0.005). At 12 years 72% of patients with TIMI 3, 67% of those with TIMI 2 and 54% of those with TIMI 0-1 flow survived (p = 0.023). Multivariate analysis identified the ejection fraction (p = 0.014), exercise duration (p = 0.013) and TIMI 3 flow (p = 0.04 compared with TIMI 0-2 flow) as important factors for five-year survival. At 12 years multivariate predictors of late survival were the ejection fraction (p = 0.006), exercise duration (p = 0.003) and myocardial score (p = 0.013). The end-systolic volume index was similar to the ejection fraction as a predictor of survival at five and 12 years. CONCLUSIONS: The survival benefits of streptokinase persist for 12 years after infarction. TIMI flow at three to four weeks is an independent predictor of five-year survival.

Cardiogenic shock with non-ST-segment elevation myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK?

OBJECTIVES: We sought to determine the outcomes of patients with cardiogenic shock (CS) complicating non-ST-segment elevation acute myocardial infarction (MI). BACKGROUND: Such patients represent a high-risk (ST-segment depression) or low-risk (normal or nonspecific electrocardiographic findings) group for whom optimal therapy, particularly in the setting of shock, is unknown. METHODS: We assessed characteristics and outcomes of 881 patients with CS due to predominant left ventricular (LV) dysfunction in the SHOCK Trial Registry. RESULTS: Patients with non-ST-segment elevation MI (n = 152) were significantly older and had significantly more prior MI, heart failure, azotemia, bypass surgery, and peripheral vascular disease than patients with ST-elevation MI (n = 729). On average, the groups had similar in-hospital LV ejection fractions (approximately 30%), but patients with non-ST-elevation MI had a lower highest creatine kinase and were more likely to have triple-vessel disease. Among patients selected for coronary angiography, the left circumflex artery was the culprit vessel in 34.6% of non-ST-elevation versus 13.4% of ST-elevation MI patients (p = 0.001). Despite having more recurrent ischemia (25.7% vs. 17.4%, p = 0.058), non-ST-elevation patients underwent angiography less often (52.6% vs. 64.1%, p = 0.010). The proportion undergoing revascularization was similar (36.8% for non-ST-elevation vs. 41.9% ST-elevation MI, p = 0.277). In-hospital mortality also was similar in the two groups (62.5% for non-ST-elevation vs. 60.4% ST-elevation MI). After adjustment, ST-segment elevation MI did not independently predict in-hospital mortality (odds ratio, 1.30; 95% confidence interval, 0.83 to 2.02; p = 0.252). CONCLUSIONS: Patients with CS and non-ST-segment elevation MI have a higher-risk profile than shock patients with ST-segment elevation, but similar in-hospital mortality. More recurrent ischemia and less angiography represent opportunities for earlier intervention, and early reperfusion therapy for circumflex artery occlusion should be considered when non-ST-elevation MI causes CS.

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.

Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy.

OBJECTIVES: This study assessed the effect of the combination of aspirin and dipyridamole on patency of the infarct-related artery between 4 weeks and 1 year after myocardial infarction. BACKGROUND: Patency of the infarct-related artery is an important determinant of prognosis after myocardial infarction. The incidence of late reocclusion and the effects of antiplatelet therapy are unknown. METHODS: To investigate the importance of antiplatelet therapy for the prevention of late reocclusion, 215 patients who had a patent infarct-related artery 4 weeks after myocardial infarction were randomized in a double-blind manner to receive either a combination of 25 mg of aspirin and 200 mg of dipyridamole twice daily or placebo. One hundred fifty-four patients underwent further coronary arteriography 1 year later. RESULTS: At 1 year, 38 (25%) of 154 patients had reocclusion of the infarct-related artery; 18 (23%) of 79 patients receiving aspirin and dipyridamole had late reocclusion versus 20 (27%) of 75 who received placebo (p = NS). The rate of reocclusion was related to the severity of the residual coronary artery stenosis at 4 weeks (< 50% stenosis 9.2%; 50% to 69% stenosis 11.6%; 70% to 89% stenosis 30.4%; > or = 90% stenosis 70%, p < 0.01). The majority of reocclusions were silent, and only 17 (45%) of 38 were clinically associated with further infarction. There were no differences for a hierarchic end point of cardiac death, myocardial infarction or revascularization (14.8% aspirin and dipyridamole vs. 17.8% placebo). CONCLUSIONS: Late reocclusion of the patent infarct-related artery is a frequent event, occurring in 25% of patients. Antiplatelet therapy with the combination of aspirin and dipyridamole does not alter the overall rate of late reocclusion. Other strategies are required to reduce late reocclusion.

