The Connecticut Cardiovascular Consortium: a unique, state-wide research collaboration to advance clinical outcomes in patients with heart disease.

The establishment of "best clinical practices" founded upon evidence-based medicine has become an increasingly important priority. Frequently, management guidelines are derived from published research data and disseminated among practitioners to help optimize patient care. The ultimate clinical impact of these guidelines in the "real world," however, is often clouded by an incomplete assessment of patient outcomes throughout the continuum of health-care delivery models. In order to address this gap in clinical outcome assessment, we propose to establish the Connecticut Cardiovascular Consortium. The Consortium will consist of a collaborative partnership among all 31 Connecticut hospitals working in concert with Connecticut Office of Health Care Access (OHCA). The primary objective of the Consortium will be to assess, compare, and optimize clinical outcomes among Connecticut residents with cardiovascular disease. As an initial goal for the Consortium, we further propose to undertake a prospective, observational study of Connecticut residents who present with ST Segment Elevation Acute Myocardial Infarction (STEMI). Recent advances in pharmacologic and mechanical reperfusion for STEMI have resulted in a need to define the optimal use of these therapies in the community at large. The primary purpose of this study will be to determine the relative merits of different treatment patterns for STEMI with regard to the use of fibrinolytic therapy and percutaneous coronary intervention (PCI). Particular emphasis will be placed on assessing the relative benefits of urgent mechanical revascularization performed at the state's seven tertiary facilities with PCI capability compared to all other treatment modalities. Successful completion of this unique collaborative endeavor is expected to have significant impact on improved patient care and on current health-care policy for medical resource allocation. Moreover, continued collaboration of health-care providers within the Connecticut Cardiovascular Consortium infrastructure should serve as a useful mechanism for ongoing improvements in evidence-based cardiovascular medicine and clinical research in the state of Connecticut.

Modulation of circulating cellular adhesion molecules in postmenopausal women with coronary artery disease.

OBJECTIVES: The present study examined the association of estrogen (E2) and the inflammatory response of endothelium in coronary artery disease (CAD) by measuring circulating cellular adhesion molecules (cCAMs) in subjects with atherosclerosis. BACKGROUND: Atherosclerotic plaque demonstrates features similar to inflammation. Endothelial cell activation by inflammatory cytokines induces expression of cellular adhesion molecules (CAMs), thereby perhaps augmenting leukocyte adhesion and recruitment and subsequent development of atherosclerosis. The incidence of CAD is lower in women; this may be due to the cardioprotective effects of E2. METHODS: Consecutive eligible subjects with CAD admitted for cardiac catheterization were studied. The groups evaluated were men, postmenopausal women receiving E2 replacement therapy (ERT), postmenopausal women not receiving ERT and premenopausal women. Control groups included men and women without CAD. Preprocedural blood samples were drawn from all groups. Measurements of cCAMs, E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 were performed by enzyme-linked immunoabsorbant assay. E2 levels were assessed by radioimmunoassay. RESULTS: We observed a statistically significant increase in all cCAMs in men with CAD and postmenopausal women with CAD not receiving ERT compared with postmenopausal women with CAD receiving ERT. Premenopausal women with CAD and postmenopausal women with CAD receiving ERT had a significant increase in VCAM-1 alone compared with the female control group. CONCLUSIONS: A possible mechanism by which E2 exerts one of its cardioprotective effects is by limiting the inflammatory response to injury by modulating the expression of CAMs from the endothelium.

Health after coronary stenting or balloon angioplasty: results from the Stent Restenosis Study.

