Updated guidelines for gene nomenclature in wheat.

KEY MESSAGE: Here, we provide an updated set of guidelines for naming genes in wheat that has been endorsed by the wheat research community. The last decade has seen a proliferation in genomic resources for wheat, including reference- and pan-genome assemblies with gene annotations, which provide new opportunities to detect, characterise, and describe genes that influence traits of interest. The expansion of genetic information has supported growth of the wheat research community and catalysed strong interest in the genes that control agronomically important traits, such as yield, pathogen resistance, grain quality, and abiotic stress tolerance. To accommodate these developments, we present an updated set of guidelines for gene nomenclature in wheat. These guidelines can be used to describe loci identified based on morphological or phenotypic features or to name genes based on sequence information, such as similarity to genes characterised in other species or the biochemical properties of the encoded protein. The updated guidelines provide a flexible system that is not overly prescriptive but provides structure and a common framework for naming genes in wheat, which may be extended to related cereal species. We propose these guidelines be used henceforth by the wheat research community to facilitate integration of data from independent studies and allow broader and more efficient use of text and data mining approaches, which will ultimately help further accelerate wheat research and breeding.

Evaluation of lower flammability limits of fuel-air-diluent mixtures using calculated adiabatic flame temperatures.

The lower flammability limit (LFL) of a fuel is the minimum composition in air over which a flame can propagate. Calculated adiabatic flame temperatures (CAFT) are a powerful tool to estimate the LFL of gas mixtures. Different CAFT values are used for the estimation of LFL. SuperChems is used by industry to perform flammability calculations under different initial conditions which depends on the selection of a threshold temperature. In this work, the CAFT at the LFL is suggested for mixtures of fuel-air and fuel-air-diluents. These CAFT can be used as the threshold values in SuperChems to calculate the LFL. This paper discusses an approach to evaluate the LFL in the presence of diluents such as N2 and CO2 by an algebraic method and by the application of SuperChems using CAFT as the basis of the calculations. The CAFT for different paraffinic and unsaturated hydrocarbons are presented as well as an average value per family of chemicals.

Combined angiotensin II receptor antagonism and angiotensin-converting enzyme inhibition further attenuates postinfarction left ventricular remodeling.

BACKGROUND: ACE inhibition (ACEI) attenuates post-myocardial infarction (MI) LV remodeling, but the effects of angiotensin II type 1 receptor (AT(1)) antagonism alone or in combination with ACEI are unclear. Accordingly, we investigated the effects of AT(1) antagonism, ACEI, and their combination in a well-characterized ovine postinfarction model. METHODS AND RESULTS: Beginning 2 days after transmural anteroapical MI, 62 sheep were treated with 1 of 5 treatment regimens: no therapy (control, n=12), standard-dose ACEI (sACEI; ramipril 10 mg/d, n=14), high-dose ACEI (hACEI; ramipril 20 mg/d, n=8), AT(1) blockade (losartan 50 mg/d, n=13), and combination therapy with sACEI+AT(1) blockade (CT; ramipril 10 mg/d+losartan 50 mg/d, n=15). MRI was performed before and 8 weeks after MI to quantify changes in LV end-diastolic and end-systolic volume indices (DeltaEDVI, DeltaESVI) and ejection fraction (DeltaEF). Change in regional percent intramyocardial circumferential shortening in noninfarcted segments adjacent to the infarct (Adj Delta%S) was measured by tagged MRI. CT resulted in the most marked blunting of LV remodeling: DeltaESVI (+1.0+/-0.4, +0.7+/-0.4, +0.6+/-0.3, +0.9+/-0.5, and +0.4+/-0.2* mL/kg); DeltaEDVI (+0.9+/-0.4, +0.7+/-0.5, +0.6+/-0.5, +0.9+/-0.5, and +0.4+/-0.3 mL/kg); DeltaEF (-24+/-7, -18+/-6, -14+/-7, -18+/-10, and -11+/-9* %); and Adj Delta%S (-8+/-4, -7+/-3, -5+/-3, -5+/-3, and -2+/-3* %) for Control, sACEI, hACEI, AT(1) blockade, and CT, respectively (*P<0.04 versus sACEI, AT(1) blockade, and control; P<0.05 versus control; P<0.002 versus AT(1) blockade and control). EDVI and ESVI at 8 weeks after MI were smallest with CT (P<0.02 versus all). CONCLUSIONS: Combination therapy with sACEI+AT(1) blockade shows promise in attenuating postinfarction LV remodeling but was not clearly superior to hACEI in the present study.

Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction.

BACKGROUND: Recent advances in high-throughput genomics technology have expanded our ability to catalogue allelic variants in large sets of candidate genes related to premature coronary artery disease. METHODS AND RESULTS: A total of 398 families were identified in 15 participating medical centers; they fulfilled the criteria of myocardial infarction, revascularization, or a significant coronary artery lesion diagnosed before 45 years in men or 50 years in women. A total of 62 vascular biology genes and 72 single-nucleotide polymorphisms were assessed. Previously undescribed variants in 3 related members of the thrombospondin protein family were prominent among a small set of single-nucleotide polymorphisms that showed a statistical association with premature coronary artery disease. A missense variant of thrombospondin 4 (A387P) showed the strongest association, with an adjusted odds ratio for myocardial infarction of 1.89 (P=0.002 adjusted for covariates) for individuals carrying the P allele. A variant in the 3' untranslated region of thrombospondin-2 (change of thymidine to guanine) seemed to have a protective effect against myocardial in individuals homozygous for the variant (adjusted odds ratio of 0.31; P=0.0018). A missense variant in thrombospondin-1 (N700S) was associated with an adjusted odds ratio for coronary artery disease of 11.90 (P=0.041) in homozygous individuals, who also had the lowest level of thrombospondin-1 by plasma assay (P=0.0019). CONCLUSIONS: This large-scale genetic study has identified the potential of multiple novel variants in the thrombospondin gene family to be associated with familial premature myocardial infarction. Notwithstanding multiple caveats, thrombospondins specifically and high-throughput genomic technology in general deserve further study in familial ischemic heart disease.

Recurrence of angina after coronary artery bypass surgery: predictors and prognosis (CASS Registry). Coronary Artery Surgery Study.

OBJECTIVES: This study sought to define the predictors and prognosis of postoperative angina in patients undergoing coronary artery bypass surgery. BACKGROUND: Angina recurs in the first postoperative year in 20% to 30% of patients after coronary artery bypass surgery. The Coronary Artery Surgery Study Registry provides an opportunity to study the predictors and prognosis of postoperative angina in a large sample. METHODS: All patients with isolated coronary artery bypass surgery in the registry were identified, and anginal status was determined on a yearly basis. The influence of angina on mortality, recurrent myocardial infarction and need for reoperation was determined. RESULTS: Angina recurred in the first year in 24% of patients and by the sixth year in 40%. The significant predictors in a multivariate analysis were minimal coronary artery disease, preoperative angina, use of vein grafts only, previous myocardial infarction, incomplete revascularization, female gender, smoking and younger age. In subsequent years important predictors were angina in the first postoperative year, female gender, younger age and incomplete revascularization. The presence of angina in the first postoperative year was associated with more frequent myocardial infarction (p = 0.04) and greater need for reoperation (p = 0.003) but did not affect survival during the 6-year follow-up period. CONCLUSIONS: These findings show that the predictors of postoperative angina are features that are or could be predicted before bypass surgery. Thus, patients with these features before bypass surgery could be advised that they would be more likely to experience postoperative angina than those without these features. Postoperative angina is associated with an increased risk of late myocardial infarction and reoperation.

Limitations of regional myocardial thallium clearance for identification of disease in individual coronary arteries.

The purpose of this study was to critically evaluate the usefulness of postexercise regional myocardial thallium-201 clearance for identifying disease in individual coronary arteries. Exercise and redistribution planar imaging studies were performed in 114 subjects, including 19 normal volunteers and 95 patients undergoing cardiac catheterization (70 with and 25 without greater than or equal to 50% narrowing in one or more coronary arteries). Thallium clearance was measured from predefined myocardial regions corresponding to the left anterior descending, left circumflex and right coronary arteries and was expressed as the percent decrease in activity at 4 h, assuming monoexponential clearance. In regions perfused by a normal or insignificantly diseased coronary artery, mean 4 h clearance was 58.9 +/- 9.4% for normal volunteers, 43.1 +/- 15.5% for catheterized patients without coronary artery disease and 36.3 +/- 24.9% for catheterized patients with coronary artery disease (p less than 0.001 patients with coronary artery disease versus normal volunteers). Clearance from normal regions was significantly associated with two measures of exercise performance: percent of predicted maximal heart rate achieved (r = 0.49) and exercise duration (r = 0.35). In regions perfused by a stenotic coronary artery, mean clearance was lower (31.1 +/- 19.8%) but was not significantly different from that in normal regions in the same patients. Clearance from diseased regions was also associated with maximal exercise heart rate (r = 0.28) and exercise duration (r = 0.41), but not with percent coronary artery stenosis (r = 0.02). After taking exercise performance into account, the number of diseased vessels or the presence or absence of disease in a given vessel had little influence on regional thallium clearance. Although measurement of regional post-exercise thallium clearance may help to identify stenotic coronary arteries in selected patients, variability related to exercise performance and other physiologic and technical factors greatly limits the clinical usefulness of absolute thallium clearance measurements.

