Destination mechanical circulatory support: proposal for clinical standards.
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Biomedical subjects
Publications and source records attributed to J Kobashigawa.
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BACKGROUND: Recipient pulmonary hypertension due to chronic congestive heart failure is a major cause of right ventricular (RV) dysfunction after heart transplantation. We hypothesized that inhaled nitric oxide (NO), in the postoperative period, would a) selectively reduce pulmonary vascular resistance and improve RV hemodynamics and b) reduce the incidence of RV dysfunction compared with a matched historical group. METHODS: Sixteen consecutive adult heart transplant recipients with lowest mean pulmonary artery (PA) pressures >25 mmHg were prospectively enrolled. Inhaled NO at 20 parts per million (ppm) was initiated before termination of cardiopulmonary bypass (CPB). At 6 and 12 hours after CPB, NO was stopped for 15 minutes and systemic and pulmonary hemodynamics were measured. RV dysfunction was defined as central venous pressure >15 mmHg and consistent echocardiographic findings. The incidence of RV dysfunction and 30-day survival in this group was compared with a historical cohort of 16 patients matched for pulmonary hypertension. RESULTS: Discontinuation of NO for 15 minutes at 6 hours after transplantation resulted in a significant rise in mean PA pressure, pulmonary vascular resistance (PVR), and RV stroke work index. Systemic hemodynamics were not affected by NO therapy. One patient in the NO-treated group, compared with 6 patients in the historical cohort group, developed RV dysfunction (P< .05). The 30-day survival in the NO-treated group and the historical cohort group were 100% and 81%, respectively (P> .05). CONCLUSION: In heart transplant recipients with pulmonary hypertension, inhaled NO in the postoperative period selectively reduces PVR and enhances RV stroke work. Furthermore, NO reduces the incidence of RV dysfunction in this group of patients when compared with a historical cohort matched for pulmonary hypertension. Inhaled NO is a useful adjunct to the postoperative treatment protocol of heart transplant patients with pulmonary hypertension.
Atrial fibrillation (AF) and atrial flutter (Afl) are common dysrhythmias that occur after orthotopic heart transplantation (OHT); however, their etiology and clinical significance have not been defined. To determine the precise incidence of sustained AF and Afl and their association with cardiac rejection, 892 consecutive patients who underwent OHT were studied. A total of 104 patients had 113 episodes of Afl; 102 patients had 117 episodes of AF. The incidence of Afl (12.7%) was the same as AF (13.1%). Sixty-nine AF episodes occurred in first 2 weeks after transplantation, and 22 of which were associated with rejection. In contrast, only 20 Afl episodes occurred the first 2 weeks after OHT, 10 of which were associated with rejection. Fifty-two episodes of Afl occurred during from the third week to 6 months after transplantation, 34 of which were associated with moderate to severe cellular or humoral rejection and/or transplant coronary artery disease (TCAD). All 41 Afl episodes that occurred 6 months after transplantation were associated with cellular and humoral rejection, and/or TCAD. The prevalence of Afl was significantly higher in biatrial than bicaval anastomosis. Atrial conduction defect, manifested by the increase of terminal force of the P wave in lead V(1) of the surface electrocardiogram, predicted the occurrence of Afl and AF associated with rejection in OHT with a sensitivity of 89% and specificity of 92%. These results demonstrate that the incidence of Afl increased after OHT, which might be a consequence of cellular and humoral rejection, and coronary vasculopathy of the transplanted hearts.
