Alan Chu

Impact of Stent Deployment Procedural Factors on Long-Term Effectiveness and Safety of Sirolimus-Eluting Stents (Final Results of the Multicenter Prospective STLLR Trial)

Drug-eluting stent failures were associated with various clinical factors. However, the clinical impact of stent deployment technique was unknown. This study was designed to evaluate the frequency and impact of suboptimal percutaneous coronary intervention on long-term outcomes of 1,557 patients treated with sirolimus-eluting stents (SESs) in 41 US hospitals. All steps of the interventional procedure were scrutinized by an independent core laboratory to determine the occurrence of geographic miss (GM). GM included longitudinal (LGM; injured or diseased segment not covered by SES) or axial GM (balloon-artery size ratio <0.9 or >1.3) mismatches. Patients with and without GM were stratified (GM vs no-GM group). Patients, investigators, and the independent clinical event adjudication committee were blind to study group assignments. The primary end point was 1-year target-vessel revascularization (TVR) rate. Incidences and predictors of GM and safety outcomes were secondary end points. GM occurred in 943 patients (66.5%): 47.6% had LGM, 35.2% had axial GM, and 16.5% had both. One-year TVR rates were 5.1% in the GM group versus 2.5% in the no-GM group (p=0.025). TVR was 6.1% in the LGM versus 2.6% in the no-LGM subgroups (p=0.001). The association of GM with 1-year TVR was independent of clinical or anatomic factors (hazard ratio 2.0, 95% confidence interval 1.0 to 4.02, p=0.05). There was a 3-fold increase in myocardial infarction rates associated with GM (2.4% vs 0.8%; p=0.04). In conclusion, GM occurred frequently during SES implantation and was associated with increased risk of TVR and myocardial infarction at 1 year. These results emphasized the need for improvement in contemporary percutaneous coronary intervention practices and technologies.

Effects of atrial natriuretic peptide on proximal epicardial coronary arteries and coronary blood flow in conscious dogs.

The effects of a trial natriuretic peptide (ANP) on proximal epicardial coronary artery dimensions and coronary blood flow were examined in 7 awake dogs chronically instrumented with miniature coronary dimension crystals and Doppler flow probes on the circumflex coronary artery. ANP (10, 50, and 150 μg) was infused as a bolus via the left atrial catheter. Aortic pressure, left ventricular end-diastolic pressure, heart rate, and dP/dt did not change significantly with any dose of ANP. ANP caused transient (1–5 minutes) dose-related Increases in coronary blood flow; maximum increases were 28.1 ±6.9%, 40.2 ± 6.2%, and 73.9 ± 12.5% with the 10-, 50-, and 150-μg doses, respectively. ANP also Induced prolonged (average 70.2 ± 28.6 minutes with 150μg dose) dose-related increases in coronary diameter; maximum increases were 3.1 ± 1.0%, 3.9± 1.5%, and 5.7± 1.3% with the 10-, 50-, and 150-μg doses, respectively. The increase in diameter was not attenuated when the transient increase in blood flow was prevented by partial occlusion with a pneumatic snare. Combined autonomic blockade with propranolol (1 mg/kg), phentolamine (1 mg/kg), and atropine (0.06 mg/kg) attenuated the relative increase in coronary flow but did not alter the increases in epicardial coronary diameter produced by ANP. These data demonstrate that bolus injection of ANP effects preferential, sustained, dose-dependent, flow-independent increases in epicardial coronary dimensions and relatively brief dose-dependent increases in coronary blood flow. The vasodilator effects of ANP on epicardial vessels are direct and are not mediated via the autonomic nervous system. The effects of ANP on the coronary vasculature are similar to those of nitrates, although the effects of ANP on epicardial vessel dimension are more gradual and more sustained.

Prognostic effect of bundle branch block related to coronary artery bypass grafting

The incidence and prognostic effect of the development of new perioperative ventricular conduction abnormalities were examined in all patients undergoing coronary artery bypass surgery at Duke University Medical Center between 1976 and 1981. Of the 913 patients included, transient (resolved before discharge) ventricular conduction abnormalities developed in 156 (17%) and persistent (until discharge) changes developed in 126 (14%). Complete right bundle branch block (BBB) was the most frequent type of new ventricular conduction abnormality, followed by left anterior hemiblock and incomplete right BBB (found in 60%, 26%, and 9%, respectively, of all patients with transient changes and 29%, 33% and 26% of all patients with persistent changes). Development of new ventricular conduction abnormalities was most strongly related to date of operation (p less than 0.0001, univariate chi 2 = 122), increasing from 2% transient and 7% persistent in 1976 to 36% transient and 22% persistent in 1981. The incidence was also higher in older patients. Preoperative ejection fraction and number of diseased vessels were related to development of perioperative ventricular conduction abnormalities but were not independently related after adjustment for other baseline characteristics. Contrary to findings in other studies, development of new perioperative ventricular conduction abnormalities, including isolated new left BBB, did not worsen the survival rate in patients followed up to 3 years after surgery.

