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Type 2 diabetes mellitus (T2DM) significantly worsens heart failure (HF) prognosis.

In VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction), vericiguat compared with placebo reduced cardiovascular death or heart failure (HF) hospitalization in patients with HF with reduced ejection fraction.

The term precision medicine refers to the tailoring of diagnostics or therapeutics to individual patients based on their unique genetic and physiologic characteristics. (1) Although 'personalized or individualized care' (i.e., [...]

Vericiguat reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HF) in patients with worsening HF and reduced left ventricular ejection fraction (LVEF).

The association between frailty and health status in patients with heart failure with preserved ejection fraction (HFpEF) is not well known.

The effect of vericiguat on sequential N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and influence of this relationship on clinical outcomes is unknown.

Background: Baseline Q waves may provide additional value compared with time from the onset of symptoms in predicting outcomes for patients with ST-segment elevation. We evaluated whether baseline Q waves superseded time from symptom onset as a prognostic marker of one-year mortality in patients with ST-segment elevation acute coronary syndrome. Our study was derived from data from patients undergoing primary percutaneous coronary intervention within 24 hours in the PLATelet inhibition and patient Outcomes trial Methods: Q waves on the baseline electrocardiogram were evaluated by a blinded core laboratory. We assessed the associations between baseline Q waves and time from symptom onset to percutaneous coronary intervention with peak biomarkers, ST-segment resolution on the discharge electrocardiogram, and one-year all-cause and vascular mortality. Results: Of 4341 patients with ST-segment elevation, 46% had baseline Q waves. Compared to those without Q waves, those with baseline Q waves were older, more frequently male, had higher heart rates, more advanced Killip class and had a longer time between the onset of symptoms and percutaneous coronary intervention. They also had higher one-year all-cause mortality than patients without baseline Q waves (baseline Q waves: 4.9%; no baseline Q waves: 2.8%; hazard ratio [HR] 1.78, 95% confidence interval [CI] 1.29-2.45, p < 0.001). Complete ST-segment resolution was greatest and all-cause mortality lowest among those with symptom onset three hours or less before percutaneous coronary intervention and no baseline Q waves. After multivariable adjustment, baseline Q waves, but not time from symptom onset, were associated with a significant increase in all-cause mortality (adjusted HR 1.42, 95% CI 1.10-2.01, p = 0.046) and vascular mortality (adjusted HR 1.58, 95% CI 1.09-2.28, p = 0.02). Interpretation: The presence of baseline Q waves provides useful additional prognostic insight into the clinical outcome of patients with ST-segment elevation. Clinical Trials.gov registration no. NCT00391872, The clinical outcome of patients with ST-segment elevation myocardial infarction (STEMI) is directly related to the extent of myocardial necrosis. (1) Because the extent of necrosis is strongly influenced by [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2009.09.015 Byline: Renato D. Lopes (a), Aijing Starr (a), Carl F. Pieper (b), Sana M. Al-Khatib (a), L. Kristin Newby (a), Rajendra H. Mehta (a), Frans Van de Werf (c), Kenneth W. Mahaffey (a), Paul W. Armstrong (d), Robert A. Harrington (a), Harvey D. White (e), Lars Wallentin (f), Christopher B. Granger (a) Keywords: Acute coronary syndrome; Antithrombotics; Atrial fibrillation; Bleeding risk Abstract: We examined warfarin use at discharge (according to Congestive heart failure, Hypertension, Age75 years, Diabetes, Prior Stroke/transient ischemic attack score and bleeding risk) and its association with 6-month death or myocardial infarction in patients with post-acute coronary syndrome atrial fibrillation. Author Affiliation: (a) Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (b) Department of Biostatistics and Bioinformatics, School of Medicine, Duke University, Durham, NC (c) Department of Cardiology, University Hospital Gasthuisberg and Leuven Coordinating Center, Leuven, Belgium (d) Department of Medicine, Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada (e) Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand (f) Uppsala Clinical Research Center, Uppsala, Sweden Article Note: (footnote) Funding: The Duke Clinical Research Institute., Conflict of Interest: The authors state that they have no conflict of interest regarding the content of the article., Authorship: All authors had access to the data and played a role in writing this manuscript.

Background: Guidelines recommend that patients with heart failure receive [beta]-blockers in doses used in the trials that have proven their efficacy. Although the adverse effects of [beta]-blockade are dose-related, it is unclear whether the benefits are. Purpose: To determine whether the survival benefits of [beta]-blockade in heart failure are associated with the magnitude of heart rate reduction or the [beta]-blocker dose. Data Sources: MEDLINE, EMBASE, CINAHL, SIGLE, Web of Science, and the Cochrane Central Register of Controlled Trials, supplemented by hand-searches of bibliographies. Study Selection: Randomized, placebo-controlled heart failure trials that reported all-cause mortality. Data Extraction: Two reviewers independently extracted data on study characteristics, [beta]-blocker dosing and heart rate reduction, and death. Data Synthesis: The mean left ventricular ejection fraction in the 23 [beta]-blocker trials ranged from 0.17 to 0.36, and more than 95% of the 19 209 patients had systolic dysfunction. The overall risk ratio for death was 0.76 (95% CI, 0.68 to 0.84); however, heterogeneity testing revealed moderate heterogeneity among trials ([l.sup.2] = 30%), which was associated with the magnitude of heart rate reduction achieved within each trial (P for meta-regression = 0.006). For every heart rate reduction of 5 beats/min with [beta]-blocker treatment, a commensurate 18% reduction (CI, 6% to 29%) in the risk for death occurred. No significant relationship between all-cause mortality and [beta]-blocker dosing was observed (risk ratio for death, 0.74 [CI, 0.64 to 0.86]) in high-dose [beta]-blocker trials vs. 0.78 [CI, 0.63 to 0.96] in low-dose [beta]-blocker trials; P for meta-regression = 0.69). Limitations: The analysis is based on aggregate data and resting heart rates. Few patients in these trials had bradycardia or diastolic dysfunction at baseline. Conclusion: The magnitude of heart rate reduction is statistically significantly associated with the survival benefit of [beta]-blockers in heart failure, whereas the dose of [beta]-blocker is not.

