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Biomedical subjects

R E Hobbs

Publications and source records attributed to R E Hobbs.

At least 19 recordsLinked to original sources

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.

Adult

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.

Age Factors

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.

Adult

Hemodynamic and physiologic changes during support with an implantable left ventricular assist device.

To evaluate hemodynamic effectiveness and physiologic changes on the HeartMate 1000 IP left ventricular assist device (Thermo Cardiosystems, Inc., Woburn, Mass.), we studied 25 patients undergoing bridge to heart transplantation (35 to 63 years old, mean 50 years). All were receiving inotropic agents before left ventricular assist device implantation, 21 (84%) were supported with a balloon pump, and 7 (28%) were supported by extracorporeal membrane oxygenation. Six patients died, primarily of right ventricular dysfunction and multiple organ failure. Nineteen (76%) were rehabilitated, received a donor heart, and were discharged (100% survival after transplantation). Pretransplantation duration of support averaged 76 days (22 to 153 days). No thromboembolic events occurred in more than 1500 patient-days of support with only antiplatelet medications. Significant hemodynamic improvement was measured (before implantation to before explantation) in cardiac index (1.7 +/- 0.3 to 3.1 +/- 0.8 L/min per square meter; p < 0.001), left atrial pressure (23.7 +/- 7 to 9 +/- 7.5 mm Hg; p < 0.001), pulmonary artery pressure, pulmonary vascular resistance, and right ventricular volumes and ejection fraction. Both creatinine and blood urea nitrogen levels were significantly higher before implantation in patients who died while receiving support. Renal and liver function returned to normal before transplantation. We conclude that support with the HeartMate device improved hemodynamic and subsystem function before transplantation. Long-term support with the HeartMate device has a low risk of thromboemboli and makes a clinical trial of a portable HeartMate device a realistic alternative to medical therapy.

Adult

Left ventricular diastolic dysfunction in lymphocytic myocarditis as assessed by Doppler echocardiography.

Pulsed-wave Doppler echocardiography of left ventricular (LV) inflows was performed in 30 consecutive patients with biopsy-proven lymphocytic myocarditis. There were 21 men and 9 women (mean age 50 +/- 15 years). LV ejection fraction was < or = 30% in 73% of the patients. Sixty-six percent were in New York Heart Association functional class III to IV. Peak early (E) velocity, late (A) velocity, deceleration time and filling pattern were assessed. These values were compared with a control population. E velocity in lymphocytic myocarditis was significantly higher than in control subjects (79 +/- 34 vs 67 +/- 14 cm/s, p = 0.0034). A velocity was lower in patients with myocarditis than in control subjects (38 +/- 20 vs 49 +/- 12 cm/s, p = 0.0001). Correspondingly, the E/A ratio was greater in the myocarditis group (2.5 +/- 1.3 vs 1.5 +/- 0.5, p < 0.0001). In particular, mean deceleration time in patients with myocarditis was significantly lower than that of control subjects (151 +/- 52 vs 194 +/- 30 ms, p < 0.0001). Diastolic filling patterns were abnormal in 29 of 30 patients (97%) with lymphocytic myocarditis, revealing a restrictive pattern in 25, abnormal relaxation in 4 and a normal pattern in 1. Lymphocytic myo-carditis is therefore associated with LV diastolic dysfunction of a predominantly restrictive pattern.

Adult

Congestive heart failure. Current and future strategies to decrease mortality.

The prevalence of and mortality from congestive heart failure increase with advancing age. The most important prognostic indicators are exercise tolerance and left ventricular function. Currently, drug treatment consists of digitalis, diuretics, and ACe inhibitors. Future management may include medications to modulate the extracardiac mechanisms of decompensation and newer surgical techniques to assist or replace the failing heart.

Age Factors

Implantable left ventricular assist device. Approaching an alternative for end-stage heart failure. Implantable LVAD Study Group.

