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Background: Greater insight into sex-based differences in health status can lay the foundation for more equitable health care. This study compares differences in health status of women and men in the CPORT-E trial (Cardiovascular Patient Outcomes Research Team Non-Primary Percutaneous Coronary Intervention) undergoing nonprimary percutaneous coronary intervention. Methods: We compared Seattle Angina Questionnaire scores at baseline, 6 weeks, and 9 months for 6851 women and 12 016 men undergoing nonprimary percutaneous coronary intervention. Results: Proportions of angina-free patients increased from 26.2% and 29.8% at baseline to 71.6% and 78.7% at 6 weeks to 78.1% and 83.0% at 9 months in women and men, respectively ( P P P Conclusions: Although health status increased significantly after percutaneous coronary intervention in both women and men, women had poorer health status outcomes than men before and after percutaneous coronary intervention. Additional investigation into therapies that address the causes of poorer health status in women with coronary artery disease is needed. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00549796.

OBJECTIVES To compare bivalirudin to heparin during non-primary percutaneous coronary intervention (PCI). BACKGROUND The optimal anticoagulant to support PCI remains uncertain. METHODS We performed a propensity score-based analysis comparing clinical outcomes of patients receiving heparin to those receiving bivalirudin during non-primary PCI. RESULTS Of 18,867 patients in the Cardiovascular Patient Outcomes Research Team Non-Primary PCI (CPORT-E) trial, we selected 7,913 patients undergoing non-staged PCI of whom 57.3% received heparin and 42.7% received bivalirudin. In-hospital myocardial infarction occurred in 4.4% of patients receiving bivalirudin and 3.0% of patients receiving heparin (relative risk [RR] 1.5, 95% confidence interval [CI] 1.1-2.1, P = 0.022); this difference persisted at 6 weeks (5.0% vs. 3.6%, RR 1.4, 95% CI 1.0-1.8, P = 0.041). There was no difference in all-cause mortality either in-hospital (0.2% vs. 0.1% for heparin vs. bivalirudin, P = 0.887) or at 6 weeks (0.5% vs. 0.7%, P = 0.567). In-hospital bleeding requiring transfusion occurred in 0.9% of patients receiving bivalirudin and 1.9% of patients receiving heparin (RR 0.4, 95% CI 0.3-0.7, P

Background The CPORT-E trial showed the noninferiority of nonprimary percutaneous coronary intervention (PCI) at hospitals without cardiac surgery on-site (SoS) compared with hospitals with SoS for 6-week mortality and 9-month major adverse cardiac events (MACE). However, target vessel revascularization (TVR) was increased at non-SoS hospitals. Therefore, we aimed to determine the consistency of the CPORT-E trial findings across the spectrum of enrolled patients. Methods Post hoc subgroup analyses of 6-week mortality and 9-month MACE, defined as the composite of death, Q-wave myocardial infarction, or TVR, were performed. Patients with and without 9-month TVR and rates of related outcomes were compared. Results There was no interaction between SoS status and clinically relevant subgroups for 6-week mortality or 9-month MACE (P for any interaction = .421 and .062, respectively). In addition to increased 9-month rates of TVR and diagnostic catheterization at hospitals without SoS, non-TVR was also increased (2.7% vs 1.9%, P = .002); there was no difference in myocardial infarction–driven TVR, non-TVR, or diagnostic catheterization. Predictors of 9-month TVR included intra-aortic balloon pump use, any index PCI complication, and 3-vessel PCI, whereas predictors of freedom from TVR included SoS, discharge on a P2Y12 inhibitor, and stent implantation. Conclusions The noninferiority of nonprimary PCI at non-SoS hospitals was consistent across clinically relevant subgroups. Elective PCI at an SoS hospital conferred a TVR benefit which may be related to a lower rate of referral for diagnostic catheterization for reasons other than myocardial infarction.

Historically, percutaneous coronary intervention (PCI) was relegated to hospitals with colocated cardiac surgery because of the potential need for emergent surgical treatment of PCI-related complications. In the current issue of Circulation , Lee and colleagues1 compare outcomes of PCI at hospitals with and without on-site cardiac surgery and show that emergency cardiac surgery is, in fact, rarely needed ( 1 million patients and demonstrates that the incidence of other PCI-related complications, including myocardial infarction, stroke, cardiogenic shock, aortic dissection, and tamponade, as well as early (within 30 days) and late (after 30 days) all-cause mortality, is not different at hospitals with and without colocated cardiac surgery.1 Article see p 388 Because of inconsistencies among the studies, other outcomes indicators of quality, including the need for target vessel revascularization, could not be evaluated in detail. However, when results from the 2 randomized, controlled trials reporting target vessel revascularization (Cardiovascular Patient Outcomes Research Team Trial [CPORT-E]2 and Percutaneous Coronary Intervention [PCI] Outcomes in Community Versus Tertiary Settings [MASS COMM]3) were combined, rates of target vessel revascularization were similar at hospitals with and without on-site cardiac surgery. This important contribution confirms and puts on a more solid evidence-based foundation current guideline recommendations that allow the performance of primary and nonprimary PCI at hospitals without on-site surgery.4 Like all important studies, this report raises a number of questions. Although PCI at hospitals without on-site cardiac surgery is safe and effective, what is the motivation for extending nonprimary PCI at these facilities? What are the consequences of extending PCI to more hospitals? How should the extensive research knowledge base summarized by Lee and colleagues be applied to the development of PCI programs at hospitals without on-site cardiac surgery? The cynical view is that …

To compare bivalirudin to heparin during non-primary percutaneous coronary intervention (PCI).The optimal anticoagulant to support PCI remains uncertain.We performed a propensity score-based analysis comparing clinical outcomes of patients receiving heparin to those receiving bivalirudin during non-primary PCI.Of 18,867 patients in the Cardiovascular Patient Outcomes Research Team Non-Primary PCI (CPORT-E) trial, we selected 7,913 patients undergoing non-staged PCI of whom 57.3% received heparin and 42.7% received bivalirudin. In-hospital myocardial infarction occurred in 4.4% of patients receiving bivalirudin and 3.0% of patients receiving heparin (relative risk [RR] 1.5, 95% confidence interval [CI] 1.1-2.1, P = 0.022); this difference persisted at 6 weeks (5.0% vs. 3.6%, RR 1.4, 95% CI 1.0-1.8, P = 0.041). There was no difference in all-cause mortality either in-hospital (0.2% vs. 0.1% for heparin vs. bivalirudin, P = 0.887) or at 6 weeks (0.5% vs. 0.7%, P = 0.567). In-hospital bleeding requiring transfusion occurred in 0.9% of patients receiving bivalirudin and 1.9% of patients receiving heparin (RR 0.4, 95% CI 0.3-0.7, P0.001), but there was no difference at 6 weeks (2.7% for heparin vs. 1.9% for bivalirudin, RR 0.7, 95% CI 0.5-1.0, P = 0.062).In patients undergoing non-primary PCI at hospitals without on-site cardiac surgery, bivalirudin was associated with a decreased risk of in-hospital bleeding requiring transfusion and an increased risk of in-hospital MI compared to heparin. © 2017 Wiley Periodicals, Inc.