Effect of postural changes, nitroglycerin and verapamil on diastolic ventricular function as determined by radionuclide angiography in normal subjects.

Whereas improvement in diastolic function indexes in response to therapeutic interventions has been attributed to a beneficial effect of the intervention, measurements of diastolic function appear to be influenced by changes in loading conditions, heart rate and sympathetic tone. To determine the effect of body position and short-term pharmacologic intervention on radionuclide angiographically determined left ventricular peak filling rate, high temporal resolution time-activity curves and absolute left ventricular volumes obtained by equilibrium-gated blood pool scans were evaluated in 12 normal subjects in the supine position at rest and in response to several postural and pharmacologic manipulations. This study confirmed the reproducibility of the technique and demonstrated that in normal subjects, peak filling rate varies in response to changes in body position and to short-term administration of sublingual nitroglycerin and intravenous verapamil. Peak filling rate ranged from 3.3 to 5.1 end-diastolic volumes (EDV)/s with a variability of 13.7% during five baseline supine measurements in the 12 subjects. Compared with values in the supine position (mean +/- SEM = 4.38 +/- 0.24 EDV/s), peak filling rate increased +16 +/- 6% to 4.75 +/- 0.27 EDV/s in the upright position (p less than 0.05) but did not change significantly with leg elevation. Peak filling rate at baseline and during postural changes correlated significantly with ejection fraction (r = +0.49), with stroke volume (r = +0.26) and inversely with end-systolic volume (r = -0.41), but did not correlate with heart rate or blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery to right ventricle fistula in heart transplant recipients: a complication of endomyocardial biopsy.

In a series of 74 heart transplant recipients undergoing annual coronary angiography, a coronary artery to right ventricle fistula was observed in 4 patients, an incidence rate of 5.4%, which is much higher than the expected incidence of congenital coronary artery fistula (0.1% to 0.2%). A traumatic origin of the fistulas is unlikely because none of the heart donors had evidence of chest trauma. An endomyocardial biopsy-related etiology of the fistulas is postulated. All fistulas were located in the biopsy sampling area. Patients with a fistula underwent more biopsies before the diagnosis compared with patients without a fistula (20 +/- 11 versus 14 +/- 6, p = 0.05). At least one large arteriole (diameter greater than 0.16 mm) was found on pathologic examination of the biopsy specimens from each of the patients with a fistula (100%) but in only 2 (16.7%) (p less than 0.01) of 12 randomly selected patients without a fistula. The size of the fistula appears to be hemodynamically insignificant in all four patients, judging from angiographic size, normal intracardiac pressures and normal cardiac output values at rest. The diagnosis of a coronary artery to right ventricle fistula is possible and should be entertained at the time of coronary angiography of heart transplant recipients. The clinical significance of the finding is unclear. As long as endomyocardial biopsy remains the diagnostic method of identifying tissue rejection, prevention of the described complication is unlikely.

Long-term survival of African Americans in the Coronary Artery Surgery Study (CASS).

OBJECTIVES: This study sought to determine the long-term (> 15 years) outcome of a clinically well characterized cohort of African Americans with known or suspected coronary artery disease (CAD). BACKGROUND: The mortality rate from CAD is higher in African Americans than in whites. An earlier analysis of data from the Coronary Artery Surgery Study (CASS) registry suggested that African American and white patients treated surgically had equal 5-year survival rates. METHODS: Survival data from the CASS registry were analyzed to determine whether 1) African American race is an independent predictor of mortality; and 2) initial therapy is predictive of mortality among African American patients. RESULTS: Overall, 60% of white and 52% of African American patients survived 16 years (p < 0.00001). Multivariate Cox models confirmed that African American race was independently associated with higher mortality in both the medical group (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.11 to 1.63) and the surgical group (HR 1.63, 95% CI 1.19 to 2.23). Initial therapy was not predictive of survival among African American patients (p = 0.81). However, smoking status significantly influenced survival: African Americans who did not smoke experienced significantly improved survival (60% vs. 48% for smokers), which equaled survival for white nonsmokers (61%, p = NS). CONCLUSIONS: In contrast to results from shorter term studies, African Americans experienced higher overall mortality rates than whites over the long term, regardless of the type of initial treatment. Survival among nonsmoking African Americans at 16 years equaled survival among nonsmoking whites.

