Predictive value of dobutamine stress echocardiography for coronary artery disease detection in liver transplant candidates.

Patients with obstructive coronary artery disease (CAD) undergoing orthotopic liver transplantation (OLT) are at increased risk of poor outcomes. The accuracy of dobutamine stress echocardiography (DSE) to detect obstructive CAD is not well established in this population. We retrospectively identified patients with end-stage liver disease who underwent both DSE and coronary angiography as part of risk stratification prior to OLT. One hundred and five patients had both DSE and angiography, of whom 14 had known CAD and 27 failed to reach target heart rate during DSE. Among the remaining 64 patients (45 men; average age 61 +/- 8 years) DSE had a low sensitivity (13%), high specificity (85%), low positive predictive value (PPV) (22%) and intermediate negative predictive value (NPV) (75%) for obstructive CAD. DSE as a screening test for obstructive CAD in OLT candidates has a poor sensitivity. The frequent chronotropic incompetence and low sensitivity in patients who achieve target heart rate, even in those with multiple cardiovascular disease risk factors, suggest that alternative or additional methods of risk stratification are necessary.

Ultrasound lung comets for the differential diagnosis of acute cardiogenic dyspnoea: a comparison with natriuretic peptides.

BACKGROUND: Acute dyspnoea as a presenting symptom is a frequent diagnostic challenge for physicians. The main differential diagnosis is between dyspnoea of cardiac and non-cardiac origin. Natriuretic peptides have been shown to be useful in this setting. Ultrasound lung comets (ULCs) are a simple, echographic method which can be used to assess pulmonary congestion. AIM: To evaluate the accuracy of ULCs for predicting dyspnoea of cardiac origin compared to natriuretic peptides. METHODS: We evaluated 149 patients admitted with acute dyspnoea. Chest sonography and NT-proBNP assessments were performed a maximum of 4 h apart and independently analyzed. ULCs were evaluated via cardiac probes placed on the anterior and lateral chest. Two independent physicians, blinded to ULCs and NT-proBNP findings, reviewed all the medical records to establish the aetiologic diagnosis of dyspnoea. RESULTS: Cardiogenic dyspnoea was confirmed in 122 patients and ruled-out in 27 patients. The number of ULCs was significantly correlated to NT-proBNP values (r=.69, p<.0001). Receiver operating characteristic analysis, showed an area under the curve of .893 for ULCs and .978 (p=.001) for NT-proBNP, in predicting the cardiac origin of dyspnoea. CONCLUSIONS: In patients admitted with acute dyspnoea, pulmonary congestion, sonographically imaged as ULCs, is significantly correlated to NT-proBNP values. The accuracy of ULCs in predicting the cardiac origin of dyspnoea is high.

Autologous hematopoietic stem cell transplantation in systemic lupus erythematosus patients with cardiac dysfunction: feasibility and reversibility of ventricular and valvular dysfunction with transplant-induced remission.

Patients with cardiac dysfunction may be at increased risk of cardiac toxicity when undergoing hematopoietic stem cell transplantation (HSCT), which may preclude them from receiving this therapy. Cardiac dysfunction is, however, common in systemic lupus erythematosus (SLE) patients. While autologous HSCT (auto-HSCT) has been performed increasingly for SLE, its impact on cardiac function has not previously been evaluated. We, therefore, performed a retrospective analysis of SLE patients who had undergone auto-HSCT in our center to determine the prevalence of significant cardiac involvement, and the impact of transplantation on this. The records of 55 patients were reviewed, of which 13 were found to have abnormal cardiac findings on pre-transplant two-dimensional echocardiography or multi-gated acquisition scan: impaired left ventricular ejection fraction (LVEF) (n = 6), pulmonary hypertension (n = 5), mitral valve dysfunction (n = 3) and large pericardial effusion (n = 1). At a median follow-up of 24 months (8-105 months), there were no transplant-related or cardiac deaths. With transplant-induced disease remission, all patients with impaired LVEF remained stable or improved; while three with symptomatic mitral valve disease similarly improved. Elevated pulmonary pressures paralleled activity of underlying lupus. These data suggest that auto-HSCT is feasible in selected patients with lupus-related cardiac dysfunction, and with control of disease activity, may improve.

