Paul J. Hendry

Long-term follow-up of Thoratec ventricular assist device bridge-to-recovery patients successfully removed from support after recovery of ventricular function.

BACKGROUND In certain forms of severe heart failure there is sufficient improvement in cardiac function during ventricular assist device (VAD) support to allow removal of the device. However, it is critical to know whether there is sustained recovery of the heart and long-term patient survival if VAD bridging to recovery is to be considered over the option of transplantation. METHODS To determine long-term outcome of survivors of VAD bridge-to-recovery procedures, we retrospectively evaluated 22 patients with non-ischemic heart failure successfully weaned from the Thoratec left ventricular assist device (LVAD) or biventricular assist device (BVAD) after recovery of ventricular function at 14 medical centers. All patients were in imminent risk of dying and were selected for VAD support using standard bridge-to-transplant requirements. There were 12 females and 10 males with an average age of 32 (range, 12-49). The etiologies were 12 with myocarditis, 7 with cardiomyopathies (4 post-partum [PPCM], 1 viral [VCM], and 2 idiopathic [IDCM]), and 3 with a combination of myocarditis and cardiomyopathy. BVADs were used in 13 patients and isolated LVADs in 9 patients, for an average duration of 57 days (range, 11-190 days), before return of ventricular function and successful weaning from the device. Post-VAD survival was compared with 43 VAD bridge-to-transplant patients with the same etiologies who underwent cardiac transplantation instead of device weaning. RESULTS Nineteen of the 22 patients are currently alive. Three patients required heart transplantation, 1 within 1 day, 2 at 12 and 13 months post-weaning, and 2 died at 2.5 and 6 months. The remaining 17 patients are alive with their native hearts after an average of 3.2 years (range, 1.2-10 years). The actuarial survival of native hearts (transplant-free survival) post-VAD support is 86% at 1 year and 77% at 5 years, which was not significantly different (p = 0.94) from that of post-VAD transplanted patients, also at 86% and 77%, respectively. CONCLUSIONS Long-term survival for bridge-to-recovery with VADs for acute cardiomyopathies and myocarditis is equivalent to that for cardiac transplantation. Recovery of the native heart, which can take weeks to months of VAD support, is the most desirable clinical outcome and should be actively sought, with transplantation used only after recovery of ventricular function has been ruled out.

Preoperative and postoperative comparison of patients with univentricular and biventricular support with the thoratec ventricular assist device as a bridge to cardiac transplantation

OBJECTIVES The goal of this study was to determine whether there are differences in populations of patients with heart failure who require univentricular or biventricular circulatory support. METHODS Two hundred thirteen patients who were in imminent risk of dying before donor heart procurement and who received Thoratec left (LVAD) and right (RVAD) ventricular assist devices at 35 hospitals were divided into three groups: group 1 (n = 74), patients adequately supported with isolated LVADs; group 2 (n = 37), patients initially receiving an LVAD and later requiring an RVAD; and group 3 (n = 102), patients who received biventricular assistance (BiVAD) from the beginning. RESULTS There were no significant differences in any preoperative factors between the two BiVAD groups. In the combined BiVAD groups, pre-VAD cardiac index (BiVAD, 1.4 +/- 0.6 L/min per square meter, vs LVAD, 1.6 +/- 0.6 L/min per square meter) and pulmonary capillary wedge pressure (BiVAD, 27 +/- 8 mm Hg, vs LVAD, 30 +/- 8 mm Hg) were significantly lower than those in the LVAD group, and pre-VAD creatinine levels were significantly higher (BiVAD, 1.9 +/- 1.1 mg/dl, vs LVAD, 1.4 +/- 0.6 mg/dl). In addition, greater proportions of patients in the BiVAD groups required mechanical ventilation before VAD placement (60% vs 35%) and were implanted under emergency conditions than in the LVAD group (22% vs 9%). The survival of patients through heart transplantation was significantly better in patients who had an LVAD (74%) than in those who had BiVADs (58%). However, there were no significant differences in posttransplantation survival through hospital discharge (LVAD, 89%; BiVAD, 81%). CONCLUSION Patients who received LVADs were less severely ill before the operation and consequently were more likely to survive after the operation. As the severity of illness increases, patients are more likely to require biventricular support.

Positron emission tomography and recovery following revascularization (PARR-1): the importance of scar and the development of a prediction rule for the degree of recovery of left ventricular function.