Angiographic findings and clinical correlates in patients with cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to delineate the angiographic findings, clinical correlates and in-hospital outcomes in patients with cardiogenic shock (CS) complicating acute myocardial infarction. BACKGROUND: Patients with CS complicating acute myocardial infarction carry a grave prognosis. Detailed angiographic findings in a large, prospectively identified cohort of patients with CS are currently lacking. METHODS: We compared the clinical characteristics, angiographic findings, and in-hospital outcomes of 717 patients selected to undergo angiography and 442 not selected, overall and by shock etiology: left or right ventricular failure versus mechanical complications. RESULTS: Patients who underwent angiography had lower baseline risk and a better hemodynamic profile than those who did not. Overall, 15.5% of the patients had significant left main lesions on angiography, and 53.4% had three-vessel disease, with higher rates of both for those with ventricular failure, compared with patients who had mechanical complications. Among patients who underwent angiography, those with ventricular failure had significantly lower in-hospital mortality than patients with mechanical complications (45.2% vs. 57.0%; p = 0.021). Importantly, for patients with ventricular failure, in-hospital mortality also correlated with disease severity: 35.0% for no or single-vessel disease versus 50.8% for three-vessel disease. Furthermore, mortality was associated with the culprit lesion location (78.6% in left main lesion, 69.7% in saphenous vein graft lesions, 42.4% in circumflex lesions, 42.3% in left anterior descending lesions, and 37.4% in right coronary artery lesions), and Thrombolysis In Myocardial Infarction (TIMI) flow grade (46.5% in TIMI 0/1, 49.4% in TIMI 2 and 26% in TIMI 3). CONCLUSIONS: Patients who underwent angiographic study in the SHOCK Trial Registry had a more benign cardiac risk profile, more favorable hemodynamic findings and lower in-hospital mortality than those for whom angiograms were not obtained. Patients with CS caused by ventricular failure had more severe atherosclerosis, and a different distribution of culprit vessel involvement but lower in-hospital mortality, than those with mechanical complications. Overall in-hospital survival correlates with the extent of coronary artery obstructions, location of culprit lesion and baseline coronary TIMI flow grade.

Impact of thrombolysis, intra-aortic balloon pump counterpulsation, and their combination in cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to investigate the potential benefit of thrombolytic therapy (TT) and intra-aortic balloon pump counterpulsation (IABP) on in-hospital mortality rates of patients enrolled in a prospective, multi-center Registry of acute myocardial infarction (MI) complicated by cardiogenic shock (CS). BACKGROUND: Retrospective studies suggest that patients suffering from CS due to MI have lower in-hospital mortality rates when IABP support is added to TT. This hypothesis has not heretofore been examined prospectively in a study devoted to CS. METHODS: Of 1,190 patients enrolled at 36 participating centers, 884 patients had CS due to predominant left ventricular (LV) failure. Excluding 26 patients with IABP placed prior to shock onset and 2 patients with incomplete data, 856 patients were evaluated regarding TT and IABP utilization. Treatments, selected by local physicians, fell into four categories: no TT, no IABP (33%; n = 285); IABP only (33%; n = 279); TT only (15%; n = 132); and TT and IABP (19%; n = 160). RESULTS: Patients in CS treated with TT had a lower in-hospital mortality than those who did not receive TT (54% vs. 64%, p = 0.005), and those selected for IABP had a lower in-hospital mortality than those who did not receive IABP (50% vs. 72%, p < 0.0001). Furthermore, there was a significant difference in in-hospital mortality among the four treatment groups: TT + IABP (47%), IABP only (52%), TT only (63%), no TT, no IABP (77%) (p < 0.0001). Patients receiving early IABP (< or = 6 h after thrombolytic therapy, n = 72) had in-hospital mortality similar to those with late IABP (53% vs. 41%, n = 64, respectively, p = 0.172). Revascularization rates differed among the four groups: no TT, no IABP (18%); IABP only (70%); TT only (20%); TT and IABP (68%, p < 0.0001); this influenced in-hospital mortality significantly (39% with revascularization vs. 78% without revascularization, p < 0.0001). CONCLUSIONS: Treatment of patients in cardiogenic shock due to predominant LV failure with TT, IABP and revascularization by PTCA/CABG was associated with lower in-hospital mortality rates than standard medical therapy in this Registry. For hospitals without revascularization capability, a strategy of early TT and IABP followed by immediate transfer for PTCA or CABG may be appropriate. However, selection bias is evident and further investigation is required.

