The effect of body mass index on survival following heart transplantation: do outcomes support consensus guidelines?

OBJECTIVE: To determine the relationship between body mass index (BMI) at the time of transplant and posttransplant survival and morbidity. SUMMARY BACKGROUND DATA: The recent International Society for Heart and Lung Transplantation listing criteria for heart transplantation stated that candidates should achieve a BMI <30 kg/m-or percent ideal body weight <140%-before listing for cardiac transplantation. However, data to support these recommendations are limited and often conflicting. METHODS: United Network of Organ Sharing provided de-identified patient-level data. Analysis included 19,593 orthotopic heart transplant recipients aged >or=18 years and transplanted January 1 1995-December 31 2005. Follow-up data were provided through February 8, 2008. Recipients were stratified by BMI at the time of transplantation: BMI <18.5 (underweight), 18.5 to 24.99 (normal weight), 25 to 29.99 (overweight), 30 to 34.99 (obesity class I), and >or=35 (obesity class II/III). The primary outcome measure was post-transplant survival. RESULTS: Risk-adjusted median survival in the underweight, normal weight, overweight, obesity I, and obesity II/III groups was 8.31, 10.20, 10.03, 9.51, and 9.05 years, respectively. In multivariate Cox proportional hazards regression, BMI in the overweight (HR = 1.08, 0.99-1.17; P = 0.055) and obesity I (HR = 1.05, 0.99-1.12; P = 0.091) ranges were not associated with significantly diminished survival. However, BMI in the underweight (HR = 1.26, 1.11-1.43; P < 0.001) and obesity II/III (HR = 1.18, 1.01-1.38; P = 0.030) ranges were associated with diminished posttransplant survival. CONCLUSION: Findings from this analysis do not suggest that obesity I (BMI of 30-34.99) is associated with significantly higher morbidity and mortality. However, underweight and obesity II/III recipients have significantly higher morbidity and mortality compared with other groups.

Long-term effects of B-type natriuretic peptide infusion after acute myocardial infarction in a rat model.

INTRODUCTION: The effects of exogenous B-type natriuretic peptide (BNP) on postmyocardial infarction (MI) are not known. We tested the hypothesis that in vivo infusion of BNP would improve cardiac function and affect left ventricular (LV) remodeling in an experimental model of MI. METHODS: MI was induced by coronary ligation in rats and confirmed by echocardiography. 19 rats were randomized to 1 of 3 groups: sham (n = 7), MI + saline (n = 5), MI + BNP (400 ng.kg(-1).minute(-1)) (n = 7). Infusions were delivered for 7 days via venous catheters tunneled to an infusion pump. Rats were followed for 8 weeks. Echocardiography, hemodynamics, histology, and in vivo and ex vivo pressure-volume relationships were examined. RESULTS: LV systolic pressure, LV dP/dtmax, and infarct size improved with BNP treatment versus control MI group (132 +/- 4 vs.110 +/- 2 mm Hg, 8097 +/- 317 vs. 5816 +/- 378 mm Hg/s, 19.3% +/- 1.6% vs. 23.3% +/- 1.9%, respectively; all P < 0.05). Ex vivo end-diastolic pressure-volume relationship demonstrated reduced diastolic dysfunction after BNP therapy (P < 0.05 vs. control MI). Serum BNP levels confirmed delivery of BNP. CONCLUSIONS: We demonstrate beneficial effects on LV function and decreased LV remodeling with BNP infusion in an experimental model of acute MI.

Eight-year experience with minimally invasive cardiothoracic surgery.