OBJECTIVES The aim of this study was to determine whether the extent of viability or scar is important in the amount of recovery of left ventricular (LV) function, and to develop a model for predicting recovery after revascularization that could be tested in a randomized trial. BACKGROUND F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) is used to define viable myocardium in patients with coronary artery disease (CAD) and severe LV dysfunction and to guide revascularization decisions. Whether this approach improves clinical outcomes has not been tested in a randomized trial. Before doing so, an objective model for prediction of recovery is required. METHODS A total of 82 patients with CAD and an ejection fraction (EF) < or =35% had FDG PET perfusion imaging before revascularization. Complete follow-up was available on 70 patients (86%). Patients had radionuclide angiograms at baseline and three months post-revascularization. RESULTS Diabetes (p = 0.029), time to operation (p = 0.008), and scar score (p = 0.001) were significant independent predictors of the change in EF. Previous coronary artery bypass graft confounded the effect of age. There was a significant interaction between the perfusion tracer used and mismatch score (p = 0.02). The multivariable prediction model incorporating PET and clinical variables had a goodness of fit with p = 0.001. Across tertiles of scar scores (I, small: 0% to 16%; II, moderate: 16% to 27.5%; III, large: 27.5% to 47%), the changes in EFs were 9.0 +/- 1.9%, 3.7 +/- 1.6%, and 1.3 +/- 1.5% (p = 0.003: I vs. III), respectively. CONCLUSIONS In patients with severe LV dysfunction, the amount of scar was a significant independent predictor of LV function recovery after revascularization. A combination of PET and clinical parameters predicts the degree of recovery. This model is being applied in a large randomized controlled trial to determine the effectiveness of therapy guided by FDG PET.

Discoordinate Modulation of Natriuretic Peptides During Acute Cardiac Allograft Rejection in Humans

BACKGROUND Increased circulating levels of the cardiac polypeptide hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) may be observed after orthotopic cardiac transplantation. Both the hypertrophic and inflammatory processes in the allograft may contribute to this increase, but no mechanistic explanation has been suggested for this observation. METHODS AND RESULTS Plasma immunoreactive ANF and BNP determinations were performed in 10 consecutive transplant patients. These were correlated with degree of rejection as reflected by histopathological findings at serial endomyocardial biopsies. Three patients had associated hemodynamic measurements and blood samples 24 hours before and after transplantation. All rejection episodes that received treatment were accompanied by a marked increase in BNP plasma levels to > approximately 400 pg/mL. Steadily increasing BNP levels preceded overt rejection as assessed by histopathological criteria. The increase in plasma BNP was not always accompanied by an increase in ANF, which suggests the specific upregulation of BNP gene expression during acute rejection episodes. Treatment of the acute rejection episodes led to a substantial decrease of BNP plasma levels. CONCLUSIONS The significant selective increase in plasma BNP levels found in the present study has not been previously described. This finding provides a new insight into the mechanism of allograft rejection and the modulation of natriuretic peptide synthesis and release. Furthermore, although preliminary, the data suggest that BNP plasma levels could form the basis for a new, noninvasive screening test to predict acute cardiac allograft rejection. Because treatment with the antilymphocyte monoclonal antibody OKT3 (murine monoclonal antibody to the CD3 antigen of the human T-cell) decreased BNP plasma levels, cytokine production by T-cells may mediate the selective increase in circulating BNP.

Very Long-Term Survival Implications of Heart Valve Replacement With Tissue Versus Mechanical Prostheses in Adults <60 Years of Age

Background— Several centers favor replacing a diseased native heart valve with a tissue rather than a mechanical prosthesis, even in younger adult patients. However, long-term data supporting this approach are lacking. We examined the survival implications of selecting a tissue versus a mechanical prosthesis at initial left-heart valve replacement in a cohort of adults <60 years of age who were followed for over 20 years. Methods and Results— Comorbid and procedural data were available from 6554 patients who underwent valve replacement at our institution over the last 35 years. Of these, 1512 patients contributed follow-up data beyond 20 years, of whom 567 were adults <60 years of age at first left-heart valve operation (mean survivor follow-up, 24.0±3.1 years). Late outcomes were examined with Cox regression. Valve reoperation, often for prostheses that are no longer commercially available, occurred in 89% and 84% of patients by 20 years after tissue aortic and mitral valve replacement, respectively, and was associated with a mortality of 4.3%. There was no survival difference between patients implanted with a tissue versus a mechanical prosthesis at initial aortic valve replacement (hazard ratio 0.95; 95% CI: 0.7, 1.3; P=0.7). For mitral valve replacement patients, long-term survival was poorer than after aortic valve replacement (hazard ratio 1.4; 95% CI: 1.1, 1.8; P=0.003), but again no detrimental effect was associated with use of a tissue versus a mechanical prosthesis (hazard ratio 0.9; 95% CI 0.5, 1.4; P=0.5). Conclusions— In our experience, selecting a tissue prosthesis at initial operation in younger adults does not negatively impact survival into the third decade of follow-up, despite the risk of reoperation.