This study was designed to compare health-related quality of life (HRQOL) in patients undergoing coronary stenting or balloon angioplasty in the randomized Stent Restenosis Study. The study sample was drawn from patients at nine U.S. clinical sites of the Stent Restenosis Study, a randomized trial comparing Palmaz-Schatz coronary stent implantation with conventional balloon angioplasty. One hundred ninety-nine consecutive patients were sent surveys 6 to 18 months after enrollment and 160 (80%) were returned. The survey sent to the patients included the Medical Outcomes Study 36-Item Short-Form Health Survey, the Canadian Cardiovascular Society Classification, and the Duke Activity Status Index. Although patients who underwent stenting had less angiographic restenosis and a tendency for fewer ischemic events, there were few differences in HRQOL after a mean of 456 days after randomization. The group that underwent stenting reported significantly less bodily pain than the group that underwent angioplasty (p = 0.02). Otherwise, there were no significant differences in generic or disease-specific measures. In a rating of their overall health, 47% of the group that underwent stenting and 45% of the group that underwent percutaneous transluminal coronary angioplasty reported very good or excellent health. In each group, 60% of the patients reported being symptom free from a cardiovascular perspective. This survey revealed no marked differences in long-term HRQOL between patients who underwent Palmaz-Schatz coronary stenting compared with those who underwent conventional angioplasty.

Physiologic assessment of ostial left circumflex coronary artery disease using a Doppler guidewire before and after rotational atherectomy facilitated angioplasty.

Intravascular Doppler assessment of coronary flow velocity has demonstrated the physiologic significance of intermediate stenoses and the success of coronary interventions. We describe a patient where Doppler evaluation confirmed the significance of an intermediate left circumflex ostial stenosis. We also describe the Doppler flow velocity characteristics after successful rotational atherectomy facilitated angioplasty.

Effects of altered left ventricular geometry on quantitative technetium 99m sestamibi defect size in humans: perfusion imaging during coronary angioplasty.

BACKGROUND: Serial myocardial perfusion imaging is used to assess exercise-induced myocardial ischemia and myocardial risk area, salvage, and viability in patients with myocardial infarction. In an experimental animal model it has been shown that abnormal regional wall motion and altered left ventricular geometry can produce apparent perfusion defects independent of changes in blood flow. The effects of regional alteration in ventricular geometry on perfusion images in humans are not defined. The purpose of our investigation was to evaluate quantitatively the effect of altered left ventricular geometry on myocardial perfusion imaging with technetium 99m sestamibi during coronary angioplasty. METHODS AND RESULTS: Nine patients with normal baseline left ventricular function referred for angioplasty of the left anterior descending coronary artery were studied. 99mTc sestamibi was administered intravenously before angioplasty. Baseline planar electrocardiographic-gated imaging was performed. Imaging was repeated in the catheterization laboratory during angioplasty vessel occlusion when altered left ventricular geometry was produced and again later after angioplasty. Summed static, end-systolic, and end-diastolic images were generated from the electrocardiographic-gated acquisitions. Circumferential count profiles of images obtained during percutaneous transluminal coronary angioplasty (PTCA) were compared with those of a normal 99mTc sestamibi database and their own baseline images. Defect integral (the area below the reference profile) and nadir (maximum percent decrease in activity) were derived. Compared with a normal database, new quantitative defects appeared on PTCA-summed images in only two patients. The defects were small to moderate in size. However, compared with their own baseline profile, six patients had quantitative defects during PTCA (mean defect integral 3 +/- 2; mean defect nadir 12% +/- 7%). Defect nadir was larger on end-diastolic images compared with summed images (22% +/- 7% and 12% +/- 7%, respectively; p < 0.05). CONCLUSIONS: Altered left ventricular geometry may create apparent, albeit small, planar myocardial perfusion defects in humans. Changes in defect size on serial images may be only partially caused by changes in regional wall motion or geometry.

Frequency of long-term lower limb ischemia associated with intraaortic balloon pump use.