Abstract Background: Previous studies examining sex-related differences in the treatment of coronary artery disease have focused on patients in hospital. We sought to examine sex-related differences at an earlier point [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.05.056 Byline: Wei-Ching Chang, Padma Kaul, Cynthia M. Westerhout, Michelle M. Graham, Paul W. Armstrong Keywords: Acute myocardial infarction; Socioeconomic status; Emergency department; Revascularization Abstract: To assess the effects of socioeconomic status on mortality in patients with acute myocardial infarction. Author Affiliation: University of Alberta, Edmonton, Alberta, Canada. Article Note: (footnote) This study was supported by a grant from the Canadian Institute of Health Research. Although the study is based in part on data provided by Alberta Health and Wellness, the interpretation and conclusions contained herein are those of the researchers and do not necessarily represent the views of the Government of Alberta. Neither the Government nor Alberta Health and Wellness express any opinion in relation to this study.

ABSTRACT Background: The optimal antithrombotic therapy to accompany tenecteplase in cases of acute ST-segment elevation myocardial infarction (STEMI) remains unclear. We undertook a prespecified pooled analysis of data from the [...]

Abstract Background: There is uncertainty about whether physician specialty influences the outcomes of outpatients with congestive heart failure after adjustment for differences in case mix. Our objective was to determine [...]

Background: Sudden cardiac death is common in persons with cardiovascular disease. Purpose: To assess the efficacy of implantable cardioverter defibrillators (ICDs) in persons at increased risk for sudden cardiac death. Data Sources: MEDLINE (1980-2002), EMBASE (1980-2002), Cochrane Controlled Clinical Trial Registry (2002, Volume 3), other databases, and conference proceedings. Primary study authors and device manufacturers were contacted, and bibliographies of relevant papers were hand searched. Study Selection: Randomized, controlled clinical trials evaluating ICDs versus usual care were selected. Data Extraction: Two reviewers extracted data independently. Data Synthesis: Eight trials were included in the final analysis (4909 patients, 1154 deaths). Compared with usual care (most commonly amiodarone therapy), ICDs significantly reduced sudden cardiac death (relative risk [RR], 0.43 [95% CI, 0.35 to 0.53]) and all-cause mortality (RR, 0.74 [CI, 0.67 to 0.82]). The included trials were divided a priori into two categories: secondary prevention (involving patients resuscitated after cardiac arrest or unstable ventricular tachycardia or ventricular fibrillation [n=1963]) and primary prevention (involving patients at increased risk for sudden cardiac death but without documented cardiac arrest, ventricular fibrillation, or ventricular tachycardia [n=2946]). Regardless of baseline risk, ICDs were equally efficacious in preventing sudden cardiac death in both types of trials (RR, 0.50 [CI, 0.38 to 0.66] for secondary prevention vs. 0.37 [CI, 0.27 to 0.50] for primary prevention). However, the magnitude of benefit in total mortality varied within the primary prevention trials depending on baseline risk for sudden cardiac death. Conclusions: Implantable cardioverter defibrillators prevent sudden cardiac death regardless of baseline risk. However, their impact on total mortality is sensitive to baseline risk for arrhythmic death. Decisions about resource allocation for ICDs depend on accurate stratification of patients according to risk.

Clinical practice guidelines are consensus statements systematically developed to help physicians, and ultimately patients, make decisions about appropriate health care for specific clinical circumstances. Over 20 years ago the American [...]

Background and Purpose. Nondistally fixated (ie, what is often referred to as 'open kinetic chain' [OKC]) knee extensor resistance training appears to have lost favor for some forms of rehabilitation due partly to concerns that this exercise will irritate the extensor mechanism. In this randomized, single-blind clinical trial, nondistally fixated versus distally fixated (ie, often called 'closed kinetic chain' [CKC]) leg extensor training were compared for their effects on knee pain. Subjects. Forty-three patients recovering from anterior cruciate ligament (ACL) reconstruction surgery (34 male, 9 female; mean age=29 years, SD=7.9, range= 16-54). Methods. Knee pain was measured at 2 and 6 weeks after ACL reconstruction surgery using visual analog scales in a self-assessment questionnaire and during maximal isometric contractions of the knee extensors. Between test sessions, subjects trained 3 times per week using either OKC or CKC resistance of their knee and hip extensors as part of their physical therapy. Results. No differences in knee pain were found between the treatment groups. Discussion and Conclusion. Open kinetic chain and CKC leg extensor training in the early period after ACL reconstruction surgery do not differ in their immediate effects on anterior knee pain. Based on these findings, further studies are needed using different exercise dosages and patient groups. [Morrissey MC, Drechsler WI, Morrissey D, et al. Effects of distally fixated versus nondistally fixated leg extensor resistance training on knee pain in the early period after anterior cruciate ligament reconstruction. Phys Ther. 2002;82:35-43.] Key Words: Anterior knee pain, Patellofemoral joint, Resistance training., We believe that since the early 1990s, there has been a shift among clinicians regarding the type of resistance exercise used for the knee extensors in knee rehabilitation. The shift, [...]