Contractile reserve and contrast uptake pattern by magnetic resonance imaging and functional recovery after reperfused myocardial infarction.

OBJECTIVES: We hypothesized that contrast-enhanced and dobutamine tagged magnetic resonance imaging (MRI) could investigate microvascular integrity and contractile reserve of reperfused myocardial infarction (MI) in one examination. BACKGROUND: In reperfused MI, microvascular integrity and contractile reserve are important determinants of functional recovery. METHODS: Twenty-three patients with a reperfused first MI were studied. On day 3+/-1 after MI, patients underwent tagged MRI at baseline and during infusion of 5 and 10 microg/kg/min of dobutamine followed by contrast-enhanced MRI (first pass and delayed imaging) after a bolus infusion of gadolinium-diethylenetriaminepenta-acetic acid. Tagged MRI was performed 9+/-1 weeks later (follow-up). Eighty-four transmural regions with hyperenhancement on delayed contrast-enhanced images were defined as COMB (first pass hypoenhancement) or HYPER (normal first pass signal enhancement). Percent circumferential segment shortening was measured within the subendocardium and subepicardum of each region of HYPER or COMB at baseline, peak dobutamine and follow-up. RESULTS: Shortening improved in COMB regions from 4+/-1% at baseline to 10+/-1% at peak dobutamine and 10+/-1% at follow-up, respectively (p<0.0003 vs. baseline for both). The HYPER regions likewise improved from 10+/-1% at baseline to 16+/-1% and 17+/-1%, respectively (p<0.0004 vs. baseline for both). Function within COMB regions was less than that of HYPER at baseline, peak dobutamine and follow-up (p<0.0003 for all). CONCLUSIONS: Dobutamine magnetic resonance tagging and contrast enhanced MRI are complementary in assessing functional recovery after reperfused MI. Regions of delayed contrast hyperenhancement demonstrate both contractile reserve and late functional recovery. However, if these regions demonstrate first pass contrast hypoenhancement, they are associated with greater myocardial damage.

Dissociation between changes in intramyocardial function and left ventricular volumes in the eight weeks after first anterior myocardial infarction.

OBJECTIVES: We sought to examine the relation between regional changes in intramyocardial function and global left ventricular (LV) remodeling in the first 8 weeks after reperfused first anterior myocardial infarction (MI). BACKGROUND: Because of limitations in imaging methods used to date, this relation has not been thoroughly evaluated. METHODS: We studied 26 patients (21 men, 5 women; mean age 51 years) by magnetic resonance imaging (MRI) on day 5 +/- 2 (mean +/- SD) and week 8 +/- 1 after their first anterior MI. All patients had single-vessel left anterior descending coronary artery disease and although they had received reperfusion therapy, all had regional LV dysfunction and an initial ejection fraction (EF) < or = 50%. Short-axis magnetic resonance tagging was performed spanning the LV. Percent intramyocardial circumferential shortening (%S) on a topographic basis, LV mass index, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index and LV ejection fraction (LVEF) were measured. RESULTS: Left ventricular mass index tended to decrease, whereas the LVEDVI increased from 82 +/- 24 to 96 +/- 27 ml/m2 (p = 0.002). Left ventricular end-systolic volume index remained unchanged, whereas LVEF increased from 39 +/- 12% to 45 +/- 14% (p = 0.002). Apical %S improved from 9 +/- 6% to 13 +/- 5% (p < 0.0001), as it did in the midanterior (6 +/- 6% to 10 +/- 7%, p < 0.02) and midseptal regions (8 +/- 7% to 12 +/- 6%, p < 0.02). Early dysfunction in remote midinferior and basal lateral regions resolved by 8 weeks. By multivariate analysis, the only significant predictor of an increase in LVEDVI over the study period was peak creatine kinase (p = 0.04). CONCLUSIONS: In the first 8 weeks after a large, reperfused anterior MI, %S improved in the apex, midanterior and midseptal regions and normalized in remote noninfarct-related regions, but LV end-diastolic volumes also increased. This increased LVEDVI correlated with infarct size by peak creatine kinase and was not related to changes in global and regional LV function.

