Patient first versus computed tomography first strategy in testing for stable coronary artery disease: dispelling the prevailing myths and biases.

We advocate an evidence-based discussion for a patient first philosophy when considering "the right test for the right patient." Numerous test options exist for the evaluation of symptoms of possible stable ischemic heart disease. Major guidelines have traditionally focused on functional testing with or without imaging to clarify symptoms, diagnose ischemia, stratify prognosis, and guide management. Recently, industry advocates have emphasized modality-specific approaches such as computed tomography (CT First) as an initial test strategy for possible stable CAD. We review the key evidence to demonstrate that current best practice would focus on a patient first approach rather than a modality-specific approach.

Clinical profile of chronic heart failure in elderly women.

The pathogenesis, clinical course, and treatment of chronic heart failure (HF) are different in elderly women from those of patients recruited in the landmark trials of chronic HF. Patients included in these landmark trials were predominantly men whose age was 10-15 years younger than the average age of patients with chronic HF in the United States. Diastolic dysfunction resulting in impaired left ventricular (LV) filling is the preponderant LV functional alteration that leads to chronic HF in elderly women. Gender differences in the LV remodeling process that accompanies chronic cardiac pressure are likely to be responsible for the preponderance of LV diastolic dysfunction over systolic dysfunction in elderly women. In response to chronic pressure overload, the LV wall becomes thicker in women than in men. Consequently, in response to chronic pressure overload, women are able to normalize LV wall stress and preserve LV systolic function to a greater extent than men. However, impaired LV filling is an undesirable consequence of the greater increase in LV wall thickness in women. Thus, clinical observations and therapeutic guidelines derived from data collected in the landmark trials of chronic HF may not apply to elderly women with chronic HF. In view of the lack of evidence-based information needed to guide the management of elderly women with chronic HF, special attention should be given to include a substantial number of elderly women in future therapeutic trials recruiting patients with chronic HF.

Evaluation of suspected ischemic heart disease in symptomatic women.

There is a wealth of evidence about the role of a variety of diagnostic testing modalities to define coronary artery disease (CAD) risk in women presenting for evaluation of suspected myocardial ischemia. The exercise electrocardiogram (ECG) is the core index procedure, which can define risk in women capable of performing maximal exercise. Stress imaging, using echocardiography or myocardial perfusion single-photon emission computed tomography/positron emission tomography, is useful for symptomatic women with an abnormal resting ECG or for those who are functionally disabled. For women with low-risk stress imaging findings, there is a very low risk of CAD events, usually < 1%. There is a gradient relationship between the extent and severity of inducible abnormalities and CAD event risk. Women at high risk are those defined as having moderate to severely abnormal wall motion or abnormal perfusion imaging findings. In addition to stress imaging, the evidence of the relationship between CAD extent and severity and prognosis has been clearly defined with coronary computed tomographic angiography. In women, prognosis for those with mild but nonobstructive CAD is higher when compared with those without any CAD. The current evidence base clearly supports that women presenting with chest pain can benefit from one of the commonly applied diagnostic testing modalities.

Gender-based divergence of cardiovascular outcomes in asymptomatic patients with type 2 diabetes: results from the DIAD study.

Gender differences in cardiovascular outcomes were compared in asymptomatic men and women with type 2 diabetes (T2DM) in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. Of 1123 participants, 290 men and 271 women were randomised to screening with stress myocardial perfusion imaging (MPI); 311 men and 251 women were randomised to no screening. Follow-up was 4.8±0.9 years for the occurrence of cardiac events (CE; cardiac death or non-fatal myocardial infarction). The frequency of abnormal screening was similar in men (24%) and women (19%), (p=0.2), although women trended to have smaller MPI abnormalities. CE rates were lower in women than men (1.7% vs. 3.8%, p=0.04). No CEs occurred in 17 high-risk (UKPDS risk engine) women, whereas 14 (11.2%) occurred in 125 high-risk men. Asymptomatic women with T2DM have significantly better cardiac outcomes than their male counterparts and represent a subgroup for which screening for coronary artery disease does not appear warranted.

Enhanced susceptibility to endotoxic shock and impaired STAT3 signaling in CD31-deficient mice.

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31), an adhesion molecule expressed on hematopoietic and endothelial cells, mediates apoptosis, cell proliferation, and migration and maintains endothelial integrity in addition to its roles as a modulator of lymphocyte and platelet signaling and facilitator of neutrophil transmigration. Recent data suggest that CD31 functions as a scaffolding protein to regulate phosphorylation of the signal transducers and activators of transcription (STAT) family of signaling molecules, particularly STAT3 and STAT5. STAT3 regulates the acute phase response to innate immune stimuli such as lipopolysaccharide (LPS) and promotes recovery from LPS-induced septic shock. Here we demonstrate that CD31-deficient mice have reduced survival during endotoxic LPS-induced shock. As compared to wild-type controls, CD31-deficient mice showed enhanced vascular permeability; increased apoptotic cell death in liver, kidney, and spleen; and elevated levels of serum tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFNgamma), MCP-1, MCP-5, sTNRF, and IL-6. In response to LPS in vivo and in vitro, splenocytes and endothelial cells from knockout mice had reduced levels of phosphorylated STAT3. These results suggest that CD31 is necessary for maintenance of endothelial integrity and prevention of apoptosis during septic shock and for STAT3-mediated acute phase responses that promote survival during septic shock.