Abstract Objective To determine whether multidisciplinary disease management programmes for patients with coronary heart disease improve processes of care and reduce morbidity and mortality. Data sources Randomised clinical trials of [...]

To determine the prevalence of decreases in left ventricular (LV) ejection fraction (EF) at rest in patients with coronary artery disease (CAD), including those with stable angina (n = 21), unstable angina (n = 13), and recent myocardial infarction (n = 11), continuous assessment of LV function for 162 [+ or -] 136 minutes was performed using a new nuclear device. The results were compared with those of a group of normal subjects (n = 10) monitored for 80 [+ or -] 28 minutes. Episodes of EF reduction of >7% from baseline for a total duration of >5% monitored time occurred in 0 of 10 normal subjects; episodes were more frequent in patients with stable angina (10 of 21, 48%; p = 0.01), with recent myocardial infarction (7 of 11, 64%; p = 0.004), and with unstable angina (11 of 13, 8S%; p = 0.0001). The number of EF decreases per hour in patients after myocardial infarction (1.7 [+ or -] 2.5 [SD]) and unstable angina (1.2 [+ or -] 0.7) was significantly more frequent than in normal subjects (0.3 [+ or -] 0.4), but was not different from that in patients with stable angina (0.8 [+ or -] 1.0). The duration of the decrease in EF, expressed as minutes per hour of monitored time in normal subjects (0.7 [+ or -] 1.0%), was significantly less than in patients with unstable angina (10 [+ or -] 8%). Patients with stable angina (6 [+ or -] 9%) and recent myocardial infarction (6 [+ or -] 6%) were not significantly different from normal subjects. EF decrease in normal subjects was distinguished by an increase in heart rate with a decrease in end-diastolic volume but no change in end-systolic volume, whereas patients with CAD had a lesser increase in heart rate, no change in end-diastolic volume, and a significant increase in end-systolic volume. It is concluded that transient asymptomatic episodes of LV dysfunction often occur at rest in patients with CAD and are longest in patients with unstable angina. (Am J Cardiol 1994;74:137-143)

The role of ambulatory myocardial ischemia detection, in addition to exercise testing and myocardial perfusion scintigraphy, in the prediction of the angiographic severity of coronary artery disease in patients with stable angina was examined. Ninety-seven patients underwent ambulatory electrocardiographic monitoring, exercise testing with scintigraphy, and coronary angiography. In addition to the number of diseased vessels involved, proximal arterial segment and coronary artery jeopardy scores were calculated to evaluate the extent of disease and amount of myocardium at risk. Thirty patients (31%) had 1.8 [+ or -] 1.8 episodes/24 hours of ambulatory ischemia (94% of episodes were asymptomatic) and were similar to 67 without ambulatory ischemia in regard to clinical characteristics, left ventricular function and mean number of diseased vessels involved. Proximal arterial segment and coronary artery jeopardy scores were greater in: (1) 30 patients with versus 67 without ambulatory ischemia (3.3 [+ or -] 1.8 vs 1.9 [+ or -] 1.5 [p = 0.0002] and 6.6 [+ or -] 3.6 vs 5.0 [+ or -] 3,4 [p = 0.03], respectively); (2) 78 with versus 19 without a positive exercise test (2.6 [+ or -] 1.8 vs 1.4 [+ or -] 0.8 [p = 0.0001] and 6.1 [+ or -] 3.5 vs 3.0 [+ or -] 2.5 [p = 0.0003], respectively); and (3) 69 with versus 6 without a positive perfusion scan (2.4 [+ or -] 1.8 vs 1.0 [+ or -] [p = 0.0008] and 5.5 [+ or -] 3.6 vs 2.3 [+ or -] 2.0 [p = 0.03), respectively). In multivariate analysis, ambulatory ischemia was the best predictor of the proximal segment score, whereas exercise testing and myocardial perfusion imaging were predictive of the coronary jeopardy score. (Am J Cardiol 1994;73:747-752)