BACKGROUND: Over the past decade, minimally invasive cardiac surgery (MICS) has emerged as an accepted approach for the management of cardiac disease that requires a surgical solution. We report the results of an 8-year, single-institution experience with MICS. METHODS: Between January 1, 2000 and December 31, 2007, a total of 910 patients underwent MICS. Major cases included aortic valve procedures (71, 7.8%), coronary artery bypass grafting (96, 10.5%), atrioseptal defect repair (103, 11.3%), and mitral valve procedures (507, 55.7%). Major outcomes of interest included the complication and mortality rates. RESULTS: The mean age of the patients was 57 +/- 15 years; the mean ejection fraction was 55% +/- 11%; and the mean body mass index was 26.1 +/- 4.9. Overall, 782 cases (85.9%) were performed through a mini-thoracotomy. Most of the cases were accomplished through central cannulation (765, 84.0%), and venous drainage was most commonly performed in a bicaval fashion (percutaneous superior vena cava and percutaneous inferior vena cava). The mean aortic cross-clamp and cardiopulmonary bypass (CPB) times were 58.1 +/- 44.9 and 101.9 +/- 66.8 min, respectively. Conversion to full sternotomy occurred in 10 patients, and the median length of stay in hospital was 6 days. The overall complication rate was 8.8%, and the 30-day mortality rate was 2.9%. In the multivariate logistic regression analysis, risk factors associated with in-hospital complications included age, CPB time, arterial cannulation location, conversion from off-CPB to on-CPB, hepatic insufficiency, and diabetes. In the multivariate hazards regression analysis, risk factors associated with mortality included postoperative stroke, renal failure, and sternal wound infection; CPB time; and previous surgery. CONCLUSIONS: In our experience, minimally invasive approaches are effective and reproducible for a variety of cardiac operations, with acceptable operating time durations, morbidity, and mortality.

Naringenin inhibits neointimal hyperplasia following arterial reconstruction with interpositional vein graft.

Vessels respond to injury by a healing process that includes the development of neointima. Stenosis secondary to neointima formation is the main cause of failure following arterial reconstructions. Vessel wall homeostasis is regulated by proinflammatory cytokines that affect smooth muscle cell proliferation, growth, migration, and death. We assessed the hypothesis that naringenin, a flavinoid possessing anti-inflammatory, antioxidant, and antiproliferative activities, reduces neointimal hyperplasia (NIH) following vascular injury.Arterial injury was created by interposition grafting of autologous right superficial epigastric vein graft into the right femoral artery (FA) in 48 male Sprague-Dawley rats. Following injury, the rats were divided into 4 groups (n = 12). Two groups were treated with naringenin (100 mg/kg intraperitoneal q daily) for 2 and 4 weeks each while 2 control groups received normal saline for the same durations. For Sham group (n = 10), the FA and vein were isolated without any additional procedure. Rats were killed at the end of treatment regimen in all groups, and FAs were harvested. Thickness of intima was measured in histologic sections, and levels of platelet derived growth factor (PDGF)-BB, TNFalpha, and Ki67 labeling index (Ki67 LI) were quantified in immunohistochemical analyses to assess the amount of NIH and mechanisms underlying its formation.Although there was no significant difference between the groups at 2 weeks, neointima thickness was lower in the naringenin treated group at 4 weeks (23.7 +/- 2.3 vs. 35.6 +/- 2.6 microm in control group; P < 0.001). The levels of PDGF-BB, and TNFalpha were lower in naringenin treated groups at both 2 weeks (PDGF-BB [0.21% +/- 0.03% versus 0.39% +/- 0.05% in control group, P < 0.001), TNFalpha (21.2% +/- 0.8% vs. 36.1% +/- 1.9% in control group, P < 0.001]) and 4 weeks (PDGF-BB [0.25% +/- 0.03% vs. 0.57% +/- 0.09% in control group, P < 0.001], TNFalpha [25.5% +/- 1.8% vs. 45.0% +/- 2.9% in control group, P < 0.001]). Ki67 LI was lower in naringenin treated groups at 2 weeks (13.9% +/- 2.8% vs. 18.7% +/- 3.7% in control group, P < 0.05), and at 4 weeks (17.5% +/- 2.6% vs. 31.1% +/- 4.7% in control group, P < 0.001), indicating a lower level of cellular proliferation.Naringenin reduces NIH following arterial reconstruction. This may be mediated by a decrease in PDGF-BB and TNFalpha levels and the resulting down-regulation of smooth muscle cells' migration and proliferation.

A pilot study to assess the effects of a guided imagery audiotape intervention on psychological outcomes in patients undergoing coronary artery bypass graft surgery.

