Rory Hachamovitch

Comparison of the Short-Term Survival Benefit Associated With Revascularization Compared With Medical Therapy in Patients With No Prior Coronary Artery Disease Undergoing Stress Myocardial Perfusion Single Photon Emission Computed Tomography

Background The relationship between the amount of inducible ischemia present on stress myocardial perfusion single photon emission computed tomography (myocardial perfusion stress [MPS]) and the presence of a short‐term survival benefit with early revascularization versus medical therapy is not clearly defined. Methods and Results A total of 10 627 consecutive patients who underwent exercise or adenosine MPS and had no prior myocardial infarction or revascularization were followed up (90.6% complete; mean: 1.9 ±0.6 years). Cardiac death occurred in 146 patients (1.4%). Treatment received within 60 days after MPS defined subgroups undergoing revascularization (671 patients, 2.8% mortality) or medical therapy (MT) (9956 patients, 1.3% mortality; P=0.0004). To adjust for nonrandomization of treatment, a propensity score was developed using logistic regression to model the decision to refer to revascularization. This model (χ2=1822, c index=0.94, P<10‐7) identified inducible ischemia and anginal symptoms as the most powerful predictors (83%, 6% of overall χ2) and was incorporated into survival models. On the basis of the Cox proportional hazards model predicting cardiac death (χ2=539, P<0.0001), patients undergoing MT demonstrated a survival advantage over patients undergoing revascularization in the setting of no or mild ischemia, whereas patients undergoing revascularization had an increasing survival benefit over patients undergoing MT when moderate to severe ischemia was present. Furthermore, increasing survival benefit for revascularization over MT was noted in higher risk patients (elderly, adenosine stress, and women, especially those with diabetes). Conclusions Revascularization compared with MT had greater survival benefit (absolute and relative) in patients with moderate to large amounts of inducible ischemia. These findings have significant consequences for future approaches to post‐single photon emission computed tomography patient management if confirmed by prospective evaluations. (Circulation. 2003;107:2900‐2906.)

Incremental Prognostic Value of Myocardial Perfusion Single Photon Emission Computed Tomography for the Prediction of Cardiac Death Differential Stratification for Risk of Cardiac Death and Myocardial Infarction

BACKGROUND The incremental prognostic value of stress single photon emission computed tomography (SPECT) for the prediction of cardiac death as an individual end point and the implications for risk stratification are undefined. METHODS AND RESULTS We identified 5183 consecutive patients who underwent stress/rest SPECT and were followed up for the occurrence of cardiac death or myocardial infarction. Over a mean follow up of 642+/-226 days, 119 cardiac deaths and 158 myocardial infarctions occurred (3.0% cardiac death rate, 2.3% myocardial infarction rate). Patients with normal scans were at low risk (< or =0.5%/y), and rates of both outcomes increased significantly with worsening scan abnormalities. Patients who underwent exercise stress and had mildly abnormal scans had low rates of cardiac death but higher rates of myocardial infarction (0.7%/y versus 2.6%/y; P<.05). After adjustment for prescan information, scan results provided incremental prognostic value toward the prediction of cardiac death. The identification of patients at intermediate risk of nonfatal myocardial infarction and low risk for cardiac death by SPECT may result in significant cost savings when applied to a clinical testing strategy. CONCLUSIONS Myocardial perfusion SPECT yields incremental prognostic information toward the identification of cardiac death. Patients with mildly abnormal scans after exercise stress are at low risk for cardiac death but intermediate risk for nonfatal myocardial infarction and thus may benefit from a noninvasive strategy and may not require invasive management.

MYOCARDIAL VIABILITY TESTING AND IMPACT OF REVASCULARIZATION ON PROGNOSIS IN PATIENTS WITH CORONARY ARTERY DISEASE AND LEFT VENTRICULAR DYSFUNCTION: A META-ANALYSIS

OBJECTIVES This study pools data from published series examining late survival with revascularization versus medical therapy after myocardial viability testing in patients with severe coronary artery disease (CAD) and left ventricular (LV) dysfunction. BACKGROUND Previous observational studies have suggested survival benefit in such patients if they are revascularized when myocardial viability is detected on imaging tests. METHODS A MEDLINE database search returned 24 viability studies reporting patient survival using thallium perfusion imaging, F-18 fluorodeoxyglucose metabolic imaging or dobutamine echocardiography. Annual death rates were extracted, pooled and analyzed with a random effects model. The risk-adjusted relationship between severity of LV dysfunction, presence of viability and survival benefit associated with revascularization was assessed by meta-regression. RESULTS There were 3,088 patients (2,228 men), ejection fraction 32 +/- 8%, followed for 25 +/- 10 months. In patients with viability, revascularization was associated with 79.6% reduction in annual mortality (16% vs. 3.2%, chi-square = 147, p < 0.0001) compared with medical treatment. Patients without viability had intermediate mortality, trending to higher rates with revascularization versus medical therapy (7.7% vs. 6.2%, p = NS). Patients with viability showed a direct relationship between severity of LV dysfunction and magnitude of benefit with revascularization (p < 0.001). There was no measurable performance difference for predicting revascularization benefit between the three testing techniques. CONCLUSIONS This meta-analysis demonstrates a strong association between myocardial viability on noninvasive testing and improved survival after revascularization in patients with chronic CAD and LV dysfunction. Absence of viability was associated with no significant difference in outcomes, irrespective of treatment strategy.

