Gustavo Rincon

Coronary angioplasty, atherectomy and bypass surgery in cardiac transplant recipients

OBJECTIVES This study sought to analyze the outcomes of revascularization procedures in the treatment of allograft coronary disease. BACKGROUND Allograft vasculopathy is the main factor limiting survival of heart transplant recipients. Because no medical therapy prevents allograft atherosclerosis, and retransplantation is associated with suboptimal allograft survival, palliative coronary revascularization has been attempted. METHODS Thirteen medical centers retrospectively analyzed their complete experience with percutaneous transluminal coronary angioplasty, directional coronary atherectomy and coronary bypass graft surgery in allograft coronary disease. RESULTS Sixty-six patients underwent coronary angioplasty. Angiographic success (< or = 50% residual stenosis) occurred in 153 (94%) of 162 lesions. Forty patients (61%) are alive without retransplantation at 19 +/- 14 (mean +/- SD) months after angioplasty. The consequences of failed revascularization were severe. Two patients sustained periprocedural myocardial infarction and died. Angiographic restenosis occurred in 42 (55%) of 76 lesions at 8 +/- 5 months after angioplasty. Angiographic distal arteriopathy adversely affected allograft survival. Eleven patients underwent directional coronary atherectomy. Angiographic success occurred in 9 (82%) of 11 lesions. Two periprocedural deaths occurred. Nine patients are alive without transplantation at 7 +/- 4 months after atherectomy. Bypass graft surgery was performed in 12 patients. Four patients died perioperatively. Seven patients are alive without retransplantation at 9 +/- 7 months after operation. CONCLUSIONS Coronary revascularization may be an effective palliative therapy in suitable cardiac transplant recipients. Angioplasty has an acceptable survival in patients without angiographic distal arteriopathy. Because few patients underwent atherectomy and coronary bypass surgery, assessment of these procedures is limited. Angiographic distal arteriopathy is associated with decreased allograft survival in patients requiring revascularization.

Occult and Frequent Transmission of Atherosclerotic Coronary Disease With Cardiac Transplantation Insights From Intravascular Ultrasound

BACKGROUND Transplant coronary artery disease is a major cause of morbidity and mortality after cardiac transplantation. However, limited data exist regarding the potential contribution of coronary atherosclerosis in the donor heart to cardiac-allograft vasculopathy. METHODS AND RESULTS We performed quantitative coronary angiography and intravascular ultrasound imaging in 50 of 62 consecutive heart-transplant recipients (40 men, 10 women, mean age, 53 +/- 9 years) 4.6 +/- 2.6 weeks after transplantation. The donor population consisted of 30 men and 20 women (mean age, 32 +/- 12 years). Ultrasound imaging visualized all three coronary arteries in 22 patients, two coronary arteries in 23, and one coronary artery in 5. Ultrasound imaging detected coronary atherosclerosis (intimal thickness > or = 0.5 mm) in 28 patients (56%). However, the angiography was abnormal in only 13 patients (26%). The sensitivity and specificity of coronary angiography were 43% and 95%, respectively. With ultrasound, the average atherosclerotic plaque thickness was 1.3 +/- 0.6 mm and the cross-sectional area narrowing was 34 +/- 16%. Atherosclerotic involvement frequently was focal (85%), eccentric (mean eccentricity index, 87 +/- 8), and near arterial bifurcations. Donors of the transplant recipients with coronary atherosclerosis were older than those without atherosclerosis (37 +/- 12 versus 25 +/- 10 years, P = .001). Maximal intimal thickness correlated with donor age (r = .54, P = .0001). Multivariate analysis demonstrated that donor age (P = .0001), male sex of donor (P = .0006), and recipient age (P = .03) were independent predictors of atherosclerosis. CONCLUSIONS Coronary atherosclerosis is frequently but inadvertently transmitted by means of cardiac transplantation from the donor to the recipient. Long-term outcomes of donor-transmitted coronary artery disease will require further evaluation.

