James D. Bergin

Successful transplantation of marginally acceptable thoracic organs.

OBJECTIVE This study evaluates the efficacy of personally inspecting marginal thoracic organ donors to expand the donor pool. SUMMARY BACKGROUND DATA The present donor criteria for heart and lung transplantation are very strict and result in exclusion of many potential thoracic organ donors. Due to a limited donor pool, 20-30% of patients die waiting for transplantation. METHODS The authors have performed a prospective study of personally inspecting marginal donor organs that previously would have been rejected by standard donor criteria. RESULTS Fourteen marginal hearts and eleven marginal lungs were inspected. All 14 marginal hearts and 10 of the marginal lungs were transplanted. All cardiac transplant patients did well. The mean ejection fraction of the donor hearts preoperatively was 39 +/- 11% (range 15-50%). Postoperatively, the ejection fraction of the donor hearts improved significantly to 55 +/- 3% (p < 0.002). Nine of the ten lung transplant patients did well and were operative survivors. Our donor pool expanded by 36% over the study period. CONCLUSIONS The present donor criteria for heart and lung transplantation are too strict. Personal inspection of marginal thoracic donor organs will help to maximize donor utilization.

Why do patients with congestive heart failure tolerate the initiation of beta-blocker therapy?

BACKGROUND Despite its negative inotropic effects, the initiation of beta-adrenergic blockade is tolerated by patients with congestive heart failure (CHF). Accordingly, we examined the acute hemodynamic effects of beta-adrenergic blockade on systolic and diastolic left ventricular (LV) function and ventriculo-arterial coupling. In addition, isolated myocardium from patients with CHF shows selective beta 1-receptor downregulation, implying a greater role for the beta 2-receptor in maintaining in vivo LV contractility. As a secondary aim, we hypothesized that nonselective beta-adrenergic blockade would have greater negative inotropic effect than beta 1-blockade in patients with CHF. METHODS AND RESULTS Patients with clinical CHF (n = 24) and control patients without CHF (n = 24) were given either the nonselective beta-blocker propranolol or the beta 1-selective blocker metoprolol. LV pressure-volume relations were obtained before and after the administration of intravenous beta-blocker, and measures of LV systolic and diastolic function were examined. Patients with CHF had a deterioration in LV systolic function with a fall in LV systolic pressure (139 +/- 6 to 125 +/- 6 mm Hg), cardiac index (2.56 +/- 0.11 to 2.20 +/- 0.11 mL.min-1 x M-1), dP/dtmax (1173 +/- 63 to 897 +/- 50 mm Hg/s), and end-systolic elastance (0.88 +/- 0.10 to 0.64 +/- 0.10 mm Hg/mL), P < .05 for all. Although there was deterioration of active LV relaxation (isovolumetric relaxation 63 +/- 2 to 73 +/- 3 milliseconds, peak filling rate 543 +/- 33 to 464 +/- 28 mL/s, P < .05 for both), there was no change in passive LV diastolic function (pulmonary capillary wedge, 24 +/- 2 to 24 +/- 1 mm Hg; chamber stiffness, 0.0154 +/- 0.0005 to 0.0163 +/- 0.0005 mL-1, P = NS for both), and a decrease in afterload (arterial elastance 3.85 +/- 0.31 to 3.38 +/- 0.24 mm Hg/mL, P < .05). Control patients had no change in these parameters other than a prolongation of isovolumetric relaxation (48 +/- 1 to 55 +/- 2 milliseconds, P < .05). The effects of propranolol (n = 12) versus metoprolol (n = 12) on these parameters in patients with CHF were similar. CONCLUSIONS These data do not support a greater in vivo physiological role of the myocardial beta 2-receptor in CHF. The preservation of passive diastolic function and ventriculo-arterial coupling provide possible explanations of why beta-adrenergic blockade is tolerated by patients with CHF.

Acute Cardiovascular Effects of OPC-18790 in Patients With Congestive Heart Failure Time- and Dose-Dependence Analysis Based on Pressure-Volume Relations