Clinical experience with primary percutaneous transluminal coronary angioplasty compared with alteplase (recombinant tissue-type plasminogen activator) in patients with acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2).

OBJECTIVES: We sought to compare outcomes after primary percutaneous transluminal coronary angioplasty (PTCA) or thrombolytic therapy for acute myocardial infarction (MI). BACKGROUND: Primary PTCA and thrombolytic therapy are alternative means of achieving reperfusion in patients with acute MI. The Second National Registry of Myocardial Infarction (NRMI-2) offers an opportunity to study the clinical experience with these modalities in a large patient group. METHODS: Data from NRMI-2 were reviewed. RESULTS: From June 1, 1994 through October 31, 1995, 4,939 nontransfer patients underwent primary PTCA within 12 h of symptom onset, and 24,705 patients received alteplase (recombinant tissue-type plasminogen activator [rt-PA]). When lytic-ineligible patients and patients presenting in cardiogenic shock were excluded, baseline characteristics were similar. The median time from presentation to initiation of rt-PA in the thrombolytic group was 42 min; the median time to first balloon inflation in the primary PTCA group was 111 min (p < 0.0001). In-hospital mortality was higher in patients in shock after rt-PA than after PTCA (52% vs. 32%, p < 0.0001). In-hospital mortality was the same in lytic-eligible patients not in shock: 5.4% after rt-PA and 5.2% after PTCA. The stroke rate was higher after lytic therapy (1.6% vs. 0.7% after PTCA, p < 0.0001), but the combined end point of death and nonfatal stroke was not significantly different between the two groups (6.2% after rt-PA and 5.6% after PTCA). There was no difference in the rate of reinfarction (2.9% after rt-PA and 2.5% after PTCA). CONCLUSIONS: These findings suggest that in lytic-eligible patients not in shock, PTCA and rt-PA are comparable alternative methods of reperfusion when analyzed in terms of in-hospital mortality, mortality plus nonfatal stroke and reinfarction.

Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the US from 1990 through 1999: the National Registry of Myocardial Infarction 1, 2 and 3.

OBJECTIVES: We sought to determine trends in the treatment of myocardial infarction from 1990 through 1999 in the U.S. and to relate these trends to current guidelines. BACKGROUND: Limited data are available to show how recent clinical trials and clinical guidelines have impacted treatment of myocardial infarction. METHODS: Temporal trends in myocardial infarction treatment and outcome were assessed by using data from 1,514,292 patients in the National Registry of Myocardial Infarction (NRMI) 1, 2 and 3 from 1990 through 1999. RESULTS: During this interval, the use of intravenous thrombolytic therapy declined from 34.3% to 20.8%, but the use of primary angioplasty increased from 2.4% to 7.3% (both p = 0.0001). The median "door-to-drug" time among thrombolytic therapy recipients fell from 61.8 to 37.8 min (p = 0.0001), primarily owing to shorter "door-to-data" and "data-to-decision" times. The prevalence of non-Q wave infarctions increased from 45% in 1994 to 63% in 1999 (p = 0.0001). From 1994 through 1999, there was increased usage of beta-blockers, aspirin and angiotensin-converting inhibitors, both during the first 24 h after admission and on hospital discharge (all p = 0.0001). Between 1990 and 1999, the median duration of hospital stay fell from 8.3 to 4.3 days, and hospital mortality declined from 11.2% to 9.4% (both p = 0.0001). CONCLUSIONS: The NRMI data from 1990 through 1999 demonstrate that the recommendations of recent clinical trials and published guidelines are being implemented, resulting in more rapid administration of intravenous thrombolytic therapy, increasing use of primary angioplasty and more frequent use of adjunctive therapies known to reduce mortality, and may be contributing to the higher prevalence of non-Q wave infarctions, shorter hospital stays and lower hospital mortality.

A composite view of cardiac rupture in the United States National Registry of Myocardial Infarction.