Background— Primary percutaneous coronary intervention (PCI) is more effective on average than fibrinolytic therapy in the treatment of ST-segment–elevation myocardial infarction. Yet, most US hospitals are not equipped for PCI, and fibrinolytic therapy is still widely used. This study evaluated the comparative effectiveness of ST-segment–elevation myocardial infarction regionalization strategies to increase the use of PCI against standard emergency transport and care. Methods and Results— We estimated incremental treatment costs and quality-adjusted life expectancies of 2000 patients with ST-segment–elevation myocardial infarction who received PCI or fibrinolytic therapy in simulations of emergency care in a regional hospital system. To increase access to PCI across the system, we compared a base case strategy with 12 hospital-based strategies of building new PCI laboratories or extending the hours of existing laboratories and 1 emergency medical services–based strategy of transporting all patients with ST-segment–elevation myocardial infarction to existing PCI-capable hospitals. The base case resulted in 609 (95% CI, 569–647) patients getting PCI. Hospital-based strategies increased the number of patients receiving PCI, the costs of care, and quality-adjusted life years saved and were cost-effective under a variety of conditions. An emergency medical services–based strategy of transporting every patient to an existing PCI facility was less costly and more effective than all hospital expansion options. Conclusion— Our results suggest that new construction and staffing of PCI laboratories may not be warranted if an emergency medical services strategy is both available and feasible.

Preamble......83 Introduction......84 Purpose......85 Writing Group Composition......85 Literature Review......85 Percutaneous Coronary Intervention......85 Evolution of Competence and Training Standards......85 Evolution of Coronary Interventional Capabilities......86 Procedural Success and

Primary percutaneous coronary intervention (PPCI) yields superior mortality outcomes compared with thrombolysis in ST-elevation acute myocardial infarction (STEMI) but takes longer to administer. Previous meta-regressions have estimated that a procedure-related delay of 60 minutes would nullify the benefits of PPCI on mortality. Using a combined database from randomized clinical trials and registries (n = 2,781) and an independently developed model of mortality risk in STEMI, we developed logistic regression models predicting 30-day mortality for PPCI and thrombolysis by examining the influence of baseline risk on the treatment effect of PPCI and on the hazard of treatment delay. We used these models to solve mathematically for "time interval to mortality equivalence," defined as the PPCI-related delay that would nullify its expected mortality benefit over thrombolysis, and to explore the influence of baseline risk on this value. As baseline risk increases, the relative benefit of PPCI compared with thrombolytic therapy significantly increases (p = 0.002); patients with STEMI at relatively low risk of mortality accrue little or no incremental mortality benefit from PPCI, but high-risk patients benefit greatly. However, as baseline risk increases, the hazard associated with longer treatment-related delay also increases (p = 0.007). These 2 effects are compensatory and yield a roughly uniform time interval to mortality equivalence of approximately 100 minutes in patients who have at least a moderate degree of mortality risk (> approximately 4%). In conclusion, the mortality benefits of PPCI and the hazard of PPCI-related delay depend on baseline risk. Previous meta-regressions appear to have underestimated the PPCI-related delay that would nullify the incremental benefits of PPCI.

> Discontent is the first necessity of progress. > > —Thomas Edison In November of 1993, 3 reports that published simultaneously in the New England Journal of Medicine demonstrated the superiority of primary percutaneous coronary intervention (PCI) over thrombolytic therapy for treatment of patients with acute ST-segment–elevation myocardial infarction (STEMI).1–3 At that time, within my hospital system, the Johns Hopkins Health System, there were 2 acute care hospitals: the Johns Hopkins Hospital, a tertiary center with both PCI and cardiac surgery capability, and the Bayview Medical Center, a community hospital that could provide neither revascularization modality. In 1993, ≈20 patients with acute STEMI presented to our tertiary facility annually, whereas our community hospital admitted >5× that number. Because State healthcare regulation prohibited performance of PCI at hospitals without colocated cardiac surgery, the superior therapy could be applied at the hospital where the minority of patients presented, whereas at the hospital where the overwhelming majority of patients with STEMI presented primary PCI was not available. Article see p 797 This situation was replicated in many areas around the country, essentially restricting access to the better form of therapy for many patients with STEMI. The rationalized solution to this dilemma offered 2 alternatives: (1) continue to simply offer the “community hospital standard of care,” thrombolytic therapy, to patients with STEMI presenting to non-PCI hospitals or (2) transfer patients from non-PCI–capable to PCI-capable facilities for primary PCI. We were not satisfied with these proposed solutions. In the first, an inferior therapy is offered to patients with STEMI simply because of an accident of geography: they presented to the “wrong” hospital. Furthermore, transfer was not practical. According to Goggle Maps, in the absence of traffic, the Hopkins tertiary and community hospitals are separated geographically by 3.1 miles and temporally by 11 minutes. Yet in …

Background This study was done to determine whether cardiovascular reactivity to mental stress is associated with exercise-induced occult ischemia in an asymptomatic population at high risk for premature coronary heart disease (CHD). Methods and Results One hundred fifty-two siblings of persons with premature CHD underwent mental stress testing. Exercise thallium tomography and 24-hour Holter monitoring were also performed. Hemodynamic changes were monitored during both stressors. Siblings positive for exercise-induced ischemia were offered cardiac catheterization. During mental stress, siblings with an abnormal exercise ECG and/or thallium scan (n=15) had greater maximal increases in systolic blood pressure (SBP, P =.0004) and diastolic blood pressure (DBP, P =.05) and had greater heart rate variability in the normalized low frequency domain of an analysis of Holter monitor recordings, compared with siblings without exercise-induced ischemia. Coronary arteriography confirmed coronary atherosclerosis in 85% of siblings with exercise-induced ischemia. Regression analyses showed that occult ischemia during exercise was a strong independent predictor of maximal change in SBP and DBP during mental stress. A multivariate logistic model demonstrated that siblings with exercise-induced occult ischemia were 21 times more likely to be “hot” responders (top quartile of change in SBP and DBP) during mental stress. Conclusions An exaggerated cardiovascular response to mental stress is associated with exercise-induced myocardial ischemia in persons with preclinical coronary heart disease.