BACKGROUND: The implantable left ventricular assist device (LVAD) was designed to provide circulatory support as an alternative to heart transplantation or to continued medical therapy of end-stage heart failure. Initial experience with the implantable LVAD used as a bridge to heart transplantation provides a clinical opportunity to study the function of the device and adaptation by the patient. METHODS AND RESULTS: Nineteen heart transplant candidates (mean age, 50 years; 17 males) underwent insertion of the HeartMate LVAD as a bridge to heart transplantation from December 1991 to November 1993. All patients were in cardiogenic shock on inotropes, and 16 (84%) were on an intra-aortic balloon pump. Three patients died because of multiple organ failure; all had right ventricular (RV) dysfunction (2 required RV assist devices). Sixteen patients (84%) improved markedly and were rehabilitated to New York Heart Association functional class I-II. Three patients are still on support. Significant improvements in hemodynamic function (based on analysis of the percent change from pre-LVAD condition to pretransplantation) were observed: cardiac index rose from 1.6 +/- 0.2 to 3.2 +/- 0.9 L/min per m2 (P = .0002), left atrial pressure fell from 22.9 +/- 9.5 to 8.0 +/- 5.5 mm Hg (P = .003), RV ejection fraction increased from 19.8 +/- 11.3% to 40.8 +/- 8.9% (P = .0004), pulmonary vascular resistance decreased from 5.2 +/- 2.6 to 2.0 +/- 0.8 Wood units (P = .004). Thirteen patients had successful transplants after a mean duration of 66 days on the LVAD (range, 22 to 101 days). There were no thromboembolic events while the patients were on the LVAD. Only aspirin with dipyridamole was given for anticoagulation during a total of > 1100 patient days of support. CONCLUSIONS: Bridge to transplant implantable LVAD experience indicates that hemodynamic improvement should be significant after insertion of the devices and that the risk of thromboembolic events with the HeartMate LVAD should be extremely low. Rehabilitation and quality of life should be markedly improved. Limitations of extrapolating this clinical experience to the permanent implantable LVAD include that these patients were hospitalized (permanent implants will be outpatients); the "vented-electric" HeartMate LVAD was not tested (it is a portable, battery-powered device), and true "chronic" LVAD support (> 1 year) was not tested, so questions regarding long-term device reliability and the chronic risk of infection are unknown.

Equipment Design

Hypertension and left ventricular hypertrophy in black vs white heart transplant patients 1 year after surgery.

To evaluate the impact of race on the prevalence of systemic hypertension and its effects on left ventricular function, structure, and allograft survival after cardiac transplantation, 31 heart transplant recipients (7 blacks and 24 whites) were studied at 1 year after surgery. Echocardiographic and hemodynamic evaluation of the allografts was performed in addition to clinical follow-up and estimation of patients' survival. There was no difference in the demographic and clinical data between black and white patients. No differences between black and white cardiac transplant recipients were detected with regard to the prevalence of systemic hypertension, left ventricular hypertrophy, left ventricular function, renal function, or patients' survival. Moreover, racial mismatch did not predispose to allograft rejection. However, black patients had significantly higher resting systolic blood pressure and lower heart rates. We conclude that the race of heart recipients is not a detrimental factor in the early outcome after cardiac transplantation. The long-term cardiovascular consequences of these findings should be explored.

Adult

Coronary artery anomalies in 126,595 patients undergoing coronary arteriography.

Coronary artery anomalies were found in 1,686 patients (1.3% incidence) undergoing coronary arteriography at the Cleveland Clinic Foundation from 1960 to 1988. Of the 1,686 patients, 1,461 (87%) had anomalies of origin and distribution, and 225 (13%) had coronary artery fistulae. Most coronary anomalies did not result in signs, symptoms, or complications, and usually were discovered as incidental findings at the time of catheterization. Eighty-one percent were "benign" anomalies: 1) separate origin of the left anterior descending and circumflex from the left sinus of Valsalva; 2) ectopic origin of the circumflex from the right sinus of Valsalva; 3) ectopic coronary origin from the posterior sinus of Valsalva; 4) anomalous coronary origin from the ascending aorta; 5) absent circumflex; 6) intercoronary communications; and 7) small coronary artery fistulae. Other anomalies may be associated with potentially serious sequelae such as angina pectoris, myocardial infarction, syncope, cardiac arrhythmias, congestive heart failure, or sudden death. Potentially serious anomalies include: 1) ectopic coronary origin from the pulmonary artery; 2) ectopic coronary origin from the opposite aortic sinus; 3) single coronary artery; and 4) large coronary fistulae. Coronary artery anomalies require accurate recognition, and at times, surgical correction.