Increasing benefit from revascularization is associated with increasing amounts of myocardial hibernation: a substudy of the PARR-2 trial.

OBJECTIVES We sought to determine: 1) whether F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) parameters identify high-risk patients who gain benefit from revascularization; 2) whether there is a cut point for such benefit; and 3) predictors of outcome in patients with severe left ventricular (LV) dysfunction due to coronary artery disease. BACKGROUND Patients with ischemic LV dysfunction might benefit from revascularization but not without risk. The FDG PET imaging can detect viable myocardium that recovers after revascularization. In the PARR-2 (PET and Recovery Following Revascularization-2) trial, FDG PET imaging showed a nonsignificant trend for improved outcome compared with standard care. Understanding the predictors of outcome from this prospective trial should help better identify patients at risk and which patients most benefit from revascularization. METHODS This post hoc analysis included 182 patients with left ventricular ejection fraction (LVEF) <35% and coronary artery disease, being considered for revascularization work-up, and randomized to the PET arm of PARR-2. The primary outcome was a composite of cardiac death, myocardial infarction, or cardiac repeat hospital stay at 1 year. RESULTS There is an interaction between PET mismatch and protocol revascularization such that higher mismatch, when combined with revascularization, yields fewer primary outcome events (p = 0.02). On the basis of adjusted Cox modeling, with reduced mismatch (<7%), the risk is not significantly different with or without revascularization. As mismatch increases above this mark, risk is reduced with revascularization. Increasing creatinine (for a 10-mumol/l increase: hazard ratio: 1.03, 95% confidence interval: 1.01 to 1.06, p = 0.010) is also associated with increased risk, whereas decreasing LVEF (for a 2% decrease: hazard ratio: 1.08, 95% confidence interval: 0.99 to 1.18, p = 0.087) trends toward an association with increased risk. CONCLUSIONS In this post hoc analysis, patients with ischemic cardiomyopathy with larger amounts of mismatch have improved outcome with revascularization. Renal function was also an independent predictor of outcome. The FDG PET seems to define high-risk patients that gain benefit from revascularization. (PET and Recovery Following Revascularization [PARR 2]; NCT00385242).

A randomized evaluation of simulation training on performance of vascular anastomosis on a high-fidelity in vivo model: The role of deliberate practice

OBJECTIVES There is mounting evidence supporting the benefit of surgical skills practice in a simulated environment. However, the use of simulation in cardiac surgical training has been limited. The purpose of the current trial was to examine the effect of independent and deliberate simulator practice, during nonclinical time, on the performance of an end-to-side microvascular anastomosis in an in vivo model. METHODS This single-blinded, randomized controlled trial received institutional review board approval. Thirty-nine first- and second-year surgical trainees were randomized to an expert-guided tutorial on a procedural trainer or to the expert-guided tutorial combined with self-directed practice on the same procedural trainer. Self-directed practice consisted of 10 anastomoses performed on the procedural trainer: a low-fidelity, commercially available bench model using 4-mm polytetrafluoroethylene graft as simulated blood vessel. Two weeks after the tutorial, subjects performed an end-to-side anastomosis in a live porcine model, under realistic operating room conditions. Assessment of outcomes was performed by 2 blinded, expert observers, uings validated measurements of technical skill. The primary outcome was the score on the Objective Structured Assessment of Technical Skill (OSATS) scale. Secondary outcomes included an anastomosis-specific end-product evaluation and time to completion. Statistical analysis was conducted using nonparametric, univariate techniques. RESULTS Compared with residents who received expert-guided simulator training alone, those who in addition practiced on a simulator independently after hours scored significantly higher on the OSATS scale (23.7 ± 4.7 vs 18.5 ± 3.9, P = .003). Residents who practiced independently also scored significantly higher on the end-product evaluation (11.4 ± 3.2 vs 8.9 ± 2.1, P = .02) and performed the anastomosis significantly faster (777 seconds vs 977 seconds, P = .04). Interrater reliability was high between the expert observers (intraclass correlation coefficient = 0.8). CONCLUSIONS Residents who had the opportunity for self-directed simulator practice performed an end-to-side anastomosis more adeptly, more quickly, and with a higher quality end product. The results of this randomized trial suggest that independent training on a procedural trainer did transfer to improved performance in an operating room environment. Simulator training should be incorporated into cardiovascular surgical curricula and residents should have access to this modality for independent after-hours practice to improve operating room performance.