BACKGROUND: Luminal narrowing in transplant coronary artery disease is thought to be primarily caused by intimal proliferation, and the role of vascular remodeling is less certain. METHODS AND RESULTS: We studied cardiac allografts from 83 prospectively recruited patients immediately and 1 year after transplant using intravascular ultrasound in a multicenter study. We measured coronary artery dimensions in 310 angiographically matched segments (175 were also fully matched by ultrasound criteria). At 1 year, lumen area changed by -1.8 +/- 3.7 mm(2) (p < 0.0001, 14% of baseline lumen area). Thirty-three percent of this luminal loss was due to intimal thickening and 67% to vessel shrinkage. Shrinkage also occurred (-0.9 +/- 3.2 mm(2), 7% of baseline total area) in segments free of detectable intimal disease at baseline and at 1 year. Using the mean baseline total vessel area (13.9 mm(2)) as the cutoff, we divided the cohort into the large and the small coronary-segment groups. The large-segment group (n = 176) shrank more (-2.6 +/- 4.4 vs. -0.03 +/- 2.8 mm(2), p < 0.0001), but intimal growth was similar in both groups (0.8 +/- 2.2 vs. 0.4 +/- 1.3 mm(2), p = not significant). Analysis of the 175 fully ultrasound matched sub-cohort showed similar results. Changes in intimal area, total vessel area, and lumen area were similar in segments with (n = 132) and segments without (n = 178) pre-existing donor disease. Despite overall shrinkage, change in total vessel area positively correlated with change in intimal area (r = 0.29, p < 0.0001). CONCLUSION: In large coronary segments, coronary artery shrinkage plays an important role in the loss of luminal diameter early after cardiac transplantation, whereas new intimal growth occurs in both large and small segments. Pre-existent donor disease does not aggravate these processes. Compensatory remodeling with increasing intimal growth retards the rate of lumen loss. As is intimal thickening, shrinkage and compensatory remodeling are important pathogenic mechanisms in transplant coronary artery disease.
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BACKGROUND: Because of the complexity of the trabeculated endocardial surface and tangential histologic sectioning, the differentiation of acute cellular rejection (ACR) from Quilty B lesions (QB) in endomyocardial biopsies (EMBs) is problematic. We hypothesized that the phenotype chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) expression of infiltrating cells and the pattern of expression of transforming growth factor-beta (TGF-beta) may distinguish ACR from QB. In previous studies, the number of RANTES-positive cells and the expression of TGF-beta correlated with the severity of rejection. METHODS: We used immunohistochemical techniques to stain sections of human EMBs with only QB (n = 14) or with only ACR (International Society for Heart and Lung Transplantation Grades 1A and 1B, n = 7; Grades 3A and 3B, n = 7) for B (CD20) and T-lymphocytes (CD3), macrophages (CD68), RANTES, and TGF-beta expression. We graded the percentage of positive cells from 0 to 4 (1 = 1% to 25%; 2 = 26% to 50%; 3 = 51% to 75%, and 4 = 76% to 100%). RESULTS: When ACR was compared with QB, we found no difference in the proportion of myocardial B cells (0.9 +/- 0.3 vs 1.1 +/- 0.3, p = 0.17); however, we found a lesser proportion of T cells (1.8 +/- 0.5 vs. 2.8 +/- 0.9, p <0.01) but more macrophages (2.9 +/- 0.5 vs. 1.1 +/- 0.6, p < 0.0001) in ACR than in QB. We also found more RANTES-positive leukocytes in ACR vs. QB (2.8 +/- 1.3 vs. 1.9 +/- 0.9, p = 0.03). In QB, many endocardial vessels stained for TGF-beta (2.9 +/- 1.6). Myocardial vessels and injured myocytes in both ACR and QB expressed TGF-beta. CONCLUSIONS: In ACR, although T-lymphocytes are numerous, more than 50% of infiltrating cells are macrophages and more than 50% express RANTES. In QB lesions, more than 50% of infiltrating cells are T-lymphocytes and less that 50% of leukocytes will express RANTES. B cells are present in both ACR and QB, but on average comprise only 25% of the cells present. Thus, a relatively simple immunohistochemical analysis of endomyocardial biopsies may be useful in distinguishing ACR from QB.
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BACKGROUND: Abnormalities of the terminal force of the P wave in Lead V1 (ptf-V1) and dispersion of corrected atrial repolarization (Ta-TcD) are believed to represent interatrial conduction defect. METHODS AND RESULTS: To determine whether atrial conduction disturbance correlates with cardiac allograft rejection, we analyzed 249 twelve-lead-electrocardiograms, echocardiograms, hemodynamic parameters, and endomyocardial biopsys from 137 patients with heart transplantation. Both ptf-V1 and Ta-TcD were significantly increased in patients with severe, moderate, and mild rejection. In 22 patients, significant increases of the ptf-V1 and Ta-TcD were observed before positive histological findings, and significantly correlated with severity of rejection during 5- week to 1-year follow-up. Increase of 0.030 mm x sec in ptf-V1 or 0.040 s1/2 in Ta-TcD indicated cardiac rejection > or =1B with sensitivity of 88 and 83%, specificity of 85 and 77%, respectively. CONCLUSION: These results suggest that the ptf-V1 and Ta-TcD might be an adjunct to detect rejection and reduce the number of surveillance EMB.
