Faculty Bibliography

PURPOSE OF REVIEW: A substantial minority of myocardial infarction (MI) patients have no obstructive coronary artery disease (CAD) at angiography. Women more commonly have this type of MI, but both sexes are affected. This is not an innocuous problem. Multiple studies have shown 2% death or reinfarction in short-term to mid-term follow-up. RECENT FINDINGS: Two large autopsy series confirmed MI without obstructive CAD as a cause of death. Intravascular ultrasound (IVUS) and cardiac MRI (CMR) were studied in patients with MI without obstructive CAD. Plaque rupture was found in nearly 40% and late gadolinium enhancement was seen in nearly 40%, with little overlap in imaging findings. Additional CMR studies in similar patients have shown variable frequencies and patterns of late enhancement, but consistently demonstrate an ability to identify nonischemic causes (myocarditis, infiltrative disease). Ischemic myocardial injury on CMR may be due to plaque rupture but also occurs in patients without plaque rupture. These cases may be caused by vasospasm, embolism, dissection, or branch occlusion. SUMMARY: MI without obstructive CAD is a heterogeneous disorder with different mechanisms in different patients. Plaque rupture is common. In the absence of clear demonstration of a nonischemic cause, treatment should include guideline-recommended secondary prevention, including antiplatelet and antiatherosclerotic medications.

BACKGROUND: The incidence and predictors of heart failure (HF) after myocardial infarction (MI) with modern post-MI treatment have not been well characterized. METHODS AND RESULTS: A total of 2,201 stable patients with persistent infarct-related artery occlusion >24 hours after MI with left ventricular ejection fraction <50% and/or proximal coronary artery occlusion were randomized to percutaneous intervention plus optimal medical therapy (PCI) or optimal medical therapy (MED) alone. Centrally adjudicated HF hospitalizations for New York Heart Association (NYHA) III/IV HF and mortality were determined in patients with and without baseline HF, defined as a history of HF, Killip Class >I at index MI, rales, S3 gallop, NYHA II at randomization, or NYHA >I before index MI. Long-term follow-up data were used to determine 7-year life-table estimated event rates and hazard ratios. There were 150 adjudicated HF hospitalizations during a mean follow-up of 6 years with no difference between the randomized groups (7.4% PCI vs. 7.5% MED, P = .97). Adjudicated HF hospitalization was associated with subsequent death (44.0% vs. 13.1%, HR 3.31, 99% CI 2.21-4.92, P < .001). Baseline HF (present in 32% of patients) increased the risk of adjudicated HF hospitalization (13.6% vs. 4.7%, HR 3.43, 99% CI 2.23-5.26, P < .001) and death (24.7% vs. 10.8%, HR 2.31, 99% CI 1.71-3.10, P < .001). CONCLUSIONS: In the overall Occluded Artery Trial (OAT) population, adjudicated HF hospitalizations occurred in 7.5% of subjects and were associated with increased risk of subsequent death. Baseline or prior HF was common in the OAT population and was associated with increased risk of hospitalization and death.

Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention to medical therapy in patients with MI with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to percutaneous coronary intervention with optimal medical therapy in 2,201 high-risk patients with occluded infarct arteries >24 hours after MI with serum creatinine levels 90 ml/min/1.73 m(2), 19.2% for eGFR 60 to 89 ml/min/1.73 m(2), and 34.9% for eGFR <60 ml/min/1.73 m(2); p <0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariate analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary end point regardless of eGFR, and there was no significant interaction between eGFR and treatment assignment on any outcome. In conclusion, lower eGFR at enrollment was independently associated with death and HF in OAT participants. Despite this increased risk, the lack of benefit from percutaneous coronary intervention in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase after MI.

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.

BACKGROUND: The OAT, a randomized study of routine percutaneous coronary intervention or optimal medical therapy (MED) alone for the treatment of a totally occluded infarct-related artery in the subacute phase after myocardial infarction, showed similar rates of death, reinfarction and congestive heart failure (CHF) between study groups. Although most percutaneous coronary intervention patients were treated with bare metal stents (BMS), drug-eluting stents (DES) were also implanted in the latter part of the study. The aim of the study was to conduct an exploratory analysis of long-term outcomes for DES vs. BMS deployment vs. MED in the OAT. METHODS: Patients enrolled after February 2003 (when first DES was implanted) were followed (DES n = 79, BMS n = 393, MED n = 552) up to a maximum of 6 years (mean survivor follow-up 5.1 years). RESULTS: The 6-year occurrence of the composite end point of death, reinfarction and class IV CHF was similar [20.4% of DES, 18.9% of BMS and 18.4% of MED (P = .66)] as were the rates of the components of the primary end point. During the follow-up period, 33.4% of DES, 44.4% of BMS and 48.1% of MED patients, developed angina (P = .037). The rate of revascularization during follow up was 11.3%, 20.5% and 22.5% among these groups, respectively (P = .045). CONCLUSIONS: There is no suggestion of reduced long-term risk of death, reinfarction or class IV CHF with DES usage compared to BMS or medical treatment alone. An association between DES use and freedom from angina and revascularization relative to medical therapy is suggested.