Depression and anxiety are associated with increased risk of postoperative cardiac events and death in patients who have undergone coronary artery bypass graft surgery. These risks persist even several months after the procedure. Guided imagery has been used with cardiac surgery patients for some time and with numerous anecdotal reports of considerable benefit. In addition, this therapy is low-cost and easy to implement, and the literature holds ample evidence for its efficacy in symptom reduction in various patient populations. It was thus hypothesized that preoperative use of guided imagery would reduce postoperative distress in patients undergoing coronary artery bypass graft. Fifty-six patients scheduled to undergo coronary artery bypass graft at Columbia University Medical Center were randomized into 3 groups: guided imagery, music therapy, and standard care control. Patients in the imagery and music groups listened to audiotapes preoperatively and intraoperatively. All patients completed psychological, complementary medicine therapies use, and other assessments preoperatively and at 1 week and 6 months postoperatively. Only preoperative distress was predictive of postoperative distress at follow-up. Use of complementary medicine therapies was high in all groups and this fact, in addition to the small sample size, may have accounted for the lack of significant relationship between imagery and postoperative distress. Regardless, this complementary and alternative medicine therapy remains palatable to patients. Given its efficacy in other patient populations, it is worth exploring its potential utility for this population with a larger sample.

Prolonged effects of B-type natriuretic peptide infusion on cardiac remodeling after sustained myocardial injury.

B-type natriuretic peptide (BNP) is an established first-line therapy for acute decompensated heart failure (HF), but its efficacy in preventing left ventricular (LV) remodeling after myocardial injury is unknown. The goal of this study was to evaluate the effects of BNP therapy on remodeling after ischemic injury in an awake canine model. Dogs were chronically instrumented for hemodynamics. Ischemia was created by daily coronary embolization (Embo; 3.1 x 10(4) beads/day) for 3 wk; 60 min after the first embolization, BNP (100 ng x kg(-1) x min(-1); n = 6) or saline (control; n = 6) was continuously infused via a left atrial catheter for 3 wk. Hemodynamics and echocardiography were performed in an awake state at baseline, 3 wk after Embo + BNP infusion, and 4 wk after stopping Embo + BNP infusion. End-systolic elastance (E(es)) and LV change in pressure over time (dP/dt) were preserved throughout Embo + BNP therapy versus control therapy (E(es): 3.76 +/- 1.01 vs. 1.41 +/- 0.16 mmHg/ml; LV dP/dt: 2,417 +/- 96 vs. 2,068 +/- 95 mmHg/s; both P < 0.05 vs. control). LV end-diastolic dimension was significantly smaller in BNP-treated dogs compared with control dogs (4.29 +/- 0.10 vs. 4.77 +/- 0.17 cm), and ejection fraction was maintained in treated dogs vs. control dogs (53 +/- 1% vs. 46 +/- 2%) (both P < 0.05 vs. control). Cyclooxygenase (COX)-2 expression in terminal LV tissue was significantly reduced after BNP therapy. Treatment with continuous infusion of BNP preserved LV geometry, improved systolic function, and prevented the progression of systolic HF after persistent ischemic injury.

Feasibility and effectiveness of a brief meditation-based stress management intervention for patients diagnosed with or at risk for coronary heart disease: a pilot study.

Extensive research has led to the development of a psychobiological model of cardiovascular disease. This model suggests that psychological factors such as depression, anxiety, hostility, and stress may affect the development and progression of coronary heart disease (CHD). Recent studies have also demonstrated that meditation-based stress reduction programs are useful interventions for patients with various medical and psychological symptoms. The objective of this pilot study was to gather preliminary information regarding the feasibility of implementing a brief meditation-based stress management (MBSM) program for patients with CHD, and those at high risk for CHD, at a major metropolitan hospital that serves a predominately non-local patient population. The secondary aim of this study was to investigate the possibility that such an intervention might reduce depression, as well as perceived stress, anxiety, and hostility, while improving general health scores. The overall feasibility results indicate that this MBSM intervention was highly feasible with regard to both recruitment and retention of participants. In fact, 40% of patients requested further training. In addition, after completion of the 4-week intervention, participants reported significant reductions in depression and perceived stress. In conclusion, the present study demonstrated that the brief meditation-based stress management program was well-received by patients and can successfully be used as a supportive program for patients at risk or diagnosed with CHD.