Background In the EPIC trial, c7E3 Fab, an antiplatelet IIb/IIIa receptor antibody, reduced 30-day ischemic end points after high-risk coronary angioplasty by 35% and 6-month ischemic events by 23% but increased in-hospital bleeding episodes. Methods and Results Of the 2099 patients randomized in EPIC, data were collected on 2038 (97%) for prospective hospital cost and major resources. Physician fees were estimated from the Medicare Fee Schedule. Regression analysis was used to examine the economic tradeoff between reduced ischemic events and increased major bleeding during the initial hospitalization. A potential cost savings of $622 per patient during the initial hospitalization from reduced acute ischemic events with c7E3 Fab was offset by an equivalent rise ($521) in costs as the result of an increase in bleeding episodes. Baseline medical costs for the bolus and infusion c7E3 Fab arm averaged $13 577 (exclusive of drug cost) compared with $13 434 for placebo ( P =.42). During the 6-month follow-up, c7E3 Fab decreased repeat hospitalization rates by 23% ( P =.004) and repeat revascularization by 22% ( P =.04), producing a mean $1270 savings per patient (exclusive of drug cost) ( P =.018). With a cost of $1407 for the bolus and infusion c7E3 Fab regimen, the cumulative net 6-month cost to switch from standard care to routine c7E3 Fab averaged $293 per patient. Conclusions In high-risk coronary angioplasty, aggressive platelet inhibition with c7E3 Fab, by significantly reducing ischemic events and repeat revascularization, recoups most of the cost of therapy and has the potential to pay for itself.

Objectives.This study investigated whether an antibody against neutrophil adhesion protein CD18 could limit myocardial infarct size and preserve left ventricular function after prolonged reperfusion in a canine model.Background.Myocardial reperfusion injury is mediated in part by accumulation of activated neutrophils. Although antibodies against CD18 have been shown to reduce neutrophil influx and infarct size after ischemia and 3 to 4 h of reperfusion, it is unknown whether protection is sustained beyond this time or whether there is meaningful preservation of ventricular function.Methods.Dogs undergoing 90-min circumflex coronary artery occlusion and 48-h reperfusion were randomized to receive 1 mg/kg bodyweight of R15.7 (an anti-CD18 antibody, n = 12) or saline (control, n = 12) 10 min before reperfusion. Contrast left ventriculography was used to measure left ventricular ejection fraction and regional chord shortening at baseline, during occlusion and at 48 h. Microspheres injected during occlusion were used to measure collateral flow and risk region size. Postmortem infarct size was measured with triphenyltetrazolium chloride.Results.In the dose administered, R15.7 bound to neutrophils in vivo, with >85% saturation of CD18 for >24 h, with sustained antibody excess in the plasma. R15.7 significantly reduced infarct size after adjusting for the effect of collateral flow (p = 0.0002, analysis of covariance). In a subgroup of dogs with collateral flow

Objectives. This study sought to analyze the outcomes of revascularization procedures in the treatment of allograft coronary disease. Background. Allograft vasculopathy is the main factor limiting survival of heart transplant recipients. Because no medical therapy prevents allograft atherosclerosis, and retransplantation is associated with suboptimal allograft survival, palliative coronary revascularization has been attempted. Methods. Thirteen medical centers retrospectively analyzed their complete experience with percutaneous transluminal coronary angioplasty, directional coronary atherectomy and coronary bypass graft surgery in allograft coronary disease. Results. Sixty-six patients underwent coronary angioplasty. Angiographic success (≤ 50% residual stenosis) occurred in 153 (94%) of 162 lesions. Forty patients (61%) are alive without retransplantation at 19 ± 14 (mean ± SD) months after angioplasty. The consequences of failed revascularization were severe. Two patients sustained periprocedural myocardial infarction and died. Angiographic restenosis occurred in 42 (55%) of 76 lesions at 8 ± 5 months after angioplasty. Angiographic distal arteriopathy adversely affected allograft survival. Eleven patients underwent directional coronary atherectomy. Angiographic success occurred in 9 (82%) of 11 lesions. Two periprocedural deaths occurred. Nine patients are alive without transplantation at 7 ± 4 months after atherectomy. Bypass graft surgery was performed in 12 patients. Four patients died perioperatively. Seven patients are alive without retransplantation at 9 ± 7 months after operation. Conclusions. Coronary revascularization may be an effective palliative therapy in suitable cardiac transplant recipients. Angioplasty has an acceptable survival in patients without angiographic distal arteriopathy. Because few patients underwent atherectomy and coronary bypass surgery, assessment of these procedures is limited. Angiographic distal arteriopathy is associated with decreased allograft survival in patients requiring revascularization.

Performance of percutaneous coronary intervention (PCI) is usually restricted to hospitals with cardiac surgery on site. We conducted a noninferiority trial to compare the outcomes of PCI performed at hospitals without and those with on-site cardiac surgery.We randomly assigned participants to undergo PCI at a hospital with or without on-site cardiac surgery. Patients requiring primary PCI were excluded. The trial had two primary end points: 6-week mortality and 9-month incidence of major adverse cardiac events (the composite of death, Q-wave myocardial infarction, or target-vessel revascularization). Noninferiority margins for the risk difference were 0.4 percentage points for mortality at 6 weeks and 1.8 percentage points for major adverse cardiac events at 9 months.A total of 18,867 patients were randomly assigned in a 3:1 ratio to undergo PCI at a hospital without on-site cardiac surgery (14,149 patients) or with on-site cardiac surgery (4718 patients). The 6-week mortality rate was 0.9% at hospitals without on-site surgery versus 1.0% at those with on-site surgery (difference, -0.04 percentage points; 95% confidence interval [CI], -0.31 to 0.23; P=0.004 for noninferiority). The 9-month rates of major adverse cardiac events were 12.1% and 11.2% at hospitals without and those with on-site surgery, respectively (difference, 0.92 percentage points; 95% CI, 0.04 to 1.80; P=0.05 for noninferiority). The rate of target-vessel revascularization was higher in hospitals without on-site surgery (6.5% vs. 5.4%, P=0.01).We found that PCI performed at hospitals without on-site cardiac surgery was noninferior to PCI performed at hospitals with on-site cardiac surgery with respect to mortality at 6 weeks and major adverse cardiac events at 9 months. (Funded by the Cardiovascular Patient Outcomes Research Team [C-PORT] participating sites; ClinicalTrials.gov number, NCT00549796.).