BACKGROUND: The OAT study randomized 2,201 patients with a totally occluded infarct-related artery on days 3 to 28 (>24 hours) after myocardial infarction (MI) to percutaneous coronary intervention (PCI) or medical treatment (MED). There was no difference in the primary end point of death, reinfarction, or heart failure at 2.9 or 6-year mean follow-up. However, in patients randomized to PCI, there was a trend toward a higher rate of reinfarction. METHODS: We analyzed the characteristics and types of reinfarction according to the universal definition. Independent predictors of reinfarction were determined using Cox proportional hazard models with follow-up up to 9 years. RESULTS: There were 169 reinfarctions: 9.4% PCI vs 8.0% MED, hazard ratio 1.31, 95% CI 0.97-1.77, P = .08. Spontaneous reinfarction (type 1) occurred with similar frequency in the groups: 4.9% PCI vs 6.7% MED, hazard ratio 0.78, 95% CI 0.53-1.15, P = .21. Rates of type 2 (secondary) and 3 (sudden death) MI were similar in both groups. There was an increase in type 4a reinfarctions (related to protocol or other PCI) (0.8% PCI vs 0.1% MED, P = .01) and type 4b reinfarctions (stent thrombosis) (2.7% PCI vs 0.6% MED, P < .001). Multivariate predictors of reinfarction were history of PCI before study entry (P = .001), diabetes (P = .005), and absence of new Q waves with the index infarction (P = .01). CONCLUSIONS: There was a trend for reinfarctions to be more frequent with PCI. Opening an occluded infarct-related artery in stable patients with late post-MI may expose them to a risk of subsequent reinfarction related to reocclusion and stent thrombosis.

Although opening an occluded infarct-related artery >24 hours after myocardial infarction in stable patients in the Occluded Artery Trial (OAT) did not reduce events over 7 years, there was a suggestion that the effect of treatment might differ by patient age. Baseline characteristics and outcomes by treatment with percutaneous coronary intervention (PCI) versus optimal medical therapy alone were compared by prespecified stratification at age 65 years. A p value <0.01 was prespecified as significant for OAT secondary analyses. The primary outcome was death, myocardial infarction, or New York Heart Association class IV heart failure. Patients aged >65 years (n = 641) were more likely to be female, to be nonsmokers, and to have hypertension, lower estimated glomerular filtration rates, and multivessel disease compared to younger patients (aged </=65 years, n = 1,560) (p <0.001). There was no significant observed interaction between treatment assignment and age for the primary outcome after adjustment (p = 0.10), and there was no difference between PCI and optimal medical therapy observed in either age group. At 7-year follow-up, younger patients tended to have angina more often compared to the older group (hazard ratio 1.21, 99% confidence interval 1.00 to 1.46, p = 0.01). The 7-year composite primary outcome was more common in older patients (p <0.001), and age remained significant after covariate adjustment (hazard ratio 1.42, 99% confidence interval 1.09 to 1.84). The rate of early PCI complications was low in the 2 age groups. The trend toward a differential effect of PCI in the young versus the old for the primary outcome was likely driven by measured and unmeasured confounders and by chance. PCI reduces angina to a similar degree in the young and old. In conclusion, there is no indication for routine PCI to open a persistently occluded infarct-related artery in stable patients after myocardial infarction, regardless of age

BACKGROUND: Long-term follow-up (up to 9 years) from the OAT allows for the examination of sex differences in outcomes and the effect of percutaneous coronary intervention (PCI) in a relatively homogeneous cohort of myocardial infarction (MI) survivors. METHODS: The OAT randomized 484 (22%) women and 1717 men to PCI of the occluded infarct-related artery vs medical therapy alone >24 hours post-MI. There was no benefit of PCI on the composite of death, MI, and class IV heart failure. We analyzed outcomes by sex and investigated for sex-based trial selection bias using a concurrent registry. RESULTS: Women were older and more likely to have left anterior descending infarct-related artery, diabetes and hypertension, history of heart failure, and rales at randomization but were less likely to smoke. The proportion and characteristics of women enrolled in the trial and the registry were similar, including left ventricular ejection fraction and extent of disease. Women had higher rates of the primary composite (hazard ratio [HR] 1.48, P = .0002), death (HR 1.50, P = .001), and heart failure (HR 2.53, P < .0001) but not reinfarction (HR 1.12, P = .57). Female sex was not independently associated with the primary end point or death on multivariate analysis. There was a trend toward independent association of female sex with heart failure (HR 1.66, P = .02). CONCLUSION: Women in OAT had a higher primary end point event rate than did men, mainly driven by heart failure. Female sex was not independently associated with death or MI in this well-defined cohort with comparable extent of coronary artery disease, similar medical therapy, and equivalent left ventricular ejection fraction by sex.