Myocardial function improved by electromagnetic field induction of stress protein hsp70.

Studies on myocardial function have shown that hsp70, stimulated by an increase in temperature, leads to improved survival following ischemia-reperfusion (I-R). Low frequency electromagnetic fields (EMFs) also induce the stress protein hsp70, but without elevating temperature. We have examined the hemodynamic changes in concert with EMF pre-conditioning and the induction of hsp70 to determine whether improved myocardial function occurs following I-R injury in Sprague-Dawley rats. Animals were exposed to EMF (60 Hz, 8 microT) for 30 min prior to I-R. Ischemia was then induced by ligation of left anterior descending coronary artery (LAD) for 30 min, followed by 30 min of reperfusion. Blood and heart tissue levels for hsp70 were determined by Western blot and RNA transcription by rtPCR. Significant upregulation of the HSP70 gene and increased hsp70 levels were measured in response to EMF pre-exposures. Invasive hemodynamics, as measured using a volume conductance catheter, demonstrated significant recovery of systolic contractile function after 30 min of reperfusion following EMF exposure. Additionally, isovolemic relaxation, a measure of ventricular diastolic function, was markedly improved in EMF-treated animals. In conclusion, non-invasive EMF induction of hsp70 preserved myocardial function and has the potential to improve tolerance to ischemic injury.

The cost of medical management in advanced heart failure during the final two years of life.

OBJECTIVE: To examine patterns of resource use and the cost of care for patients with advanced heart failure treated with medical management (MM) during the final 2 years of life. METHODS AND RESULTS: The study population (n=47, mean age 70.4 years+/-7.06) included patients randomized to the MM arm of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. Inpatient and outpatient use data were obtained from the clinical dataset and Centers for Medicare and Medicaid Services (beginning January 1, 1998). Cost and resource use were tracked from the date of death (t(d)) backward in 3-month intervals (eg, t(d-1), t(d-2)). In the primary analysis, costs were summed across intervals. The mean cost of MM in the final 2 years of life was $156,169, with 50.5% ($78,880.39) expended in the final 6 months. The mean quarterly cost increased (P < .01) 4.9-fold from t(d-8) ($8,816 +/- $14,270) to t(d-1) ($42,836 +/- $41,407). The number of inpatient days increased (P < .01) 6.6-fold from 3.8+/-4.7 days to 22.2+/-23.5 days during the same time intervals. CONCLUSION: This current economic analysis extends on previous findings by demonstrating that medical therapy in advanced and end-stage heart failure is associated with significant costs and resource consumption; these costs and resource consumption increase significantly as death approaches.

Risk analysis of deep sternal wound infections and their impact on long-term survival: a propensity analysis.

The objectives of this study are to determine risk factors associated with deep sternal wound infections (DSWIs) following cardiac surgery, and to describe their impact on long-term survival. Data was obtained from a departmental database. Analysis included 7,978 consecutive patients who underwent cardiac surgery between 1997 and 2003. To identify risk factors for DSWI, regression analysis was performed. The probability scores obtained from logistic regression were used for propensity analysis of 2 groups. Kaplan-Meier analysis with log-rank test and Cox proportional hazard models were then used in survival analysis. DSWI developed in 123 of 7,978 patients (1.5%). Preoperative predictors of DSWI were body mass index >30 kg/m(2) (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.4; P < 0.05), diabetes mellitus (OR, 2.4; 95% CI, 1.6 to 3.4; P < 0.001), urgent operation (OR, 1.7; 95% CI, 1.2 to 2.6; P < 0.05), smoking history within past year (OR, 2.7; 95% CI, 1.5 to 4.9; P < 0.001), smoking history within past 2 weeks (OR, 2.6; 95% CI, 1.5 to 4.5; P < 0.001), and a history of stroke (OR, 1.9; 95% CI, 1.1 to 3.1; P < 0.005). In addition, total length of hospital stay (OR, 1.01; 95% CI, 1.01 to 1.02; P < 0.05) and sepsis and/or endocarditis following surgery (OR, 5.1; 95% CI, 2.9 to 9.0; P < 0.001) were also predictive of DSWI. Patients with DSWI had a prolonged total length of hospital stay (40.3 days versus 16.1 days; P < 0.001), and higher 30-day mortality (1.6% versus 7.3% in DSWI group, P < 0.05). There were no differences between groups in 4-year and 8-year survival rates, with 77.2% and 61.8%, respectively, in patients with DSWI compared with 78.0% and 67.5% in patients without DSWI (P = 0.16). After adjustments for preoperative, intraoperative, and postoperative factors, the adjusted hazard ratio of long-term mortality for patients with DSWI was 0.9 (95% CI, 0.6 to 1.2, P = 0.39). Though DSWIs are associated with increased early mortality, patients undergoing cardiac surgery complicated by DSWI do not experience worse long-term survival.