OBJECTIVES: This study was done to determine the incidence, timing and prevalence as a cause of death from cardiac rupture in patients with acute myocardial infarction. BACKGROUND: Several clinical trials and overview analyses have suggested that the survival benefit conferred by thrombolytic therapy may be offset by a paradoxic increase in early deaths from cardiac rupture. METHODS: Demographic, procedural and outcome data from patients with acute myocardial infarction were collected at 1,073 United States hospitals collaborating in the United States National Registry of Myocardial Infarction. RESULTS: Among the 350,755 patients enrolled, 122,243 received thrombolytic therapy. In-hospital mortality for the overall patient population, those not treated with thrombolytics (n = 228,512) and those given thrombolytics were 10.4%, 12.9% and 5.9%, respectively (p<0.001). Cardiogenic shock was the most common cause of death in each patient group. Although the incidence of cardiac rupture was low (<1.0%), it was responsible for 7.3%, 6.1% and 12.1%, respectively, of in-hospital deaths (p<0.001). Death from rupture occurred earlier in patients given thrombolytic therapy, with a clustering of events within 24 h of drug administration. Despite the early risk, death rates were comparatively low in thrombolytic-treated patients on each of the first 30 days. By multivariable analysis, thrombolytics, prior myocardial infarction, advancing age, female gender and intravenous beta-blocker use were independently associated with cardiac rupture. CONCLUSIONS: This large registry experience, including over 350,000 patients with myocardial infarction, suggests that thrombolytic therapy accelerates cardiac rupture, typically to within 24 to 48 h of treatment. The possibility that rupture represents an early hemorrhagic complication of thrombolytic therapy should be investigated.

Selective versus routine predischarge coronary arteriography after therapy with recombinant tissue-type plasminogen activator, heparin and aspirin for acute myocardial infarction. TIMI II Investigators.

To ascertain whether predischarge arteriography is beneficial in patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA), heparin and aspirin, the outcome of 197 patients in the Thrombolysis in Myocardial Infarction (TIMI) IIA study assigned to conservative management and routine predischarge coronary arteriography (routine catheterization group) was compared with the outcome of 1,461 patients from the TIMI IIB study assigned to conservative management without routine coronary arteriography unless ischemia recurred spontaneously or on predischarge exercise testing (selective catheterization group). The two groups were similar with regard to important baseline variables. During the initial hospital stay, coronary arteriography was performed in 93.9% of the routine catheterization group and 34.7% of the selective catheterization group (p less than 0.001), but the frequency of coronary revascularization (angioplasty or coronary artery bypass surgery) was similar in the two groups (24.4% versus 20.7%, p = NS). Coronary arteriograms showed a predominance of zero or one vessel disease (stenosis greater than or equal to 60%) in both groups (routine catheterization group 73.1%, selective catheterization group 61.3%). During the 1st year after infarction, rehospitalization for cardiac reasons and the interim performance of coronary arteriography were more common in the selective catheterization group (37.9% versus 27.6%, p = 0.007 and 28.6% versus 11.6%, p less than 0.001, respectively); however, the interim rates of death, nonfatal reinfarction and performance of coronary revascularization procedures were similar. At the end of 1 year, coronary arteriography had been performed one or more times in 98.9% of the routine catheterization group and 59.4% of the selective catheterization group (p less than 0.001), whereas death and nonfatal reinfarction had occurred in 10.2% versus 7.0% (p = 0.10) and 8.6% versus 9.0% (p = 0.87), respectively. Because the selective coronary arteriography policy exposes about 40% fewer patients to the small but finite risks and inconvenience of the procedure without compromising the 1 year survival or reinfarction rates, it seems to be an appropriate management strategy.

Better functional status in American than Canadian patients with heart disease: an effect of medical care?

OBJECTIVES: This study compared functional status in Americans and Canadians with and without prior symptoms of heart disease to separate the effects of medical care from nonmedical factors. BACKGROUND: Coronary angiography and revascularization are used more often in the United States than in Canada, yet rates of mortality and myocardial infarction are similar in the two countries. Recent data suggest that functional status after myocardial infarction is better among Americans than Canadians, but it is uncertain whether this difference is due to medical care or nonmedical factors. METHODS: Quality of life was measured in patients enrolled in seven American and one Canadian site in the Bypass Angioplasty Revascularization Investigation. Prior symptoms of heart disease were defined as angina, myocardial infarction or congestive heart failure before the episode of illness leading to randomization. Functional status was measured with the Duke Activity Status Index and overall emotional and social health using Medical Outcome Study measures on the basis of patient status before the index episode of acute ischemic heart disease. RESULTS: Quality of life was generally better in the 934 Americans than in the 278 Canadians, with overall health rated as excellent or very good in 30% of Americans versus 20% of Canadians (p = 0.0001), higher median Duke Activity Status Index scores (16 vs. 13.5, p = 0.03) but equivalent emotional health (76 vs. 76, p = 0.74) and social health scores (100 vs. 80, p = 0.07). Among the 350 patients without prior symptoms of heart disease, Americans and Canadians had similar overall health, Duke Activity Status Index and emotional and social health scores. However, of the 860 patients with previous symptoms of heart disease, Americans had higher overall health (p = 0.0001) and Duke Activity Status Index scores (p = 0.0008) but similar emotional and social health scores. The results were essentially unchanged after statistical adjustment for potential confounding factors. CONCLUSIONS: The functional status of patients without prior symptoms of heart disease is similar in Americans and Canadians. However, among patients with previous symptomatic heart disease, functional status is higher in Americans than in Canadians. This difference may be due to different patterns of medical management of heart disease in the two countries.