Effects of early captopril administration after thrombolysis on regional wall motion in relation to infarct artery blood flow.

OBJECTIVES: To determine whether early administration of captopril lessens infarct zone regional wall motion abnormalities when infarct artery blood flow is abnormal. BACKGROUND: The interaction between angiotensin-converting enzyme (ACE) inhibitor therapy, ventricular function and infarct artery blood flow has not been well described. METHODS: A total of 493 patients aged < or = 75 years with first infarctions, presenting within 4 h of symptom onset, were randomized to receive 6.25 mg captopril, increasing to 50 mg t.d.s. or a matching placebo 2.1+/-0.4 h after commencing intravenous streptokinase (1.5 x 10(6) U over 30 to 60 min). Trial therapy was stopped 48 h prior to angiography at 3 weeks, to determine regional wall motion and infarct artery flow. RESULTS: There were no differences in ejection fractions or end-systolic volumes between patients randomized to receive captopril and those randomized to receive a placebo. Among patients with anterior infarction (n = 216), randomization to captopril resulted in fewer hypokinetic chords (40+/-13; vs. 44+/-13; p=0.028) and a trend toward fewer chords >2 SD below normal (26+/-17 vs. 30+/-17; p=0.052) in the infarct zone. In patients randomized to receive captopril who had anterior infarction and Thrombolysis in Myocardial Infarction (TIMI) 0-2, flow there were fewer hypokinetic chords (44+/-12 vs. 50+/-9; p=0.043) and a trend toward fewer chords >2 SD below normal (33+/-15 vs. 39+/-13; p=0.057). Patients receiving captopril who had anterior infarction and corrected TIMI frame counts > 27 had fewer hypokinetic chords (42+/-13 vs. 46+/-12; p=0.015) and fewer chords >2 SD below normal (27+/-17 vs. 32+/-17; p= 0.047). Captopril had no effect in patients with inferior infarction. There were 20 late cardiac deaths (median follow-up 4 years) in the captopril group and 35 in the placebo group (p=0.036). CONCLUSIONS: Randomization to receive captopril 2 h after streptokinase improved regional wall motion at 3 weeks. The greatest benefit was seen in patients with anterior infarction particularly when infarct artery blood flow is reduced.

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.

Phorbol 12-myristate 13-acetate, A23187 and L-adrenaline inhibit phospholipid methylation in human monocytes and lymphocytes. Inhibition is independent of oxyradical production and phospholipid hydrolysis.

