Challenge of surrogate endpoints.

Surrogate endpoints are biomarkers that are intended to substitute for clinical endpoints. They have been used to find novel therapeutic targets, improve the statistical power and shorten the duration of clinical trials, and control the cost of conducting research studies. The more generalized use of surrogate endpoints in clinical decision making can be hazardous and should be undertaken with great caution. This article reviews prior work with surrogate endpoints and highlights caveats and lessons learned from studies using surrogate endpoints.

Paging the worldwide cardiology consultant: the Army Knowledge Online Telemedicine Consultation Program in cardiology.

BACKGROUND: Global operations place large numbers of military and nonmilitary personnel in austere environments. Aeromedical evacuation for cardiovascular issues is periodically required. The Army Knowledge Online (AKO) Telemedicine Consultation Program was initiated by the Office of the Surgeon General to electronically link deployed medical providers with subspecialty consultants to assist and guide triage and disposition. METHODS: Electronic consultation triggered a text page to an on-call staff cardiologist at Brooke Army Medical Center. Cardiology teleconsultations for the first 3.5 years were analyzed. RESULTS: Two hundred seven cardiology teleconsults were managed, with an average response time of 4 hours 54 minutes. The three most prevalent reasons for teleconsultation were electrocardiographic abnormalities, chest pain syndromes, and syncope. Six evacuations were avoided; 29 evacuations were facilitated. An estimated $144,000 was saved, plus intangible benefits. CONCLUSIONS: Cardiology teleconsultation provides a valuable service to deployed providers, decreases medical evacuation costs, and facilitates transfer of patients to appropriate facilities.

Aortic root dilatation with sinus of valsalva and coronary artery aneurysms associated with ankylosing spondylitis.

The HLA-B27-related spondyloarthopathies are associated with cardiovascular disease in 2% to 10% of cases. Inflammation and sclerosis of the aortic root and ventricular septum have been linked to the development of isolated aortic regurgitation and conduction abnormalities; however, aneurysms of the aortic sinuses and coronary arteries have not been previously described. We report the case of a 58-year-old white man who presented for evaluation of dyspnea and was found to have aneurysms of the sinuses of Valsalva and the circumflex coronary artery. The patient underwent aortic root replacement. Approximately 3 months later, he presented with symptoms, radiographs, and laboratory data consistent with ankylosing spondylitis. To our knowledge, these particular cardiovascular manifestations of HLA-B27-related disease have not been previously reported. This case expands the clinical spectrum of the disease and should prompt the clinician to consider the possibility of HLA-B27-associated cardiovascular disease in patients who have aortic and coronary aneurysms.

Addition of right-sided and posterior precordial leads during stress testing.

BACKGROUND: Exercise treadmill testing has limited sensitivity for the detection of coronary artery disease, frequently requiring the addition of imaging modalities to enhance the predictive value of the test. Recently, there has been interest in using nonstandard electrocardiographic (ECG) leads during exercise testing. METHODS: We consecutively enrolled all patients undergoing exercise myocardial imaging with four additional leads recorded (V4R, V7, V8, and V9). The test characteristics of the 12-lead, the 15-lead (12-lead, V7, V8, V9), and the 16-lead (12-lead, V4R, V7, V8, V9) ECGs were compared with stress imaging in all patients. In the subset of patients who underwent angiography within 60 days of stress testing, these lead arrays were compared with the catheterization findings. RESULTS: There were 727 subjects who met entry criteria. The mean age was 58.5 +/- 12.3 years, and 366 (50.3%) were women. Pretest probability for disease was high in 241 (33.1%), intermediate in 347 (47.7%), and low in 139 (19.1%). A total of 166 subjects had an abnormal 12-lead ECG during exercise. The addition of 3 posterior leads to the standard 12-lead ECG resulted in 7 additional subjects having an abnormal electrocardiographic response to exercise. The addition of V4R resulted in only 1 additional patient having an abnormal ECG during exercise. The sensitivity of the ECG for detecting ischemia as determined by stress imaging was 36.6%, 39.2%, and 40.0% (P = NS) for the 12-lead, 15-lead, and 16-lead ECGs, respectively. In those with catheterization data (n = 123), the sensitivity for determining obstructive coronary artery disease was 43.5%, 45.2%, and 45.2% (P = NS) for the 12-lead, 15-lead, and 16-lead ECGs, respectively. The sensitivity of imaging modalities was 77.4% when compared with catheterization. CONCLUSIONS: In patients undergoing stress imaging studies, the addition of right-sided and posterior leads did not significantly increase the sensitivity of the ECG for the detection of myocardial ischemia. Additional leads should not be used to replace imaging modalities for the detection of coronary artery disease.

