Heart transplantation for Chagas cardiomyopathy in the United States.

Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.

Neuroinvasive West Nile Virus Post-Heart Transplantation: A Case Report.

First described in the United States in the late 1990s, West Nile virus (WNV) infection following solid organ transplantation is a rare but life-threatening complication. The many ways in which WNV may be acquired, patient specific risk factors, and variability in clinical severity present challenges to health care providers caring for these patients.

Use of Anti-Thymocyte Globulin for Induction Therapy in Cardiac Transplantation: A Review.

The most common causes of death after heart transplantation (HTx) include acute rejection and multi-organ failure in the early period and malignancy and cardiac allograft vasculopathy (CAV) in the late period. Polyclonal antibody preparations such as rabbit anti-thymocyte globulin (ATG) may reduce early acute rejection and the later occurrence of CAV after HTx. ATG therapy depletes T cells, modulates adhesion and cell-signaling molecules, interferes with dendritic cell function, and induces B-cell apoptosis and regulatory and natural killer T-cell expansion. Evidence from animal studies and from retrospective clinical studies in humans indicates that ATG can be used to delay calcineurin inhibitor (CNI) exposure after HTx, thus benefiting renal function, and to reduce the incidence of CAV and ischemia-reperfusion injury in the transplanted heart. ATG may reduce de novo antibody production after HTx. ATG does not appear to increase cytomegalovirus infection rates with longer prophylaxis (6-12 months). In addition, ATG may reduce the risk of lymphoproliferative disease and does not appear to confer an additive effect on acquiring lymphoma after HTx. Randomized, controlled trials may provide stronger evidence of ATG association with patient survival, graft rejection, renal protection through delayed CNI initiation, as well as other benefits. It can also help establish optimal dosing and patient criteria to maximize treatment benefits.

Comparative analysis of von Willebrand factor profiles after implantation of left ventricular assist device and total artificial heart.

Essentials Bleeding is a major source of morbidity during mechanical circulatory support. von Willebrand factor (VWF) multimer loss may contribute to bleeding. Different patterns of VWF multimer loss were seen with the two device types. This is the first report of total artificial heart associated VWF multimer loss. SUMMARY: Background Bleeding remains a challenge during mechanical circulatory support and underlying mechanisms are incompletely understood. Functional von Willebrand factor (VWF) impairment because of loss of high-molecular-weight multimers (MWMs) produces acquired von Willebrand disease (VWD) after left ventricular assist device (LVAD). Little is known about VWF multimers with total artificial hearts (TAHs). Here, VWF profiles with LVADs and TAHs are compared using a VWD panel. Methods VWD evaluations for patients with LVAD or TAH (2013-14) were retrospectively analyzed and included: VWF activity (ristocetin cofactor, VWF:RCo), VWF antigen (VWF:Ag), ratio of VWF:RCo to VWF:Ag, and quantitative VWF multimeric analysis. Results Twelve patients with LVADs and 12 with TAHs underwent VWD evaluation. All had either normal (47.8%) or elevated (52.2%) VWF:RCo, normal (26.1%) or elevated (73.9%) VWF:Ag and 50.0% were disproportional (ratio ≤ 0.7). Multimeric analysis showed abnormal patterns in all patients with LVADs: seven with high MWM loss; five with highest MWM loss. With TAH, 10/12 patients had abnormal patterns: all with highest MWM loss. High MWM loss correlated with presence of LVAD and highest MWM loss with TAH. Increased low MWMs were detected in 22/24. Conclusion Using VWF multimeric analysis, abnormalities after LVAD or TAH were detected that would be missed with measurements of VWF level alone: loss of high MWM predominantly in LVAD, loss of highest MWM in TAH, and elevated levels of low MWM in both. This is the first study to describe TAH-associated highest MWM loss, which may contribute to bleeding.

Combined Heart and Kidney Transplantation: A 23-Year Experience.