Lower limb ischemia is a frequent complication of intraaortic balloon pump (IABP) use. The incidence and risk factors for acute ischemia have been well-defined, but little is known about long-term ischemic complications. This prospective study evaluated the incidence, nature, progression and predisposing factors for long-term lower limb ischemia in 151 patients who were previously treated with the IABP. These persons were interviewed and their lower extremities examined 12 to 20 months after undergoing IABP counterpulsation. Limb ischemia, characterized primarily by ipsilateral discomfort and diminished pulses, occurred in 18% of those evaluated. Evidence of ischemia worsened over time in 14%. Logistic regression analysis, which was based on variables found to be significant in bivariate analysis, revealed that the occurrence of limb ischemia acutely, cardiogenic shock as an indication for IABP insertion, and smoking (at the time of hospitalization or having quit < 10 years previously) were risk factors for long-term lower limb ischemia. The adjusted odds ratio for acute limb ischemia was 8.89 (95% confidence interval 2.80 to 28.21), for cardiogenic shock 3.59 (95% confidence interval 1.01 to 12.75), and for smoking 2.87 (95% confidence interval 1.10 to 7.46). Increasing numbers of patients are undergoing IABP counterpulsation and a greater proportion of these are surviving their acute event and resuming active lives. It is essential to recognize that detrimental consequences of this device can persist long after hospitalization.

Equine arch vessel anomaly associated with coarctation of the aorta.

Angiography in a 30-year-old man revealed the unique combination of aortic coarctation and an unusual arch anomaly. Proximal to the coarctation, a single arch vessel trifurcated into the brachiocephalic, left common carotid and left subclavian arteries. This anomalous arch vessel is a normal equine variant.

Right ventricular infarction.

Right ventricular myocardial infarction, long unrecognized because of a lack of diagnostic methods and unsupported beliefs regarding the dispensability of the right ventricle, may now be diagnosed using well-accepted criteria. Right ventricular infarction is clearly associated with anterior left ventricular infarction as well as inferior infarction. It may occur in 30% to 40% of patients with inferior infarction, although a much smaller percentage experience hemodynamic instability on the basis of right ventricular infarction. Pathophysiologically, right ventricular systolic and diastolic dysfunction are exacerbated by pericardial restraint and concomitant left ventricular dysfunction, accounting for the characteristic findings of cardiogenic shock and marked preload dependence in many patients. Right ventricular infarction may be suspected on the grounds of clinical presentation, physical examination, and enzymatic findings, and is confirmed using well-defined electrocardiographic, radionuclide, echocardiographic, and hemodynamic criteria. Once diagnosed, right ventricular infarction requires specific hemodynamic and pharmacologic management, including the judicious use of volume expansion and inotropic support. Several forms of mechanical and surgical intervention are of therapeutic value in treating hemodynamic disturbances and recognized complications. With appropriate management, the prognosis for patients with right ventricular infarction is generally favorable.

Validation of continuous radionuclide left ventricular functioning monitoring in detecting silent myocardial ischemia during balloon angioplasty of the left anterior descending coronary artery.

Silent myocardial ischemia has been inferred from transient ST-segment depression during continuous electrocardiographic monitoring. Recently, continuous ambulatory monitoring of left ventricular (LV) function using a radionuclide technique (VEST) has demonstrated episodes of significant silent LV dysfunction in the absence of electrocardiographic changes. To validate the demonstration of silent LV dysfunction with this technique, 12 men were studied during percutaneous transluminal coronary angioplasty. A total of 18 left anterior descending coronary artery balloon inflations were performed. Balloon inflations at 8 +/- 2 atm (4 to 10 atm) lasted 70 +/- 16 seconds. Seventeen of 18 inflations were associated with a decrease in LV ejection fraction greater than 0.10. Mean LV ejection fraction decreased from 0.53 +/- 0.08 to 0.28 +/- 0.11 (p less than 0.0001). In contrast, there was pain in only 10 inflations and ST-segment changes in 7. LV dysfunction was associated with a minimal increase in end-diastolic volume (4 +/- 3%, p less than 0.003), and a major increase in relative end-systolic volume (69 +/- 43%, p less than 0.001). These data suggest that continuous monitoring of LV function with the VEST can sensitively detect silent ischemic decreases in LV function occurring during angioplasty, and provide further validation of the use of this technique for detecting silent myocardial ischemia.