BACKGROUND OPC-18790 is a water-soluble quinolinone derivative that shares the pharmacological properties of vesnarinone and that may be useful for treating heart failure. We studied the contribution and relative dose sensitivities of the inotropic, lusitropic, and vascular effects of OPC-18790 in patients with dilated cardiomyopathy. METHODS AND RESULTS Pressure-volume (PV) analysis was performed in 17 patients who received either 5 micrograms.kg-1.min-1 (low dose, n = 10) or 10 micrograms.kg-1.min-1 (high dose, n = 7) OPC-18790 by 1-hour IV infusion. Right heart pressures and flow and left heart PV relations (conductance catheter) were measured at baseline and every 15 minutes during infusion. Transient inferior vena caval obstruction was used to determine PV relations. Both doses produced venodilation reflected by a 10% decline in left ventricular end-diastolic volume and a 30% fall in atrial and pulmonary artery pressures. Arterial dilation was four times greater at the high dose, with an approximately 40% fall in effective arterial elastance and systemic resistance. Contractility rose by 25% to 100% (depending on PV index) with both doses. Ventricular-arterial coupling (ratio of ventricular end-systolic to arterial elastances) was approximately 0.25 at baseline and doubled (or tripled) at low (or high) dose, correlating with improved efficiency. Isovolumetric relaxation shortened, whereas the diastolic PV relation was generally unchanged. Heart rate was unaltered. CONCLUSIONS OPC-18790 has potent venous and arterial vasodilator effects and moderate inotropic and lusitropic effects without a change in heart rate. These combined actions suggest a unique potential of OPC-18790 for heart failure treatment.

Donor Age Is Associated With Chronic Allograft Vasculopathy After Adult Heart Transplantation: Implications for Donor Allocation

BACKGROUND Chronic allograft vasculopathy (CAV) is a major cause of long-term complications and mortality after heart transplantation. Although recipient factors have been implicated, little is known of the role of donor factors in CAV development. We sought to identify donor factors associated with development of CAV after heart transplantation. METHODS We reviewed the United Network for Organ Sharing heart transplant database from August 1987 to May 2008. Univariate and multivariate analyses were performed to assess the association between donor variables and the onset of CAV for adult recipients. Donor age was matched to recipient age and analyzed with respect to development of CAV. RESULTS Of the 39,704 recipients, a total of 11,714 (29.5%) experienced CAV. Multivariate analysis demonstrated seven donor factors as independent predictors of CAV: age, ethnicity, sex, weight, history of diabetes, hypertension, and tobacco use. When matching young donors (0 to 19.9 years) and old donors (> or =50 years) to each recipient age group, older donors (> or =50 years) conferred a higher risk of developing CAV. Further modeling demonstrated that for each recipient group, older donor age (> or =50 years) conferred a higher risk of CAV development compared with younger donor age (0 to 19.9 years; p < 0.0001). CONCLUSIONS Donor factors including sex, hypertension, diabetes, and tobacco use are independently associated with recipient CAV. Older donor age confers a greater risk of CAV development regardless of the age of the recipient. A heightened awareness for the development of CAV is warranted when using older donors in adult cardiac transplantation, in particular with recipients 40 years of age or older.

General surgical complications can be predicted after cardiopulmonary bypass.

OBJECTIVE The authors review the general surgical complications of cardiopulmonary bypass, including newer procedures such as heart and lung transplantation, to identify patients at higher risk. SUMMARY BACKGROUND DATA Although rare, the general surgical complications of cardiopulmonary bypass are associated with high mortality. The early identification of patients at increased risk for these complications may allow for earlier detection and treatment of these problems to reduce mortality. METHODS A retrospective review was performed of 1831 patients undergoing cardiopulmonary bypass from 1991 to 1993. This was done to identify factors that significantly contributed to an increased risk of general surgical complications. RESULTS Factors associated with an increased risk of general surgical complications included prolonged cardiopulmonary bypass (p < 0.005) and intensive care unit stay (p < 0.002), occurrence of arrhythmias (p < 0.001), use of inotropic agents (preoperatively or postoperatively p < 0.001), insertion of the intra-aortic balloon pump (preoperatively p < 0.005, postoperatively p < 0.001), use of steroids (p < 0.001), and prolonged ventilator support (p < 0.001). Multivariate analysis identified use of the intra-aortic balloon pump (p < 0.001) as the strongest predictor of the general surgical complications of cardiopulmonary bypass. A variety of factors not contributing significantly to an increased risk also were identified. CONCLUSIONS Factors indicative of or contributing to periods of decreased end-organ perfusion appear to be significantly related to general surgical complications after cardiopulmonary bypass.

Bolus intravenous nitroglycerin predominantly reduces afterload in patients with excessive arterial elastance.

