Abstract-Atherosclerotic cardiovascular disease results in Ͼ19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances in Ca2+ release and reuptake from the sarcoplasmic reticulum (SR), whereas functional studies of the cardiac Na(+)-Ca2+ exchanger, another important determinant of myocyte homeostasis, are lacking for the failing human heart. Using a cardiac Na(+)-Ca2+ exchanger cDNA recently cloned from a guinea pig cDNA library, we investigated the gene expression of the cardiac Na(+)-Ca2+ exchanger in relation to the SR Ca(2+)-ATPase. Expression of both genes was quantified in left ventricular myocardium from 24 failing human cardiac explants and 7 control heart samples in relation to beta-myosin heavy chain mRNA by slot blot analysis. Compared with patients with nonfailing hearts, patients with dilated cardiomyopathy (DCM, n = 13) showed a 55% increase in Na(+)-Ca2+ exchanger mRNA levels (P < .05 versus control value) and a 41% increase in patients with coronary artery disease (CAD, n = 11). In the same hearts, SR Ca(2+)-ATPase mRNA levels were decreased by 50% in DCM and by 45% in CAD (P < .05 for both versus control value). There was a positive correlation between Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase mRNA levels both in normal and failing human hearts, albeit with different slopes and intercepts of the regression line. The Na(+)-Ca2+ exchanger protein levels as assessed by Western blot analysis and normalized to beta-myosin heavy chain protein were increased in DCM and CAD (P < .05 and P < .01 versus control value, respectively), whereas SR Ca(2+)-ATPase protein levels were reduced (P < .05 for both groups versus control values). Thus, the Na(+)-Ca2+ exchanger gene expression is enhanced in failing human hearts and may, in part, compensate for the depressed SR function with regard to diastolic Ca2+ removal.