Kwok L. Yun

Stanford experience with obliterative bronchiolitis after lung and heart-lung transplantation

BACKGROUND Obliterative bronchiolitis (OB) is the main chronic complication after heart-lung (HLTx) and lung transplantation (LTx), limiting the long-term success of both transplant procedures. METHODS Since 1981, 135 HLTxs and 61 isolated LTxs were performed in 184 patients at Stanford University. RESULTS The overall prevalence of OB in patients surviving longer than 3 months postoperatively was 64% after HLTx and 68% after LTx. The actuarial freedom from OB was 72%, 51%, 44%, and 29% at 1, 2, 3, and 5 years, respectively, after HLTx and LTx. An analysis of potential risk factors revealed that the frequency and severity of acute rejection episodes (p < 0.001) and the appearance of lymphocytic bronchiolitis on biopsy (p < 0.05) were significantly associated with the development of OB. With regard to diagnosis of OB, pulmonary function tests show early reductions of the forced expiratory flow between 25% and 75% of the forced vital capacity with subsequent decreases in the forced expiratory volume in 1 second. The sensitivity of transbronchial biopsies has increased to 71% since 1993. Current treatment consists of augmented immunosuppression. Concurrent acute rejection episodes or active OB on biopsy have been treated aggressively with high-dose steroid pulses. Analysis of data from 73 patients with OB after HLTx and LTx revealed actuarial 1-, 3-, 5-, and 10-year survival of 89%, 71%, 44%, and 17% versus 86%, 77%, 63% and 56% in patients without OB (p < 0.05 by log-rank analysis). The main complication and cause of death in patients with OB was superimposed respiratory tract infection, which was treated aggressively. CONCLUSIONS Early diagnosis of OB using pulmonary function tests or transbronchial biopsy is possible and important, because immediate treatment initiation has led to acceptable survival rates, with nearly 50% of affected patients still alive 5 years after transplantation. Current experimental research on OB suggests that immune injury is the main pathogenetic event of airway obliteration in animal models; rapamycin and leflunomide are new immunosuppressive agents that may have the potential to prevent and treat airway obliteration.

Alterations in left ventricular diastolic twist mechanics during acute human cardiac allograft rejection.

BACKGROUND Contraction of obliquely oriented left ventricular (LV) fibers results in a twisting motion of the left ventricle. The purpose of this study was to assess the effects of acute human cardiac allograft rejection on LV twist pattern and the twist-volume relation. METHODS AND RESULTS Tantalum markers were implanted into the LV midwall in 15 transplant recipients to measure time-varying, three-dimensional chamber twist using computer-assisted analysis of biplane cinefluoroscopic images. Twist was defined as the mean longitudinal gradient of circumferential rotation about the LV long axis. When plotted against normalized percent ejection fraction (%EF), the resulting twist-normalized %EF relation could be divided into three phases. In systole, LV twist was linearly related to ejection of blood. In contrast, diastolic untwist was characterized by early rapid recoil with little change in LV volume, followed by more gradual untwisting when the bulk of diastolic filling occurred. During 10 acute rejection episodes in 10 patients, maximum twist, peak systolic twist rate, and the slope of the systolic twist-normalized %EF relation did not change. In contrast, the slope of the early (first 15% of filling) diastolic twist-normalized %EF relation (M(early-dia)) decreased significantly (-0.194 +/- 0.062 [prerejection] versus -0.103 +/- 0.054 rad/cm [rejection], p = 0.0003), resulting in a prolonged tau 1/2 (time required to untwist by 50% [20 +/- 5% versus 28 +/- 5% of diastole], p = 0.0003) and decrease in percent untwisting at 15% diastolic LV filling (62 +/- 11% versus 36 +/- 13%, p = 0.0003). Therefore, a greater proportion of LV untwisting occurred later in diastole during rejection, as reflected by an increase in the slope (M(mid-dia)) of the middle to late (from 15 to 90% filling) diastolic twist-normalized %EF relation (-0.018 +/- 0.009 versus -0.030 +/- 0.010 rad/cm, p = 0.0015). Peak rate of untwist was not affected. With resolution of rejection, M(early-dia) and percent untwist during early diastole returned to baseline levels (p = NS versus baseline). There was also a trend for M(mid-dia) to return toward prerejection values (p = NS versus baseline), but this change did not reach statistical significance compared with rejection values. CONCLUSION Acute cardiac allograft rejection is associated with altered diastolic twist mechanics in the absence of any demonstratable systolic abnormalities. During rejection, myocardial edema and other factors may result in intrinsic changes of the elastic properties of the myocardium, thereby leading to modification of recoil forces responsible for the early, rapid unwinding of the deformed ventricle.