Feasibility of remote echocardiography with satellite transmission and real-time interpretation to support medical activities in the austere medical environment.

Echocardiography is an essential tool in the evaluation of patients with cardiac emergencies and chest trauma. The objective of our study was to establish the feasibility and diagnostic accuracy of a portable satellite transmission system in the assessment of cardiac emergencies for the real-time support of mass casualty and humanitarian relief efforts. Twelve patients with various degrees of cardiac structural disease identified by conventional inhospital transthoracic echocardiography were transported to a remote portable field hospital where transthoracic echocardiography was performed with a handheld echocardiographic device. Images were then relayed by a commercial satellite to a level III trauma center where they were interpreted in real time by a cardiologist. Remote studies were recorded at the field hospital before satellite transmission and again on download at the receiving facility. The remotely acquired studies before and after satellite transmission were compared with each other and subsequently compared with conventional hospital transthoracic echocardiograms for technical quality and diagnostic accuracy using a blinded, single-reader, side-by-side comparison. Excellent agreement was found between the recorded field-site and satellite-transmitted images with an overall average of 95% concordance. When the field data acquired with the handheld device and satellite transmission were compared with conventional inhospital echocardiography, a high degree of agreement was demonstrated in overall technical quality (83%) and assessments of left ventricular ejection fraction (100%), pericardial effusion (100%), and left ventricular size (92%). This study demonstrates the feasibility and diagnostic accuracy of remote, real-time echocardiography using satellite transmission for mass casualty triage or humanitarian relief efforts.

Chamber dimensions and functional assessment with coronary computed tomographic angiography as compared to echocardiography using American Society of Echocardiography guidelines.

BACKGROUND: The correlation between normal cardiac chamber linear dimensions measured during retrospective coronary computed tomographic angiography as compared to transthoracic echocardiography using the American Society of Echocardiography guidelines is not well established. METHODS: We performed a review from January 2005 to July 2011 to identify subjects with retrospective electrocardiogram-gated coronary computed tomographic angiography scans for chest pain and transthoracic echocardiography with normal cardiac structures performed within 90 days. Dimensions were manually calculated in both imaging modalities in accordance with the American Society of Echocardiography published guidelines. Left ventricular ejection fraction was calculated on echocardiography manually using the Simpson's formula and by coronary computed tomographic angiography using the end-systolic and end-diastolic volumes. RESULTS: We reviewed 532 studies, rejected 412 and had 120 cases for review with a median time between studies of 7 days (interquartile range (IQR25,75) = 0-22 days) with no correlation between the measurements made by coronary computed tomographic angiography and transthoracic echocardiography using Bland-Altman analysis. We generated coronary computed tomographic angiography cardiac dimension reference ranges for both genders for our population. CONCLUSION: Our findings represent a step towards generating cardiac chamber dimensions' reference ranges for coronary computed tomographic angiography as compared to transthoracic echocardiography in patients with normal cardiac morphology and function using the American Society of Echocardiography guideline measurements that are commonly used by cardiologists.

Matrix metalloproteinases in patients with myocardial infarction and percutaneous revascularization.

BACKGROUND: Extracellular matrix remodeling is a component of coronary artery disease (CAD). Matrix metalloproteinases (MMPs) are enzymes involved in extracellular matrix degradation. The extrapolation of the role MMPs play in the clinical setting of acute coronary syndromes has not yet been defined. METHODS: Samples from 100 subjects undergoing cardiac catheterization were analyzed for serum levels of MMP-1, MMP-2, and MMP-9. These markers were assessed before, immediately after, and 24 hours after cardiac catheterization. Relationships among MMP levels, baseline characteristics, angiography findings and clinical course were assessed. RESULTS: Comparing subjects with myocardial infarction versus those without, baseline MMP-1 levels were not different at baseline but increased during the hospital stay, MMP-2 levels were higher at baseline and throughout the monitoring period and MMP-9 levels lower and decreased over time. MMP-1 was higher 24 hours after catheterization in subjects undergoing revascularization. Subjects undergoing percutaneous revascularization had higher MMP-9 levels following revascularization than those subjects undergoing angiography without angioplasty. CONCLUSIONS: Serial monitoring of MMPs indicates a differential subtype response to myocardial infarction and percutaneous revascularization. Results of this study indicate that MMP subtypes may play differing roles in the manifestation of acute coronary syndromes and response to revascularization.