Natural history of severe proximal coronary artery disease as documented by coronary cineangiography

Abstract Studying the natural history of patients with severe proximal coronary arterial lesions may assist evaluation of coronary revascularization surgery. We reviewed the mortality statistics of 469 patients with 80 to 100 percent occlusive lesions in the proximal coronary tree as diagnosed by selective angiography. Only patients with normal or moderately impaired left ventricular function were included in the study; patients with severe cardiomegaly, congestive heart failure or severe left ventricular impairment by left ventriculography were excluded. Follow-up periods ranged from 6 to 11 years for 178 patients with single vessel disease, 177 with double vessel disease and 114 with triple vessel disease. Patients with isolated disease of the left anterior descending artery had a 4 percent average yearly attrition rate or a 6 year mortality rate of 25.5 percent (17 of 69). Those with isolated disease of the right coronary artery demonstrated only a 2.3 percent yearly attrition rate or a 14 percent mortality rate in 6 years (11 of 77). Patients with double and triple vessel disease had, respectively, 41.5 and 63 percent 6 year mortality rates. Survival was related to the number of vessels involved. Patients with single vessel disease of the left anterior descending artery had a significant annual mortality rate. The prognosis improved when good angiographic collateralization was present, particularly in single vessel disease with total occlusion. Functional disability, classified according to the New York Heart Association criteria, was related to mortality rates and proved a useful indicator in large patient groups. Prior myocardial infarction, location of the lesion above or below the major septal perforator in left anterior descending artery disease, and left main trunk lesions did not alter the prognosis significantly.

Dichotomous pattern of coronary atherosclerosis 1 to 9 years after transplantation: Insights from systematic intravascular ultrasound imaging

OBJECTIVE The aim of this study was to evaluate the extent and distribution of coronary atherosclerosis after transplantation. BACKGROUND Transplant coronary artery disease is an important cause of death after cardiac transplantation. Unlike coronary angiography, intravascular ultrasound is a sensitive tool for detection and quantitation of this disease. METHODS We performed intravascular ultrasound imaging in 132 (106 men, 50 +/- 10 years) patients, 1 to 9 years after transplantation using a 30-MHz ultrasound catheter. RESULTS All three coronary arteries were visualized in 49, two in 62 and one in 21 patients. Of the 1,188 coronary artery segments, 706 were imaged (74% proximal, 64% mid- and 40% distal). At least one site with atherosclerosis (intimal thickness > or = to 0.5 mm) was found in 83% of patients. Atherosclerosis was noted in 64% of proximal, 43% of mid- and 26% of distal segments. Disease was diffuse in 48% and focal in 52%, circumferential in 66% and noncircumferential in 34%. Focal atherosclerosis was more common in proximal (59%) than mid- (48%) and distal segments (27%) (p=0.001). Noncircumferential plaques were more common in the proximal (42%) than mid- (28%) and distal segments (12%) (p=0.001). This pattern of focal and noncircumferential disease proximally, diffuse and circumferential disease distally, was observed irrespective of the time from transplantation. CONCLUSION Atherosclerosis was detected in more than 80% of patients, with proximal segments most frequently involved. Diffuse and circumferential atherosclerosis was more common in mid- and distal segments. However, focal and noncircumferential involvement was more frequent proximally, a similar pattern to native atherosclerosis. These findings suggest that transplant coronary artery disease has a dual etiology based on the dichotomous pattern of atherosclerosis seen by intravascular ultrasound.

Surgical treatment of coronary artery disease: Pure graft operations, with a study of 741 patients followed 3–7 Yr

This report reviews the experience with bypass graft surgery in the pure form, without associated cardiac procedures, in 6828 patients operated upon from 1967 through 1974. The hospital mortality rate in this group was 1.4%. The incidence of definite perioperative myocardial infarction was 6.9% prior to 1971, and 4.1% in the past 3 yr. Graft patency in postoperative studies performed an average of over 12 mo after surgery was 83.6%, and 89% of patients had one or more functioning grafts. In a subgroup of 741 consecutive patients operated upon with pure graft techniques from 1967 through 1970, survival seemed to be improved when compared to another group of similar, but nonoperated patients. The average annual mortality rate was 3.3% per yr in the surgical group (including surgical mortality) compared to 8.8% per year in the medical group. Differences in survival were most striking in patients with isolated anterior descending, double and triple vessel involvement. In the 741-patient subgroup the incidence of new occlusions of grafted arteries was related to the severity of the lesion(s) for which the operation was performed, and unrelated to graft patency. Arteriographically demonstrated new occlusions of ungrafted arteries were infrequent, and few patients developed significant new lesions during the period of observation. Symptomatic improvement is related to completeness of revascularization as determined by postoperative arteriography.