Whether non-primary PCI performed at hospitals without on-site cardiac surgery is safe and effective remains controversial. The Cardiovascular Patient Outcomes Research Team Trial (CPORT-E) compared outcomes of non-primary percutaneous coronary intervention (PCI) performed at hospitals with (SOS)

A prospective study of 53 patients employed in the 6-month period before coronary angioplasty was performed to determine the direct and indirect costs of lag time in work resumption. The total direct costs calculated were $273,480; indirect costs for this sample were $150,944. When these costs are generalized to all patients in the US undergoing uncomplicated percutaneous transluminal coronary angioplasty, the costs are more than $1.2 billion. This study demonstrated that even in patients with a high a priori probability of work return, delay in work resumption results in a greater cost to the individual and society through absence from the labor force.

Context Percutaneous coronary interventions are performed at centers without onsite surgery, despite current guidelines discouraging this. Objective To assess literature comparing rates of in-hospital mortality and emergency coronary artery bypass grafting surgery at centers with and without on-site surgery. Data Sources A systematic search of studies published between January 1990 and May 2010 was conducted using MEDLINE, EMBASE, and Cochrane Review databases. Study Selection English-language studies of percutaneous coronary intervention performed at centers with and without on-site surgery providing data on in-hospital mortality and emergency bypass were identified. Two study authors independently reviewed the 1029 articles originally identified and selected 40 for analysis. Data Extraction Study title, time period, indication for angioplasty, and outcomes were extracted manually from all selected studies, and quality of each study was assessed using the strengthening the reporting of observational studies in epidemiology (STROBE) checklist. Data Synthesis High-quality studies of percutaneous coronary interventions performed at centers with and without on-site surgery were included. Pooled-effect estimates were calculated with random-effects models. Analyses of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction of 124 074 patients demonstrated no increase in in-hospital mortality (no on-site surgery vs on-site surgery: observed risk, 4.6% vs 7.2%; odds ratio [OR], 0.96; 95% CI, 0.88-1.05; I 2 = 0%) or emergency bypass (observed risk, 0.22% vs 1.03%; OR, 0.53; 95% CI, 0.35-0.79; I 2 = 20%) at centers without on-site surgery. For nonprimary percutaneous coronary interventions (elective and urgent, n = 914 288), the rates of in-hospital mortality (observed risk, 1.4% vs 2.1%; OR, 1.15; 95% CI, 0.93-1.41; I 2 = 46%) and emergency bypass (observed risk, 0.17% vs 0.29%; OR, 1.21; 95% CI, 0.52-2.85; I 2 = 5%) were not significantly different at centers without or with on-site surgery. Conclusion Percutaneous coronary interventions performed at centers without on-site surgery, compared with centers with on-site surgery, were not associated with a higher incidence of in-hospital mortality or emergency bypass surgery.

The ischemic pain associated with balloon inflation during coronary angioplasty remains a significant source of procedural discomfort and sets a limit on the duration of percutaneous transluminal intravascular interventions. The present study examined whether intracoronary lidocaine reduced the pain of coronary angioplasty. Sixteen patients undergoing elective coronary angioplasty underwent three 90 sec balloon inflations: the first with administration of no intracoronary agent, and the second and third with administration of one or the other of placebo or an equal volume of lidocaine (10-16 mg). Placebo or lidocaine were randomized in administration sequence and were given just before balloon inflation. During the occlusions, pain was scored on an ordinal scale (0 = no pain; 10 = most severe pain). Lidocaine delayed the onset of pain (23 +/- 4 vs. 48 +/- 7 sec, P < 0.005) and reduced its magnitude (at end-inflation: 7.8 +/- 1.3 vs. 3.2 +/- 1.3, P < 0.01). There were no significant hemodynamic or electrophysiologic effects in this group of patients, although atrioventricular conduction was delayed when lidocaine was administered into the epicardial coronary which had the atrioventricular node artery as a branch. Intracoronary analgesia with lidocaine is safe and effective in a select group of patients with normal ventricular function undergoing elective coronary angioplasty.

A lethal complication associated with acute heart failure syndrome (AHFS) is out-of-hospital cardiac arrest due to a sudden ventricular arrhythmia, either ventricular fibrillation (VF) or ventricular tachycardia (VT) deteriorating into VF (1, 2, 3, 4, 5, 6). However, the unique morbidity of AHFS makes management more of a challenge. One potential intervention that should be considered is evolving technology for automated external defibrillation, the main focus of this chapter.

The hypothesis that rheological properties of the coronary perfusate account for the curvilinearity and high zero-flow pressure (Pf = 0) of the diastolic coronary-pressure flow relationship (DCPFR) was tested by measuring these relationships using coronary perfusates of varying rheological character. In 16 open-chest, heart-blocked dogs the left circumflex coronary artery was cannulated and perfused using an extra-corporeal circuit, and autoregulation was abolished with intracoronary adenosine. DCPFRs were constructed from data obtained at multiple steady-state levels of coronary pressure during long diastoles while left ventricular diastolic pressure was held constant. Although isovolumic hemodilution reduced hematocrit from 46 +/- 3% to 32 +/- 3% and increased coronary conductance, it neither abolished the curvilinearity nor changed Pf = 0, which remained significantly higher than left ventricular diastolic pressure. In 10 additional animals, DCPFRs obtained during blood perfusion were compared with those obtained using crystalloid perfusate. Crystalloid perfusion increased coronary conductance and failed to abolish curvilinearity. However, with crystalloid perfusate, Pf = 0 was reduced to a value essentially equal to left ventricular diastolic pressure. We conclude that while the rheological properties of coronary perfusates do not fully account for the curvilinearity of the DCPFR, they do importantly influence coronary conductance and Pf = 0.

