Further information: Coronary Artery Disease: Pathologic Anatomy and Pathogenesis (see p593), Arterial Compliance (see p1811), Atrial Fibrillation and Flutter (see p1955), and Sudden Cardiac Death (see p2039) from Cardiovascular Medicine, 3rd Edn*

In 1985 and 1986 respectively, two articles were published in Circulation [1,2] that reported that myocardial platelet thrombi were embolic and that the emboli were a cause of acute coronary syndromes (ACS). Although prior histopathological studies had shown intramyocardial microemboli and microvascular obstruction (MVO) were present in patients with ischemic cardiac death, the association between culprit coronary morphology and intramyocardial emboli had not been reported. Therefore, the investigators in this study [3] determined to evaluate the frequency of intramyocardial microemboli and MVO in sudden cardiac death from acute coronary thrombosis. Differentiating between plaque rupture and plaque erosion were important elements of the study. Plaque rupture was defined as “disruption of a fibrocellular cap overlying a pool of lipid with pultaceous debris,” and plaque erosion was defined as “surface ulceration of the upper plaque layers without rupture into a lipid core.”

Through analysis at autopsy of coronary arteries of 44 hearts, 26 plaque ruptures and 21 erosions were found, and there was a mean of 4.5 microemboli per heart. Microemboli and MVO occurred in eroded plaques more often, and although all vessels contained fibrin and platelets, microemboli and occluded intramyocardial vessels were more common in the LAD of the coronary artery. The mean stenosis of the culprit lesion was 74% in the arteries with microemboli and 75% in those without (P=NS). Intramyocardial microemboli were more common in plaque erosion than in plaque rupture.

The investigators concluded that plaque erosion was dominant in the histopathology of clot embolization causing sudden cardiac death, was more likely to occur in vessels of less than 120 µm, and was associated with focal necrosis.

[1] Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 1985;71:699-708

[2] Davies MJ, Thomas AC, Knapman PA, Hangartner JR. Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 1986;73:418-27

[3] Schwartz RS, Burke A, Farb A, et al. Microemboli and microvascular obstruction in acute coronary thrombosis and sudden coronary death. J Am Coll Cardiol 2009;54:2167-73

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* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Medical Treatment of Unstable Angina, Acute Non–ST-Elevation Myocardial Infarction, and Coronary Artery Spasm (see p937), Pathophysiology and Clinical Impact of Diastolic Heart Failure (see p1201) and Dilated Cardiomyopathy (see p1233) from Cardiovascular Medicine, 3rd Edn*

This article [1] contains observations from the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary-Thrombolysis in Myocardial Infarction 36) Trial (MERLIN-TIMI 36), a trial conducted at 440 sites between 2004 and 2007 to determine the efficacy and safety of ranolazine in long-term treatment of 6500 patients with non-ST segment elevation acute coronary syndromes (ACS). As part of the MERLIN-TIMI 36 trial, investigators designed a prospective evaluation of the interaction between B-type natriuretic peptide (BNP) and the effect of ranolazine in patients with ACS. Because elevated BNP and the N-terminal portion of BNP prohormone identify patients at high risk of death and heart failure (HF), intense effort is being made to find treatments that would mitigate the risk of elevated BNP. There were 4543 baseline samples in which BNP had been measured from patients who had been randomized to ranolazine or placebo, and the patients were followed for 343 days. BNP elevation was defined as >80 pg/ml. The primary end point was a composite of cardiovascular (CV) death, myocardial infarction (MI), and recurrent ischemia.

Results showed that in 1935 patients with elevated BNP (>80 pg/ml), the risk of the primary end-point was higher (26.4% vs. 20.4%, P=0.0001), higher for CV death (8.0% vs. 2.1%, P<0.001, and higher for MI (10.6% vs. 5.8%, P<0.001) at 1 year. The primary end-point was reduced by ranolazine (hazard ratio [HR]; 0.79; 95% confidence internal [CI]: 0.66–0.94, P=0.009). For recurrent ischemia in patients with elevated BNP, the effect of ranolazine was directionally similar (HR: 0.78; 95% CI: 0.62–0.98; P=0.04) and CV death or MI (HR: 0.83; 95% CI: 0.66–1.05, P=0.12). Ranolazine had no effect on patients without elevated BNP, did not reduce BNP concentration over time, and did not reduce the clinical end-point for patients with new or worsening HF. Nevertheless, it did identify patients at high risk of recurrent myocardial ischemia ameliorated by ranolazine. Therefore, the investigators concluded that the effects of ranolazine warrant additional study.

In an editorial [2] in this same issue of JACC, the authors stated that while this carefully done study does not provide conclusive evidence that ranolazine should be used in patients with ACS and elevated BNP levels, it does lay the groundwork for a prospective clinical trial.

[1] Morrow DA, Scirica BM, Sabatine MS, et al. B-Type Natriuretic Peptide and the Effect of Ranolazine in Patients with Non-ST Segment Elevation Acute Coronary Syndromes. J Am Coll Cardiol 2009;55:1189-96

[2] Califf RM, Shah SH, Newby LK. Biomarker Bonanza? J Am Coll Cardiol 2009;55:1197-99
 
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* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.

Further information: Exercise Testing (see p729),
Coronary Angiography (see p745),
Echocardiographic Evaluation of Coronary Artery Disease (see p811)
and Myocardial Perfusion Imaging Utilizing Single Photon Emission Computed Tomography Techniques (see p841) from Cardiovascular Medicine, 3rd Edn*

At University Medical Center in Rotterdam, The Netherlands, investigators conducted an observational study [1] to compare the accuracy of noninvasive diagnostic testing in the diagnosis of coronary artery disease (CAD) in patients with chest symptoms. The reference standard for diagnosing CAD is invasive coronary angiography (ICA), an expensive test when compared to noninvasive diagnostic testing. Noninvasive diagnostic stress tests include exercise electrocardiography (ECG), single-photon emission computed tomography (SPECT), or stress echocardiography, and while these tests are less expensive, they are also less accurate. A newer noninvasive diagnostic test is computed tomography coronary angiography (CTCA).

The purpose of the study was to compare the accuracy and clinical utility of CTCA with stress testing when determining which patients required invasive testing. In two enrollment periods, investigators enrolled 517 patients who had been referred to the medical center by their physicians. The first group of 297 patients underwent stress testing, CTCA, and ICA. The second group of 220 patients underwent stress testing and CTCA.

Investigators concluded that in patients with low pretest probability of CAD, stress testing was adequate as a first diagnostic test. They determined that CTCA was more accurate when used in patients with a pretest intermediate probability because it was better able to determine which patients required invasive testing. In patients with a high pretest probability, neither stress testing nor CTCA served as an additional diagnostic tool, and physicians should prescribe ICA immediately.

[1] Weustink AC, Mollet NR, Neefjes LA, et al. Diagnostic accuracy and clinical utility of noninvasive testing for coronary artery disease. Ann Intern Med 2010;152:630-39

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* To view the online text from the book, please navigate to SpringerLink or use the DVD to access electronic content. SpringerLink is a subscription service. For further information, click here.