Impact of intracoronary aspiration thrombectomy during primary angioplasty on left ventricular remodelling in patients with anterior ST elevation myocardial infarction.

OBJECTIVE: To evaluate prospectively the impact on left ventricular (LV) remodelling of an intracoronary aspiration thrombectomy device as adjunctive therapy in primary percutaneous coronary intervention (PCI) in patients with anterior ST elevation myocardial infarction (STEMI). METHODS: 76 consecutive patients with anterior STEMI (65.3 (11.2) years, 48 men) were randomly assigned to intracoronary thrombectomy and stent placement (n = 38) or to conventional stenting (n = 38) of the infarct related artery. Each patient underwent transthoracic echocardiography immediately after PCI and at six months. At the time of echocardiographic control, major adverse cardiovascular events (MACE) in terms of death, new onset of myocardial infarction, and hospitalisation for heart failure were also evaluated. RESULTS: After a successful primary PCI, patients in the thrombectomy group achieved a higher rate of post-procedure myocardial blush grade 3 (36.8% v 13.1%, p = 0.03) and effective ST segment resolution at 90 minutes (81.6% v 55.3%, p = 0.02). Six months after the index intervention, 19 patients (26.8%) developed LV dilatation, defined as an increase in end diastolic volume (EDV) >or= 20%: 15 in the conventional group and four in the thrombectomy group (p = 0.006). Accordingly, at six months patients treated conventionally had significantly higher end systolic volumes (82 (7.7) ml v 75.3 (4.9) ml, p < 0.0001) and EDV (152.5 (18.1) ml v 138.1 (10.7) ml, p < 0.0001) than patients treated with thrombectomy. No differences in cumulative MACE were observed (10.5% in the conventional group v 8.6% in the thrombectomy group, not significant). CONCLUSION: Compared with conventional stenting, adjunctive aspiration thrombectomy in successful primary PCI seems to be associated with a significantly lower incidence of LV remodelling at six months in patients with anterior STEMI.

Hematopoietic stem cell transplantation for cardiac and peripheral vascular disease.

Recent studies have suggested that marrow and blood hematopoietic stem cells may contribute to nonhematopoietic tissue repair in multiple organ systems. In animal models and more recently in limited human trials, unpurified marrow mononuclear cells and/or subsets of adult hematopoietic stem cells have been reported to contribute to neoangiogenesis. Since the subset of hematopoietic stem cells (HSCs) that are both CD34+ and AC133+ are endothelial cell precursors, clinical trials using autologous AC133+ HSCs isolated with the Miltenyi CLIMACS cell separator and transplanted into patients with ischemic and refractory peripheral vascular or coronary artery disease are being implemented at Northwestern University.

Myocardial Na,K-ATPase: the molecular basis for the hemodynamic effect of digoxin therapy in congestive heart failure.

Congestive heart failure may be deemed the epidemic of cardiology in the 21st century in the industrialized part of the world. Although new therapies improving morbidity and mortality from chronic heart failure have emerged it is likely that there is a growing role for digoxin. Thus, digoxin treatment is known to control symptoms of congestive heart failure when added to standard therapy. In this setting, we review the prevailing knowledge of the Na,K-ATPase, the cellular receptor for the inotropic action of digitalis glycosides, in relation to the hemodynamic effect of digoxin. It is concluded that if improvement of hemodynamics is needed in congestive heart failure, this knowledge should be taken into account and in many cases digoxin should be added to standard therapy. Digoxin is still the only safe inotropic drug for oral use that improves hemodynamics. Digoxin should be used to heart failure patients in sinus rhythm when they after institution of mortality reducing treatment still have heart failure symptoms, and to patients intolerant to heart failure mortality reducing drugs. Digoxin should probably in heart failure patients with sinus rhythm be given in the lowest possible dose that relieves symptoms sufficiently.