Survival after heart transplantation is not diminished among recipients with uncomplicated diabetes mellitus: an analysis of the United Network of Organ Sharing database.

BACKGROUND: This study compares posttransplantation outcomes of survival and morbidity among recipients with and without diabetes mellitus (DM). METHODS AND RESULTS: The United Network of Organ Sharing (UNOS) provided deidentified patient-level data. Primary analysis focused on 20,412 first-time heart transplant recipients aged > or = 18 years who underwent transplantation between January 1, 1995, and December 31, 2005. To determine severity of DM, DM recipients were stratified by their aggregate number of diabetes-related complications (DRCs), including pretransplantation history of renal failure (serum creatinine = 2.5 mg/dL), peripheral vascular disease, cerebrovascular accident, and severe obesity (body mass index > or = 35 kg/m2). Kaplan-Meier analysis was performed to compare time to event. Although posttransplantation survival was significantly better (P<0.001) among patients without DM (median survival 10.1 years) than among those with DM (9.0 years), survival did not differ (P=0.08) between those without DM (10.1 years) and those with uncomplicated DM (0 DRCs; 9.3 years). Among those with DM, survival was worse with each additional DRC: 0 DRC, 9.3 years; 1 DRC, 6.7 years; and > or = 2 DRCs, 3.6 years. Although acute rejection and transplant coronary artery disease-free survival did not differ between groups, renal failure and severe infection-free survival were worse in those with DM and were inversely related to the number of DRCs. CONCLUSIONS: Posttransplantation survival among patients with uncomplicated DM was not significantly different than that among nondiabetics. However, when stratified by disease severity, recipients with more severe diabetes had significantly worse survival than nondiabetics. Therefore, although DM alone should not be a contraindication to heart transplantation, given the critical shortage of transplantable organs, maximal benefit may be achieved by exploring alternative treatment options in patients with severe DM. These include use of high-risk transplant lists and destination therapy.

Effect of passive cardiac containment on ventricular synchrony and cardiac function in awake dogs.

OBJECTIVE: Passive restraint of the left ventricle (LV) has been shown to have beneficial effects on acute hemodynamics and reverse remodeling in both animal and human models. The goals of this study were to test whether a left ventricular support device (LVSD) improves LV synchrony and/or affects cardiac performance. METHODS: Ten dogs were chronically instrumented to measure hemodynamics and LV volume (sonomicrometry). Congestive heart failure (CHF) was induced by repeated intracoronary microembolization via a chronically implanted coronary catheter. The LVSD was implanted after establishment of CHF in five animals, and five animals were observed as controls. All animals were then observed for 8 weeks. A mathematical model to measure LV synchrony was used to evaluate LV motion over time. RESULTS: Mean arterial pressure and LV pressures was significantly increased after LVSD therapy, and LV pressure-volume relationships were shifted leftwards, although no change was seen in ejection fraction, end-systolic elastance, or LV dP/dt versus control. There was no significant change in diastolic function in LVSD animals compared with control animals. End-diastolic volumes were reduced by 15% after 8 weeks with LVSD treatment, versus an increase of 8% in control animals (p<0.05). Synchrony was significantly improved with LVSD therapy compared with control (9% vs 76% of baseline) in 1 of 11 ventricular dimension axes (Anterior-Apex). CONCLUSIONS: LVSD therapy provided only minimal improvement in ventricular synchrony and partially improved hemodynamics. Further study into mechanisms of benefit are warranted.

