Coronary flow reserve may predict myocardial recovery after myocardial infarction in patients with TIMI grade 3 flow.

BACKGROUND: The aim of the study was to determine whether the recovery of global and regional left ventricular function after successful percutaneous transluminal angioplasty (PTCA) could be predicted by measuring coronary flow reserve before performing the intervention. METHODS AND RESULTS: Thirty-two patients underwent PTCA 6.9 +/- 3.4 days after a recent myocardial infarction. Coronary flow reserve was determined in the infarct-related artery before PTCA by using an intracoronary Doppler tipped wire. Global and regional wall motion were determined by 2-dimensional echocardiography before the Flowire study and again 7 weeks after the angioplasty. Whereas the global and regional wall motion score indices improved in 20 patients (recovery group), they deteriorated or did not change in 9 patients (nonrecovery group). Coronary flow reserve distal to the lesion in the infarct-related artery was significantly higher in the recovery group (1.43 +/- 0.57 vs 0.98 +/- 0.70, P = .0001). Coronary flow reserve distal to the lesion in the infarct-related artery was < 1.1 in patients whose global or regional left ventricular function did not improve at follow-up, whereas flow reserve ranged between 1.1. and 1.8 while patients in whom left ventricular function improved. CONCLUSIONS: These results suggest that the absence of inducible coronary flow reserve may predict failure of left ventricular systolic function to improve between the first and sixth week after infarction. Measurement of flow reserve with a Flowire at the time of diagnostic angiography after recent myocardial infarction may ultimately prove helpful in deciding whether to proceed with revascularization.

Intracoronary Doppler assessment of moderate coronary artery disease: comparison with 201Tl imaging and coronary angiography. FACTS Study Group.

BACKGROUND: Coronary angiography may not reliably predict whether a stenosis causes exercise-induced ischemia. Intracoronary Doppler ultrasound may enhance diagnostic accuracy by providing a physiological assessment of stenosis severity. The goal of this study was to compare intracoronary Doppler ultrasound with both 201Tl imaging and coronary angiography. METHODS AND RESULTS: Fifty-five patients with 67 stenotic coronary arteries underwent coronary angiography with intracoronary Doppler ultrasound and had exercise 201Tl testing within a 1-week period. Coronary flow reserve was measured, and analyses were performed by independent core laboratories. The mean stenosis was 59+/-12%; 51 of 67 stenoses were intermediate in severity (40% to 70%). A coronary flow reserve < 1.7 predicted the presence of a stress 201Tl defect in 56 of 67 stenoses (agreement=84%; kappa=0.67; 95% CI=0.48 to 0.86). In the patients who achieved 75% of their predicted maximum heart rate, the Doppler and 201Tl imaging data agreed in 46 of 52 stenoses (agreement=88%; kappa=0.77; 95%CI=0.57 to 0.97). Scatter was evident when angiography was compared with coronary flow reserve (r=.43), and the angiogram did not reliably predict the results of the 201Tl stress test (kappa=0.21; agreement=57% to 63%). CONCLUSIONS: Doppler-derived coronary flow reserve accurately predicts the presence of exercise-induced ischemia on stress 201Tl imaging, and coronary angiography does not reliably assess the physiological significance of an intermediate coronary stenosis.

Fate of side branches after intracoronary implantation of the Gianturco-Roubin flex-stent for acute or threatened closure after percutaneous transluminal coronary angioplasty.

Side branch occlusion may occur in the course of percutaneous transluminal coronary angioplasty (PTCA), particularly if complicated by site dissection. Concern that the additional placement of a stent may further jeopardize side branches is logical. Consequently, this study analyzed pre-PTCA, post-PTCA, poststent, and 6-month follow-up angiograms of 100 consecutive patients in whom 103 Gianturco-Roubin stents were implanted for acute or threatened closure after PTCA. Side branches were defined as major (> 50% of the stented vessel diameter) and minor (< 50%). Minor branches, often < 1 mm in diameter, were assessed only for patency. One hundred eight major branches, of which 33 were diseased (> 50% stenosis), and 129 minor branches were analyzed. Seven major branches (6%), all of which were diseased before PTCA, and 23 minor branches (18%) were lost after PTCA. Immediately after stent insertion, only 1 additional major and 1 minor branch were lost, whereas 2 of 7 major (29%) and 9 of 23 minor (39%) branches reappeared. At follow-up angiography, 7 major branches (6%) were more stenosed and 6 (6%) were improved compared with the angiogram before PTCA. Only 2 major (2%) and 5 minor (4%) branches remained occluded. Additionally, 2 major and 1 minor branch, which were patent after PTCA and stenting, were occluded at follow-up as a result of total occlusion of the stented segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipofectin-mediated versus adenovirus-mediated gene transfer in vitro and in vivo: comparison of canine and porcine model systems.