Prognostic usefulness of the six-minute walk in patients with advanced congestive heart failure secondary to ischemic or nonischemic cardiomyopathy.

Clinicians have relied on history and results from physical examinations to guide treatment of patients with advanced congestive heart failure, but these results may not reflect disease severity or hemodynamic status. We assessed how the distance walked in 6 minutes relates to clinical outcomes and symptoms of such patients. We compared the rates of death, hospitalization, and their composite at 1 year by the distance walked in 6 minutes at baseline and at 1 month, and by the change in distance between baseline and 1 month in 440 patients enrolled in a randomized trial. We also assessed the relations of baseline distance walked to symptom score and New York Heart Association class. The median distance increased from 218 m at baseline to 280 m at 1 month. Of 365 patients able to perform the baseline walk, 121 (33%) died and 217 (60%) were hospitalized compared with 46 (61%) and 34 (45%) of 75 patients unable to walk at baseline. Baseline distance significantly predicted mortality (hazard ratio 0.58/100-m increase, 95% confidence interval 0.50 to 0.68, p <0.001), even after adjustment. Baseline distance also significantly predicted hospitalization and the composite end point, as did the 1-month distance walked. The change in distance walked from baseline to 1 month did not predict any end point. Baseline distance correlated only moderately with symptom score (r = -0.385, p <0.001) and New York Heart Association class (r = -0.468, p <0.001). Distance walked during 6 minutes independently and strongly predicts mortality and hospitalization in patients with advanced congestive heart failure. This may be a simple, noninvasive, objective way to risk-stratify these patients and standardize their treatment.

Comparison of two aspirin doses on ischemic stroke in post-myocardial infarction patients in the warfarin (Coumadin) Aspirin Reinfarction Study (CARS).

The Coumadin Aspirin Reinfarction Study demonstrated that combination treatment with fixed dose warfarin (1 or 3 mg) + aspirin 80 mg was not superior to aspirin 160 mg alone after myocardial infarction for reducing nonfatal reinfarction, nonfatal stroke, and cardiovascular death. In this analysis, we examined the importance of aspirin dose in the protection against the secondary end point of ischemic stroke. The comparison arms for this analysis were warfarin 1 mg + aspirin 80 mg versus aspirin 160 mg. In the Coumadin Aspirin Reinfarction Study, 2,028 patients were randomized to aspirin 80 mg plus warfarin 1 mg, and 3,393 were randomized to aspirin 160 mg alone. A predictive model for ischemic stroke was developed using the Cox proportional-hazards model. A reduced Cox proportional-hazards model was developed to test for the effect of aspirin dose on ischemic stroke in predefined subgroups. The incidence of ischemic stroke was lower in patients treated with aspirin 160 mg than in patients treated with aspirin 80 mg + warfarin 1 mg (0.6% vs 1.1%; p = 0.0534). Age, previous stroke or transient ischemic attack, and aspirin dose were independent predictors of ischemic stroke. In addition, the highest risk patients, those with Q-wave myocardial infarction and male patients, appeared to receive greater benefit from aspirin 160 mg than from aspirin 80 mg + warfarin 1 mg. The results of this secondary analysis suggest that aspirin 160 mg is more effective than aspirin 80 mg + warfarin 1 mg in preventing ischemic stroke in post-myocardial infarction patients.

Improvement in hypertension in patients with diabetes mellitus after kidney/pancreas transplantation.

