Richard Holubkov

Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981. The National Heart, Lung, and Blood Institute Registry

In August 1985, the Percutaneous Transluminal Coronary Angioplasty Registry of the National Heart, Lung, and Blood Institute reopened at its previous sites to document changes in angioplasty strategy and outcome. The new registry entered 1802 consecutive patients who had not had a myocardial infarction in the 10 days before angioplasty. Patient selection, technical outcome, and short-term major complications were compared with those of the 1977 to 1981 registry cohort. The new-registry patients were older and had a significantly higher proportion of multivessel disease (53 vs. 25 percent, P less than 0.001), poor left ventricular function (19 vs. 8 percent, P less than 0.001), previous myocardial infarction (37 vs. 21 percent, P less than 0.001), and previous coronary bypass surgery (13 vs. 9 percent, P less than 0.01). The new-registry cohort also had more complex coronary lesions, and angioplasty attempts in these patients involved more multivessel procedures. Despite these differences, the in-hospital outcome in the new cohort was better. Angiographic success rates according to lesion increased from 67 to 88 percent (P less than 0.001), and overall success rates (measured as a reduction of at least 20 percent in all lesions attempted, without death, myocardial infarction, or coronary bypass surgery) increased from 61 to 78 percent (P less than 0.001). In-hospital mortality for the new cohort was 1 percent, and the nonfatal myocardial infarction rate was 4.3 percent. Both rates are similar to those for the old registry. The long-term efficacy of current angioplasty remains to be determined.

Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study

BACKGROUND CT imaging of head-injured children has risks of radiation-induced malignancy. Our aim was to identify children at very low risk of clinically-important traumatic brain injuries (ciTBI) for whom CT might be unnecessary. METHODS We enrolled patients younger than 18 years presenting within 24 h of head trauma with Glasgow Coma Scale scores of 14-15 in 25 North American emergency departments. We derived and validated age-specific prediction rules for ciTBI (death from traumatic brain injury, neurosurgery, intubation >24 h, or hospital admission >or=2 nights). FINDINGS We enrolled and analysed 42 412 children (derivation and validation populations: 8502 and 2216 younger than 2 years, and 25 283 and 6411 aged 2 years and older). We obtained CT scans on 14 969 (35.3%); ciTBIs occurred in 376 (0.9%), and 60 (0.1%) underwent neurosurgery. In the validation population, the prediction rule for children younger than 2 years (normal mental status, no scalp haematoma except frontal, no loss of consciousness or loss of consciousness for less than 5 s, non-severe injury mechanism, no palpable skull fracture, and acting normally according to the parents) had a negative predictive value for ciTBI of 1176/1176 (100.0%, 95% CI 99.7-100 0) and sensitivity of 25/25 (100%, 86.3-100.0). 167 (24.1%) of 694 CT-imaged patients younger than 2 years were in this low-risk group. The prediction rule for children aged 2 years and older (normal mental status, no loss of consciousness, no vomiting, non-severe injury mechanism, no signs of basilar skull fracture, and no severe headache) had a negative predictive value of 3798/3800 (99.95%, 99.81-99.99) and sensitivity of 61/63 (96.8%, 89.0-99.6). 446 (20.1%) of 2223 CT-imaged patients aged 2 years and older were in this low-risk group. Neither rule missed neurosurgery in validation populations. INTERPRETATION These validated prediction rules identified children at very low risk of ciTBIs for whom CT can routinely be obviated. FUNDING The Emergency Medical Services for Children Programme of the Maternal and Child Health Bureau, and the Maternal and Child Health Bureau Research Programme, Health Resources and Services Administration, US Department of Health and Human Services.

Controlled Trial of Intravenous Immune Globulin in Recent-Onset Dilated Cardiomyopathy

BackgroundThis prospective placebo-controlled trial was designed to determine whether intravenous immune globulin (IVIG) improves left ventricular ejection fraction (LVEF) in adults with recent onset of idiopathic dilated cardiomyopathy or myocarditis. Methods and ResultsSixty-two patients (37 men, 25 women; mean age ±SD 43.0±12.3 years) with recent onset (≤6 months of symptoms) of dilated cardiomyopathy and LVEF ≤0.40 were randomized to 2 g/kg IVIG or placebo. All underwent an endomyocardial biopsy before randomization, which revealed cellular inflammation in 16%. The primary outcome was change in LVEF at 6 and 12 months after randomization. Overall, LVEF improved from 0.25±0.08 to 0.41±0.17 at 6 months (P <0.001) and 0.42±0.14 (P <0.001 versus baseline) at 12 months. The increase was virtually identical in patients receiving IVIG and those given placebo (6 months: IVIG 0.14±0.12, placebo 0.14±0.14; 12 months: IVIG 0.16±0.12, placebo 0.15±0.16). Overall, 31 (56%) of 55 patients at 1 year had an increase in LVEF ≥0.10 from study entry, and 20 (36%) of 56 normalized their ejection fraction (≥0.50). The transplant-free survival rate was 92% at 1 year and 88% at 2 years. ConclusionsThese results suggest that for patients with recent-onset dilated cardiomyopathy, IVIG does not augment the improvement in LVEF. However, in this overall cohort, LVEF improved significantly during follow-up, and the short-term prognosis remains favorable.