BACKGROUND: We report clinical experience with combined heart and kidney transplantation (HKTx) over a 23-year time period. METHODS: From June 1992 to August 2015, we performed 83 combined HKTx procedures at our institution. We compared the more recent cohort of 53 HKTx recipients (group 2, March 2009 to August 2015) with the initial 30 previously reported HKTx recipients (group 1, June 1992 to February 2009). Pre-operative patient characteristics, peri-operative factors, and post-operative outcomes including survival were examined. RESULTS: The baseline characteristics of the two groups were similar, except for a lower incidence of ethanol use and higher pre-operative left-ventricular ejection fraction, cardiac output, and cardiac index in group 2 when compared with group 1 (P = .007, .046, .037, respectively). The pump time was longer in group 2 compared with group 1 (153.30 ± 38.68 vs 129.60 ± 37.60 minutes; P = .007), whereas the graft ischemic time was not significantly different between the groups, with a trend to a longer graft ischemic time in group 2 versus group 1 (195.17 ± 45.06 vs 178.07 ± 52.77 minutes; P = .056, respectively). The lengths of intensive care unit (ICU) and hospital stay were similar between the groups (P = .083 and .39, respectively). In addition, pre-operative and post-operative creatinine levels at peak, discharge, 1 year, and 5 years and the number of people on post-operative dialysis were similar between the groups (P = .37, .75, .54, .87, .56, and P = .139, respectively). Overall survival was not significantly different between groups 2 and 1 for the first 5 years after transplant, with a trend toward higher survival in group 2 (P = .054). CONCLUSIONS: The most recent cohort of combined heart and kidney transplant recipients had similar ICU and hospital lengths of stay and post-operative creatinine levels at peak, discharge, and 1 and 5 years and a similar number of patients on post-operative dialysis when compared with the initial cohort. Overall survival was not significantly different between the later and earlier groups, with a trend toward higher overall survival at 5 years in the more recent cohort of patients. In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation is safe to perform and has excellent outcomes.

Leading Efforts to Increase Organ Donation Through Professionalization of Organ Procurement Organizations and Establishment of Organ and Tissue Donor Registries.

OBJECTIVE: The influence of new donor registrations through the California Organ and Tissue Donor Registry on the local OneLegacy Organ Procurement Organization (OPO) was examined during a 6-year period. METHODS: Publicly available data from Donate Life America for California were examined for the 6 calendar years of 2009-2014. Performance data from OneLegacy for the same 6 years for organ donors and number of transplants were also examined. The donor designation rate (DDR) was defined as the rate at which new individuals joined the state donor registry as a percentage of all driver licenses and ID cards issued within a calendar year. The total donor designation (TDD) was defined as the sum of the new and existing people who were registered organ donors. Donor designation share (DDS) was the total number of designated donors as a percentage of all residents of the state who were ≥18 years old. The business practices and educational efforts of the OneLegacy OPO were examined as well. RESULTS: In California, from 2009 through 2014, the DDR was 25.5%-28%. When added to the existing donor registrations, the TDD and DDS increased each year from 2009 through 2014. With the current level of growth, it is projected that California will be able to reach a DDS of 50% by 2017. For the OneLegacy OPO, designated donors from the California Organ and Tissue Donor Registry made up 15% of the total donations in 2009, and 39% of the total donations in 2014, increasing by ∼5% each year since 2009. By increasing professionalization and transparency, and widening its educational and training efforts, OneLegacy was able to take advantage of an increasing percentage of donors who were designated donors and to increase the overall number of donors and organs transplanted, becoming one of the largest OPOs in the nation. CONCLUSIONS: This can be a model for OPOs in other donor service areas, and it may set the stage for the United States to serve as an example to the global community in the practice of organ donation.

Total Artificial Heart as Bridge to Heart Transplantation in Chagas Cardiomyopathy: Case Report.

Chagas disease (CD) is becoming an increasingly recognized cause of dilated cardiomyopathy outside of Latin America, where it is endemic, due to population shifts and migration. Heart transplantation (HTx) is a therapeutic option for end-stage cardiomyopathy due to CD, but may be considered a relative contraindication due to potential reactivation of the causative organism with immunosuppression therapy. The total artificial heart (TAH) can provide mechanical circulatory support in decompensated patients with severe biventricular dysfunction until the time of HTx, while avoiding immunosuppressive therapy and removing the organ most affected by the causative organism. We report herein a patient with CD and severe biventricular dysfunction, who had mechanical circulatory support with a TAH for more than 6 months, followed by successful orthotopic HTx and treatment with benznidazole for 3 months. The patient had no evidence of recurrent disease in the transplanted heart based on endomyocardial biopsy up to 1 year post-transplantation, and remains alive more than 30 months after insertion of a TAH and 24 months after HTx.

Similar Mortality and Morbidity of Orthotopic Heart Transplantation for Patients 70 Years of Age and Older Compared With Younger Patients.