BACKGROUND: Restenosis after coronary angioplasty might be prevented by locally delivered gene therapy in conjunction with percutaneous transluminal coronary angioplasty (PTCA), since this approach should provide a sustained source of therapeutic protein within the dilated lesion. However, the potential application of gene therapy is limited by the technical barrier of efficiently transferring genes to vascular cells. METHODS: We used cultured coronary smooth muscle cells of human, porcine, and canine origin to evaluate three methods of gene transfer: recombinant adenovirus, liposomal complexes (Lipofectin), and Lipofectin supplemented with hemagglutinin. We then compared Lipofectin- and adenovirus-mediated direct gene transfer in canine and porcine coronary arteries. RESULTS: The lipofection of cultured smooth muscle cells was enhanced by adding hemagglutinin, yielding luciferase levels that were 631-fold (human), ninefold (porcine), and sevenfold (canine) higher than with Lipofectin alone. However, the recombinant adenovirus directed even higher levels of gene expression, yielding luciferase levels that were 113,000-fold (human), 450-fold (porcine), and 230-fold (canine) higher than with Lipofectin alone. After percutaneous transluminal local delivery to intact canine coronary arteries, the adenovirus produced 55 times more luciferase than did Lipofectin. In living porcine coronary arteries, adenovirus produced 95 times more luciferase than did Lipofectin. CONCLUSION: Recombinant adenovirus produces far more recombinant protein than does Lipofectin after percutaneous transluminal direct gene transfer to canine and porcine coronary arteries. Adenoviral vectors may therefore prove useful in evaluating the potential of gene therapy in large animal models of coronary restenosis.

Heterotopic heart transplantation: catheterization, endomyocardial biopsy, and coronary angiography of the donor heart.

UNLABELLED: Follow-up after heart transplantation presently requires invasive techniques to assess graft viability and function. As the heterotopic transplant technique assumes a more important therapeutic role for patients not eligible for an orthotopic allograft, an understanding of the inherent challenges associated with management of these patients is mandatory to optimize patient care. Heterotopic transplant technique was used in 19 of 135 (14%) consecutive heart transplant procedures over a 41 month period. Invasive diagnostic procedures performed in follow-up revealed 1) adequate tissue for histologic evaluation in 140/158 (89%) biopsy procedures, 2) successful pulmonary wedge pressure measurements in 142/158 (90%) right heart catheterizations, and 3) successful coronary arteriography in 18 patients undergoing angiography (both vessels in 12 and one vessel in six patients). Thus, biopsy and surveillance procedures are feasible and productive in patients who have undergone heterotopic heart transplantation. BACKGROUND: Although heterotopic heart transplantation has become an increasingly utilized therapy for some patients with heart failure, there are no guidelines for routine biopsy and angiographic techniques in these patients. The objective of this study was to determine the feasibility of angiographic and endomyocardial biopsy procedures in heterotopic heart transplant recipients. METHODS: The complete experience with heterotopic heart transplant recipients at Baylor College of Medicine and The Methodist Hospital over a 41 month period including endomyocardial biopsy, right heart catheterization, and selective coronary arteriography results were analyzed. RESULTS: Eighteen patients underwent 310 procedures without significant complications. Of 158 biopsy procedures, 140 (89%) yielded tissue adequate for histologic evaluation. Right heart pressures were obtained in almost all patients undergoing right heart catheterization. Pulmonary wedge pressures were obtained in 137 (90%). A rapid decrease in right heart pressures was noted following transplant; however, a gradual but significant rise in mean arterial pressure occurred. Eighteen selective coronary arteriogram procedures were performed; 12 (66%) resulted in successful cannulation of both coronary arteries. Of 12 patients followed for at least 1 year, five (40%) have developed evidence of allograft arteriopathy. The 1 and 2 year survival rates were 67% and 53%, respectively. CONCLUSIONS: Invasive diagnostic techniques can be performed safely and reliably and should not preclude the use of heterotopic heart transplantation in selected patients who are otherwise unsuitable for orthotopic transplantation.