OBJECTIVES We hypothesized that bolus intravenous nitroglycerin would be an afterload-reducing agent in patients with excessive initial afterload for their level of left ventricular systolic function. Conversely, bolus intravenous nitroglycerin should be a preload-reducing agent in patients without excessive initial afterload. BACKGROUND Although nitroglycerin has both preload- and afterload-reducing actions, methods to predict its predominant site of action in an individual patient have not been previously described. METHODS Left ventricular pressure-volume relations were recorded with micromanometer and conductance catheters during bolus injection of intravenous nitroglycerin in 27 patients with both normal left ventricular systolic function and varying degrees of congestive heart failure. Preload was determined by end-diastolic volume, afterload by effective arterial elastance, left ventricular systolic function by end-systolic elastance and coupling of afterload and ventricular function by the ratio of effective arterial elastance to end-systolic elastance (Ea/Ees ratio). An Ea/Ees ratio > 1 was defined as excessive afterload for the level of ventricular function. RESULTS Patients with an initial Ea/Ees ratio < 1 (Group 1) constituted a group of normotensive patients with intact ventricular function who exhibited a predominant reduction in preload in response to intravenous nitroglycerin. Those with an initial Ea/Ees ratio > 1 and normal or mildly depressed ventricular function (Group 2a) constituted a group of patients, most of whom were hypertensive, who exhibited a predominant afterload reduction. Finally, those with an initial Ea/Ees ratio > 1 and abnormal ventricular function (Group 2b) constituted a group of patients with clinical congestive heart failure who exhibited both preload and afterload reduction but a predominant afterload reduction because stroke volume increased. CONCLUSIONS Patients with normal arterial elastance and ventricular function respond to nitroglycerin with a predominant preload reduction, whereas patients with either excessive arterial elastance or abnormal ventricular function respond with a predominant afterload reduction.

Surgically Placed Left Ventricular Leads Provide Similar Outcomes to Percutaneous Leads in Patients with Failed Coronary Sinus Lead Placement

BACKGROUND Cardiac resynchronization therapy using a left ventricular (LV) lead inserted via the coronary sinus (CS) improves symptoms of congestive heart failure, decreases hospitalizations, and improves survival. An epicardial LV lead is often placed surgically after a failed percutaneous attempt, but whether it offers the same benefits is unknown. OBJECTIVE The purpose of this study was to determine if patients who receive a surgical LV lead after failed CS lead placement for cardiac resynchronization therapy derive the same benefit as do patients with a successfully placed CS lead. METHODS A total of 452 patients underwent attempted CS lead insertion. Forty-five patients who had failed CS lead placement and then had surgical LV lead placement were matched with 135 patients who had successful CS lead placement. RESULTS No major differences in preoperative variables were seen between groups. Postprocedural complications of acute renal injury (26.2% vs 4.9%, P <.001) and infection (11.9% vs 2.4%, P = .03) were more common in the surgical group. Mean long-term follow-up was 32.4 +/- 17.5 months for surgical patients and 39.4 +/- 14.8 months for percutaneous patients. At follow-up, all-cause mortality (30.6% vs 23.8%, P = .22) and readmission for congestive heart failure (26.2% vs 31.5%, P = .53) were similar between surgical and percutaneous groups. Improvement in New York Heart Association functional class (60.1% vs 49.6%, P = .17) was similar between surgical and percutaneous groups. CONCLUSION Surgical LV lead placement offers functional benefits similar to those of percutaneous placement but with greater risk of perioperative complications, including acute renal failure and infection.

Sonication of Explanted Cardiac Rhythm Management Devices for the Diagnosis of Pocket Infections and Asymptomatic Bacterial Colonization

Background: Correct diagnosis of the causative organism is critical for the treatment of pacemaker and defibrillator pocket infections. No gold standard for this exists, although swab and tissue cultures are frequently used. The purpose of this study was to determine the value of ultrasonication of explanted generators in the diagnosis of pocket infections and asymptomatic bacterial colonization.

Early thrombus in a HeartMate II™ Left Ventricular Assist Device: A Potential Cause of Hemolysis and Diagnostic Dilemma

Thromboembolic events occur in 2–3% of patients receiving the HeartMate II™ (HMII) left ventricular assist device (LVAD). Even though several surfaces of the HMII are textured and thromboresistant, long-term anticoagulation is indicated.1 We report the case of an early postoperative distal inflow-conduit thrombus resulting in hemolysis, in a patient undergoing HMII and concomitant bioprosthetic aortic valve replacement (AVR).

A random effects four-part model, with application to correlated medical costs

In this paper we propose a four-part random effects model, with application to correlated medical cost data. Four joint equations are used to model respectively: (1) the probability of seeking medical treatment, (2) the probability of being hospitalized (conditional on seeking medical treatment), and the actual amount of (3) outpatient and (4) inpatient costs. Our model simultaneously takes account of the inter-temporal (or within-cluster) correlation of each patient and the cross-equation correlation of the four equations, by means of joint linear mixed models and generalized linear mixed models. The estimation is accomplished by the high-order Laplace approximation technique in Raudenbush et al. [Raudenbush, S.W., Yang, M., Yosef, M., 2000. Maximum likelihood for generalized linear models with nested random effects via high-order, multivariate Laplace approximation. Journal of Computational and Graphical Statistics 9, 141-157] and Olsen and Schafer [Olsen, M.K., Schafer, J.L., 2001. A two-part random effects model for semicontinuous longitudinal data. Journal of the American Statistical Association 96, 730-745]. Our model is used to analyze monthly medical costs of 1397 chronic heart failure patients from the clinical data repository (CDR) at the University of Virginia.