Patient-specific characteristics determine success of surgical atrial fibrillation ablation in patients with persistent atrial fibrillation.

Surgical atrial fibrillation ablation (SAFA) has not achieved the efficacy of Cox's original maze procedure, although technical improvements continue to be made. It is possible that biologic factors determine SAFA success. Therefore we examined how patient-specific characteristics affected SAFA success in 353 atrial fibrillation (AF) patients who underwent SAFA at a single institution. Among these, 257 (72.8%) had continuous AF and 96 (27.2%) had intermittent AF. For 297 patients (84.1%) postoperative follow-up was > 3 months. We compared SAFA success in patients whose procedure involved only pulmonary vein isolation with those whose procedure involved extensive lesion sets. Multivariate analysis included AF duration, left atrial size, preoperative atrial flutter, concomitant procedures, lesion sets, and energy source. Early SAFA success was classified as freedom from AF between postoperative months 3 and 6, and intermediate success between postoperative months 6 and 12. Receiver-operating characteristic (ROC) curves and stratum-specific likelihood ratios (SSLR) were generated to compare intermediate failure by left atrial size (LAS) thresholds. SAFA was more successful in the intermittent than the continuous AF group (n = 66, 86% vs n = 165, 71%; P = .014). When pulmonary vein isolation was compared only to more extensive lesion sets, there was no difference in success in the intermittent (34, 91% vs 32, 81%; P = .24) or continuous groups (67, 73% vs. 98, 69%; P = .603). Success for intermittent AF patients was not correlated with variables considered; in continuous AF patients, predictors included presence of concomitant mitral valve repair/replacement (P = .075), decreasing LAS (P = .025) and absence of preoperative atrial flutter (P = .001). In the continuous AF group, ROC curves and corresponding areas under the curve (AUC) were 0.60 (0.50-0.71) for failure at 6 months to 1 year. SSLR analysis generated 2 strata for LAS: < 8 cm with SSLR = 0.87 (0.74-1.0) and < or = 8 cm SSLR = 2.98 (1.07-8.3). In patients with intermittent AF, SAFA achieved acceptable results regardless of tested preoperative and intraoperative variables. In continuous AF, patient-specific characteristics affected success more than intraoperative variables. Failure was more than 3-fold greater in continuous AF patients with an LAS < or = 8 cm. In both patient types, more extensive lesion sets were not shown to improve outcomes. Future improvements in SAFA may depend on pharmacologic and/or surgical substrate modification.

Surgery for myocardial salvage in acute myocardial infarction and acute coronary syndromes.

This article addresses the pathophysiology, the treatment options, and their rationale in the setting of life-threatening acute myocardial infarction and acute on chronic ischemia. Although biases may exist between cardiologists and surgeons, with this review, we hope to provide the reader with information that will shed light on the options that best suit the individual patient in a given set of circumstances.

Coronary artery bypass grafting in patients with low ejection fraction.

BACKGROUND: Patients with low ejection fraction (EF) are at a higher risk for postoperative complications and mortality. Our objective was to assess the effect of low EF on clinical outcomes after coronary artery bypass grafting (CABG). METHODS AND RESULTS: We analyzed 55,515 patients from New York State database who underwent CABG between 1997 and 1999. Patients were stratified into 1 of the 4 EF groups: Group I (EF< or =20%), Group II (EF 21% to 30%), Group III (EF 31% to 40%), and Group IV (EF>40%). History of previous myocardial infarction, renal failure, and congestive heart failure were higher in patients with low EF (all P<0.001). Group I experienced a higher incidence of postoperative respiratory failure (10.1% versus 2.9%), renal failure (2.5% versus 0.6%), and sepsis (2.5% versus 0.6%) compared with Group IV. In-hospital mortality was significantly higher in Group I (6.5% versus 1.4%; P<0.001). Multivariate analysis showed hepatic failure [odds ratio (OR), 11.2], renal failure (OR, 4.1), previous myocardial infarction (OR, 3.4), reoperation (OR, 3.4), emergent procedures (OR, 3.2), female gender (OR, 1.7), congestive heart failure (OR, 1.6), and age (OR, 1.04) as independent predictors of in-hospital mortality in the low EF group. The discharges to home rate were significantly lower in Group I versus Group IV (73.1% and 87.7%, respectively; P<0.001). CONCLUSIONS: Patients with low EF are sicker at baseline and have >4 times higher mortality than patients with high EF. However, outcomes are improving over time and are superior to historical data. Therefore, CABG remains a viable option in selected patients with low EF.