The influence of tissue plasminogen activator (t-PA) and heparin versus heparin alone on anatomic characteristic of patent infarct-related coronary arteries and the development of these angiographic descriptors in coronary arteries that remain patent during the hospital course was examined in 108 patients who participated in a placebo-controlled trial of recombinant tissue-type plasminogen activator in acute myocardial infarction. Coronary angiography was performed 18 [+ or -] 6 hours after treatment in 47 patients (group A) and at 10 days in 61 patients (group B). Quantitative coronary angiography of the infarct-related lesion was performed, and luminal irregularity was quantitated with an ulceration index. Of the 47 patients in group A, 7 (29%) treated with placebo had Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion, whereas 18 (78%) treated with t-PA had grade 2 or 3 (p Angiographic studies demonstrated the capacity of thrombolytic therapy to reestablish patency of occluded, infarct-related coronary arteries in patients presenting with acute transmural myocardial infarction. However, reocclusion after initial successful thrombolysis remains a difficult clinical problem, with an incidence ranging between 15 and 30%.[1] It has been suggested that reocclusion occurs more frequently at the site of severe residual coronary stenosis[2]; however, this issue remains controversial.[3] It is also now known that after thrombolytic therapy has been completed and patency reestablished, considerable remodeling of the residual coronary stenosis may occur during the subsequent hospital course.[4] However, there is little information concerning the angiographically defined natural history of coronary vessels that reperfuse spontaneously in patients who are not treated with thrombolytic therapy. If significant changes were to occur in these patients, it would be important to account for them in evaluating future, angiographically based, mechanistic studies of the efficacy of thrombolytic therapy. New studies of this problem are unlikely to emerge given the current ethical imperative to administer thrombolytic therapy to such patients. We previously reported the results of a randomized, placebo-controlled, double-blind trial of tissue plasminogen activator (t-PA) versus placebo in heparinized patients with acute Q-ware myocardial infarction in which left ventricular global and regional function was the principal end point.[5] In the present report of those patients, we compare the influence of t-PA and heparin versus heparin alone on: (1) qualitative and quantitative anatomic characteristics of patent infarct-related coronary arteries soon after presentation of acute myocardial infarction, and (2) the development of these angiographic descriptors in coronary arteries that remain patent during the hospital course. METHODS The details of this protocol were reported previously.[5] Inclusion criteria for study entry were: age between 20 and 75 years; and typical ischemic chest pain lasting >30 minutes, with ST elevation [is greater than or equal to] 1 mm in [is greater than or equal to] 2 inferior leads or leads and aVL, or [is greater than or equal to] 1.5 mm in [is greater than or equal to] 2 anterior precordial leads. Patients were excluded if they presented >3.75 hours after the onset of chest pain. Patients were recruited from 10 collaborating Toronto hospitals and randomized to receive either double-chain t-PA (Burroughs Wellcome) or matching placebo. Study drug: The first 39 patients received the study drug intravenously at 0.4 MU/kg/hour for hour 1, 0.14 MU/kg/hour for hour 2, and 0.03 MU/kg/hour for the subsequent 8 hours; the final 79 patients received 0.4 MU/kg/hour for hour 1, 0.08 MU/kg/hour for hour 2, and 0.03 MU/kg/hour for the subsequent 4 hours. Ten percent of the first hour's dose was administered as an initial bolus injection. This change in infusion duration was made as a result of independent studies with this agent indicating that longer infusion times may increase hemorrhagic risk without providing improved patency.[6] All patients received heparin, concomitant with the study drug, commencing with a bolus injection of 4,000 IU, followed by an infusion of 1,000 IU/hour. Heparin administration was continued for 96 hours with the objective of maintaining the partial thromboplastin time between 1.5 and 2 times the control value. In all patients, 325 mg/day of enteric-coated aspirin was commenced orally before cessation of heparin therapy. Cardiac catheterization: Angiography was performed according to the schema outlined in Figure 1. Forty-seven patients initially admitted to 3 core institutions with facilities for cardiac catheterization underwent coronary and left ventricular angiography, according to protocol, 18 [+ or -] 6 hours after administration of study drug (group A). Because we also wanted to examine the development of both quantitative and qualitative angiographic features between the first and second angiograms obtained in group A patients, we performed this comparison in all patients who did not have 100% obstruction of the infarct-related coronary artery on the initial angiogram (i.e., eligible patients for this analysis were those with Thrombolysis in Myocardial Infarction [TIMI] perfusion grades 1 to 3). Repeat coronary angiography was performed in those patients on hospital day 10. Of 66 patients initially admitted to hospitals without facilities for catheterization (group B), 61 underwent coronary angiography only on day 10 after transfer to 1 of 3 randomly assigned core hospitals. One patient from each of groups A and B was excluded from angiographic analysis, because their angiograms were not available for interpretation at the core laboratory. Four patients in group B did not undergo angiography for other reasons (2 died and 2 refused). Angiographic assessment of the infarct-related artery: All coronary angiograms were independently reviewed at the core angiographic site without knowledge of treatment assignment or timing of angiography. The infarct-related coronary artery lesion was determined using the admission electrocardiogram and left ventricular angiogram, and by identification of characteristic infarct-lesion morphology.[7] Infarct-related perfusion was classified according to the criteria of the TIMI investigators; for purposes of analysis of reocclusion, patency in group A was defined as TIMI perfusion grade 2 or 3.[8] Quantitative coronary angiography was performed by obtaining 2 orthogonal projections of the infarct-related lesion. Each projection was quantitative analyzed using the Coronary Angiography Analysis System method of Reiber et al.[9] The lumen was identified by an automatic edge-detection algorithm.[10] The lesion outline was corrected for magnification and pincushion distortion, and the minimal lesion diameter, diameter of the adjacent normal segment and percent diameter stenosis were determined geometrically for each projection. The cross-sectional area could then be determined by the product of the diameters in the right and left anterior oblique projections.[10] In 11 angiograms, analysis could only be performed in 1 projection; in these cases, the lumen was assumed to be circular. The degree of luminal irregularity was quantitated by calculation of an ulceration index according to methods described previously.[7] The infarct-related lesion was divided into 10 equal segments. The diameter of the artery at its second most stenotic point was divided by the maximal intralesional diameter. This number, the ulceration index, is inversely proportional to the degree of luminal irregularity within the lesion and is independent of the maximal luminal stenosis. Care was taken to reproduce similar projection views in the repeat studies of patients with 2 angriograms. Statistical analysis: Demographic and clinical baseline characteristics of the 2 treatment groups were summarized previously.