BACKGROUND: Hypertension persists in many patients with diabetes mellitus after kidney transplantation. However, the impact of control of diabetes as well as kidney failure on hypertension by combined kidney and pancreas transplantation has not been studied. METHODS AND RESULTS: Between March 1993 and August 1998, 111 patients with type 1 diabetes mellitus underwent successful pancreas transplantation (108 kidney/pancreas transplantation) and another 28 patients with type 1 diabetes mellitus underwent isolated kidney transplantation. Blood pressure measurements and all antihypertensive medications were determined for both groups before transplantation and at 1, 3, 6, and 12 months and at the most recent outpatient evaluation after transplantation. At baseline, the mean blood pressure was 151/88 and 151/83 mm Hg for the kidney/pancreas and isolated kidney transplant patients, respectively. The mean blood pressure decreased to 134/77 mm Hg 1 month after kidney/pancreas transplantation (P<0.001) and decreased further to 126/70 mm Hg (P<0.001) at a mean follow-up of 18 months. This reduction in blood pressure after transplantation occurred despite a decrease in antihypertensive medications and the institution of immunosuppressive agents. At 1 month after kidney/pancreas transplantation, the average number of antihypertensive medications per patient was 0.9+/-1.0, compared with 2.5+/-1.1 before surgery (P<0.001). At 18 months after transplantation, 34% of patients were both normotensive (blood pressure

Relative lymphocyte count: a prognostic indicator of mortality in elderly patients with congestive heart failure.

BACKGROUND: A reduction in the relative lymphocyte count is a marker of the stress response; however, its prognostic value remains undetermined. The objective of this study was to investigate the predictive value of the relative lymphocyte count for survival in elderly patients with congestive heart failure (CHF). METHODS AND RESULTS: One thousand two hundred seventy-four consecutive patients above the age of 65 years hospitalized with heart disease were enrolled in the CHF Italian Study and followed up for 3 years. Of these, 413 patients were excluded because of factors that could affect the lymphocyte count. Of the remaining 861 patients, 423 (49%) met the criteria for the diagnosis of CHF (mean age 76 +/- 7 years, 51% men), of whom 162 patients (38%) had a relative lymphocyte count < or = 20%. The 3-year all-cause mortality in patients with CHF and a relative lymphocyte count < or = 20% was 64% compared with 40% in patients with a relative lymphocyte count > 20% (P < .0001). The age- and sex-adjusted hazard ratio for death in patients with CHF and low relative lymphocyte count was 1.76 (95% confidence interval 1.34-2.32, P = .0001). After adjustment for baseline differences and variables associated with or known to affect lymphocyte count, the hazard ratio remained significantly different from 1.0 (hazard ratio 1.73, 95% confidence interval 1.21-2.48, P = .0026). CONCLUSION: A low relative lymphocyte count is an independent marker of poor prognosis in elderly patients with CHF. The relative lymphocyte count is a simple, accurate, widely available, and inexpensive marker that can help to identify elderly patients with CHF who are at increased risk for mortality. The pathophysiologic mechanism of this observation remains to be determined.

Hemodynamic profiles of advanced heart failure: association with clinical characteristics and long-term outcomes.

BACKGROUND: Classifying patients with advanced congestive heart failure (CHF) by baseline measures of congestion and perfusion has been used to estimate hemodynamic status and to select and titrate therapy. We describe clinical characteristics of 4 hemodynamic profiles-wet/cold, wet/warm, dry/cold, and dry/warm-in patients with advanced CHF and assess relations between symptoms, physical signs, and outcomes with each profile. METHODS AND RESULTS: We retrospectively assessed baseline symptoms, physical-examination variables, and 1-year outcomes of 440 patients in a randomized trial. With univariable and multivariable logistic regression, we examined relations of physical-examination variables to hemodynamic profiles. We also assessed the rates of death and death or readmission by profile. Severity of CHF symptoms did not predict the wet-versus-dry profile or cold-versus-warm status, despite significant differences in hemodynamics among groups. Of the physical-examination variables, only a lower proportional pulse pressure was a significant multivariable predictor of the wet category. Among wet patients (n = 348), this same variable was the only significant multivariable predictor of the cold category. For dry patients (n = 92), the cold category was predicted in multivariable analysis by supine heart rate and hepatomegaly. Survival was similar among profiles: wet/cold, 54.2% (n = 91); wet/warm, 58.3% (n = 105); dry/cold, 78.9% (n = 15); and dry/warm, 67.1%, P =.13 (n = 49). Event-free survival also was similar among profiles: wet/cold, 22.0% (n = 37); wet/warm, 29.4% (n = 53); dry/cold, 42.1% (n = 8); and dry/warm, 31.5%, P =.44 (n = 23). CONCLUSIONS: The patient's history and physical examination alone may lead to inaccurate estimation of hemodynamic status and thus suboptimal management for patients with advanced CHF.