Mechanical unloading during left ventricular assist device support increases left ventricular collagen cross-linking and myocardial stiffness.

BACKGROUND: Left ventricular assist devices (LVADs) induce reverse remodeling of the failing heart except for the extracellular matrix, which exhibits additional pathophysiological changes, although their mechanisms and functional consequences are unknown. METHODS AND RESULTS: Hearts were obtained at transplant from patients with idiopathic dilated cardiomyopathy (DCM) not requiring LVAD support (n=30), patients requiring LVAD support (n=16; LVAD duration, 145+/-33 days), and 5 nonfailing hearts. Left (LV) and right ventricular (RV) ex vivo pressure-volume relationships were measured, and chamber and myocardial stiffness constants were determined. Myocardial tissue content of total and cross-linked collagen, collagen types I and III, MMP-1, MMP-9, TIMP-1, and angiotensin (Ang) I and II were measured. LV size, mass, and myocyte diameter decreased after LVAD compared with DCM without LVAD (P<0.05). Total and cross-linked collagen and ratio of type I to III collagen increased in DCM compared with nonfailing hearts and increased further after LVAD (P<0.05 versus DCM and nonfailing). Concomitantly, chamber and myocardial stiffness increased with LVAD. The ratio of MMP-1 to TIMP-1 increased in DCM and almost normalized after LVAD, favoring decreased collagen degradation. Tissue Ang I and II also increased during LVAD. There was no significant change in the RV of LVAD-supported heart compared with DCM. CONCLUSIONS: LVAD support increases LV collagen cross-linking and the ratio of collagen type I to III, which is associated with increased myocardial stiffness. Decreased tissue MMP-1-to-TIMP-1 ratio (decreased degradation) and increased Ang levels (stimulants of synthesis) are likely mechanisms for these changes. Lack of significant effects on the RV suggest that hemodynamic unloading of the LV (not provided to the RV) might be the primary factor that regulates these extracellular matrix changes.

Left ventricular assist device support normalizes left and right ventricular beta-adrenergic pathway properties.

OBJECTIVES: We hypothesized that some aspects of left ventricular assist device (LVAD) reverse remodeling could be independent of hemodynamic factors and would primarily depend upon normalization of neurohormonal milieu. BACKGROUND: The relative contributions of LVAD-induced hemodynamic unloading (provided to the left ventricle [LV]) and normalized neurohormonal milieu (provided to LV and right ventricle [RV]) to reverse remodeling are not understood. METHODS: Structural and functional characteristics were measured from hearts of 65 medically managed transplant patients (MED), 30 patients supported with an LVAD, and 5 nonfailing donor hearts not suitable for transplantation. RESULTS: Compared with MED patients, diastolic pulmonary pressures trended lower (p < 0.01) and cardiac output higher (p < 0.001) in LVAD patients; V(30) (ex vivo ventricular volume yielding 30 mm Hg, an index of ventricular size) in LVAD patients was decreased in the LV (p < 0.05) but did not change significantly in RV. The LVAD support improved force generation in response to beta-adrenergic stimulation in isolated LV (increase in developed force from 6.3 +/- 0.6 to 18.5 +/- 4.4 mN/m(2), p < 0.01) and RV (increase in developed force, from 10.9 +/- 2.0 to 20.5 +/- 3.1 mN/m(2), p < 0.05) trabeculae. The LVAD patients had higher myocardial beta-adrenergic receptor density in LV (p < 0.01) and RV (p < 0.01). Protein kinase A (PKA) hyperphosphorylation of the ryanodine receptor 2 (RyR2)/calcium release channel was significantly reduced by LVAD in both RV and LV (p < 0.01). CONCLUSIONS: Improved beta-adrenergic responsiveness, normalization of the RyR2 PKA phosphorylation, and increased beta-adrenergic receptor density in LV and RV after LVAD support suggest a primary role of neurohormonal environment in determining reverse remodeling of the beta-adrenergic pathway.