Hemodynamic Effects of a Single Intravenous Injection of Synthetic Human Brain Natriuretic Peptide in Patients With Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

Synthetic human brain natriuretic peptide (sBNP) is a polypeptide with the same amino acid sequence as the naturally occurring hormone. Preclinical studies have demonstrated that BNP has potent hemodynamic, diuretic, and natriuretic effects that might be beneficial in treating patients with heart failure. This study was a randomized, double-blind, placebo-controlled, ascending-dose trial of sBNP administered as a single intravenous bolus in 27 heart failure patients. Six groups of patients received sequentially increasing doses of sBNP (0.3, 1, 3, 10, 15, and 20 micrograms/kg, respectively) as a single intravenous injection, and hemodynamics were assessed by pulmonary artery monitoring catheter. The 10 and 15 micrograms/kg doses of sBNP resulted in significant reductions in pulmonary capillary wedge pressure (-73%, p < 0.001), mean pulmonary artery pressure (-41%, p < 0.001), mean arterial blood pressure (-28%, p = 0.001), and systemic vascular resistance (-53%, p = 0.004). Significant increases occurred in cardiac index (68%, p < 0.001) and stroke volume index (72%, p < 0.001). The magnitude and duration of hemodynamic changes were dose dependent. There were no adverse effects. sBNP injected as a single intravenous bolus in heart failure patients improves hemodynamics in a dose-related fashion. Further clinical investigations to determine the use of sBNP in decompensated heart failure are clearly warranted.

Impact of lipid abnormalities in development and progression of transplant coronary disease: a serial intravascular ultrasound study

OBJECTIVES We sought to determine the role of conventional atherosclerosis risk factors in the development and progression of transplant coronary artery disease (CAD) using serial intravascular ultrasound imaging. BACKGROUND Transplant artery disease is a combination of allograft vasculopathy and donor atherosclerosis. The clinical determinants for each of these disease processes are not well characterized. Intravascular ultrasound imaging is the most sensitive tool to serially study these processes. METHODS Baseline intravascular ultrasound imaging was performed 0.9 +/- 0.5 months after transplantation to identify donor atherosclerosis. Follow-up imaging was performed at 1.0 +/- 0.07 year to evaluate progression of donor atherosclerosis and development of transplant vasculopathy. Conventional risk factors for CAD included recipient age, gender, smoking history, diabetes mellitus, hypertension and hypercholesterolemia. RESULTS Donor-transmitted atherosclerosis was present in 36 patients (39%). At follow-up, progression of donor lesions was seen in 15 patients (42%) and 42 patients (45%) developed transplant vasculopathy, leaving 35 patients (38%) without any disease. There was no difference in any conventional risk factors in patients with and without allograft vasculopathy. However, the severity of allograft vasculopathy was associated with a larger increase in low density lipoprotein (LDL) cholesterol from baseline (p = 0.02). High one-year posttransplant serum triglyceride level and pretransplant body mass index were the only significant predictors (p = 0.03) for progression of donor atherosclerosis. CONCLUSIONS Conventional atherosclerosis risk factors do not predict development of allograft vasculopathy, but greater change in serum LDL cholesterol level during the first year after transplant is associated with more severe vasculopathy. Therefore, maintenance of LDL cholesterol as close to pretransplant values as possible may help to limit the rate of progression of acquired allograft vasculopathy.