Practical aspects of using beta-adrenergic blockade in systolic heart failure.

Heart failure exacts a severe human and public health toll. In the United States, heart failure afflicts approximately 5 million patients and is responsible for or contributes to 3 million hospitalizations and 300,000 deaths yearly. Physicians can have a major impact on this disease by using effective agents for the treatment of heart failure (particularly angiotensin-converting enzyme [ACE] inhibitors and beta blockers), yet the actual clinical use of these drugs (especially the use of beta blockers by primary physicians) is disappointingly low. Many physicians appear to be reluctant to prescribe beta blockers for two reasons. First, they are concerned about the potential interference of beta blockers with important compensatory mechanisms that support the failing heart and fear that such interference may lead to clinical deterioration. Second, they fail to identify patients with heart failure (especially those with mild or moderate symptoms) or regard such patients as being too well to require additional treatment. These reasons should no longer be used as excuses to avoid the use of these drugs, given the persuasive evidence that beta blockers can improve symptoms and prolong life in patients with heart failure. Instead, physicians must recognize that long-term activation of the sympathetic nervous system primarily exerts deleterious (rather than compensatory) effects in patients with heart failure and that these actions can be antagonized effectively and safely by the appropriate use of beta-blocking drugs.

Hemodynamics as surrogate end points for survival in advanced heart failure: an analysis from FIRST.

BACKGROUND: Hemodynamics often are used as surrogate end points in phase II trials of acute heart failure (HF). We reviewed the Flolan International Randomized Survival Trial (FIRST) database to identify the hemodynamic variables that best predict survival in patients with advanced HF receiving epoprostenol therapy and to determine whether hemodynamics could predict the overall effect of a drug. METHODS: The trial enrolled 471 patients with class IIIb/IV HF and ejection fraction or=3 months, all of whom underwent screening pulmonary artery catheter insertion. Patients were randomly assigned to receive either epoprostenol (n = 201) or placebo (n = 235); epoprostenol therapy was guided by pulmonary artery catheter measures, and standard treatment was guided by clinical findings. Multivariable modeling was used to identify and quantify the demographic, clinical, and hemodynamic variables most associated with 1-year survival. RESULTS: In multivariable modeling, HF class, decreased pulmonary capillary wedge pressure (PCWP), and age best predicted 1-year survival. After adjustment for age and HF class, decreased PCWP still significantly predicted survival (hazard ratio, 0.96 for every 1-mm Hg decrease; 95% confidence interval, 0.94 to 0.99; P = .003). Survival was significantly higher with decreases in PCWP >or=9 versus <9 mm Hg, even after adjustment for age and HF class. Survival of patients in the PCWP >or=9 group was comparable with, and that of the PCWP <9 group was significantly higher than, survival of patients in the control group (hazard ratio, 1.44; 95% confidence interval, 1.05 to 1.99; P = .024). CONCLUSIONS: The reduction in PCWP was the hemodynamic measure most predictive of survival in patients with advanced HF. However, patients with a >or=9-mm Hg decrease had no better survival than patients in the control group, who had limited changes in hemodynamics. Thus, improvement in hemodynamics may not predict the overall effect of a drug.

Simultaneous pancreas-kidney transplantation in the mycophenolate mofetil/tacrolimus era: evolution from induction therapy with bladder drainage to noninduction therapy with enteric drainage.