Effects of serotonin-receptor blockade on angioplasty-induced vasospasm in an atherosclerotic rabbit model.

Vasospasm occurs both in patients and animal models after angioplasty and may be associated with early closure of the dilated vessel. To investigate the mechanism of angioplasty-induced vasospasm, the effect of serotonin-receptor blockade with two serotonin2 (S2) antagonists, LY53857 and sergolexole, was examined in rabbits with focal femoral artery atherosclerosis. In preliminary studies, local infusion of 1-100 micrograms serotonin caused significant femoral artery vasoconstriction (p less than 0.05) in both normal and atherosclerotic rabbits. There was no significant difference in the degree of vasoconstriction induced by equal doses of serotonin in normal and atherosclerotic animals. Infusion of 10 micrograms serotonin produced a 23 +/- 5% decrease in luminal diameter in atherosclerotic femoral arteries. This was blocked by pretreatment with both S2 inhibitors given separately in different animals before serotonin infusion (p less than 0.002). In contrast, LY53857 (sergolexole was not tested) had no significant effect on phenylephrine-induced vasoconstriction, confirming its specificity as an S2-receptor antagonist. Balloon angioplasty of atherosclerotic vessels caused a significant increase in vessel diameter at the angioplasty site (45% increase from baseline diameter, p less than 0.05). This was associated with significant luminal narrowing both proximal (21% reduction from baseline, p less than 0.05) and distal (17% reduction from baseline, p less than 0.03) to the angioplasty site. These proximal and distal changes are most likely due to vasospasm, as there was no histological evidence of thrombus or dissection at these sites to explain the luminal narrowing. Pretreatment of animals with 10 mg LY53857 or 20 mg sergolexole blocked the proximal vasospasm (2.6 +/- 0.4 before versus 2.2 +/- 0.1mm after angioplasty for LY53857, 2.1 +/- 0.4 before versus 2.1 +/- 0.4 mm after angioplasty for sergolexole; p = NS). Treatment with 20 mg LY53857 inhibited both proximal (2.3 +/- 0.1 before versus 2.2 +/- 0.2 mm after angioplasty, p = NS) and distal (1.7 +/- 0.1 before versus 1.6 +/- 0.2 mm after angioplasty, p = NS) vasospasm after angioplasty. Proximal (2.3 +/- 0.5 before versus 2.5 +/- 0.3 mm after) and distal (1.7 +/- 0.2 before versus 1.7 +/- 0.4 mm after) vasospasm was also prevented by pretreatment with 40 mg sergolexole.(ABSTRACT TRUNCATED AT 400 WORDS)

Pulmonary embolism presenting as exercise-induced hypotension.

A 68-year-old man with remote history of previous myocardial infarction presented with a four-week history of intermittent dyspnea. After developing hypotension during an exercise tolerance test, he underwent cardiac catheterization, revealing significant pulmonary hypertension and two-vessel coronary artery disease. Pulmonary angiography confirmed the presence of pulmonary emboli which partially resolved after thrombolytic therapy. Subsequent treadmill testing confirmed the absence of exercise-induced hypotension two months following treatment. This case underscores the importance of considering pulmonary embolism as a potential cause of exercise-induced hypotension, since it can be successfully treated with thrombolytic agents weeks after the initial onset of symptoms.

Clinical experience with the Palmaz-Schatz coronary stent. Initial results of a multicenter study.