Evaluation of myocardial motion tracking with cine-phase contrast magnetic resonance imaging.

RATIONALE AND OBJECTIVES.The accuracy of myocardial motion measurements, computed from cine-phase contrast (cine-PC) magnetic resonance (MR) velocity data, was compared with directly visualized motion of ME signal voids caused by implanted tantalum markers in anesthetized dogs. METHODS.Magnetic resonance imaging (MRI) data were electrocardiogram-gated and divided into 16 phases per cardiac cycle. Myocardial trajectories as a function of time in the cardiac cycle were measured using both methods for four to seven markers in each of eight animals. RESULTS.The peak observed in-plane excursion was 4.0 ±2.1 mm. The average deviation between displacements derived from velocity data versus displacements visualized directly was 1.1 ± 0.7 mm (27.5% of the peak displacement). The difference was less if three separate MR scans were used to measure each velocity component in the cine-PC method. This improvement is probably caused by improved temporal resolution. CONCLUSIONS.Cine-PC MRI offers a noninvasive method for accurate quantification of myocardial motion.

Time related quality of life after elective cardiac operation

BACKGROUND Due to improved operative techniques, myocardial preservation, and perioperative care, open heart procedures are now being performed in older and sicker patients. As a result, the quality of life has become an important issue in the decision making process. METHODS Between January 1993 and October 1994, 604 patients above 65 years of age who underwent non-emergent open heart operations were followed prospectively over a 2-year period. The Health Status Questionnaire forms were distributed to all patients preoperatively and to hospital survivors at 3, 12, and 24 months. The questionnaire contains 36 questions and is divided into eight categories. Follow-up was 100% complete with 99.6% of questionnaires returned. RESULTS Significant quality of life improvements were noted in all categories after surgery. After reaching a peak at 12 months, there were small, but significant declines in scores relating to physical health and health perception at 24 months. In contrast, measurements for mental attributes continued to increase with time. By multivariate analysis, diabetes, older age, and female gender had a relatively adverse influence on quality of life despite improvement after operation. Similarly, patients with chronic obstructive pulmonary disease or having redo operations had lower health perception with some physical limitations. While procedure type (coronary artery bypass grafting) was associated with preoperative bodily pain, congestive heart failure symptoms were not an independent factor affecting quality of life. CONCLUSIONS Quality of life improves with cardiac surgical interventions in this studied age group and should not be denied even in the elderly population.

Durability of the hancock MO bioprosthesis compared with standard aortic valve bioprostheses

To compare the durability of the Hancock modified orifice (Hancock MO, model 250 [H-MO]) valve with two other commonly used standard aortic valve bioprostheses, a cohort of 1,602 patients undergoing aortic valve replacement using porcine valves between 1971 and 1990 (excluding simultaneous mitral valve replacement) was analyzed retrospectively using Cox model multivariate techniques. Five hundred sixty-one patients received a composite H-MO valve, 652 received a standard Hancock model 242 (H) valve, and 389 received a Carpentier-Edwards model 2625 (C-E) valve. Mean age was 60 +/- 15 years (+/- 1 standard deviation) (71% male). Follow-up (10,247 patient-years) extended to 15 years and was 97% complete. The main focus of this study was bioprosthetic durability, using The American Association for Thoracic Surgery/The Society of Thoracic Surgeons guidelines to define structural valve deterioration (SVD). Multivariate analysis revealed that (younger) age (p < 10(-5), liver disease (p = 0.02), and 1981 to 1985 operative period (p = 0.012) were the only significant, independent predictors of SVD. In concordance with previous reports, the SVD freedom estimate was greater than 90% at 15 years for patients older than 70 years of age. Hepatic dysfunction had an adverse effect on SVD (estimated freedom from event at 10 years was 34 +/- 17% [standard error of mean] versus 78 +/- 2% for those without liver disease), but this affected only 3% of patients. Interestingly, one operative period (1981 to 1985) was associated with a slightly higher risk of SVD compared to the three other 5-year time windows. Valve type did not emerge as a significant risk factor for SVD.(ABSTRACT TRUNCATED AT 250 WORDS)

Importance of mitral subvalvular apparatus in terms of cardiac energetics and systolic mechanics in the ejecting canine heart.