Discontinuation of chronic diuretic therapy in stable congestive heart failure secondary to coronary artery disease or to idiopathic dilated cardiomyopathy.

To assess the feasibility of diuretic discontinuation in patients with stable congestive heart failure (CHF) and to identify risk factors for subsequent development of congestion, a prospective, 12-week clinical trial of unmasked diuretic withdrawal was conducted with continuation of background CHF therapy and double-blind randomization to placebo or lisinopril. Forty-one patients with a history of CHF and continuous diuretic use for > or = 3 months had all diuretic therapy discontinued, and therapy with lisinopril 5 mg (target 20 mg)/day (n = 20) or placebo (n = 21) begun the next day. A diuretic was restarted if new or worsening CHF symptoms and signs developed. Twelve patients (29%) did not require diuretic reinitiation at any time during follow-up, whereas 29 (71%) restarted diuretic therapy after a median of 15 days (range 2 to 42). Fourteen patients taking lisinopril and 15 taking placebo required diuretic drugs (p = NS). The baseline daily furosemide dose of > 40 mg, a left ventricular ejection fraction < or = 0.27, and history of systemic hypertension were independently predictive of early diuretic reinitiation by Cox proportional-hazards analysis. The probability of remaining diuretic-free after 6 weeks was 71% if none of these criteria were present. This trial demonstrates the feasibility of discontinuing diuretic drugs in certain patients with stable CHF and predicts those patients likely to require reinitiation of therapy. Diuretic withdrawal may be warranted when the furosemide dose is < or = 40 mg/day, left ventricular ejection fraction is > 0.27 and when no history of systemic hypertension is present.

Comparison of three porcine restenosis models: the relative importance of hypercholesterolemia, endothelial abrasion, and stenting.

BACKGROUND: Porcine models of post-angioplasty restenosis commonly rely on hypercholesterolemia, endothelial abrasion, and intracoronary stenting to induce neointimal thickening. Although stenting clearly induces marked thickening, the influence of pre-stenting endothelial abrasion, and pre- and post-stenting hypercholesterolemia, on the degree and nature of post-stenting neointimal thickening is not clear. In order to assess this influence, we compared the quantity and quality of neointimal thickening in three stented swine restenosis models. METHODS: Twenty-three Hanford miniature swine completed one of three protocols. Model A animals (n = 9) were fed a cholesterol-raising diet, underwent endothelial abrasion of the left anterior descending (LAD) and circumflex (CFX) coronary arteries after 2 weeks on this diet, had balloon-expandable tantalum coil stents placed in the right coronary artery (RCA), LAD, and CFX after 9 weeks on the diet, and were killed 4 weeks later (total of 13 weeks on diet). Model B animals (n = 7) were also fed the cholesterol-raising diet, underwent stenting after 5 weeks on the diet, and were killed 4 weeks later (total of 9 weeks on diet). Model C animals (n = 7) were fed normal swine food, underwent stenting, and were killed 4 weeks later. Endothelial abrasion was not performed in models B and C. RESULTS: Quantitative angiography revealed no significant differences between models in the change of minimal lumen diameter (mm +/- SD) of stented vessels from post-stenting to pre-sacrifice (LAD: 1.05 +/- 0.74, 0.75 +/- 0.62 and 1.05 +/- 0.34; CFX: 1.00 +/- 0.65, 0.83 +/- 0.51 and 1.17 +/- 0.38; RCA: 0.99 +/- 0.35, 0.20 +/- 0.34, and 0.94 +/- 0.80 for models A, B, and C, respectively; all P = NS). Likewise, morphometric analysis showed no differences in percentage area stenosis (% +/- SD) over the same time (LAD: 55 +/- 15, 44 +/- 24, and 42 +/- 16; CFX: 54 +/- 12, 55 +/- 17, and 40 +/- 15; RCA: 39 +/- 20, 34 +/- 11, and 26 +/- 13 for models A, B, and C, respectively; P = NS). The neointima in each model predominantly consisted of smooth muscle cells and collagen matrix. CONCLUSIONS: The degree and nature of coronary artery neointimal thickening 4 weeks after stenting in normolipemic swine are similar to those in stented swine after 9 weeks on a high-cholesterol diet or 13 weeks on a high-cholesterol diet and early endothelial abrasion. The insertion of an intracoronary stent appears to be the major stimulus to neointimal thickening in these swine models of post-angioplasty restenosis.

Amiprilose in the prevention of restenosis after coronary intervention in a swine model.