[5] Continuous data are presented as mean [+ or -] SE. Categoric variables were compared using chi-square. Normally distributed, continuous variables were compared using Student's t test (2-tailed), with paired or unpaired observations as appropriate. Non-normally distributed continuous variables were compared using Wilcoxon signed-rank test. RESULTS The distribution of TIMI perfusion grades in the 47 group A patients who underwent early catheterization is depicted in Figure 2 according to treatment assignment. Seven patients (29%) treated with placebo had TIMI grade 2 or 3 perfusion, whereas 18 (78%) treated with t-PA had grade 2 or 3 patency (p In Figure 3, the frequency of TIMI grade 2 or 3 perfusion in patients undergoing early catheterization is compared with that in those undergoing only late catheterization (group B). In contrast to the early patency data from group A (placebo 29% and t-PA 78%), group B showed a placebo patency of 59% (17 of 29) at day 10 as compared with a t-PA patency of 75% (24 of 32) (p = 0.10) (observed difference 16%; 95% confidence interval -8 to 40%). The development of minimal luminal area and ulcerative index for group A patients with patent arteries is shown in Table I; analogous data for patients in group B who were studied only on hospital day 10 are also shown. The minimal luminal area increased significantly in both placebo- and t-PA-treated patients between 18 hours and 10 days. Although this change on an individual basis was proportionately greater in patients treated with t-PA than with placebo (87 vs 41%), it did not achieve statistical significance. There was no difference in luminal characteristics among patients treated with t-PA when this analysis was performed according to the 2 different t-PA maintenance regiments. Although the luminal area of the culprit vessel tended to be larger on hospital day 10 in patients treated with t-PA than with placebo in both groups A and B, this difference also did not achieve statistical significance. There was no difference in reference diameters between patients treated with placebo and t-PA, nor in the anatomic distribution of culprit vessels. The ulcerative index was similar in placebo and t-PA subsets in groups A and B, and there was no change in the ulcerate index over time in either placebo or t-PA patients in group A. The luminal areas of the 2 patients in the placebo group and the 2 in the t-PA group who reoccluded after early study in group A were 0.53, 0.15, 0.37 and [1.07 mm.sup.2], respectively. [TABULAR DATA I OMITTED] DISCUSSION These data provide new insights into the natural history of the infarct-related coronary artery of patients presenting with acute myocardial infarction and ST-segment elevation. Although t-PA produced marked and rapid improvement in overall patency (as defined by TIMI grade 2 or 3 perfusion) early after infarction as compared with heparin alone, this difference was attenuated at 10 days because of spontaneous recanalization in the placebo group. Although there was no statistically significant difference in the area of the infarct vessel lumen either early or later in the hospital course in the 2 treatment groups of patients who had The data on ulceration index indicate no difference in infarct-vessel morphology irrespective of whether patients received t-PA or placebo. The data contrast with the recent report of Davies et al,[4] which suggested substantial improvement in a modified ulceration index in patients with myocardial infarction treated with streptokinase and maintained on heparin during their hospital course. Davies calculated an ulceration index using the maximal intralesional diameter divided by the minimal diameter, as opposed to use of the second most severe diameter within the lesion, as in the present report. Hence, the Davies index is closely linked to the degree of stenosis and would be expected to decrease with time because of lessening of the maximal lesion stenosis. Difference in thrombolytic agents, the timing of sequential angiography, and other protocol features may also explain the disparity between their findings and ours. The similarity to group A lumen areas in group B patients who were studied only at hospital discharge gives further support to the substantial remodeling and increase in lumen area, which occur in the culprit infarct-related artery after the presentation. Future studies of the efficacy of new thrombolytic agents should consider the substantial improvement we found in the luminal areas of patients receiving heparin alone. Acknowledgment: It is a pleasure to acknowledge the technical assistance of Lois Adams, and the secretarial assistance of Linda Gray. [1] White CW. Recurrent ischemic events after successful thrombolysis in acute myocardial infarction. The Achilles' heel of thrombolytic therapy. Circulation 1989;80:1482-1485. [2] Badger RS, Brown BG, Kennedy JW, Mathey D, Gallery CA, Bolson EL, Dodge HT. Usefulness of recanalization to luminal diameter of 0.6 millimeter or more with intracoronary streptokinase during acute myocardial infarction in predicting 'normal' perfusion status, continued arterial patency and survival at one year. Am J Cardiol 1987;59:519-522. [3] Ellis SG, Topol EJ, George BS, Kereiakes DJ, Debowey D, Sigmon KN, Pickel A, Lee KL, Califf RM. Recurrent ischemia without warning -- analysis of risk factors for in-hospital ischemic events following successful thrombolysis with intravenous tissue plasminogen activator. Circulation 1989;80:1159-1165. [4] Davies SW, Marchant B, Lyons JP, Timmis AD, Rothman MT, Layton CA, Balcon R. Coronary lesion morphology in acute myocardial infarction: demonstration of early remodeling after streptokinase treatment. J Am Coll Cardiol 1990; 16:1079-1986. [5] Armstrong PW, Baigrie RS, Daly PA, Haq A. Gent M, Robert RS, Freeman MR, Burns R, Liu P, Morgan CD. Tissue plasminogen activator. Toronto (TPAT) placebo-controlled randomized trial in acute myocardial infarction. J Am Coll Cardiol 1989;13:1469-1476. [6] Kalbfleish J, Thadani U, LittleJohn JK, Brown G, Magorien R, Kutcher M, Taylor G, Maddox WT, Campbell WB, Perry J, Spann JF, Vetrovec G. Kent RS, Armstrong PW, Evaluation of a prolonged infusion of recombinant tissue-type plasminogen activator (duteplase) in preventing reocclusion following successful thrombolysis in acute myocardial infarction. Am J Cardiol 1992;69:1120-1127. [7] Wilson RF, Holida MD, White CW. Quantitative angiographic morphology of coronary stenoses leading to myocardial infarction or unstable angina. Circulation 1986;73:286-293. [8] TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial: phase 1 findings. N Engl J Med 1985;312:923-296. [9] Reiber JHC, Serruys PW, Koodman CJ, Wijns W, Slager CH, Gerbrands, JJ, Schuurbiers JCH, Den Boer A, Hugenholtz P. Assessment of short-, medium- and long-term variations in arterial dimensions from computer-assisted quantitation of coronary cineangiograms. Circulation 1985;71:280-288. [10] Langer A, Wilson RF, Comparison of manual versus automated edge detection for determining degrees of luminal narrowing by quantitative coronary angiography. Am J Cardiol 1990;67:885-888. [11] Van Lierde J, DeGeest H, Verstraete M, Van de Werf F. Angiographic assessment of the infarct-related residual coronary stenosis after spontaneous or therapeutic thrombolysis. J Am Coll Cardiol 1990;16:1545-1549. [12] Morgan CD, Roberts RS, Haq A, Baigrie RS, Daly PA, Gent M, Armstrong PW. Results from the Tissue Plasminogen Activator: Toronto (TPAT) placebo-controlled trial. Coronary patency, infarct size and left ventricular function following thrombolytic therapy for acute myocardial infarction. J Am Coll Cardiol 1991; 17:1451-1457. Amin Haq, MD, Christopher D. Morgan, MD, Robert F. Wilson MD, Paul A. Daly, MD, Robert S. Baigrie, MD, Carl W. White, MD, Robert Roberts, MTech, Michael Gent, MSc, and Paul W. Armstrong, MD, and the Toronto Tissue Plasminogen Activator Trial Study Group From St. Michael's Hospital; the Western and General Divisions, The Toronto Hospital; Sunnybrook Health Science Centre; and University of Toronto, Toronto, Ontario, Canada; the Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota; and the Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada. This study was supported by Burroughs Wellcome Co., Research Triangle Park, North Carolina.