BACKGROUND: In the past, enteric drainage or the omission of induction immunotherapy has been shown to be predictive of suboptimal outcomes of simultaneous pancreas-kidney (SPK) transplantation. We have reassessed the need for bladder drainage and induction immunotherapy to optimize the outcome of SPK transplantation. METHODS: One hundred consecutive recipients of SPK transplants who received mycophenolate mofetil and tacrolimus immunosuppression were studied. The first 50 recipients had bladder-drained pancreas allografts and received induction immunotherapy. The results were compared with the next 50 recipients who had enteric-drained pancreas allografts, which included a subgroup (n = 17 patients) who were randomized to receive no induction immunotherapy. RESULTS: The 1-year actuarial patient, kidney, and pancreas survival rates in the bladder-drainage group were 98.0%, 94.0%, and 94.0%, respectively. The 1-year actuarial patient, kidney, and pancreas survival rates in the enteric-drainage group were 96.8%, 96.8%, and 89.4%, respectively. In the enteric-drainage group, the incidence of rejection at 1 year was 6.1% in recipients who received induction therapy versus 23.5% in recipients who did not receive induction therapy. The average number of readmissions per recipient was 1.8 in the bladder-drainage group versus 0.9 in the enteric-drainage group. CONCLUSIONS: Primary enteric drainage of the pancreas allograft in recipients of SPK transplantation is the preferred surgical technique in the tacrolimus/mycophenolate mofetil era.

Transthoracic and transesophageal echocardiography in the hemodynamic assessment of patients with congestive heart failure.

All methods for estimating the severity of heart failure, such as clinical and radiographic examination, measures of ventricular performance, and exercise capacity, when used independently, have major limitations. Echocardiography can be used, not only to assess left-ventricular ejection fraction but also other determinants of prognosis (i.e., left-ventricular size and shape, estimation of left atrial and pulmonary artery pressures, right side involvement). The availability of continuous-wave Doppler has permitted us to evaluate pulmonary artery systolic pressure from tricuspid regurgitation, and this contributes to additional powerful data. In long-standing heart failure, pulmonary artery wedge pressure is a predictor of survival, and aggressive therapy to reduce wedge pressure improves survival. Noninvasive estimation of left-atrial pressure and left-ventricular filling pressure have been attempted by continuous-wave Doppler echocardiography in patients with heart failure and mitral regurgitation and by tissue Doppler imaging at the mitral annulus level. A significant relation has been reported between profiles of pulmonary venous flow and left-atrial pressure, but pulmonary venous flow indexes can be better assessed by transesophageal echocardiography (TEE) in terms of detection rate. It has recently been recognized that TEE can provide valuable information on intracardiac hemodynamics and ventricular function. Two-dimensional evaluation of ventricular function and pulsed- and continuous-wave Doppler recordings from the pulmonary artery, pulmonary vein, and mitral inflow are combined to provide these data, which are both qualitative and quantitative, and permit estimation of ventricular ejection fraction, left-atrial pressure, and cardiac output. It would be important to be able to stratify patients with congestive heart failure according to groups with the highest risk for early death because heart transplantation or aggressive medical treatment could be specifically applied to this population. Serial echocardiographic evaluations of the classic variables of systolic left-ventricular function as well as Doppler transmitral flow may be useful in monitoring the progression of the disease and the effects of medical treatment. The degree of pulmonary hypertension is independently associated with the restrictive left-ventricular diastolic filling pattern and with the degree of functional mitral regurgitation. Future studies on the impact of these hemodynamic variables on the outcome of patients with left-ventricular dysfunction are desirable.

Rationale and design of the OPTIME CHF trial: outcomes of a prospective trial of intravenous milrinone for exacerbations of chronic heart failure.