Vein Graft Surgery for Coronary Artery Disease: Survival and Angiographic Results in 1,000 Patients

One thousand patients were operated upon with vein graft techniques for severe coronary artery obstructions between May 1967 and July 1970, with a hospital mortality rate of 4% and a 5.6% incidence of angiographically confirmed in-hospital myocardial infarctions. Postoperative angiograms, performed in 619 of the survivors, revealed patency of one or more vein grafts in 84.2% of patients, and 82.5% of all grafts were patent in studies performed 1 to 49 months after surgery.The hospital survivors were followed for 22 to 60 months; only three patients were lost to follow-up. The survival curve for this group of patients was compared with that of another group of 469 patients who also had severe coronary artery disease and were potential surgical candidates, but were studied in an earlier period and did not have surgical treatment. The annual rate of attrition for each of the four years of follow-up in the surgical group averaged 4.8% per year (2.5% per year excluding hospital mortality), and 9.3% per year in the nonsurgical group. Remission of symptoms correlated closely with the completeness of revascularization.Myocardial revascularization with vein graft techniques can be accomplished successfully and with low risk in the majority of properly selected patients, resulting in a significant improvement in symptoms, as well as in long-term survival.

Does acute cellular rejection correlate with cardiac allograft vasculopathy

BACKGROUND Previous studies of the association between acute cellular rejection and cardiac allograft vasculopathy (CAV) have yielded conflicting conclusions. We explored a possible association between acute cellular rejection and the extent of CAV, and we found a potential confounding variable that may obscure such an association. METHODS We investigated 140 patients (mean age, 51 +/- 11 years) who underwent serial intravascular ultrasound examinations at baseline and at 1 year after heart transplantation to assess CAV as change in maximal intimal thickness (CMIT). Patients were classified according to the presence or absence of biopsy-proven myocardial fibrosis. We used a standard biopsy-scoring system and a novel biopsy-scoring system, developed in our institution, to assess acute cellular rejection. Using univariate analysis, we found that CMIT was not associated with acute cellular rejection in the overall patient population (n = 140). However, we observed a correlation between CMIT and acute cellular rejection (standard method, r = 0.30, p = 0.01; novel method, r = 0.51, p < 0.0001) in patients who had no evidence of ischemic injury or fibrosis in their biopsy specimens (n = 57). Step-wise multiple regression showed that the rejection score derived from our novel method was associated more closely with the CMIT than was that derived from the traditional method. CONCLUSIONS This data indicate that the presence of myocardial fibrosis masks an actuarial association between acute cellular rejection and the development of de novo allograft vasculopathy. As previously suspected, myocardial fibrosis is a marker for non-immune-mediated graft injury independently associated with an increased incidence of CAV.

Cellular rejection and rate of progression of transplant vasculopathy: a 3-year serial intravascular ultrasound study.

Intravascular ultrasound (IVUS) is established as the optimal method for early detection of transplant vasculopathy. The association between cellular rejection and development of transplant vasculopathy remains controversial. This study attempts to determine the rate of progression of transplant vasculopathy lesions and its relationship with cellular rejection in a long-term (> 1 year) IVUS serial follow-up.A study cohort of 47 patients undergoing heart transplantation from 1993 to 1995 was evaluated. Intravascular ultrasound was performed at baseline (within 8 weeks) and annually for a period of 3 years to determine maximum intimal thickness and maximum plaque area in each coronary segment. Significant allograft vasculopathy was defined as a site with intimal thickness > 0.5 mm not present at baseline. Biopsy results were scored by assigning a numerical weight to each ISHLT grade during the first year. Donor lesions ranged from 0.86 to 1.1 mm, showing no evidence of progression at serial follow-up. De novo lesions were identified in 30 patients. These lesions appeared yearly but progressed slowly. The average biopsy score in the entire cohort was 1.1 +/- 0.8. Average biopsy score was > 1.0 in 35 patients with significant linear correlation between the rate of intimal progression and biopsy score (r = 0.42, p = 0.01). Multivariate analysis demonstrated that only the biopsy score correlated with the rate of progression. Lesions of donor atherosclerosis do not change significantly after transplantation. However, de novo lesions continue to develop every year. In patients with evidence of rejection, the rate of progression of transplant vasculopathy correlates with the severity of rejection.