For coronary artery disease (CAD), female gender is ’protective’, so that women typically present with clinically apparent CAD a decade later than men. We examined the extent to which traditional cardiovascular risk factor influence the age at presentation with STEMI in men and women. The Cardiovascular Patient Outcomes Research Team (C-PORT) primary PCI registry includes 7197 patients (5070 males and 2109 females) who presented with STEMI at 33 participating hospitals. The table below depicts the average age at presentation with STEMI in males and females with and without diabetes, hypercholesterolemia, hypertension, a family history of coronary artery disease and smoking history (current or former). The effect of smoking, family history and hypertension on age at presentation remained significant in multivariate analysis in both men and women. In both males and females, a family history of CAD and a positive smoking history are associated with presentation with STEMI at a younger age. Both have a greater effect in females. This is particularly true of smoking with lowers the age of presentation by 9 years in women, compared with 3.8 years in men. Male and female patients with a history of hypertension are older at presentation with STEMI, perhaps because the anti-ischemic effects of anti-hypertensive medications. We conclude that while the effect of most traditional risk factors for CAD on age at presentation with STEMI are similar in men and women, smoking lowers the age at presentation to a much greater degree in women. In women who do not smoke, STEMI is delayed for a decade or more compared to men; for women who do, the protective effect of female gender is nearly obliterated.

Developers of systems to improve access to primary percutaneous intervention (PCI) must recognize that most ST-elevation myocardial infarction (STEMI) patients present to hospitals that do not have PCI capability. Indeed, only ≈25% of US hospitals are currently capable of delivering this intervention.1 These non-PCI-capable institutions are often located in rural areas and face real challenges related to distance from PCI centers. In addition, these institutions face significant financial challenges2 in pursuing any of the 3 potential strategies to increase timely access to primary PCI. These 3 strategies include the following3: (1) hospitals currently without PCI capability can develop primary PCI services without cardiac surgery on-site (SOS); (2) non-PCI-capable facilities can rapidly diagnose and transfer STEMI patients to primary PCI-capable hospitals and thereby serve as STEMI referral hospitals; or (3) communities can develop systems that bypass non-PCI-capable hospitals. Each of these strategies is addressed in this article. For each, we review the current status, the ideal system, gaps in and barriers to development of the ideal system, and recommendations. ### Current Status Early observational studies from single institutions demonstrated potential efficacy and safety of primary PCI without SOS. In the Myocardial Infarction, Triage and Intervention (MITI) trial, 233 of 441 primary PCIs were performed at hospitals without SOS. Emergency cardiac surgery was rare (1.4% of patients), and its presence or absence did not affect survival after myocardial infarction.4 In another observational study, among 334 patients undergoing primary PCI at a hospital without SOS, there were no deaths, and no patient required emergency coronary artery bypass grafting (CABG).5 In a nonrandomized comparison of patients undergoing primary PCI at hospitals without SOS with those undergoing primary PCI after transfer to a tertiary hospital, there was no difference in 30-day or 1-year mortality, although time to reperfusion was significantly shorter, and …

Primary percutaneous coronary intervention (PCI) yields better outcomes than thrombolytic therapy in the treatment of patients with ST-segment elevation myocardial infarctions (STEMIs). Emergency medical service systems are potentially important partners in efforts to expand the use of PCI. This study was conducted to explore the probable impact on patient mortality and hospital volumes of competing strategies for the emergency transport of patients with STEMIs. Emergency transport was simulated for 2,000 patients with STEMIs from the Atlantic Cardiovascular Patient Outcomes Research Team (C-PORT) trial in a geospatial model of Dallas County, Texas. Patient mortality estimates were obtained from a recently developed predictive model comparing PCI and thrombolytic therapy. A strategy of transporting patients to the closest hospital and treating with PCI if available and thrombolytic therapy if not yielded a 5.2% 30-day mortality rate (95% confidence interval [CI] 4.2% to 6.3%). A strategy of universal PCI, in which patients were transported only to PCI-capable hospitals, yielded 4.4% (95% CI 3.6% to 5.4%) mortality and an increase in patient volume at 2 full-time PCI hospitals of >1,000%. A strategy of targeted PCI, in which high-benefit patients were transported or transferred to PCI-capable hospitals, yielded 4.5% (95% CI 3.8% to 5.5%) mortality if transfers were decided in the emergency department and 4.2% (95% CI 3.4% to 5.1%) if transport was decided in the emergency vehicle. Targeted PCI strategies increased patient volumes at full-time PCI hospitals by about 700%. In conclusion, the selection of high-benefit patients for transport or transfer to PCI-capable hospitals can reduce mortality while minimizing major shifts in hospital patient volumes.

AMI is a life-threatening condition. Poor performance on the part of caregivers can result in the death of a patient. It is critical that a PPCI capability be developed in such a way that error is minimized. It is not enough that the system works well or very well. Aviation is often used as the example that medical systems should emulate. In developing the many interrelated systems required to function properly to ensure safe, effective,prompt, and appropriate application of PPCI,an aviation parallel should be kept in mind. If you were walking on the jetway toward a plane and were greeted by the pilot who said to you, "You know, I can land this thing 99% of the time," you would never get on that plane. It is important to develop a PPCI system that is absolutely never the cause of harm to any patient. Doing so requires exquisite attention to detail, algorithms of care when possible, redundancy, and clear orders for all drugs and procedures.

UNLABELLED It has been speculated but never proven that tachycardia-induced ischemia per se may lead to myocardial infarction. In 17 anesthetized dogs, the proximal left anterior descending (LAD) artery was cannulated and perfused via bypass from the left subclavian artery. Distal LAD pressure was reduced by a screw clamp to cause > or =20% decrease in wall thickening during pacing tachycardia but no decrease in resting heart rate (approximately 90 bpm). Dogs were randomly assigned to three groups: 1) control (n = 6) maintained at resting heart rate (approximately 90 bpm) and mean coronary pressure of 49+/-5 mm Hg for 4 h; 2) 4-h ischemia (n = 6), paced at 150 bpm and mean coronary pressure maintained at 59+/-6 mm Hg for 4 h; and 3) 1-h ischemia (n = 5), paced at 150 bpm and mean coronary pressure of 54+/-8 mm Hg for 1 h. Myocardial blood flow and infarct area were measured by radiolabeled microspheres and triphenyl-tetrazolium chloride staining, respectively. Despite the higher coronary pressure in the 4-h ischemia group (P = 0.02), patchy subendocardial necrosis occurred in all these dogs and in two of the 1-h ischemia dogs, and one control dog had minimal papillary muscle necrosis. Infarct area was largest in the 4-h ischemic group (15.5%+/-9.1%) compared with control and 1-h ischemia groups (0.09%+/-0.2% and 1.6%+/-2.1%, respectively) (P < 0.002). Relative (risk/ nonrisk areas) subendocardial flow was lower at the end of ischemia in the 4- and 1-h ischemia groups compared with the control group (0.3+/-0.1 and 0.4+/-0.1 vs 0.9+/-0.2; P = 0.008 and 0.01, respectively). Prolonged tachycardia-induced ischemia, in the face of fixed coronary stenosis causing no ischemia at the resting heart rate, leads to patchy subendocardial necrosis, despite anticoagulation and antiplatelet treatment. IMPLICATIONS Prolonged tachycardia-induced ischemia, in the face of fixed coronary stenosis causing no ischemia at the resting heart rate, leads to subendocardial infarction in dogs. These findings suggest a possible mechanism for postoperative myocardial infarction.