Relation between regional distribution of thallium-201 and myocardial blood flow in normal, acutely ischemic, and infarcted myocardium☆

Myocardial localization of thallium-201 was compared with direct measurements of myocardial perfusion in normal, acutely ischemic, and recently infarcted myocardium. Studies were performed in 6 chronically instrumented dogs that were subjected to myocardial infarction by occlusion of the proximal left circumflex coronary artery. Four days after myocardial infarction, thallium-201 and 9 +/- 1 micrometer niobium-95-labelled microspheres were injected simultaneously after acute left anterior descending coronary arterial occlusion; the animals were killed 5 minutes later and the entire left ventricle was sectioned into 1 to 2 g samples. Regression analyses between thallium-201 activity and regional myocardial blood flow using all myocardial samples demonstrated a very close linear relation in each dog; r values were 0.98 or greater, indicating that the initial localization of thallium-201 in acutely ischemic and recently infarcted myocardium as a function of regional blood flow was essentially identical. Consequently, in each dog the regional distribution of thallium-201 closely approximated myocardial perfusion over a wide range of blood flow and potentially different local metabolic conditions that may be encountered in the clinical use of the isotope.

Effects of atrial natriuretic peptide on transmural blood flow and reactive hyperemia in the presence of flow-limiting coronary stenosis in the awake dog: evidence for dilation of the intramural vasculature.

The effects of atrial natriuretic peptide (ANP) on transmural myocardial blood flow distribution and the reactive hyperemic response in the presence and absence of flow-limiting coronary stenosis were examined in chronically instrumented conscious dogs. Ten-second coronary occlusion without subsequent flow restriction resulted in marked reactive hyperemic responses (Doppler flow probes), mean flow debt repayment was 481±55percent;. When the 10-second coronary occlusions were followed by a 20-second partial restriction that allowed normal preocclusion coronary inflow, the subsequent reactive hyperemia was significantly augmented, mean flow debt repayment was 938±91percent; (p<0.05). Pretreatment with ANP (3μg/kg) did not alter the flow debt repayment after a 10-second occlusion without restriction (474±30percent;, NS) but attenuated the augmentation of reactive hyperemia resulting from the 20-second inflow restriction, flow debt repayment (613±±66percent;, NS). Regional myocardial blood flow to the ischemic region was measured during restricted inflow after a 10-second coronary occlusion before and after ANP pretreatment. Before ANP, subendocardial flow decreased (0.54±0.04 ml/min/g) and subepicardial flow significantly increased (1.03±0.12 ml/min/g) when compared with the nonischemk zone (subendocardial, 1.03±0.09 ml/min/g; subepicardial, 0.87±0.09 ml/ min/g, p<0.05), indicating maldistribution of the restricted inflow. The resultant subendocardial-to-subepicardial ratio in the ischemic region was significantly decreased when compared with the nonischemic region (0.56±0.03 vs. 1.18±0.04, p<0.05). After ANP pretreatment, subendocardial flow to the ischemic region significantly increased (0.71±0.07 ml/min/g, p<0.05) and the subendocardial-to-subepicardial ratio in the ischemic zone was significantly unproved (0.91±0.10, p<0.05). Myocardial flow measured daring coronary occlusion was not altered after ANP pretreatment, indicating no change in native collateral flow to the ischemic region. Myocardial oxygen consumption, aortic and left ventricular end-diastolic pressures, dP/dt, and heart rates were also not affected by pretreatment with ANP. These data indicate that ANP favorably redistributed blood flow to the subendocardium and reduced subendocardial ischemia after a transient occlusion in the presence of a flow limiting coronary stenosis. The reversal of subendocardial hypoperfusion by ANP hi the absence of alterations of intrinsic vascular reactivity or native collateral flow supports a dilation effect of ANP on the intramural arteries.