Thehe hypothesis that an infusion of recombinant tissue-type plasminogen activator (rt-PA) maintained for up to 24 hours could prevent reocclusion after early coronary patency had been established was evaluated in patients with acute myocardial infarction. The rt-PA studied was an investigation double chain rt-PA (Duteplase(R), Burroughs Wellcome Co.), administered according to body weight. Coronary patency was documented in 139 of 213 patients who had 90-minute angiograms recorded after an initial lytic dose of rt-PA. In these responders a further 90-minute infusion at one third the initial lytic dose was given before assignment to 1 of 4 maintenance dose rate (0.012, 0.024, 0.036, 0.048 MIU/kg/hour) which were continued for the subsequent 9 to 21 hours. The principal end point was the status of the infarct-related coronary artery 12 to 24 hours after the start of therapy, and before termination of rt-PA, in patients with initially patent vessels at 90 minutes. Of the 103 responders with repeat angiograms after a 9 to 21 hour maintenance infusion of rt-PA, a total of 17 (16.5%) patients reoccluded across all doses administered. There was no significant relationship between the maintenance dose rate and the incidence of reocclusion. However, ther was strong association between total dose of rt-PA administered and the incidence (16%) of serious or life-threatening bleeding exclusive of surgery. Other factors associated with serious bleeding included low body weight, female gender, and total duration of rt-PA infusion. Re-occlusion was independent of the 90 minute Thrombolysis in Myocardial Infarction trial perfusion grade and diameter of infarct vessel. Rethrombosis after establishment of early patency after rt-PA remains a significant problem that is un-affected by sustained rt-PA infusion in doses that can be tolerated. (Am J Cardiol 1992;69:1120-1127)

Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating diseased coronary arteries that are narrowed or blocked, usually by fatty atherosclerotic plaques. PTCA involves inserting a balloon-tipped catheter into the constricted region and inflating the balloon to widen the diameter of the artery. The procedure can be dangerous, particularly in patients with heart problems affecting the left ventricle, which pumps blood from the heart to the body. PTCA can cause temporary blockages in coronary vessels and result in ischemia, or diminished blood flow to the heart, aggravating preexisting conditions. This study examined the use of hemoperfusion during PTCA; this technique involves injecting blood into the heart during PTCA to prevent ischemia. Measurements of left ventricular function and ischemia were recorded in nine patients who underwent PTCA, with and without hemoperfusion. The patients were men and had an average age of 52 years. Chest pain was reported in three patients during PTCA when hemoperfusion was not used, and in one when it was used. Left ventricular (LV) systolic pressure (during contraction) was significantly decreased during PTCA without hemoperfusion, but remained stable with it. LV end-diastolic pressure (when the ventricle fills with blood) increased to a much greater extent without hemoperfusion than with it. Other measures of LV function were better when hemoperfusion was used during PTCA than when it was not. These results indicate that hemoperfusion can be effective in protecting the heart from ischemia during PTCA, especially in high-risk patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

The prevalence of silent myocardial ischemia and its relation to autonomic dysfunction and pain threshold was studied in 58 men with diabetes mellitus and without cardiac symptoms. All patients underwent 48-hour ambulatory electrocardiographic monitoring and exercise testing after assessment of their autonomic function and pain threshold. Silent myocardial ischemia, defined as [is greater than or equal to] 1 mm of ST-segment depression on either exercise testing or ambulatory electrocardiographic monitoring, was corroborated by exercise-induced reversible defect(s) on tomographic thallium scintigraphy. Automatic function was assessed by heart rate response to: (1) Valsalva maneuver, (2) deep breathing, and (3) upright posture, as well as by diastolic blood pressure response to sustained handgrip and systolic blood pressure response to upright posture. Autonomic dysfunction was defined as [is greater than or equal to] 2 abnormal responses. Pain threshold measurements were performed using electrical cutaneous stimulation of both forearms. Of the 58 diabetic patients, 21 were found to have autonomic dysfunction (36%). Silent myocardial ischemia was detected in 10 patients (17%), and was significanlty more frequent in patients with than without autonomic dysfunction (38 vs 5%, p = 0.003). There was no difference in the electrical pain threshold or tolerance in subjects with and without silent myocardial ischemia. It is concluded that silent myocardial ischemia in asymptomatic diabetic men occurs frequently and in association with autonomic dysfunction, suggesting that diabetic neuropathy may be implicated in the mechanism of silent myocardial ischemia. (Am J Cardiol 1991;67:1073-1078), More than half of diabetic patients die from coronary artery disease, often before symptoms appear. The higher incidence of coronary artery disease and peripheral neuropathy (degeneration of nerves in the extremities) among diabetics provides a good opportunity to study the causes of silent myocardial ischemia (asymptomatic, transient reduction in blood flow to the heart). Fifty-eight men with diabetes, but no symptoms of coronary artery disease were assessed to determine the number of patients with silent myocardial ischemia, dysfunction (abnormalities) of the autonomic nervous system (which regulates the activity of the heart), and decreased sensitivity to pain. Seventeen percent of the participants were found to have silent myocardial ischemia, and the one-third who had dysfunction of the autonomic nervous system were seven times as likely to suffer silent ischemia as those who did not. Degeneration of the autonomic system among diabetics is common, and signals a much poorer outcome. These findings support earlier research indications that patients who died of silent (asymptomatic) heart attacks had typical diabetic degeneration of the sympathetic and parasympathetic branches of the autonomic nervous system. Pain threshold and tolerance did not discriminate between those with and those without ischemia, but autonomic dysfunction did, suggesting that diabetic neuropathy is implicated in the cause of silent myocardial ischemia. Diabetics without symptoms of heart disease, especially those with impaired autonomic nervous systems, should be examined for myocardial ischemia. The relation of myocardial ischemia to the development of heart attack, symptomatic ischemia, heart failure and sudden cardiac death in patients with diabetes needs to be evaluated. (Consumer Summary produced by Reliance Medical Information, Inc.)

IMPORTANCE: The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH. OBJECTIVE: To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTS: Analysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (&lt;6 months) worsening HF (ejection fraction &lt;45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020. INTERVENTION: Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS: Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms. CONCLUSIONS AND RELEVANCE: Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02861534

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Angina (cardiac chest pain) can be classified as stable or unstable. Unstable angina occurs with little or no exertion and with increasing frequency. Because unstable angina carries a relatively high risk of heart attack (myocardial infarction) and death, efforts have been made to find the most clinically useful tests to identify patients at greatest risk. Current strategies include 24-hour electrocardiogram (Holter) monitoring, standard stress testing, exercise testing with nuclear imaging, and coronary angiograms. Fifty-four patients with unstable angina, who were admitted to a coronary care unit, were studied with 24-hour electrocardiograms immediately on admission, and were stabilized with anti-anginal medications. When the patients were pain-free for 24 hours, they underwent routine exercise stress testing and nuclear stress testing. In the latter, thallium is injected during maximal exercise and special photographic images are taken of the heart that outline areas of muscle receiving inadequate oxygen supplies during exercise. Holter monitoring was not predictive of future adverse cardiac events, and routine stress tests were similarly unhelpful in predicting future risks. However, thallium stress tests were more useful. Thallium studies were even more accurate than coronary angiograms in identifying patients with unstable angina who were likely to have adverse cardiac events, such as myocardial infarction or even death. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Background: Emerging evidence suggests that coronary intensive care units are evolving into intensive care environments with an increasing burden of non-cardiovascular illness, but previous studies have been limited to older populations or single center experiences.Methods: Canadian national health-care data was used to identify all patients ≥18 years admitted to dedicated coronary intensive care units (2005–2015) and admissions were categorized as primary cardiac or non-cardiac. The outcomes of interest included longitudinal trends in admission diagnoses, critical care therapies, and all-cause in-hospital mortality.Results: Among the 373,992 patients admitted to a coronary intensive care unit, minimal changes in the proportion of patients admitted with a primary cardiac (88.2% to 86.9%; p<0.001) and non-cardiac diagnoses (11.8% to 13.1%; p<0.001) were observed. Among cardiac admissions, a temporal increase in the proportion of ST-segment elevation myocardial infarction (19.4% to 24.1%, p<0.001), non-ST-segment elevation myocardial infarction (14.6% to 16.2%, p<0.001), heart failure (7.3% to 8.4%, p<0.001), shock (4.9% to 5.7%, p<0.001), and decline in unstable angina (4.9% to 4.0%, p<0.001) and stable coronary diseases (21.3% to 12.4%, p<0.001) was observed. The proportion of patients requiring critical care therapies (57.8% to 63.5%, p<0.001) including mechanical ventilation (9.6% to 13.1%, p<0.001) increased. In-hospital mortality rates for patients with primary cardiac (4.9% to 4.4%; adjusted odds ratio 0.71, 95% confidence interval 0.63–0.79) and non-cardiac (17.8% to 16.1%; adjusted odds ratio 0.84, 0.73–0.97) declined; results were consistent when stratified by academic vs community hospital, and by the presence of on-site percutaneous coronary intervention.Conclusion: In a national dataset we observed a changing case-mix among patients admitted to a coronary intensive care unit, though the proportion of patients with a primary cardiac diagnosis remained stable. There was an increase in clinical acuity highlighted by critical care therapies, but in-hospital mortality rates for both primary cardiac and non-cardiac conditions declined across all hospitals. Our findings confirm the changing coronary intensive care unit case-mix and have implications for future coronary intensive care unit training and staffing.