Analysis of high frequency (150–250 Hz) in the signal-averaged electrocardiogram (SAECG) is one of the emerging methods for detecting vessel patency in acute myocardial infarction following thrombolytic therapy and angioplasty. Root-mean-square voltage (RMSV) of the filtered QRS has been used in earlier studies to detect reperfusion; however, previous analysis indicated that RMSV is sensitive to residual noise in the SAECG and errors in QRS delineation (onset/offset). A new measurement is proposed, high-frequency energy (HFQE), and the robustness of the RMSV and HFQE was evaluated for simulated errors in QRS delineation. In this study, two measures (RMSV and HFQE) were tested on 24 control subjects and 21 patients undergoing thrombolytic therapy. Results indicate that unfiltered QRS duration is more stable than filtered QRS duration for the control subjects and patients and that HFQE had less fluctuation than RMSV in thrombolytic therapy patients. In the control group, HFQE was sensitive to the amplitude variation of the filtered SAECG. Therefore, another new measurement is proposed high-frequency integral of absolute value (HFAV), for reducing the sensitivity to amplitude changes in the filtered SAECG. This new feature was tested on control subjects and was found to be more stable than HFQE. In the thrombolytic therapy group, HFAV provided similar information as HFQE. These three measurements—RMSV, HFQE, and HFAV—provide a comprehensive analysis of the high-frequency SAECG for detecting vessel patency and reocclusion. Relative merits of these measures need to be evaluated on a larger database of patients undergoing thrombolysis and angioplasty for acute myocardial infarction.

The hypothesis that an increase in the amplitude (root-mean-square voltage) of the high frequency (150-250 Hz) components of the QRS complex occurs with successful reperfusion following thrombolytic therapy in acute myocardial infarction (AMI) and fails to occur when thrombolysis fails was tested. Clinical markers for successful or failed reperfusion following thrombolytic therapy for AMI are notoriously insensitive. The amplitude of the high-frequency components of the QRS complex decreases during ischemia and returns to normal with resolution of ischemia, but neither the variability in measurement of these potentials nor their patterns of change during the course of AMI have been described. In 32 control subjects, the average coefficient of variation for the amplitude of the highfrequency QRS complex was 10% or 0.3 uV. Based on these data, for the acute infarction population a significant change in this measurement was therefore defined as a change in amplitude > 20% or 0.6 uV on two consecutive recordings. In 30 patients with AMI treated with a thrombolytic agent, either cardiac catheterization, serial serum myoglobin, or complete resolution of ST-segment elevation were used to define successful or failed reperfusion. High-frequency QRS electrocardiograms were obtained at the start of treatment with a thrombolytic agent and for 3 h thereafter using a signal-averaging technique and digital filtering. Standard 12-lead electrocardiograms were obtained at the same time. In patients who reperfused successfully, the high-frequency QRS amplitude increased significantly (1.2 ± 0.9 uV above its nadir at 83 ± 36 min after initiation of thrombolytic therapy) in 23 of 25 patients. In contrast, the highfrequency QRS amplitude did not change or declined in all five patients who failed to reperfuse (-0.4 ± 0.4 uV, p < 0.05 compared with successful reperfusion). Traditional clinical markers such as resolution of chest pain and ST-segment elevation failed to distinguish successful and failed reperfusion. High-frequency QRS electrocardiography is a rapid, reliable bedside technique for discriminating between successful and failed reperfusion in patients treated with thrombolytic agents for AMI.

The hypothesis that the ATP-sensitive potassium channel provides the link between change in coronary blood flow and myocardial oxygen demand was tested in 9 dogs instrumented to measure coronary flow and regional wall thickening in the basal state and at a high level of myocardial oxygen consumption produced by systemic infusion of phenylephrine and simultaneous atrial pacing at an elevated heart rate. Measurements were recorded before and after blockade of ATP-sensitive potassium channels with intracoronary glibenclamide (2 mumol/min). While glibenclamide reduced the absolute level of coronary flow in the basal state, the increase in flow due to increased metabolic demand was unchanged compared with control. Thus, activity of the ATP-sensitive potassium channel determines the set point from which adjustments of coronary flow in response to metabolic stimuli occur, but does not provide a link between changes in oxygen demand and changes in coronary flow.

The factors which determine coronary blood flow in myocardium subjected to ischemia and reperfusion are numerous, complex, and interrelated. They can be conveniently, if arbitrarily, divided into three broad categories. First, cellular and protein elements of the coronary perfustate, such as the leukocyte and fibrinogen, may affect coronary blood flow through effects on the microvasculature and on blood rheological properties, respectively. Second, the coronary conduit itself, the blood vessel, can also be affected by ischemia and reperfusion, particularly in its endothelial component and the associated vascular responses. Finally, the environment in which the coronary vessel finds itself, determined by characteristics of the myocyte and the interstitial space, can affect coronary flow by itself being profoundly changed after ischemia and reperfusion. While ischemia and reperfusion affects all three of these major determinants of coronary blood flow, whether or not coronary blood flow responses following reperfusion have a role in producing myonecrosis is unclear at this time.