The Ca++ ionophore A23187 and phorbol 12-myristate 13-acetate (PMA) caused dose-dependent inhibition of phospholipid (PL) methylation in unfractionated mononuclear cells (MNC), monocytes, and lymphocytes as measured by incorporation of 3H-methyl-groups from [3H-methyl]-L-methionine into phosphatidylcholine (PC), dimethyl phosphatidylethanolamine (PE), and monomethyl PE. This inhibitory effect did not correlate with monocyte superoxide release and was unaltered by the presence of either catalase and superoxide dismutase or the NADPH oxidase inhibitor, diphenylene iodonium (DPI), indicating that oxyradical-mediated oxidation of methionine was not the major cause of inhibition of PL methylation. Furthermore L-adrenaline, which elevates cAMP and does not stimulate superoxide release, also inhibited PL methylation. Inhibition by PMA was not due to reduction in intracellular levels of methionine or S-adenosyl methionine. A23187 caused reduction of S-adenosyl methionine levels only at 1 microM, and had no effect at lower concentrations. Inhibition of PL methylation was shown not to be due to phospholipase A2-dependent hydrolysis of newly methylated PL. Attempts to reverse the inhibitory effect of either A23187 or PMA with the putative protein kinase inhibitors W-7 and H-7 were inconclusive. The mechanism of inhibition of PL methylation by A23187 and PMA remains unclear, but does not appear to be due to oxidation of methionine or hydrolysis of newly methylated PL.

Calcium ionophore A23187 enhances human neutrophil superoxide release, stimulated by phorbol dibutyrate, by converting phorbol ester receptors from a low- to high-affinity state.

The calcium ionophore A23187 acted synergistically with phorbol dibutyrate (PDBu) to stimulate human neutrophil superoxide production. A23187 shortened the lag period and markedly increased the initial rate of neutrophil superoxide production induced by suboptimal concentrations of PDBu. 1 microM A23187 reduced the EC50 value for superoxide release from 56 to 8 nM PDBu. This effect of A23187 was correlated with enhanced binding of [3H]PDBu to its receptor and a reduction in the dissociation constant (Kd) from 27 to 10 nM, without altering the apparent total number of phorbol dibutyrate receptors. These actions of A23187 were abolished in the presence of EGTA or TMB-8, confirming a dependence on Ca2+.

Abnormal coronary flow in infarct arteries 1 year after myocardial infarction is predicted at 4 weeks by corrected Thrombolysis in Myocardial Infarction (TIMI) frame count and stenosis severity.

Because 24% to 30% of patent infarct-related arteries occlude in the year following thrombolytic therapy for acute myocardial infarction, angiographic factors including corrected Thrombolysis in Myocardial Infarction (TIMI) frame count which may predict abnormal infarct-artery flow, require definition. We examined changes in coronary flow and infarct-artery lesion severity by computerized quantitative angiography over 1 year in 154 patients with a patent infarct-related artery 4 weeks after myocardial infarction. These patients were randomized to receive either ongoing daily therapy of 50 mg aspirin and 400 mg dipyridamole, or placebo. All angiograms were interpreted blind in our core angiographic laboratory. Infarct-artery flow, assessed by corrected TIMI frame counts, was normal (< or = 27) in 46% and 45% of patients at 4 weeks and 1 year, respectively. At 4 weeks, patients with corrected TIMI frame counts < or = 27 had higher ejection fractions (60+/-11% vs 56+/-12%; p = 0.04) than those with corrected TIMI frame counts >27. On multivariate analysis, corrected TIMI frame count and stenosis severity were predictive of late abnormal infarct-artery flow (TIMI 0 to 2 flow, both p <0.01). Only stenosis severity at 4 weeks predicted reocclusion at 1 year (p <0.0001). Aspirin and dipyridamole had no effect on flow or reocclusion. Thus, corrected TIMI frame count and stenosis severity at 4 weeks was highly correlated with infarct-artery flow at 1 year.

Results of percutaneous coronary angioplasty in patients <40 years of age.

This study examined factors influencing the outcome of percutaneous transluminal coronary angioplasty (PTCA) in patients <40 years of age. We followed 86 patients (mean age 37 years) treated from 1982 to 1994. The primary procedural success was 90%. At follow-up of 83 patients (97%) at a mean of 48 +/- 33 months (range 5 to 147), there had been 3 late deaths. Actuarial survival at 5 and 10 years was 95% and 91%, respectively. At review only 5% of patients had class III angina and no patient had class IV angina. Repeat revascularization (PTCA alone in 21 [25%], surgery in 8 [10%], or both in 10 [12%] patients) was performed for restenosis in 29 patients (35%) and for disease progression at other sites in 10 patients (12%). On multivariate analysis, a history of diabetes mellitus (p <0.02) was the only factor associated with death or a subsequent cardiovascular event (myocardial infarction, stroke, or hospital admission with unstable angina). At follow-up, 20 patients (24%) still smoked, 64 (77%) had a total cholesterol level > or = 200 mg/dl, 20 (24%) had a body mass index > or = 30, and 15 (18%) were not taking aspirin. In conclusion, PTCA in adults <40 years of age has excellent early results with a low morbidity and mortality. The medium-term prognosis and control of symptoms was good, although by 5 years, further revascularization was required in almost half of the patients.