Stenting of native coronary arteries with a balloon-expandable stent was attempted in 226 patients after elective angioplasty. Delivery of the device was successful in 213 (94%) of the patients. Of these, 39 received aspirin and dipyridamole only (group 1) and 174 received aspirin, dipyridamole, and warfarin for 1-3 months (group 2). There was no abrupt closure (less than or equal to 1 day) or perioperative death in either group. In-hospital or perioperative complications in group 1 compared with group 2 were as follows: subacute closure (1-14 days), seven (18%) patients versus one (0.6%) patient, respectively, p less than 0.0001; myocardial infarction, five (13%) patients versus one (0.6%) patient, respectively; condition requiring urgent bypass surgery, one (2.5%) patient versus no patients, respectively. Thus, the incidence of major complications such as death, myocardial infarction, or a condition requiring urgent bypass surgery was 15% in group 1 and 0.6% in group 2. Clinical follow-up revealed that 92% of the patients were asymptomatic at 3 months after stenting compared with 6% before stenting (p less than 0.0001). Of the 13 patients who were symptomatic, nine underwent cardiac catheterization and, ultimately, successful elective coronary angioplasty or bypass surgery. We conclude that a high delivery success rate can be expected with this device and that clinical thrombosis is less frequent in anticoagulated patients than in nonanticoagulated patients. Furthermore, in this selected patient population, coronary stenting results in a low incidence of in-hospital and perioperative complications. Clinical success, defined by absence of symptoms, appears to be sustained at 3 months.

Risk for systemic embolization of atrial fibrillation without mitral stenosis.

The risk for systemic embolization was studied in 272 patients without mitral stenosis or prosthetic valves who were referred to the echocardiography laboratory with atrial fibrillation (AF). During a mean follow-up period of 33 months (range less than 1 to 83), 27 (10%) patients had a systemic embolic event, which was cerebral in 23 patients (85%) and peripheral in 4 (15%). In the analysis of individual variables, the risk of embolization was increased by female sex, underlying heart disease and left atrial size greater than or equal to 4.0 cm, but not by age, hypertension or type of AF (paroxysmal vs chronic). In multivariable analysis, left atrial size greater than or equal to 4.0 cm was the single strongest predictor of increased risk for embolization (p less than 0.001), but female sex (p = 0.014) and underlying heart disease (p = 0.027) also contributed. When each of these 3 factors was assigned 1 point in a risk score, embolic events were found to occur in none (0%) of 24 patients with a risk score of 0, in 2 (3%) of 83 patients with a risk score of 1, in 13 (11%) of 118 patients with a risk score of 2 and in 12 (26%) of 47 patients with a risk score of 3. The score allows patients with AF and without mitral stenosis to be stratified into high-, medium- and low-risk groups for systemic embolization. Such information could be useful in decision making for anticoagulation in patients with AF.

Predictors of success in percutaneous transluminal coronary angioplasty of chronic total occlusions.

Earlier studies have indicated that percutaneous transluminal coronary angioplasty (PTCA) of chronic total occlusions has a low success rate. To determine success rate and assess clinical and angiographic variables associated with success and complications, 57 total occlusions in 56 patients undergoing PTCA were analyzed. The clinical duration of occlusion was 51 +/- 86 days. Success (less than 50% residual stenosis) was achieved at 40 of 57 (70%) dilatation sites. Of these 57 total occlusions, 5 were attempted within 24 hours of acute myocardial infarction, 35 between 1 day and 8 weeks of clinical occlusion, 13 greater than 8 weeks and 4 were of unknown duration. Success rates were 4 of 5, 25 of 35, 9 of 13 and 2 of 4, respectively, in each group (difference not significant, comparison of all time groups). Of the 9 narrowings with a successful PTCA for an occlusion greater than 8 weeks, the mean duration of occlusion was 93 +/- 41 days (range 60 to 180). None of the attempted dilatations of occlusions with a clinical duration of greater than 180 days (n = 3) was successful. None of the clinical or angiographic variables (including tortuosity, length of occlusion gap, distance of the occlusion from the vessel origin, thrombus, lesion calcium, collaterals, prior myocardial infarction, vessel dilated or diffuse disease) impacted on success rate (difference not significant for all). No patient died, had a Q-wave infarction, required emergency coronary artery bypass grafting or underwent repeat PTCA within 7 days of the procedure. Non-Q-wave infarction occurred in 2 of 56 patients (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary and pleural complications of cardiac disease.

