Faculty Bibliography

BACKGROUND: The pathobiological basis of ischemic heart disease and thus the manifestations and response to therapy can differ between women and men. In prior studies, sex-based treatment differences have been observed with the antiischemic ranolazine, with a possibly diminished effect in women. METHODS AND RESULTS: We conducted a prospectively planned analysis of the clinical, biomarker, angiographic, and continuous ECG features and 1-year outcomes of women with unstable ischemic heart disease randomized to ranolazine or placebo in Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36). Compared with men (n=4269), women (n=2291) were older with more risk factors (P<0.001). On presentation, women were less likely than men to have significant epicardial coronary artery disease (no stenosis >or=50% on angiography, 19.4% versus 8.6%; P<0.001) or elevated troponin (57.1% versus 68.9%; P<0.001). Yet, women were more likely to have an elevated B-type natriuretic peptide (47.0% versus 40.2%; P<0.001), worse median angina frequency scores (80 versus 100; P<0.001), and an ischemic episode on continuous ECG administered during the first 7 days (22.5% versus 19.3%; P=0.0025). Women and men were at similar adjusted risk for the primary end point of cardiovascular death, myocardial infarction, or recurrent ischemia (adjusted hazard ratio, 1.11; 95% confidence interval, 0.96 to 1.29; P=0.15). Ranolazine was associated with a significant reduction in recurrent ischemia in women (13.0% versus 18.2%; hazard ratio, 0.71; 95% confidence interval, 0.57 to 0.88; P=0.002). CONCLUSIONS: Women with a clinical syndrome consistent with unstable ischemic heart disease, despite having less obstructive coronary artery disease, were more likely than men to report anginal episodes and had more recorded ischemic periods on continuous ECG. In this setting, ranolazine may be a particularly useful antiischemic agent in women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00099788

AIM: To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF). METHODS: Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR). Rates of early post-MI HF were compared among eGFR groups. Logistic regression was used to explore independent predictors of HF. RESULTS: Reduced eGFR was present in 71.1% of 2160 patients, with significant renal impairment (eGFR < 60 mL/min every 1.73 m(2)) in 14.8%. The prevalence of HF was higher with worsening renal function: 15.5%, 17.8% and 29.4% in patients with CKD stages 1, 2 and 3 or 4, respectively (P < 0.0001), despite a small absolute difference in mean EF across eGFR groups: 48.2 +/- 10.0, 47.9 +/- 11.3 and 46.2 +/- 12.1, respectively (P = 0.02). The prevalence of HF was again higher with worsening renal function among patients with preserved EF: 10.1%, 13.6% and 23.6% (P < 0.0001), but this relationship was not significant among patients with depressed EF: 27.1%, 26.2% and 37.9% (P = 0.071). Moreover, eGFR was an independent correlate of HF in patients with preserved EF (P = 0.003) but not in patients with depressed EF (P = 0.181). CONCLUSION: A significant proportion of post-MI patients with occluded IRAs have impaired renal function. Impaired renal function was associated with an increased rate of early post-MI HF, the association being strongest in patients with preserved EF. These findings have implications for management of peri-infarct HF

In the Occluded Artery Trial (OAT), percutaneous coronary intervention (PCI) of an infarct-related artery on days 3 to 28 after acute myocardial infarction was of no benefit compared to medical therapy alone. The present analysis was conducted to determine whether PCI might provide benefit to the subgroup of higher risk patients with a depressed ejection fraction (EF). Of 2,185 analyzed patients (age 58.6 +/- 11.0 years) with infarct-related artery occlusion on days 3 to 28 after acute myocardial infarction in the Occluded Artery Trial, 1,094 were assigned to PCI and 1,091 to medical therapy. The primary end point was a composite of death, reinfarction, and New York Heart Association class IV heart failure. The outcomes were analyzed by EF (first tertile, EF < or =44%, vs second and third tertiles combined, EF >44%). Interaction of the treatment effect with EF on the study outcomes were examined using the Cox survival model. The 5-year rates of the primary end point (death, reinfarction, or New York Heart Association class IV heart failure) were not different in either subgroup (PCI vs medical therapy, hazard ratio 1.25, 99% confidence interval 0.83 to 1.88, for EF < or =44%; hazard ratio 0.98, 99% confidence interval 0.64 to 1.50, for EF >44%). However, in patients with an EF >44%, PCI reduced the rate of subsequent revascularization (p = 0.004, interaction p = 0.05). In conclusion, optimal medical therapy remains the overall treatment of choice for stable patients with a persistent total occlusion of the infarct-related artery after acute myocardial infarction, irrespective of the baseline EF. In patients with normal or moderately impaired left ventricular contractility, PCI reduced the need for subsequent revascularization but did not otherwise improve outcomes

A decrease in mechanical complications after ST-elevation myocardial infarction may have contributed to improved survival rates associated with reperfusion by primary percutaneous coronary intervention (PCI). Mechanical complications occurred in 52 of 5,745 patients (0.91%) in the largest reported randomized trial in which primary PCI was the reperfusion strategy. The frequencies were 0.52% (30) for cardiac free-wall rupture (tamponade), 0.17% (10) for ventricular septal rupture, and 0.26% (15) for papillary muscle rupture (3 patients had 2 complications). Ninety-day survival rates were 37% (11) for cardiac free-wall rupture, 20% (2) for ventricular septal rupture, and 73.3% (11) for papillary muscle rupture. These mechanical complications occurred at a median of 23.5 hours (interquartile range 5.0 to 76.8) after symptom onset and were associated with 44% (23 of 52) survival through 90 days, which accounted for 11% of the 90-day mortality. Factors associated with mechanical complications were older age, female gender, Q waves, presence of radiologic pulmonary edema, and increased prerandomization troponin levels. In conclusion, rates of mechanical complications are lower with primary PCI than those previously reported after fibrinolytic therapy

Patients from the Indian subcontinent have a distinct cardiovascular risk profile with profound health consequences. South Asians tend to develop more severe coronary artery disease at a younger age, and may also suffer from earlier myocardial infarction and heart failure. The genesis of this risk is multi-factorial. One important culprit is increased insulin resistance, possibly due to recently identified genetic polymorphisms. Another possible explanation is subclinical inflammation and a prothrombotic environment, as evidenced by increased levels of homocysteine, plasminogen activator inhibitor-1, and fibrinogen. The lipid profile of South Asians may play a role, as this population is known to have elevated levels of lipoprotein (a), as well as lower levels of HDL. In addition, this HDL may be dysfunctional, as this population may have a higher prevalence of low levels of HDL2b, as well as an increased preponderance of smaller HDL. Current guidelines for primary and secondary prevention have not reflected our growing insight into the unique characteristics of the South Asian population, and may need to evolve to reflect our knowledge