Four-year survival of patients with acute coronary syndromes without ST-segment elevation and prognostic significance of 0.5-mm ST-segment depression.

We prospectively evaluated all patients admitted to our coronary care unit during 1993 with ischemic chest pain but without ST-segment elevation on the presenting electrocardiogram, and determined the influence of the extent of ST-segment depression, measured using calipers and blinded to the outcome, on 4-year survival. The presenting symptoms of 367 patients (mean age 64 years) were coded according to the Braunwald classification, 86% being in class IIIB (primary unstable angina with rest angina within 48 hours) and 7.4% in class IIIC (postinfarction angina). Thirty-two patients (8.6%) had myocardial infarction at presentation (defined as a creatine kinase level exceeding twice the reference range within 18 hours). During hospitalization 97% of patients received aspirin, 67% received intravenous heparin, 37% underwent angiography, and 35% underwent revascularization. The vital status of 99% of the patients was determined after a median of 52 months (interquartile range 48 to 55). At follow-up, 88% of patients were taking aspirin, 45% were taking beta blockers, and 50% had undergone revascularization. The survival rate was 70% in patients with > or = 0.5-mm ST-segment depression (53%, 77%, and 82% survival for > or = 2-, 1-, and 0.5-mm ST-segment depression, respectively; p <0.0001). Patients with a normal electrocardiogram had a greater survival rate (94%) than that of patients with 0.5-mm ST-segment depression (82%, p = 0.020), but not significantly different from that of patients with T-wave inversion (84%, p = NS). Independent predictors of mortality (odds ratio [95% confidence interval]) were: age in yearly increments (1.05 [1.03 to 1.06], p = 0.003), revascularization during follow-up (0.40 [0.29 to 0.56], p = 0.006), pulmonary edema (3.45 [2.19 to 5.45], p = 0.007), and ST-segment depression (1.37 [1.20 to 1.55], p = 0.015). Thus, ST-segment depression of > or = 0.5 mm predicts 4-year survival in patients with acute ischemic syndromes.

Association of angiographically detected coronary artery disease with low levels of high-density lipoprotein cholesterol and systemic hypertension.

The prevalence of risk factors for atherosclerosis in 488 consecutive patients undergoing cardiac catheterization for the investigation of chest pain was compared with that in 868 subjects from a population sample. The presence and severity of angiographic coronary artery disease (CAD) (defined as mean diameter stenosis > 50%), total and high-density lipoprotein (HDL) cholesterol, triglycerides, history of systemic hypertension, smoking, diabetes mellitus, family history and drug therapy were assessed. Low HDL cholesterol (< 0.9 mmol/liter [35 mg/dl]) was more prevalent in patients with CAD than in the population sample in both men (44% [95% confidence interval 38 to 48] vs 21% [12 to 28]; p < 0.01) and women (12% [9 to 15] vs 1% [0 to 3]; p < 0.01). There were no differences in total cholesterol levels between these 2 groups. Total:HDL cholesterol ratios were significantly greater in patients with CAD. History of systemic hypertension was more prevalent in both men and women with CAD than in the population sample (47% [37 to 57] vs 20% [16 to 25] for men, and 31% [26 to 36] vs 21% [17 to 26] for women; p < 0.01). The prevalence of other risk factors was not significantly different between the 2 groups. In patients with CAD, the severity of disease was inversely correlated with levels of HDL cholesterol in both men and women (p < 0.01), and positively correlated with total cholesterol in men aged < 55 years (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)