American College of Cardiology/American Heart Association expert consensus document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease

Coronary artery calcification is part of the development of atherosclerosis; it occurs exclusively in atherosclerotic arteries and is absent in the normal vessel wall. Electron-beam computed tomography (EBCT), the focus of this document, is a highly sensitive technique for detecting coronary artery calcium and is being used with increasing frequency for the screening of asymptomatic people to assess those at high risk for developing coronary heart disease (CHD) and cardiac events, as well as for the diagnosis of obstructive coronary artery disease (CAD) in symptomatic patients. The use of EBCT has the greatest potential for further determination of risk, particularly in elderly asymptomatic patients and others at intermediate risk. The calcium score has been advocated by some as a potential surrogate for age in risk-assessment models. EBCT has also been proposed as a useful technique for assessing the progression or regression of coronary artery stenosis in response to treatment of risk factors such as hypercholesterolemia. EBCT uses an electron beam in stationary tungsten targets, which permits very rapid scanning times. Serial transaxial images are obtained in 100 ms with a thickness of 3 to 6 mm for purposes of detecting coronary artery calcium. Thirty to 40 adjacent axial scans are obtained during 1 to 2 breath-holding sequences. Current EBCT software permits quantification of calcium area and density. Histological studies support the association of tissue densities of 130 Hounsfield units (HU) with calcified plaque. However, a plaque vulnerable to fissure or erosion can be present in the absence of calcium. Also, sex differences play a role in the development of coronary calcium, the prevalence of calcium in women being half that of men until age 60 years. EBCT calcium scores have correlated with pathological examination of the atherosclerotic plaque. This American College of Cardiology (ACC)/American Heart Association (AHA) Writing Group reviewed …

Exercise Myocardial Perfusion SPECT in Patients Without Known Coronary Artery Disease Incremental Prognostic Value and Use in Risk Stratification

BACKGROUND We evaluated the incremental prognostic value, the role in risk stratification, and the impact on patient management of myocardial perfusion single-photon emission computed tomography (SPECT) in a population of patients without prior myocardial infarction, catheterization, or revascularization. METHODS AND RESULTS We examined 2200 consecutive patients who at the time of their dual-isotope SPECT had not undergone catheterization, coronary artery bypass surgery, or percutaneous transluminal coronary angioplasty and had no known history of previous myocardial infarction. Follow-up was performed at a mean of 566 +/- 142 days (97% complete) for hard events (cardiac death and myocardial infarction) and for referral to cardiac catheterization or revascularization within 60 days after nuclear testing. Examination of clinical, exercise, and nuclear models by use of pre-exercise tolerance test (ETT), post-ETT, and nuclear information using a stepwise Cox proportional hazards model and receiver-operating characteristic curve analysis revealed that nuclear testing added incremental prognostic value after inclusion of the most predictive clinical and exercise variables (global chi2 = 12 for clinical variables; 31 for clinical + exercise variables; 169 for nuclear variables; gain in chi2, P < .0001 for all; receiver-operating characteristic areas: 0.66 +/- 0.04 for clinical, 0.73 +/- 0.04 for clinical + exercise variables, 0.87 +/- 0.03 for nuclear variables, P = .03 for gain in area with exercise variables; P < .001 for increase with nuclear variables). Multiple logistic regression analysis revealed that scan information contributed 95% of the information regarding referral to catheterization with further additional information provided by presenting symptoms and exercise-induced ischemia. Referral rates to early catheterization and revascularization paralleled the hard event rates in all scan categories - very low referral rates in patients with normal scans and significant increases in referral rates as a function of worsening scan results. Even after stratification by clinical and exercise variables such as the Duke treadmill score, pre- and post-ETT likelihood of coronary artery disease, presenting symptoms, sex, and age, the nuclear scan results further risk-stratified the patient subgroups, thus demonstrating clinical incremental value. CONCLUSIONS In a patient population with no evidence of previous coronary artery disease at overall low risk (1.8% hard event rate), myocardial perfusion SPECT adds incremental prognostic information and risk-stratifies patients even after clinical and exercise information is known. It appears that referring physicians use this test in an appropriate manner in selecting patients to be referred to catheterization or revascularization.

Angiogenesis Gene Therapy Phase I Assessment of Direct Intramyocardial Administration of an Adenovirus Vector Expressing VEGF121 cDNA to Individuals With Clinically Significant Severe Coronary Artery Disease

BACKGROUND Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

The economic consequences of available diagnostic and prognostic strategies for the evaluation of stable angina patients : An observational assessment of the value of precatheterization ischemia

OBJECTIVES The study aim was to determine observational differences in costs of care by the coronary disease diagnostic test modality. BACKGROUND A number of diagnostic strategies are available with few data to compare the cost implications of the initial test choice. METHODS We prospectively enrolled 11,372 consecutive stable angina patients who were referred for stress myocardial perfusion tomography or cardiac catheterization. Stress imaging patients were matched by their pretest clinical risk of coronary disease to a series of patients referred to cardiac catheterization. Composite 3-year costs of care were compared for two patients management strategies: 1) direct cardiac catheterization (aggressive) and 2) initial stress myocardial perfusion tomography and selective catheterization of high risk patients (conservative). Analysis of variance techniques were used to compare costs, adjusting for treatment propensity and pretest risk. RESULTS Observational comparisons of aggressive as compared with conservative testing strategies reveal that costs of care were higher for direct cardiac catheterization in all clinical risk subsets (range:

Interrelation of Coronary Calcification, Myocardial Ischemia, and Outcomes in Patients With Intermediate Likelihood of Coronary Artery Disease A Combined Positron Emission Tomography/Computed Tomography Study

2,878 to

Adenosine myocardial perfusion single-photon emission computed tomography in women compared with men: Impact of diabetes mellitus on incremental prognostic value and effect on patient management

4,579), as compared with stress myocardial perfusion imaging plus selective catheterization (range:

Impact of ischaemia and scar on the therapeutic benefit derived from myocardial revascularization vs. medical therapy among patients undergoing stress-rest myocardial perfusion scintigraphy

2,387 to