IMPORTANCE: Conducting a clinical trial involves significant risks, time, and resources. The return on investment for these trials, measured by advancing health care and contributions to the scientific literature, is often uncertain. OBJECTIVE: To assess the long-term effects of major clinical trials of acute coronary syndromes contemporary to the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial, which did not achieve its primary objective. EVIDENCE REVIEW: The Cochrane Central Register of Controlled Trials database was screened for clinical trials of acute coronary syndromes (including unstable angina, ST-elevation myocardial infarction, and non–ST-elevation myocardial infarction) with more than 1000 participants and primary results published between January 1, 2005, and December 31, 2009, in Circulation, European Heart Journal, JAMA, Journal of the American College of Cardiology, The Lancet, and The New England Journal of Medicine. For identified trials, bibliographic information, citations, trial name, registration, inclusion diagnosis, intervention type, sample size, primary outcome result, sponsor information, and academic involvement were extracted. To identify secondary analyses, bibliographic information for citing articles, their citations, and their abstracts were extracted. Clinical practice guideline bibliographies for citations of trial publications were reviewed, and the class and level of evidence of resulting recommendations were extracted. FINDINGS: Of 784 records screened, 30 were primary publications of 25 clinical trials. Through December 31, 2018, these trials were cited a median of 497 times (interquartile range [IQR], 424-931 citations). Trials that did not achieve their primary objective had fewer primary citations (the number of times that each published journal article with the primary [main] results of a trial was cited) (median, 443 [IQR, 396-468] vs 868 [IQR, 645-1774] citations, P = .006). The frequency of secondary analyses peaked within 5 years of the primary trial at 643. Trials that did not achieve the primary objective had fewer secondary analyses (median, 15 [IQR, 5-31] vs 18 [IQR, 10-43] analyses, P = .44) that were not cited significantly less often (median, 484 [IQR, 191-1299] vs 1124 [IQR, 410-4283] citations, P = .16). All trials were cited by at least 1 clinical practice guideline. CONCLUSIONS AND RELEVANCE: This review found that trials that achieved the primary objective were frequently cited. Secondary research activity did not differ by primary result, and the primary trials and secondary analyses contributed to clinical practice recommendations. These data show the long-term importance of clinical trials regardless of primary outcome result.

The purpose of this study was to examine the treatment effect of vericiguat in relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at randomization.

Background: Despite guideline recommendations, the majority of patients with symptoms suggestive of acute coronary syndrome do not use emergency medical services to reach the emergency department (ED). The aim of this study was to investigate the factors associated with EMS utilisation and subsequent patient outcomes.Methods: Using administrative data, all patients who presented to an ED in the metropolitan areas of Edmonton and Calgary in the years of 2007–2013 with main ED diagnosis of acute coronary syndrome, stable angina or chest pain were included. The travel distance was estimated using the geographic information system method to approximate the distance between the ED and patient home. The clinical endpoints were the 7-day and 30-day all-cause events (death, re-hospitalisation and repeat ED visit).Results: Of 50,881 patients, 30.5% presented by emergency medical services. Patients with older age, female sex, ED diagnosis of acute coronary syndrome, more comorbidities and lower household income were more likely to use emergency medical services to reach the hospital. Longer travel distance was associated with higher emergency medical services use (odds ratio 1.09, 95% confidence interval 1.09–1.10), but it was not a predictor of clinical events. After adjustment for covariates and inverse propensity score weighting, emergency medical services use was associated with a higher risk of 7-day and 30-day clinical events.Conclusion: Several demographic and clinical features were associated with higher emergency medical services use including geographical variation. Although longer travel distance was shown to be linked to higher emergency medical services use, it was not an independent predictor of patient outcome. This has implications for the design of emergency medical services systems, triage and early diagnosis and treatment options.

Aims: The purpose of this study was to compare outcomes associated with medical management of ST-elevation myocardial infarction and non-ST-elevation myocardial infarction patients presenting to hospitals with and without onsite catheterization facilities.Methods All patients (n=25,921) with ST-elevation myocardial infarction (n=10,563) or non-ST-elevation myocardial infarction (n=15,358) in Alberta, Canada between April 2010–March 2016 were categorized according to availability of catheterization facilities at the hospital they presented to and their management strategy (medically managed without coronary angiography or medically managed after coronary angiography).Results: Overall, 51% presented to hospitals without catheterization facilities; and 34% were managed medically (18% without coronary angiography, and 16% after coronary angiography). Rates of medical management were higher at hospitals without versus those with catheterization facilities (43% vs. 24%, p<0.01). However, both the rate of presentation to hospitals without catheterization facilities (70% non-ST-elevation myocardial infarction, 24% ST-elevation myocardial infarction, p<0.01) and medical management (45% non-ST-elevation myocardial infarction, 18% ST-elevation myocardial infarction, p<0.01) differed by myocardial infarction type. The lack of catheterization facilities at the presenting hospital had no association with in-hospital mortality in patients medically managed without coronary angiography, but was associated with a lower risk of mortality among patients medically managed after coronary angiography. However, the latter benefit was restricted to non-ST-elevation myocardial infarction patients only (adjusted hazard ratio 0.43, 95% confidence interval: 0.25–0.76).Conclusion: The availability of catheterization facilities at the hospital at which non-ST-elevation myocardial infarction and ST-elevation myocardial infarction patients presented influenced their likelihood of being medically managed, but was not associated with adverse short- or long-term mortality outcomes.

The effect of sex on self-reported frailty in acute coronary syndromes (ACS) is unclear. We examined the prevalence of self-reported frailty and its association with all-cause death among men and women.

Background: Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF. Methods: The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.3 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. Results: Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, [is less than] 120 mm Hg; creatinine, [is greater than or equal to] 132.6 [micro]mol/L [[is greater than or equal to] 1.5 mg/dL]; age, [is greater than or equal to] 70 years; and patients with diabetes) generally tolerated the high-dose strategy. Conclusions: These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted. Arch Intern Med. 2001;161:165-171