Asymptomatic Cardiac Ischemia Pilot (ACIP) study: effects of coronary angioplasty and coronary artery bypass graft surgery on recurrent angina and ischemia. The ACIP investigators.

OBJECTIVES: The Asymptomatic Cardiac Ischemia Pilot (ACIP) study showed that revascularization is more effective than medical therapy in suppressing cardiac ischemia at 12 weeks. This report compares the relative efficacy of coronary angioplasty or coronary artery bypass graft surgery in suppressing ambulatory electrocardiographic (ECG) and treadmill exercise cardiac ischemia between 2 and 3 months after revascularization in the ACIP study. BACKGROUND: Previous studies have shown that coronary angioplasty and bypass surgery relieve angina early after the procedure in a high proportion of selected patients. However, alleviation of ischemia on the ambulatory ECG and treadmill exercise test have not been adequately studied prospectively after revascularization. METHODS: In patients randomly assigned to revascularization in the ACIP study, the choice of coronary angioplasty or bypass surgery was made by the clinical unit staff and the patient. RESULTS: Patients assigned to bypass surgery (n = 78) had more severe coronary disease (p = 0.001) and more ischemic episodes (p = 0.01) at baseline than those assigned to angioplasty (n = 92). Ambulatory ECG ischemia was no longer present 8 weeks after revascularization (12 weeks after enrollment) in 70% of the bypass surgery group versus 46% of the angioplasty group (p = 0.002). ST segment depression on the exercise ECG was no longer present in 46% of the bypass surgery group versus 23% of the angioplasty group (p = 0.005). Total exercise time in minutes on the treadmill exercise test increased by 2.4 min after bypass surgery and by 1.4 min after angioplasty (p = 0.02). Only 10% of the bypass surgery group versus 32% of the angioplasty group still reported angina in the 4 weeks before the 12-week visit (p = 0.001). CONCLUSIONS: Angina and ambulatory ECG ischemia are relieved in a high proportion of patients early after revascularization. However, ischemia can still be induced on the treadmill exercise test, albeit at higher levels of exercise, in many patients. Bypass surgery was superior to coronary angioplasty in suppressing cardiac ischemia despite the finding that patients who underwent bypass surgery had more severe coronary artery disease.

Effects of smoking on survival and morbidity in patients randomized to medical or surgical therapy in the Coronary Artery Surgery Study (CASS): 10-year follow-up. CASS Investigators.

OBJECTIVES: The goal of this study was to ascertain how continued cigarette smoking or smoking cessation related to long-term survival and morbidity in patients with established coronary artery disease managed with medical therapy or coronary bypass surgery. BACKGROUND: Although the association of cigarette smoking with coronary artery disease is well established, the morbidity and mortality associated with smoking behavior in patients with such disease receiving medical or surgical therapy are less well established. METHODS: The 780 patients randomized to medical therapy or coronary bypass surgery in the Coronary Artery Surgery Study (CASS) were subgrouped according to smoking behavior during a mean 11.2-year follow-up interval. Comparisons between smokers and nonsmokers were accomplished by univariate and Cox time-dependent multivariate analyses. RESULTS: Survival at 10 years after entry into the study was 82% among 468 patients who reported no smoking during follow-up (nonsmokers) compared with 77% among the 312 smokers (p = 0.025). Survival was 80% among those who smoked at entry but stopped (quitters) versus 69% among those who continued smoking (p = 0.025). For patients who smoked at baseline and were randomized to bypass surgery, survival at 10 years was 84% among quitters and 68% among nonquitters (p = 0.018); the difference in survival between quitters (75%) and nonquitters (71%) was less among those randomized to medical therapy (p = NS). Among those who smoked at baseline, continued smoking increased the relative risk of death by 1.73. After 10 years, smokers, in comparison with nonsmokers, were less likely to be angina free and more likely to be unemployed and had more activity limitation and more hospital admissions (primarily for chest pain, heart attack, cardiac catheterization, peripheral vascular surgery and stroke). CONCLUSIONS: Thus, among patients with documented coronary artery disease, continued cigarette smoking may result in decreased survival--especially among those undergoing bypass surgery. Moreover, smokers have more angina, more unemployment, a greater limitation of physical activity and more hospital admissions.