Restenosis following coronary angioplasty can usually be treated effectively and safely by repeated angioplasty. However, the presence of a complex lesion morphology may bias the clinician away from angioplasty toward either recommending bypass surgery or continuing medical therapy alone in spite of recurrence of the symptoms which were sufficient indication for the initial angioplasty. One type of complex morphology at the site of the restenosis is due to the presence of a focal, eccentric aneurysmal dilatation similar in appearance to a saccular aneurysm. In two previously reported cases in the literature both were referred to bypass surgery. We report eight additional cases including the use of repeat successful angioplasty in six of the cases in spite of the potential problems posed by the complexity of the restenosed lesion. In addition, this case review suggests that this type of complex lesion morphology with restenosis may be more common when the initial angioplasty was associated with deep arterial injury, as in patients whose initial angloplasty was done in an infarct-related vessel or was associatedwith evidence of a large dissection.

ContextTrials comparing primary percutaneous coronary intervention (PCI) and thrombolytic therapy for treatment of acute myocardial infarction (MI) suggest primary PCI is the superior therapy, although they differ with respect to the durability of benefit. Because PCI is often limited to hospitals that have on-site cardiac surgery programs, most acute MI patients do not have access to this therapy.ObjectiveTo determine whether treatment of acute MI with primary PCI is superior to thrombolytic therapy at hospitals without on-site cardiac surgery and, if so, whether superiority is durable.DesignThe Atlantic Cardiovascular Patient Outcomes Research Team (C-PORT) trial, a prospective, randomized trial conducted from July 1996 through December 1999.SettingEleven community hospitals in Massachusetts and Maryland without on-site cardiac surgery or extant PCI programs.PatientsFour hundred fifty-one thrombolytic-eligible patients with acute MI of less than 12 hours' duration associated with ST-segment elevation on electrocardiogram.InterventionsAfter a formal primary PCI development program was completed at all sites, patients were randomly assigned to receive primary PCI (n = 225) or accelerated tissue plasminogen activator (bolus dose of 15 mg and an infusion of 0.75 mg/kg for 30 minutes followed by 0.5 mg/kg for 60 minutes; n = 226). After initiation of assigned treatment, all care was determined by treating physicians.Main Outcome MeasuresSix-month composite incidence of death, recurrent MI, and stroke; median hospital length of stay.ResultsThe incidence of the composite end point was reduced in the primary PCI group at 6 weeks (10.7% vs 17.7%; P = .03) and 6 months (12.4% vs 19.9%; P = .03) after index MI. Six-month rates for individual outcomes were 6.2% vs 7.1% for death (P = .72), 5.3% vs 10.6% for recurrent MI (P = .04), and 2.2% vs 4.0% for stroke (P = .28) for primary PCI vs thrombolytic therapy, respectively. Median length of stay was also reduced in the primary PCI group (4.5 vs 6.0 days; P = .02).ConclusionsCompared with thrombolytic therapy, treatment of patients with primary PCI at hospitals without on-site cardiac surgery is associated with better clinical outcomes for 6 months after index MI and a shorter hospital stay.

Although augmentation of flow does not improve the performance of normal myocardium, the hyperemic response after brief coronary occlusion is associated with transient hyperfunction in the previously ischemic region. In this study we assessed the effect of vasodilator-enhanced coronary blood flow on the systolic function of postischemic stunned myocardium. In 18 open-chest, anesthetized dogs the anterior descending artery was occluded for 5 min, followed by a 10 min period of reflow, repeated 12 times with a final 90 min recovery period. After the recovery period, either 0.06 mg/min dipyridamole (n = 6), 1 mg/min papaverine (n = 6), or 1.5 micrograms/kg/min nitroglycerin (n = 6) was infused intravenously for 15 min. Regional myocardial blood flow, which had returned to normal before administration of vasodilator, was increased 150% above baseline by dipyridamole and 80% by papaverine, but was unchanged by nitroglycerin. Segmental shortening decreased after repeated occlusions: from 17.5% to 0.9% in the group later treated with dipyridamole, from 18.6% to 6.7% in the papaverine group, and from 19.2% to-1.9% in the nitroglycerin group (p less than .005 for all groups). Segmental shortening increased to 8.8% after dipyridamole, 13.6% after papaverine, and 5.1% after nitroglycerin (p less than .05 for all groups), although the load-independent end-systolic pressure-length relationship (ESPLR) showed a significant shift to the left, reflecting enhanced performance, only after dipyridamole and papaverine. For all dogs combined, the percent improvement in ESPLR was correlated with the percent increase in flow (R = -.73, p less than .001). Performance was unchanged in the control region despite similar augmentation of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Dimension change measures of regional ventricular function, such as absolute or percent wall thickening (delta T or % delta T) or segmental shortening (delta L or % delta L), are highly load dependent. In 16 anesthetized mongrel dogs we assessed use of the end-systolic pressure-thickness and end-systolic pressure-length relationships (ESPTR, ESPLR) as more load-independent measures of regional function. We found that the ESPTR and ESPLR could be measured without detectable baroreceptor-mediated reflex changes in cardiac contractile state. Systemic administration of dobutamine shifted the ESPTR to the right and the ESPLR to the left of control, mainly due to a change in the slope (Ees) of the relationships. Both delta T, % delta T and delta L, % delta L failed to detect the positive inotropic effect of dobutamine because of an associated reduction in preload. With systemic administration of propranolol, ESPTR, ESPLR, delta T, % delta T, and delta L, % delta L detected the negative inotropic effect. Thus systemic propranolol shifted the ESPTR to the left and the ESPLR to the right of control, mainly due to a change in Ees. Regional administration of dobutamine shifted the ESPTR and the ESPLR in the direction of positive contractility in the region receiving the drug, whereas simple dimension change measures of regional function failed to detect the inotropic effect because preload fell and the timing of regional end-systole was altered. With regional propranolol both the ESPTR, ESPLR and simple dimension change measures detected the negative inotropic effect. Thus the ESPTR, ESPLR is a reliable measure of regional ventricular function and may be better than simple dimension change measures of regional function, particularly when loading conditions or the timing of regional systole is altered by an intervention.

Percutaneous aortic valvuloplasty using a single dilating balloon has been associated with significant but modest reduction in transvalvular pressure gradient and increase in valve area. The balloon diameter is usually 20 mm or smaller to avoid disruption of aortic root structure and to permit forward blood flow during inflation. To evaluate the safety and efficacy of valvuloplasty using a combination of balloons with larger maximum inflated diameters, we compared results of aortic valvuloplasty in 21 patients using either the single or double balloon technique. Mean maximum inflated balloon diameter was 19.4 mm +/- 1.4 for the single balloon technique, while the mean sum of diameters for the simultaneous double balloon technique was 36.3 mm +/- 3.9. The mean age, aortic annulus diameter, and predilatation aortic valve area were not different among groups. Mean aortic transvalvular gradient reduction and mean aortic valve area increase were greater for the double balloon technique. The procedure was well tolerated with no major complications. No change in the degree of aortic regurgitation was noted. The double balloon technique for aortic valvuloplasty is safe and more effective at improving aortic valve area and transvalvular gradient than the conventional single balloon technique.

