Robert E. Hobbs

High Prevalence of Coronary Atherosclerosis in Asymptomatic Teenagers and Young Adults Evidence From Intravascular Ultrasound

Background—Most of our knowledge about atherosclerosis at young ages is derived from necropsy studies, which have inherent limitations. Detailed, in vivo data on atherosclerosis in young individuals are limited. Intravascular ultrasonography provides a unique opportunity for in vivo characterization of early atherosclerosis in a clinically relevant context. Methods and Results—Intravascular ultrasound was performed in 262 heart transplant recipients 30.9±13.2 days after transplantation to investigate coronary arteries in young asymptomatic subjects. The donor population consisted of 146 men and 116 women (mean age of 33.4±13.2 years). Extensive imaging of all possible (including distal) coronary segments was performed. Sites with the greatest and least intimal thickness in each CASS segment were measured in multiple coronary arteries. Sites with intimal thickness ≥0.5 mm were defined as atherosclerotic. A total of 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were analyzed. An atherosclerotic lesion was present in 136 patients, or 51.9%. The prevalence of atherosclerosis varied from 17% in individuals <20 years old to 85% in subjects ≥50 years old. In subjects with atherosclerosis, intimal thickness and area stenosis averaged 1.08±0.48 mm and 32.7±15.9%, respectively. For all age groups, the average intimal thickness was greater in men than women, although the prevalence of atherosclerosis was similar (52% in men and 51.7% in women). Conclusions—This study demonstrates that coronary atherosclerosis begins at a young age and that lesions are present in 1 of 6 teenagers. These findings suggest the need for intensive efforts at coronary disease prevention in young adults.

One hundred patients with the heartmate left ventricular assist device: Evolving concepts and technology

BACKGROUND Implantable left ventricular assist devices are common as a bridge to transplantation but are just reaching their goal as an alternative to transplantation. METHODS From December 1991 until December 1996, 97 left ventricular assist devices were implanted as a bridge to transplantation, one as an alternative to transplantation, and two as a bridge to recovery. Included were 64 pneumatic devices and 36 electric devices. Most patients (69%) had ischemic cardiomyopathy and most (53%) had had previous cardiac surgery. Preoperative circulatory support (extracorporeal membrane oxygenation) was used in 25. RESULTS Perioperative insertion of a right ventricular assist device was unusual (11%). The mean duration of support with a left ventricular assist device (bridge to transplantation) was 70 +/- 41 days (up to 206 days). Survival to transplantation was 76%. Cause of death included multiple organ failure (n = 13), perioperative stroke (n = 5), device failure (n = 5), and controller disconnect (n = 1). Significant risk factors for death included (1) preoperative need for ventilator or extracorporeal membrane oxygenation, (2) elevated blood urea nitrogen, creatinine, or bilirubin, and (3) low pulmonary artery pressures. Risks after insertion of the left ventricular assist device were reoperation for bleeding, support with a right ventricular assist device, dialysis, or device failure. Catastrophic failure of the device occurred 14 times in 12 patients and was treated by emergency pump exchange in six instances. Only two device-related thromboembolic episodes were detected. Positive blood cultures were found in 59% of patients, driveline infection in 28%, and pump infection in 11%. CONCLUSIONS The HeartMate device provided excellent hemodynamic support with low device-related thromboembolic events. Infection and reliability of the device contributed to the high cost of therapy. These areas need to be improved for the left ventricular assist device to attain its goal as a viable alternative to transplantation.

The prevalence of coronary artery disease in liver transplant candidates over age 50