Prognostic significance of ventricular premature depolarizations measured 1 year after myocardial infarction in patients with early postinfarction asymptomatic ventricular arrhythmia.

OBJECTIVES: The objective of this study was to examine the relation between death and the frequency of premature ventricular depolarizations measured approximately 1 year after myocardial infarction. BACKGROUND: The reported association between premature ventricular depolarizations and death in the weeks after myocardial infarction is in part the basis for the use of antiarrhythmic drugs. Such an association has not been reported on for observations obtained at a much greater interval after myocardial infarction. METHODS: We examined the association between mortality and premature ventricular depolarization rates measured 1 year after myocardial infarction in patients with asymptomatic ventricular arrhythmia early (between 6 and 90 days, median 28) after infarction, as measured by 24-h ambulatory electrocardiographic recording. The study group consisted of 502 patients enrolled in the Cardiac Arrhythmia Pilot Study during 1983 to 1985. They were followed up during the course of the study and subsequently by a National Death Index search (average follow-up interval 1,080 days). RESULTS: Death was recorded for 87 patients through 1987. Because patients were admitted to the Cardiac Arrhythmia Pilot Study only if they had greater than or equal to 10 ventricular premature depolarizations/h, the arrhythmia rate measured at baseline (that is, early after infarction) was not expected to, and did not, predict mortality. In 360 patients ventricular premature depolarization rates were measured approximately 1 year from their index myocardial infarction while they were not receiving antiarrhythmic therapy. In these patients, who had survived 1 year after the index infarction, the rate of ventricular premature depolarizations/h measured 1 year after infarction was highly predictive of subsequent death (p less than 0.001). Recent heart failure and a history of diabetes mellitus were also strongly predictive of death. CONCLUSION: The prognostic value of ventricular premature depolarizations observed 1 year after a myocardial infarction may be significant even in a sample selected for frequent ventricular premature depolarizations observed early after the event.

Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling.

OBJECTIVES: We examined the association of sympathetic denervation and reduced blood flow with mechanical dysfunction in adjacent noninfarcted regions late after myocardial infarction (MI). BACKGROUND: Using a well characterized ovine model of left ventricular (LV) remodeling after transmural anteroapical MI, we previously showed that histologically normal adjacent noninfarcted regions demonstrate mechanical dysfunction. METHODS: Ten sheep underwent coronary ligation. Magnetic resonance imaging was performed before and 8 weeks after infarction for measurement of LV mass, volumes, ejection fraction and regional intramyocardial circumferential shortening (%S). Iodine-123 metaiodobenzylguanidine (I-123 MIBG) and fluorescent microspheres before and after administration of adenosine were infused before death for measurement of sympathetic innervation, blood flow and blood flow reserve from matched postmortem regions. RESULTS: From baseline to 8 weeks after infarction, LV end-diastolic volume increased from (mean +/- SD) 1.5 +/- 0.3 to 2.6 +/- 0.5 ml/kg (p < 0.001), and LV mass increased from 2.0 +/- 0.3 to 2.6 +/- 0.5 g/kg (p = 0.001). Regionally, the decline in subendocardial %S was greater in adjacent (19 +/- 5% to 8 +/- 5%) than in remote noninfarcted regions (20 +/- 6% to 19 +/- 6%, p < 0.002). No difference in regional blood flow or blood flow reserve was found between adjacent and remote regions, whereas I-123 MIBG uptake was lower in adjacent than in remote myocardium (1.09 +/- 0.30 vs. 1.31 +/- 0.40 nmol/g, p < 0.003). Topographically, from apex to base at 8 weeks after infarction, %S correlated closely with I-123 MIBG uptake (r = 0.93, p = 0.003). CONCLUSIONS: In mechanically dysfunctional noninfarcted regions adjacent to chronic transmural myocardial infarction in the remodeled left ventricle, blood flow and blood flow reserve are preserved, yet sympathetic innervation is reduced. Chronic sympathetic denervation in adjacent noninfarcted regions, in association with regional mechanical dysfunction, may contribute to LV remodeling after infarction.