Objectives.This study attempted to determine whether neutrophil sequestration in reperfused myocardium can be inhibited and infarct size reduced by treatment with a chimeric, monoclonal IgG4 antibody (CLB54) directed against CD18 in a primate model of acute myocardial ischemia and reperfusion.Background.Reperfusion injury, in part mediated by neutrophils, may limit the potential benefit of reestablishing infarctrelated artery patency in patients with acute myocardial infarction.Methods.Nineteen closed-chest baboons (10 control, 9 treated with CLB54) had the left anterior descending coronary artery occluded for 90 min, followed by 4 h of reflow. CLB54 (mean [±SD] 11 ± 2 mg/kg body weight) or saline solution was administered intravenously 20 min before reflow. Coronary flow was determined using radiolabeled microspheres, infarct size by triphenyltetrazolium chloride staining, global and regional ventricular function by contrast ventriculography and neutrophil accumulation by a myeloperoxidase assay.Results.Risk region size was the same in both groups. CLB54 treatment reduced infarct size expressed as a percent of the risk region from 41 ± 20% in the saline-treated group to 19 ± 17% in the CLB54-treated group (p < 0.02). This was associated with diminished myeloperoxidase activity and greater postreperfusion coronary flow in the risk region in CLB54-treated than in control baboons. Ejection fraction declined to the same extent in both groups, whereas anterior wall regional cord shortening was better preserved in CLB54-treated baboons.Conclusions.Inhibition of neutrophil sequestration with CLB54 administered before reperfusion reduces infarct size, preserves ischemic zone microvascular perfusion and minimizes the decline of regional wall motion.

Stunned myocardium can be produced by repeated short episodes of ischemia. Histochemical and ultrastructural abnormalities such as sarcomere lengthening and myofiber thinning have been noted in myocardium soon after the onset of ischemia and have been attributed to the mechanical stretching that occurs during ventricular systole. To test whether mechanical forces alone could produce the residual dysfunction seen in stunned myocardium, regional dyskinesia was produced in open chest dogs by six repeated intracoronary infusions of either potassium chloride, 0.2 mEq/min for 2.5 minutes, or lidocaine, a 10 mg bolus followed by 1 to 3 mg/min for 5 minutes. These dogs were matched with dogs that had six repeated coronary occlusions of 2.5 and 5 minutes' duration, respectively. Regional function was analyzed using fractional systolic shortening and the load-independent end-systolic pressure-length relation. Both potassium chloride and lidocaine produced regional dyskinesia that was similar to the dyskinesia produced by coronary occlusion. Although regional ventricular function after repeated coronary occlusions remained significantly reduced, function returned completely to normal within 5 minutes after the last druginduced dyskinesia. In conclusion, regional dysfunction produced by potassium chloride and lidocaine does not produce residual dysfunction despite mechanical forces during systole similar to those seen during coronary occlusion.

This study was done to determine whether coronary vasodilator reserve is exhausted when coronary flow falls and regional function becomes abnormal during low-pressure perfusion. In 10 open-chest, anesthetized dogs the left circumflex coronary artery (LC) was cannulated and perfused via a blood-filled reservoir. At LC pressures of 35 and 50 mmHg, regional segment lengths were measured with sonomicrometer crystals and regional flow with radiolabeled microspheres before and after adenosine vasodilation. Control measurements were made at 80 mmHg perfusion pressure. Prior to adenosine, flow fell transmurally when LC pressure was reduced to 50 and 35 mmHg and rose significantly following adenosine. No change in function occurred at an LC pressure of 50 mmHg, but at 35 mmHg LC segmental shortening fell to 30 +/- 14% of control, and LC flow fell to 42 +/- 5% of control, with endocardial and epicardial flows of 0.40 +/- 0.04 and 0.70 +/- 0.09 ml . min-1 . g-1, respectively. After adenosine, endocardial and epicardial LC flow rose to 0.69 +/- 0.08 and 1.81 +/- 0.47 ml . min-1 . g-1, respectively (P less than 0.05). LC segment shortening improved modestly to 50 +/- 15% of control (P less than 0.02). We conclude that transmural vasodilator reserve is maintained in the face of functionally significant reductions of coronary flow at low perfusion pressure. Adenosine-induced flow increases are associated with a modest improvement in segmental function.

The influence of afterload resistance on the end-systolic pressure-thickness relationship (ESPTR) was assessed in six isolated canine left ventricles made to eject into a simulated arterial system. An increase of simulated peripheral resistance from 1.5 to 6.0 mmHg.s.ml-1 resulted in a modest but significant shift of the ESPTR upward and to the right, indicating augmented contractile performance. A relationship between the extent of systolic wall thickening and end-systolic performance was also observed: increased wall thickening impairing and decreased wall thickening enhancing end-systolic performance. The dependence of end-systolic performance on wall thickening history in this setting is consistent with shortening deactivation. This phenomenon appears to account at least in part for the observed shift in the ESPTR with altered afterload resistance.

To study the influence of ischemic zone size on function in nonischemic regions, wall thickening and the end-systolic pressure-thickness (ESPTR) relationship were measured before and during a 90-s coronary occlusion, which produced either a small or large (24 or 35% of left ventricular mass) area of ischemia. With both size ischemic areas, nonischemic zone isovolumic and ejection phase wall thickening increased during occlusion, primarily because of increased preload and, to a lesser extent, a reduced pressure component of afterload. The nonischemic region ESPTR was unchanged from preocclusion control with small ischemic mass. With larger ischemic mass, the nonischemic region ESPTR was shifted downward and to the left, indicating reduced end-systolic performance. The decline in the nonischemic zone ESPTR with large ischemic zone size was not due to reduced blood flow, shortening deactivation, reflex effects, or "tethering" but rather to the associated decline in coronary perfusion pressure. Thus the increase of nonischemic region wall thickening during acute ischemia is due to a change in ventricular loading conditions and not augmentation of contractile performance. Larger ischemic zone size can impair function in nonischemic myocardium by reducing the erectile component of end-systolic performance.