The prevalence of angiographically proven coronary artery disease (CAD) in adults with end-stage liver disease who undergo evaluation for liver transplantation is unknown; also it is unclear if cholestatic liver disease represents an independent risk factor. Patients with end-stage liver disease over age 50 having liver transplantation were studied using coronary angiography. Arterial stenosis was graded as normal, mild (< 30%), moderate (30 to 70%), or severe (> 70%). Risk factors for CAD were also assessed (male sex, smoking, hypertension, diabetes, family history of premature heart disease). Complications related to the angiography and decision making based on the findings were recorded. Thirty seven patients (23 females) with a median age of 61 years (range 50 to 71) underwent angiography. Thirteen patients (35.1%) had cholestatic liver disease. Thirty patients had no history of heart disease. The overall prevalence of severe coronary artery disease was 16.2% (95% confidence interval [CI] = 6.2% to 32.0%). No association was detected between CAD and cholestatic liver disease (P = 0.72). After eliminating seven patients with a prior history of angina (n = 1), myocardial infarction (n = 1), or coronary revascularization (n = 5), the frequency of moderate or severe CAD was 13.3% (95% CI = 3.8% to 30.7%). No association was detected between unsuspected CAD and cholestatic liver disease (P = 0.61). Diabetes was the most important risk factor for moderate or severe disease (P = 0.01). Patients without risk factors had significantly less CAD than the group as a whole regardless of the liver disease type (P = 0.02). Two patients experienced transient renal insufficiency after the angiography. Three patients with severe CAD were denied transplantation. We conclude that CAD represents a significant problem in patients over age 50 undergoing liver transplant evaluation. Cholestatic liver disease was not associated with a significantly higher prevalence of moderate or severe CAD in our population. Diabetes was the most predictive risk factor, and those without risk factors do not require extensive preoperative cardiac evaluation.

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.

Ineffectiveness of dipyridamole spect thallium imaging as a screening technique for coronary artery disease in patients with end-stage renal failure

The efficacy of dipyridamole single photon emission computed tomography (SPECT) thallium as a screening test for coronary artery disease (CAD), was studied in 45 patients with end-stage renal failure undergoing evaluation for renal transplantation. Coronary arteriography, dipyridamole SPECT thallium imaging and clinical follow-up were performed in all patients. Nineteen patients (42%) had an obstruction of 50% or more in at least one coronary artery. Fourteen patients had a positive thallium scan, but 7 of these were false-positives (sensitivity 37%, specificity 73%). The sensitivity was considerably lower than that quoted for non-ESRF patients in the literature, and significantly lower than a control group of 19 patients without ESRF having comparable severity and distribution of CAD. Five of the 6 patients who died of cardiac causes over a mean follow-up period of 25 months had normal thallium imaging, but all had significant coronary artery disease at cardiac catheterization. Dipyridamole SPECT thallium imaging has not proved a useful screening test for angiographically significant CAD, and does not predict cardiac prognosis in this population.

Effect of the Implantable Left Ventricular Assist Device on Neuroendocrine Activation in Heart Failure

BACKGROUND The HeartMate left ventricular assist device has been successfully used as a bridge to cardiac transplantation. Because many patients exhibit marked clinical improvement in their heart failure after HeartMate implantation, we studied the physiological effect of this device on the neurohormonal axis. METHODS AND RESULTS In 13 patients awaiting transplant (mean cardiac index, 1.7 +/- 0.3 L.min-1.m-2) who underwent HeartMate implantation, venous atrial natriuretic peptide, epinephrine, norepinephrine, plasma renin activity, angiotensin, and arginine vasopressin were measured immediately before insertion and at explant/transplantation. Mean time to explant was 86 +/- 40 days. All patients were taken off inotropic medications within 1 month. Mean cardiac index on support before explant was 3.1 +/- 0.9 L.min-1.m-2. Plasma renin activity decreased from 57 +/- 56 ng.mL-1.h-1 at baseline (before insertion) to 3 +/- 3 ng.mL-1.h-1 at explant (mean percent change, 92%; P < .001). Angiotensin II level decreased from 237 +/- 398 U/L at baseline to 14 +/- 14 U/L at explant (mean percent change, 73%; P < .001). Plasma epinephrine level fell from 6800 +/- 1323 pg/mL at baseline to 46 +/- 46 pg/mL at explant (mean percent change, 86%; P < .001). Norepinephrine level decreased from 2953 +/- 1457 pg/mL at baseline to 518 +/- 290 pg/mL at explant (mean percent change, 79%; P < .001). Atrial natriuretic peptide fell from baseline values of 227 +/- 196 to 168 +/- 40 pg/mL at explant (mean percent change, -49%; P = 519); and arginine vasopressin level decreased from 6 +/- 6 pg/mL at baseline to 0.8 +/- 0.5 pg/mL (mean percent change, 69%; P = .002). CONCLUSIONS We provide data supporting that the neurohormonal axis markedly improves after HeartMate implantation, providing biochemical confirmation of the improvement in hemodynamic status.