BACKGROUND: Amiprilose hydrochloride is a synthetic carbohydrate with anti-inflammatory and antiproliferative properties. This study tested the potential benefit of amiprilose in preventing coronary artery restenosis in a swine model. METHODS: The swine restenosis model was prepared using Hanford miniature swine made atherosclerotic with coronary abrasion, high-fat and high-cholesterol feeding, and intracoronary stenting. Eighteen animals were randomized to receive amiprilose, 100 mg/kg body weight orally twice per day (n = 9), or no amiprilose (n = 9) beginning 5 days before stenting and continuing through 4 weeks until sacrifice. Presacrifice quantitative coronary angiography and postsacrifice histologic examination revealed the degree of intimal proliferation. RESULTS: Coronary angiography revealed no difference in percentage-diameter stenosis between the amiprilose and control groups (left anterior descending artery [LAD], 46% +/- 10% vs 44% +/- 17%; circumflex artery [CFX], 43% +/- 21% vs 42% +/- 15%; right coronary artery [RCA], 37% +/- 11% vs 34% +/- 9%; P = not significant [NS]), respectively, or in change in lumen diameter from poststenting to presacrifice (LAD, -1.0 +/- 0.4 mm vs -1.1 +/- 0.7 mm; CFX, -1.2 +/- 0.8 mm vs -1.0 +/- 0.7 mm; RCA, -1.1 +/- 0.4 mm vs -1.0 +/- 0.4 mm; P = NS). Morphometric histologic analysis likewise showed no difference in percentage-area stenosis (LAD, 55% +/- 14% vs 55% +/- 15%; CFX, 53% +/- 15% vs 54% +/- 12%; RCA, 39% +/- 17% vs 39% +/- 20%; P = NS) or in maximal intimal thickness. CONCLUSION: Amiprilose hydrochloride did not prevent coronary intimal proliferation in this swine model of restenosis.

The myocardial renin-angiotensin system: existence, importance, and clinical implications.

Major components of the renin-angiotensin system have been localized to cardiac tissue. Cardiac-derived angiotensin II may benefit myocardial contractility but may promote detrimental myocardial hypertrophy, coronary vasoconstriction, and arrhythmias. The benefits of ACE inhibition probably extend beyond the classic circulating RAS to include the heart directly.

Sudden death caused by bradycardia and asystole in a heart transplant patient with coronary arteriopathy.

The mechanism of death as a result of allograft ischemic heart disease is not well characterized. Ventricular tachycardia and fibrillation may not be the terminal events they often are in the general population. We report observations in a 41-year-old man with cardiac allograft arteriopathy who died suddenly while wearing an ambulatory monitor. The lethal rhythm was a progressive bradycardia terminating in asystole. Autopsy revealed epicardial and small vessel intramyocardial, coronary arteriopathy, and only mild allograft rejection. It is our belief that ischemia caused the bradycardic sudden death. We would like to hypothesize that prophylactic permanent pacemaker implantation may prevent bradycardic sudden death and improve survival in heart transplant patients with coronary disease.

Effect of 1,25-dihydroxyvitamin D3 on calcium absorption in the colon of healthy humans.

Calcium absorption in patients with short bowel syndrome is significantly higher when the colon is left intact. To study calcium transport in the large bowel, we investigated whether exogenous 1,25-dihydroxyvitamin D3 [1,25(OH2)D3] can induce or enhance colonic calcium absorption in healthy subjects ingesting a normal diet. Steady-state colon perfusion studies were performed before and after 1 wk of 1,25(OH)2D3 administration (2 micrograms/day, 10 subjects). Serum 1,25-dihydroxyvitamin D concentration rose from 23.0 +/- 2.2 to 39.5 +/- 4.3 pg/ml (mean +/- SE, P less than 0.01). In the basal state the mean net movement of calcium was not significantly different from zero when a 5 mM calcium gluconate solution was perfused (100 +/- 84 mumol X h-1 X entire colon secreted-1). Vitamin D administration resulted in a significant change toward calcium absorption (106 +/- 47 mumol X h-1 X entire colon absorbed-1, P less than 0.02). 1,25(OH)2D3 had no effect on colonic magnesium, phosphate, water, and electrolyte movement. This study demonstrates that in healthy humans exogenous 1,25(OH)2D3 can change colonic calcium movement toward absorption. We suspect that similar changes in colonic calcium transport are caused by endogenous 1,25(OH)2D3 when calcium deficiency has occurred in short bowel syndrome.