Disorders of the heart frequently cause pulmonary dysfunction because of the close structural and functional association of the heart and lungs. The pulmonary vasculature is very commonly affected by cardiac pathology. The pulmonary vasculature is normally a low-pressure, low-resistance circuit with high compliance and tremendous vascular reserve. Although resting vascular tone is low, there are many identified mediators of pulmonary arterial tone that may help mediate pulmonary blood flow. Alveolar hypoxia is clearly a stimulus for increasing pulmonary vascular resistance although factors that mediate the response to hypoxia are not fully understood. Patients with left-to-right shunting due to congenital heart disease because of elevations in pulmonary artery flow and pressure tend to develop progressive anatomic changes in the pulmonary vasculature. This leads to an increase in pulmonary vascular resistance, irreversible pulmonary hypertension, right heart failure, reversal of shunt flow, and Eisenmenger's syndrome. The degree of anatomic vascular damage due to left-to-right shunting can be graded histologically. Lesser grades of damage are reversible with corrective surgery, whereas more severe grades show no improvement or progression with operation. Chronic left-sided congestive heart failure seen in rheumatic mitral stenosis can cause secondary changes in the pulmonary vasculature. Pulmonary hypertension and increased pulmonary vascular resistance can increase reflexly and form a "second stenosis" that further limits cardiac output. Unlike congenital heart disease, severe grades of pulmonary arterial damage are not seen in left heart failure from mitral stenosis or other causes, and consequently with surgical correction pulmonary hypertension reverses. Pulmonary function testing is adversely affected by congestive heart failure. Both restrictive (stiff lungs) and obstructive (cardiac asthma) defects are observed in congestive heart failure. DLCO is abnormally decreased. With treatment of heart failure these defects reverse. Both elevated systemic and pulmonary venous pressures affect fluid filtration in the pleural space and cause pleural fluid accumulation. The fluid is transudative with low protein, low lactate dehydrogenase, and low cell counts. Transudative effusions from heart failure resolve with treatment. With large effusions and cardiomegaly, pulmonary dysfunction results because of atelectasis from compression and space-occupying effects of the heart and pleural fluid. Following myocardial infarction, cardiac surgery, or other cardiac trauma, the postcardiac injury syndrome can result. The syndrome is characterized by exudative pleural and pericardial effusions along with pulmonary infiltrates, fever, chest pain, leukocytosis, and an elevated ESR. The syndrome must be diagnosed by exclusion of bacterial pneumonia, pulmonary emboli, and congestive heart failure. Treatment is with nonsteroidal anti-inflammatory agents or systemic co

Relation of peak creatine kinase levels during acute myocardial infarction to presence or absence of previous manifestations of myocardial ischemia (angina pectoris or healed myocardial infarction).

The hypothesis that acute myocardial infarction (MI) is more extensive in patients without previous angina or healed MI was evaluated in 177 patients with documented recent acute MI. Ninety-nine patients (56%) had no previous angina or healed MI (negative history group), and the remaining 78 patients (44%) had a previous history of angina or healed MI (positive history group). The mean peak creatine kinase (CK) level in the negative history group was 784 compared with 419 IU in the positive history group (p less than 0.0001). The mean peak CK-MB level in the negative history group was 128 compared with 76 IU in the positive history group (p less than 0.001). The mean peak CK-MB level was higher in the negative history group after controlling for age, streptokinase administration, previous coronary artery bypass grafting or treatment with beta-blocking agents. Despite the high frequency of healed MI in the positive history group (73%), the rates of in-hospital complications were similar for the 2 groups. Patients with acute MI without previous angina or healed MI have substantially higher peak CK and CK-MB levels; this implies a larger MI than in patients with previous angina or healed MI.