Incidence and consequences of periprocedural occlusion. The 1985-1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry.

Of 1,801 patients in the 1985-1986 Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry, 122 (6.8%) had periprocedural occlusion (4.9% in the catheterization laboratory, 1.9% outside the laboratory). Baseline patient factors independently associated with increased occlusion rates included triple-vessel disease, high risk status for surgery, and acute coronary insufficiency. Lesion characteristics showing significant positive association included severe stenosis before PTCA, diffuse or multiple discrete morphology, thrombus, and collateral flow from the lesion. Intimal tear and dissection were also very strongly associated with occlusion. Sixty patients (49%) had a transient occlusion that was reopened with PTCA, 43 (35%) were not redilated and managed with bypass surgery, and 19 (16%) were not redilated and managed medically. In-hospital mortality was 5% in each of these treatment groups, compared with 1% in occlusion-free patients. In-hospital infarction rates ranged from 27% in patients with transient occlusion to 56% in the patients managed with surgery, compared with 2% in patients without occlusion. During 2 years of follow-up, somewhat increased mortality continued in patients with occlusion, whereas follow-up infarction rates were comparable for all patients regardless of occlusion. Patients with an occlusion that was reopened or managed medically had increased rates of surgery during follow-up. Rates of repeat PTCA were comparable (about 23% by 2 years) in patients with transient occlusion and those without occlusion. Occlusion remains a serious complication of angioplasty and is associated most strongly with major events and surgical procedures that occur during the in-hospital period.

Percutaneous Coronary Intervention in the Current Era Compared With 1985–1986 The National Heart, Lung, and Blood Institute Registries

Background—Although refinements have occurred in coronary angioplasty over the past decade, little is known about whether these changes have affected outcomes. Methods and Results—Baseline features and in-hospital and 1-year outcomes of 1559 consecutive patients in the 1997–1998 Dynamic Registry who were having first coronary intervention were compared with 2431 patients in the 1985–1986 National Heart, Lung, and Blood Institute Registry. Compared with patients in the 1985–1986 Registry, Dynamic Registry patients were older (mean age, 62 versus 58 years;P <0.001) and more often female (32.1% versus 25.5%;P <0.001). In the Dynamic Registry, procedures were more often performed for acute myocardial infarction (22.9% versus 9.9%;P <0.001) and treated lesions were more severe (84.5% versus 82.5% diameter reduction;P <0.001), thrombotic (22.1% versus 11.3%;P <0.001) or calcified (29.5% versus 10.8%;P <0.001). Stents were used in 70.5% of Dynamic Registry patients, whereas 1985–1986 patients received balloon angioplasty alone. Procedural success was higher in the Dynamic Registry (92.0% versus 81.8%;P <0.001) and the rate of in-hospital death, myocardial infarction, and emergency coronary bypass surgery combined was lower (4.9% versus 7.9%;P =0.001) than in the 1985–1986 Registry. The 1-year rate for CABG was lower in the Dynamic Registry (6.9% versus 12.6%;P <0.001). Conclusions—Although Dynamic Registry patients had more unstable and complex coronary disease than those in the 1985–1986 Registry, their rate of procedural success was higher whereas rates of complications and subsequent CABG were lower. Results of percutaneous coronary intervention have improved substantially over the past decade.

Comparison of complications during percutaneous transluminal coronary angioplasty from 1977 to 1981 and from 1985 to 1986: The National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry

Because the effects of changing technology in percutaneous transluminal coronary angioplasty, increased operator experience and use of the procedure in patients with extensive disease are unknown in regard to complication patterns, the initial 1977-1981 cohort and the recent 1985-1986 cohort of the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry were analyzed with respect to complications. Compared with the initial cohort of 1,155 patients, the 1,801 new cohort patients were older and had an increased prevalence of multivessel coronary artery disease, depressed left ventricular function and prior infarction. Overall complication rates in the recent cohort were either unchanged or decreased from the rates in the initial cohort despite a higher risk patient population. The most significant decreases were in the incidence of coronary spasm (p less than 0.001) and the need for emergency coronary bypass surgery (p less than 0.01). Overall in-hospital mortality was low but was dependent on the extent of vessel disease--0.2% for single vessel disease, 0.9% for double vessel disease and 2.2% for triple vessel disease (p less than 0.001 for linear trend). Acute coronary complications of branch occlusion, dissection or abrupt closure were associated with increased rates of death, nonfatal infarction or need for emergency surgery. Factors showing a multivariate association with increased mortality included a history of congestive heart failure (p less than 0.001), age greater than or equal to 65 years (p less than 0.01), triple vessel or left main coronary artery disease (p less than 0.05), female gender (p less than 0.05) and new onset angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Revascularization in Diabetic Patients A Comparison of the Randomized and Observational Components of the Bypass Angioplasty Revascularization Investigation (BARI)