Congestive cardiomyopathy and illness related to the acquired immunodeficiency syndrome (AIDS) associated with isolation of retrovirus from myocardium.

Excerpt Most clinical signs and symptoms reported in persons infected with the human immunodeficiency virus (HIV) are due to opportunistic infections or malignancies that flourish in the presence o...

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.

Development of Transplantation Vasculopathy and Progression of Donor-Transmitted Atherosclerosis Comparison by Serial Intravascular Ultrasound Imaging

BACKGROUND Transplant coronary artery disease is a combination of atherosclerosis transmitted from the donor and new lesions of allograft vasculopathy. We sought to determine the morphological characteristics of allograft vasculopathy and differentiate it from donor-transmitted atherosclerosis with serial intravascular ultrasound. METHODS AND RESULTS Intravascular ultrasound examination was performed in 93 patients at 27.2+/-15.0 and 369. 7+/-23.9 days after transplantation. The maximally and minimally diseased sites were selected in each segment as defined by Coronary Artery Surgery Study classification. For each matched site, maximal plaque thickness was measured. Lesions (maximum plaque thickness >/=0.5 mm) present at baseline examination were defined as donor lesions. On follow-up, lesions that developed at previously normal sites were defined as de novo lesions. The distribution and severity of donor and de novo lesions were similar in proximal, mid, and distal segments. The de novo lesions were less focal (43% vs 74%) and more circumferential (69% vs 45%) compared with the donor lesions, but there was significant morphological heterogeneity. Similar numbers of patients with and those without donor lesions developed de novo lesions. Moreover, progression of donor lesions was not associated with the presence or absence of de novo lesions. CONCLUSIONS Differentiation between early allograft vasculopathy from conventional atherosclerosis by distribution and morphology of lesions alone is difficult. Serial intravascular ultrasound imaging with early baseline examination is necessary to make this distinction. This distinction is important because the progression of donor lesions and the development of de novo lesions are independent of each other.

Long-term outcome and impact of surgery on adults with coronary arteries originating from the opposite coronary cusp.

Background— An anomalous coronary artery from the opposite sinus of Valsalva may increase sudden death risk in children and young adults, and surgical intervention is often recommended. The impact of this lesion when recognized in the adult and its management are ill defined. Methods and Results— We reviewed 210 700 cardiac catheterizations performed over a 35-year period at a single institution and identified 301 adults with an anomalous coronary artery from the opposite sinus of Valsalva, either anomalous right coronary artery from the left cusp or anomalous left main coronary artery from the right cusp. Patients were stratified by the pathway of the anomalous artery and the chosen treatment. Among the 301 patients with anomalous coronary artery from the opposite sinus of Valsalva (0.14% of the cohort), 79% had anomalous right coronary artery from the left cusp, and 18% had an interarterial course (IAC). Patients with IAC were younger (52±13 versus 59±13 years; P=0.001) and more likely to undergo surgical intervention (52% versus 27%; P<0.001), but mortality was not increased with IAC. Among the 54 patients with IAC, 28 underwent surgical repair with no perioperative deaths. Patients evaluated since 2000 were significantly more likely to be referred for surgery (P=0.004). Surgical patients were more likely to have abnormal stress tests (90% versus 43%; P=0.01) and had more extensive atherosclerosis but less diabetes mellitus (0% versus 23%; P=0.01). Long-term survival at 10 years appeared similar in both groups. Conclusions— In this single-center cohort study of patients with an anomalous coronary artery from the opposite sinus of Valsalva, surgical management appears to have been favored recently. Despite no perioperative mortality, a positive impact on long-term survival was not observed. The impact of surgery in older adults with anomalous coronary arteries arising from the opposite coronary sinus with IAC deserves further study.