Giant cell myocarditis: clinical presentation, bridge to transplantation with mechanical circulatory support, and long-term outcome

BACKGROUND The multicenter Giant Cell Myocarditis Registry recorded 64 cases from 36 centers before 1996. The median transplant-free survival of 30 patients without immunosuppression was 3 months. Of 34 patients who received heart transplantations, 9 experienced recurrence of giant cell myocarditis in their transplanted hearts and 1 patient died. METHODS We reviewed our experience in 340 heart transplantations since 1984. Unexpected giant cell myocarditis was found in the explanted hearts of 7 patients (6 men and 1 female, aged 18-65 years). RESULTS The duration from the onset of symptoms to assist-device implant or transplantation ranged from 11 days to 9 years, whereas the time interval from referral or deterioration ranged from 2 days to 4 months. Four patients required mechanical circulatory support before surgery (total artificial hearts in 2 and left ventricular assist devices in 2), and 3 patients required inotropic drugs. Six patients are alive with no sign of recurrent giant cell myocarditis at 12 to 113 months after surgery. One patient died suddenly 75 months after surgery, and autopsy showed severe graft vascular disease with no recurrence of giant cell myocarditis. Surveillance, right ventricular endomyocardial biopsy specimens showed recurrent asymptomatic giant cell myocarditis in 3 patients at 5 to 13 months after surgery, and found recurrence in 1 patient 30 months after surgery. This patient received augmented immunosuppression. CONCLUSIONS Giant cell myocarditis often is not diagnosed before transplantation. It can present as dilated cardiomyopathy with late deterioration, or it can present with rapid hemodynamic deterioration. In our experience, these patients can be bridged successfully to transplant with mechanical circulatory assist. Giant cell myocarditis may recur after transplantation but may respond to augmented immunosuppression.

Bronchopleural complications of nasogastric feeding tubes.

Enteral alimentation via small soft feeding tubes is becoming more common as the importance of nutrition is recognized in the debilitated patient. The monofilament wire stylets that stiffen these tubes during their insertion may cause potentially lethal bronchopleural complications unless correct insertion techniques are used and the tubes position is carefully checked before starting enteral nutrition.

Reoperation of Left Heart Valve Bioprostheses According to Age at Implantation

Background— Evidence supporting the use of bioprostheses for heart valve replacement in young adults is accumulating. However, reoperation data, which may help guide clinical decision making in young patients, remains poorly defined in the literature. Methods and Results— We examined the need for reoperation in 3975 patients who underwent first-time bioprosthetic aortic valve replacement (AVR) (n=3152) or mitral valve replacement (MVR) (n=823). There were 895 patients below the age of 60 years at bioprosthesis implant (AVR, n=636; MVR, n=259). The median interval to reoperation of contemporary, stented aortic bioprostheses was 7.74 years (95% CI 7.28 to 9.97 years) in patients less than 40 years, and 12.93 years (95% CI 11.10 to 15.76 years) in patients between 40 and 60 years of age. Multivariable risk factors associated with reoperation following bioprosthetic AVR include age (hazard ratio [HR] 0.94 per year, 95% CI 0.91 to 0.96, P<0.001) and concomitant coronary artery bypass grafting (HR 0.34, 95% CI 0.11 to 0.99, P=0.04). The median interval to reoperation of contemporary mitral bioprostheses was 8.11 years (95% CI 5.79 to 16.50 years) in patients less than 40 years, and 10.14 years (95% CI 8.64 to 11.14 years) in patients between 40 and 60 years of age. As for AVR, age (HR 0.96 per year, 95% CI 0.95 to 0.98, P<0.001) and concomitant coronary artery bypass grafting (HR 0.55, 95% CI 0.32 to 0.93, P=0.03) were associated with decreased reoperation risk following bioprosthetic MVR. Conclusions— These data constitute clinically relevant age-specific prognostic information regarding reoperation in young patients, who may wish to select a bioprosthesis at initial left heart valve replacement.