BACKGROUND Patients with treated diabetes in the randomized-trial segment of the Bypass Angioplasty Revascularization Investigation (BARI) who were randomized to initial revascularization with PTCA had significantly worse 5-year survival than patients assigned to CABG. This treatment difference was not seen among diabetic patients eligible for BARI who opted to select their mode of revascularization. We hypothesized that differences in patient characteristics, assessed and unmeasured, together with the treatment selection in the registry, at least partially account for this discrepancy. METHODS AND RESULTS Among diabetics taking insulin or oral hypoglycemic drugs at entry, angiographic and clinical presentations were comparable between randomized and registry patients. However, more registry patients were white, and registry diabetics tended to be more educated and more physically active and to report better quality of life. Procedural characteristics and in-hospital complications were comparable. The 5-year all-cause mortality rate was 34.5% in randomized diabetic patients assigned to PTCA versus 19.4% in CABG patients (P=0.0024; relative risk [RR]=1.87); corresponding cardiac mortality rates were 23.4% and 8.2%, respectively (P=0.0002; RR=3.10). The CABG benefit was more apparent among patients requiring insulin. In the registry, all-cause mortality was 14.4% for PTCA versus 14.9% for CABG (P=0.86, RR=1.10), with corresponding cardiac mortality rates of 7.5% and 6. 0%, respectively (P=0.73; RR=1.07). These RRs in the registry increased to 1.29 and 1.41, respectively, after adjustment for all known differences between treatment groups. CONCLUSIONS BARI registry results are not inconsistent with the finding in the randomized trial that initial CABG is associated with better long-term survival than PTCA in treated diabetic patients with multivessel coronary disease suitable for either surgical or catheter-based revascularization.

Results of percutaneous transluminal coronary angioplasty in women. 1985-1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty Registry.

BACKGROUND The National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) 1978-1981 Registry cohort indicated that PTCA risk was higher and efficacy was lower in women. Data from the 1985-1986 PTCA Registry are used to address the question of whether compared with men, women still have a worse outcome after PTCA. METHODS AND RESULTS The 1985-1986 NHLBI PTCA Registry collected data on consecutive, first-PTCA cases at 16 centers. Initial results are reported for 2,136 patients, 546 of whom were women. Four-year follow-up status was available on 95% of the cohort. Although women were an average of 4.5 years older than the male patients and had more cardiovascular risk factors and more severe angina, their coronary artery disease as assessed by angiography was not more extensive. Rates of angiographic success on a per-lesion basis were similar for women and men (89% versus 88%), and the clinical success rates (79%) were the same. Women had more initial complications (29% versus 20%, p < 0.001) and a considerably higher procedural mortality rate (2.6% versus 0.3%, p < 0.001). For patients who survived the initial procedure, 4-year survival was similar for men and women. At 4 years, women had slightly fewer events (myocardial infarction, repeat PTCA, and/or coronary artery bypass grafting). Despite the higher proportion of women reporting the presence of angina and medication use at 4 years, the proportion reporting improvement in symptomatic status was similar to that of men. CONCLUSIONS Women undergoing PTCA have a higher procedural mortality risk than men; this is explained in part by their worse cardiovascular risk factor profile. Otherwise, the success rate and long-term prognosis after PTCA are excellent, and PTCA should be considered for women in need of revascularization.

Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory).

The purpose of this study is to provide a contemporary qualitative and quantitative analysis of coronary angiograms from a large series of women enrolled in the Womens Ischemia Syndrome Evaluation (WISE) study who had suspected ischemic chest pain. Previous studies have suggested that women with chest pain have a lower prevalence of significant coronary artery disease (CAD) compared with men. Detailed analyses of angiographic findings relative to risk factors and outcomes are not available. All coronary angiograms were reviewed in a central core laboratory. Quantitative measurement of percent stenosis was used to assess the presence and severity of disease. Of the 323 women enrolled in the pilot phase, 34% had no detectable, 23% had measurable but minimal, and 43% had significant ( > 50% diameter stenosis) CAD. Of those with significant CAD, most had multivessel disease. Features suggesting complex plaque were identified in < 10%. Age, hypertension, diabetes mellitus, prior myocardial infarction (MI), current hormone replacement therapy, and unstable angina were all significant, independent predictors of presence of significant disease (p < 0.05). Subsequent hospitalization for a cardiac cause occurred more frequently in those women with minimal and significant disease compared with no disease (p = 0.001). The common findings of no and extensive CAD among symptomatic women at coronary angiography highlight the need for better clinical noninvasive evaluations for ischemia. Women with minimal CAD have intermediate rates of rehospitalization and cardiovascular events, and thus should not be considered low risk.

Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children

BACKGROUND Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. METHODS We conducted this trial of two targeted temperature interventions at 38 childrens hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. RESULTS A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P=0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P=0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P=0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. CONCLUSIONS In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH ClinicalTrials.gov number, NCT00878644.).