Myocardial Infarction and Risk Region Relationships: Evaluation by Direct and Noninvasive Methods

Optimal quantitation of myocardial infarction requires resolution of the three-dimensional geometry of the ischemic region at a time that progression of tissue necrosis has been completed and can be sharply delineated from noninfarcted myocardium but before significant remodeling of the ventricular chamber. Although this can be achieved at two to three days after coronary occlusion by histologic techniques, a variety of technologies including two-dimensional echo, CTT, SPECT, PET, and NMR have demonstrated potential for providing noninvasive quantitative measurements of the extent of myocardial infarction. Additional studies are needed to clarify the utility of these technologies for resolving the highly variable transmural distribution of infarction that is present in the clinical setting. Assessment of the region at risk for infarction, the ischemic zone, requires quantitative measurements of the degree of ischemia as well as the size of the ischemic region. Although the above technologies may provide quantitative measurements of the dimensions of the ischemic zone, the utility for resolving the highly variable transmural distribution of regional myocardial blood flow using clinically applicable methodologies has not been convincingly established at present. It is possible that cine CT, new generation PET, and NMR technologies may eventually provide noninvasive quantitative measurements of regional myocardial blood flow.

Ischemia-induced epicardial vasoconstriction. A potential mechanism for distant myocardial ischemia.

This study evaluated the effects of transient coronary occlusion on the diameter of a nonischemic vessel or a nonischemic coronary segment proximal to the site of occlusion. Awake mongrel dogs chronically instrumented with dimension crystals, Doppler flow probes, and distal pneumatic occluders on the circumflex coronary arteries were subjected to transient 2-minute circumflex occlusions (n = 9) under constant heart rate (120 beats/min). Left ventricular end-diastolic pressure increased by 60% (from 10 +/- 1 to 16 +/- 2 mm Hg), and dP/dt decreased by 8% (from 2,048 +/- 130 to 1,885 +/- 110 mm Hg/sec); systemic hemodynamics were unaltered. Epicardial coronary diameter proximal to the site of occlusion decreased by 4.37% (from 3.62 +/- 0.25 to 3.46 +/- 0.29 mm, p less than 0.05). Constriction began 15-20 seconds after the onset of ischemia and progressed to maximum in 1-2 minutes. Combined alpha- and beta-receptor blockade (n = 8) with phentolamine (2 mg/kg) and propranolol (1 mg/kg) or cyclooxygenase inhibition (n = 5) with indomethacin (7.5 mg/kg) did not attenuate the ischemia-induced vasoconstriction response. Transient 2-minute occlusion of the left anterior descending coronary artery (n = 6) also elicited significant epicardial vasoconstriction in the circumflex coronary artery in the first minute (from 3.88 +/- 0.31 to 3.81 +/- 0.31 mm, p less than 0.05); the constriction was attenuated subsequently by an increase (25.5%) in circumflex flow. When left anterior descending occlusion was repeated (n = 6) with circumflex flow held constant, the ischemia-induced circumflex constriction was augmented; diameter decreased 3.7% (from 3.83 +/- 0.29 to 3.69 +/- 0.29 mm, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Endogenous Nitric Oxide on Basal Vasomotor Tone and Stimulated Endothelium-Dependent Responses in the Coronary Arterial Circulation

This study assesses the role of nitric oxide in basal vasomotor tone and stimulated endothelium-dependent dilations in the coronary arteries of chronically-instrumented awake dogs by examining the responses to inhibiting endogenous nitric oxide formation with the specific inhibitor of nitric oxide formation, NG-monomethyl-L-arginine (L-NMMA). Basal epicardial coronary diameter (piezoelectric crystals), acetylcholine-stimulated endothelium-dependent dilation, flow induced endothelium-dependent dilation of the epicardial arteries, and phasic blood flow (Doppler probes) were recorded before, and after infusion of 5, 15, 50, and 120 mg/kg of L-NMMA. L-NMMA induced a dose-related increase in basal epicardial coronary vasomotor tone. There was an accompanying increase in aortic pressure and a decrease in heart rate. At doses ≥ 50 mg/kg, rest phasic coronary blood flow was also decreased. Left ventricular end-diastolic pressure and contractility were not significantly changed. In contrast, the flow-induced or acetylcholine-stimulated endothelium-dependent responses were attenuated approximately 50% only after infusion of the highest doses of L-NMMA (120mg/kg). The changes in basal vasomotor tone and acetylcholine-stimulated endothelium-dependent responses returned towards the control states in the presence of L-arginine (660 mg/kg). These data support the view that nitric oxide plays a significant role in modulating basal vasomotion and endothelium-dependent dilation stimulated by acetylcholine or increase in blood flow in epicardial coronary arteries and also influences the regulation of coronary blood flow during physiologic conditions.