BACKGROUND: We reviewed 37 patients who received donor hearts with left ventricular hypertrophy (LVH) to determine which factors affected outcomes. METHODS: Thirty-seven patients underwent orthotopic heart transplantation (1994 through 1998) with donor hearts qualified as having LVH by echocardiography (EC) and/or electrocardiogram (ECG). We performed univariate analysis on 18 donor and recipient risk factors for mortality. We calculated 12-month survival curves using Kaplan-Meier estimates and compared them using the log-rank test. A contemporaneous cohort of 221 patients who received optimal hearts within the same institution served as a control for survival. RESULTS: Median follow-up was 18 months (1 to 53). Median recipient age was 58 ye ars (25 to 75), and median donor age was 47 years (12 to 63). Median donor/recipient height and weight ratios were 1.01 (0.9 to 1.19) and 1.16 (0.77 to 2.02), respectively. Two-month survival was 86.4%, and 12-month survival was 73.0%. Survival for the control group was 91. 6% at 2 months and 86.9% at 12 months. Clinically inferior survival curves were observed when donors had known hypertension (n = 17, 95% vs 71% at 2 months, 76% vs 65% at 12 months), ischemia > 180 minutes (n = 18, 95% vs 72% at 2 months, 78% vs 65% at 12 months), LVH by ECG (n = 10, 85% vs 80% at 2 months, 77% vs 56% at 12 months), and greater than mild or unknown ECHO grade (n = 18, 89% vs 72% at 2 months, 84% vs 59% at 12 months, p = 0.11). CONCLUSIONS: Donor hearts with mild LVH may be used selectively, particularly if there are no ECG criteria and if ischemia time is short. Caution is indicated for donors with documented history of hypertension. Precise measurement of LV wall thickness by EC is needed in all donors to estimate severity and to complement ECG interpretation.
Cross-sectional studies by intravascular ultrasound (IVUS) in heart transplant recipients have suggested that vascular remodeling occurs in coronary arteries years after transplant. However, no reports describe vascular remodeling in the same cohort of patients studied prospectively using morphometric analysis (10 evenly spaced images obtained from a slow pullback from the left anterior descending coronary artery). Morphometric analysis better reflects total vessel anatomy compared with previously reported site (2 to 3 images) analysis. We reviewed 20 patients studied by IVUS at 2 months, 1 year, 2 years, and 3 years after heart transplant.Over time, the coronary artery luminal area decreased from baseline level of 12.0 mm(2) to a 3-year mark of 9.7 mm(2) (p = 0.02). Vessel shrinkage was seen in 16/20 patients. After an initial rise in intimal parameters (maximal intimal thickness, intimal index, and plaque area) from baseline to 1 year, we found a significant decrease in intimal parameters between Year 1 and Year 3 after transplant. For example, plaque area decreased from 2.05 mm(2) at 1 year post-transplant to 1.48 mm(2) by 3 years post-transplant (p = 0.05). In a majority of heart transplant patients, early intimal thickening in the first year post-transplant is accompanied by constrictive remodeling. Over the subsequent 2 years, further constrictive remodeling is seen despite a decrease in intimal area.
1. The consecutive pre- and post-1994 eras have demonstrated improved survival for all age groups. This is linked to improved preservation methods, surgical technique and immunosuppression agents. 2. The use of marginal donor hearts for Status I and alternate elderly patients has followed the model of matching donor and recipient risk without affecting patient outcome and minimized the use of implantable assist devices. 3. A donor history of systemic gram-negative infection, hypertension, or traumatic intracranial bleeds was an important marker for risk. Younger age and shorter ischemia time could compensate for other hazards. 4. Heart transplantation in carefully selected elderly recipients yielded clinical results similar to those of younger patients with less rejection. 5. An adult alternate recipient list proved useful to prevent diversion of standard donors away from younger recipients. 6. Retransplantation for TCAD is acceptable but much less satisfactory for acute graft failure. 7. Trends show an increase in the use of implantable devices; refinement in technology for mechanical assist and replacement is forthcoming.
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