To assess the importance of the intact mitral subvalvular apparatus for left ventricular (LV) energetics, data from nine open-chest ejecting canine hearts were analyzed using piezoelectric crystals to measure LV volume. After mitral valve replacement with preservation of all chordae tendineae, baseline LV function was assessed during transient caval occlusion: A quadratic fit of the LV end-systolic pressure-volume data was used to determine the curvilinear end-systolic pressure-volume relationship (ESPVR). All chordae were then divided with exteriorized snares. Reassessment revealed deterioration of global LV pump function: (a) the coefficient of nonlinearity, decreased (less negative) by 90% (P = 0.06); (b) slope of the curvilinear ESPVR at the volume axis intercept, decreased by 75% (P = 0.01); and V100, end-systolic volume at 100 mmHg end-systolic pressure, increased by 42% (P less than 0.02). Similarly, preload recruitable stroke work fell significantly (-14%) and Vw1,000 (end-diastolic volume [EDV] at stroke work [SW] of 1,000 mmHg.ml) rose by 17% (P less than 0.04). With respect to LV energetics, the total mechanical energy generated by the ventricle decreased, as indicated by a decline in the slope of the pressure volume area (PVA)-EDV relationship (120 +/- 13 [mean +/- SD] vs. 105 +/- 13 mmHg, P less than 0.001). Additionally, comparison of LV SW and PVA from single beats with matched EDV showed that the efficiency of converting mechanical energy to external work (SW/PVA) declined by 14% (0.65 +/- 0.13 vs. 0.56 +/- 0.08, P less than 0.03) after chordal division. While effective systemic arterial elastance, Ea, also fell significantly (P = 0.03) after the chordae were severed, the Ea/Ees ratio (Ees = slope of the linear ESPVR) increased by 124% (0.91 +/- 0.53 vs. 2.04 +/- 0.87, P = 0.001) due to a proportionally greater decline in Ees. This indicates a mismatch in ventriculo-arterial interaction, deviating from that required for maximal external output (viz., Ea/Ees = 1). These adverse effects of chordal division may be related to the observed changes in LV geometry (i.e., eccentricity). We conclude that the intact mitral subvalvular apparatus is important in optimizing LV energetics and ventriculo-vascular coupling in addition to the enhancement of LV systolic performance.

Dose Response of Fish Oil versus Safflower Oil on Graft Arteriosclerosis in Rabbit Heterotopic Cardiac Allografts

With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotopic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2,3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/ kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5,6, and 7 animals were supplemented with equivalent doses of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin-induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high-dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% ± 5.9% versus 41.4% ± 7.6%, p ≤ 0.017) and intimal thickness (7.9 ± 1.9 μm versus 34.0 ± 13.0 μm, analysis of variance: p = 0.054). Low-dose safflower

Arterial switch and resection of hepatic hemangioendothelioma.

We report on the management of a neonate undergoing arterial switch for transposition of the great arteries and concomitant resection of a hepatic infantile hemangioendothelioma. A preoperative aortogram demonstrated the arterial supply of the hepatic hemangioendothelioma. Pulmonary artery hypertension and myocardial ischemia were noted after separation from cardiopulmonary bypass. Resection of the hepatic malformation produced an immediate reduction in pulmonary hypertension and resolution of the myocardial ischemia. The patient had an uneventful postoperative recovery.

Esophageal atresia with triple congenital tracheoesophageal fistulae

The surgical management of an infant with esophageal atresia and three (2 proximal and 1 distal) congenital tracheoesophageal fistulae is described. The pitfalls in the diagnosis of proximal fistulae are discussed.