Arteriovenous Fistula

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.

Adult

Hypertension revisited: the concept of relative hypertension in congestive heart failure.

Although hypertension has been defined numerically as blood pressure levels above 140/90 mmHg, there is no doubt that a blood pressure level within the "normal" range increases the stress on a diseased heart. For this reason, vasodilator therapy is often successful in treating congestive heart failure. The authors propose the term relative hypertension to illustrate the latter situation.

Blood Pressure

Lymphocytic myocarditis and dilated cardiomyopathy: treatment with immunosuppressive agents.

Thirty-four patients with history of congestive heart failure, dilated cardiomyopathy, and biopsy-proven lymphocytic myocarditis were treated for six months with immunosuppressive agents (prednisone and azathioprine) in addition to standard therapy for congestive heart failure. Seventy-three percent had improvement or resolution of the lymphocytic infiltrate, whereas 27% had persistent infiltrates. Improvement in myocardial histologic findings was unpredictable and did not correlate with age, gender, duration of symptoms, initial functional class, severity of left ventricular dysfunction, intensity of initial inflammatory infiltrate, or degree of myocardial cell injury. Histologic response was associated with significant improvement in left ventricular ejection fraction, but not cardiothoracic ratio, left ventricular dimensions, or survival. Functional class improved equally whether patients' disease did or did not respond to the treatment, and was not necessarily associated with objective improvement in cardiac function. Immunosuppressive therapy resulted in serious or fatal side effects in 24% of patients. Overall long-term survival was 79% at one year and 76% at two years. Poor survival was related to left ventricular ejection fraction less than 20%, male sex, age less than 50 years, and marked left ventricular dilation, but not to myocardial histologic findings. These findings indicate that the potential benefits nu the risks of immunosuppressive therapy must be weighed carefully in the individual patient.

Adult

Cyclosporin-associated microfibrils in cardiac transplant patients.

Endomyocardial biopsies from 21 cyclosporin-treated cardiac transplant patients were studied at the ultrastructural level. Eight patients exhibited focal interstitial accumulation of filaments, which most commonly measured 8-10 nm in diameter (range 7-16 nm). The filaments were straight, hollow, and nonbranching. Filament accumulation was observed as early as 4 days posttransplant. No filament accumulation was observed in 17 donor endomyocardial biopsies obtained at the time of transplantation. The ultrastructure of the filaments was similar to that of amyloid fibrils. Stains for amyloid at the light microscopic level were uniformly negative, however. Until the exact nature of the filaments is determined, we propose that they be referred to as cyclosporin associated microfibrils.

Actin Cytoskeleton

Reversibility of myocyte injury in moderate and severe acute rejection in cyclosporine-treated cardiac transplant patients.

Myocyte injury in acute cardiac transplant rejection was studied ultrastructurally in 45 patients. Mild myocyte injury consisted of increased glycogen granules and mitochondria, and condensation and streaming of myofilaments. More severe cell injury was characterized by clumping of Z-band material at the periphery of the cell and loss of sarcomeric units. Cell swelling was not seen, and intramitochondrial dense deposits (indicative of irreversible cell injury) were rarely seen. Restoration of normal myocyte ultrastructure occurred after treatment for rejection. Although the light microscopic appearance of moderate or severe acute rejection may suggest myocyte necrosis, this is rarely observed ultrastructurally. We conclude that the majority of cell injury in acute rejection is potentially reversible.

Biopsy