Epicardial cardiac ablation using laser energy.

We describe epicardial ablation using a new device that utilizes 980 nm wavelength laser energy. The device can be used in both open and minimally invasive approaches and should make ablation therapy safe, effective, and easy to use.

Off-pump epicardial atrial fibrillation surgery utilizing a novel bipolar radiofrequency system.

BACKGROUND: Over the past several years, pulmonary vein isolation for the treatment of atrial fibrillation has gained significant popularity. This study was undertaken to evaluate a novel radiofrequency (RF)-enabled clamp system designed to create transmural lesions epicardially on the beating heart using bipolar RF. METHODS: A set of differently shaped clamps modified to deliver bipolar RF energy were used to create a series of lesions in a beating heart canine model. The pulmonary veins and atrial appendages of 6 dogs were electrically isolated using bipolar RF energy. The right and left atrial appendages served as controls for the right and left pulmonary veins, respectively. Temperature-controlled RF energy was delivered to maintain a tissue temperature of 80 degrees C for 15 seconds. Electrical isolation was assessed acutely and after 4 weeks by a bipolar pacing protocol. RESULTS: A total of 24 circumferential lesions were created. By pacing analysis, 100% (24/24) of these lesions were electrically isolated acutely and 95% (19/20) were still isolated 4 weeks later. At 4 weeks, 92% (22/24) of lesions were transmural by histologic analysis, and 96% (23/24) demonstrated endocardial continuity. One animal experienced a fatal cardiac arrhythmia during initiation of the post-survival procedure, prior to electrophysiologic evaluation, accounting for the reduced number of potential electrically isolated lesions. CONCLUSION: Bipolar RF ablation utilizing a novel bipolar RF clamp device results in electrical isolation and histologic transmurality in an off-pump epicardial model.

Radiofrequency and microwave energy sources in surgical ablation of atrial fibrillation: a comparative analysis.

BACKGROUND: Due to its complexity and risk of bleeding, the Maze III procedure has been largely replaced by surgical ablation for atrial fibrillation (AF) using alternative energy sources. Radiofrequency (RF) and microwave (MW) are the most commonly used energy forms. In this study, we sought to compare these energy modalities in terms of clinical outcomes. METHODS: Two hundred five patients underwent surgical ablation of AF, from October 1999 to May 2004 at our institution via an endocardial approach. Patients were categorized into 2 groups: RF and MW. Baseline characteristics, operative details, and clinical outcomes were compared between the 2 groups. Rhythm success was defined as freedom from AF and atrial flutter as determined by postoperative electrocardiograms. RESULTS: One hundred twenty patients (58.5%) were ablated using RF, whereas 85 (41.5%) were ablated with MW. Most of the patients had persistent AF in both the RF and MW groups (85.7% versus 80.0%, respectively; P = .363). Intraoperative left atrial size was 6.4 +/- 1.7 cm for the RF group and 6.4 +/- 1.7 cm for the MW group (P = .820). Postoperative rhythm success at 6 and 12 months was 72.4% versus 71.4% (P +/- .611) and 75.0% versus 66.7% (P = .909) for the RF and MW groups, respectively. Hospital length of stay was comparable for both groups (15.4 +/- 14.0 versus 13.3 +/- 13.9 days; P = .307). Postoperative survival at 6 months, 1 year, and 3 years was 90.4%, 89.5%, and 86.1% for RF patients compared to 87.9%, 86.5%, and 84.4% for MW patients, respectively (log rank P = .490). CONCLUSIONS: RF and MW energy forms yield comparable postoperative rhythm success, hospital length of stay, and postoperative survival. Both sources are rapid, safe, and effective alternatives to "cut and sew" techniques for surgical treatment of AF.