BACKGROUND: The optimal management of an acute exacerbation of chronic heart failure (CHF) is uncertain. There is little randomized evidence available to support the various treatment strategies for patients hospitalized with an exacerbation of CHF. Inotropic agents may produce beneficial hemodynamic effects, and although they are currently used in these patients, their effect on clinical response and impact on clinical outcome is unclear. We present a unique and simple study designed to determine whether a treatment strategy for CHF exacerbations that includes an intravenous agent with inotropic properties can reduce hospital length of stay and lead to improved patient outcome. METHODS: The OPTIME CHF (Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure) trial is an ongoing multicenter, randomized, placebo-controlled trial of a treatment strategy for patients with acute exacerbations of CHF. The design of this study provides a novel approach to the evaluation of treatment strategies in the care of this population. The OPTIME CHF design uses early initiation of intravenous milrinone as both an adjunct to the best the medical therapy and to facilitate optimal dosing of standard oral therapy for heart failure. Patients with known systolic heart failure requiring hospital admission for a CHF exacerbation are randomly assigned within 48 hours of admission to receive a 48-hour infusion of either intravenous milrinone or placebo. The primary end point of this design is a reduction in the total hospital days for cardiovascular events within 60 days after therapy. Enrollment of 1000 patients began July 7, 1997, at 80 US centers and is projected to conclude in late 1999.

Effect of beta-blockade on the premature ventricular beats/heart rate relation and heart rate variability in patients with coronary heart disease and severe ventricular arrhythmias.

We examined the effects of beta-blockers on the associations between heart rate and number of premature ventricular beats (PVBs) and on heart rate variability and myocardial ischemia in patients with coronary heart disease. After 2 weeks of run-in placebo treatment, 18 patients with coronary artery disease were randomized to a 7-day treatment with either propranolol (40 mg) three times a day or placebo. During run-in and after 7 days of treatment, patients underwent 24-hour Holter monitoring and exercise tests. We analyzed the 24-hour Holter recordings with customized software that computes the correlation between heart rate and occurrence of PVBs. We also computed spectral measures of heart rate variability on the same recordings. Propranolol caused a significant decrease in the log-transformed total number of PVBs recorded over 24 hours and during the day. The number of PVBs was much lower during the night than during the day both after placebo and after propranolol. There were no differences between the two treatments. During the day, there was a positive correlation between heart rate and the number of PVBs in all 18 patients. The mean correlation coefficients between heart rate and number of PVBs increased significantly after propranolol treatment both during the 24-hour monitoring (p < 0.05) and during the day (p < 0.05). The night-recorded correlation coefficients between heart rate and number of PVBs were not significantly different in the placebo versus propranolol group. Propranolol significantly increased the total power during the day. Placebo caused a significant decrease in the low-frequency band (LF) and a significant increase in the high-frequency band (HF) during the night compared with the day. During the day, propranolol significantly reduced LF power and increased HF power, with respect to placebo. After propranolol treatment, the values of LF and HF power during the day were comparable to those recorded at night. The LF/HF ratio decreased significantly after propranolol treatment with respect to placebo in the day and became similar to that recorded during sleep. Propranolol significantly reduced heart rate and systolic blood pressure at rest and at peak exercise and reduced signs of myocardial ischemia. Propranolol administration reduces PVBs in patients with coronary artery disease and severe ventricular arrhythmias possibly through an improvement of cardiac autonomic regulation and through anti-ischemic effects, antiarrhythmic effects, or both.

Pancreas transplantation at Northwestern University.

The collective advances made by many groups have significantly improved the results of pancreas transplantation. We have focused on the development of safe and effective immunotherapy, including a new protocol of rapid withdrawal of corticosteroids, the analysis of surgical technique of pancreas exocrine drainage on outcome and the role of SPK transplantation in patients with significant cardiovascular disease. We have found that multimodal immunotherapy including induction with tacrolimus-based maintenance combined with either MMF or sirolimus, with or without corticosteroids, resulted in excellent patient and graft survival rates with low rates of rejection. In this setting, enteric drainage was preferable to bladder drainage because of a lower rate of complications leading to hospital readmissions. Careful pretransplant screening for cardiovascular disease should be routinely performed for all SPK candidates. If successful coronary revascularization can be achieved, these patients can safely undergo SPK transplantation, with 5-year outcomes similar to those for recipients without coronary disease. Finally, we have observed that pancreas transplantation has an important ameliorating effect on hypertension that is independent of the method of pancreas exocrine drainage.