BACKGROUND: The upper age limit of heart transplantation remains controversial. The goal of the present study was to investigate the mortality and morbidity of orthotopic heart transplantation (HT) for recipients ≥70 compared with those <70 years of age. METHODS: Of 704 adults who underwent HT from December 1988 to June 2012 at our institution, 45 were ≥70 years old (older group) and 659 were <70 years old (younger group). Survival, intraoperative blood product usage, intensive care unit (ICU) and hospital stays, and frequency of reoperation for chest bleeding, dialysis, and >48 hours ventilation were examined after HT. RESULTS: The older group had 100% 30-day and 60-day survival compared with 96.8 ± 0.7% 30-day and 95.9 ± 0.8% 60-day survival rates in the younger group. The older and younger groups had similar 1-year (93.0 ± 3.9% vs 92.1 ± 1.1%; P = .79), 5-year (84.2 ± 6.0% vs 73.4 ± 1.9%; P = .18), and 10-year (51.2 ± 10.7% vs 50.2 ± 2.5%; P = .43) survival rates. Recipients in the older group had higher preoperative creatinine levels, frequency of coronary artery disease, and more United Network for Organ Sharing status 2 and fewer status 1 designations than recipients in the younger group (P < .05 for all). Pump time and intraoperative blood usage were similar between the 2 groups (P = NS); however, donor-heart ischemia time was higher in the older group (P = .002). Older recipients had higher postoperative creatinine levels at peak (P = .003) and at discharge (P = .007). Frequency of postoperative complications, including reoperation for chest bleeding, dialysis, >48 hours ventilation, pneumonia, pneumothorax, sepsis, in-hospital and post-discharge infections, were similar between groups (P = NS for all comparisons). ICU and hospital length of stays were similar between groups (P = .35 and P = .87, respectively). In Cox analysis, recipient age ≥70 years was not identified as a predictor of lower long-term survival after HT. CONCLUSIONS: HT recipients ≥70 years old had similar 1, 5, and 10-year survival rates compared with younger recipients. Both patient groups had similar intra- and postoperative blood utilization and frequencies of many postoperative complications. Older and younger patients had similar morbidity and mortality rates following HT. Carefully selected older patients (≥70 years) can safely undergo HT and should not be excluded from HT consideration based solely on age.

Adult Heart Transplantation Following Ventricular Assist Device Implantation: Early and Late Outcomes.

PURPOSE: The impact of prior implantation of a ventricular assist device (VAD) on short- and long-term postoperative outcomes of adult heart transplantation (HTx) was investigated. METHODS: Of the 359 adults with prior cardiac surgery who underwent HTx from December 1988 to June 2012 at our institution, 90 had prior VAD and 269 had other (non-VAD) prior cardiac surgery. RESULTS: The VAD group had a lower 60-day survival when compared with the Non-VAD group (91.1% ± 3.0% vs 96.6% ± 1.1%; P = .03). However, the VAD and Non-VAD groups had similar survivals at 1 year (87.4% ± 3.6% vs 90.5% ± 1.8%; P = .33), 2 years (83.2% ± 4.2% vs 88.1% ± 2.0%; P = .21), 5 years (75.7% ± 5.6% vs 74.6% ± 2.9%; P = .63), 10 years (38.5% ± 10.8% vs 47.6% ± 3.9%; P = .33), and 12 years (28.9% ± 11.6% vs 39.0% ± 4.0%; P = .36). The VAD group had longer pump time and more intraoperative blood use when compared with the Non-VAD group (P < .0001 for both). Postoperatively, VAD patients had higher frequencies of >48-hour ventilation and in-hospital infections (P = .0007 and .002, respectively). In addition, more VAD patients had sternal wound infections when compared with Non-VAD patients (8/90 [8.9%] vs 5/269 [1.9%]; P = .005). Both groups had similar lengths of intensive care unit (ICU) and hospital stays and no differences in the frequencies of reoperation for chest bleeding, dialysis, and postdischarge infections (P = .19, .70, .34, .67, and .21, respectively). Postoperative creatinine levels at peak and at discharge did not differ between the 2 groups (P = .51 and P = .098, respectively). In a Cox model, only preoperative creatinine ≥1.5 mg/dL (P = .006) and intraoperative pump time ≥210 minutes (P = .022) were individually considered as significant predictors of mortality within 12 years post-HTx. Adjusting for both, pre-HTx VAD implantation was not a predictor of mortality within 12 years post-HTx (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.77-1.97; P = .38). However, pre-HTx VAD implantation was a risk factor for 60-day mortality (HR, 2.86; 95% CI, 1.07-7.62; P = .036) along with preoperative creatinine level ≥2 mg/dL (P = .0006). CONCLUSIONS: HTx patients with prior VAD had lower 60-day survival, higher intraoperative blood use, and greater frequency of postoperative in-hospital infections when compared with HTx patients with prior Non-VAD cardiac surgery. VAD implantation prior to HTx did not have an additional negative impact on long-term morbidity and survival following HTx. Long-term (1-, 2-, 5-, 10-, and 12-year) survival did not differ significantly in HTx patients with prior VAD or non-VAD cardiac surgery.

Relationship between regional cardiac hyperinnervation and ventricular arrhythmia.

BACKGROUND: Sympathetic nerve activity is known to be important in ventricular arrhythmogenesis, but there is little information on the relation between the distribution of cardiac sympathetic nerves and the occurrence of spontaneous ventricular arrhythmias in humans. METHODS AND RESULTS: We studied 53 native hearts of transplant recipients, 5 hearts obtained at autopsy of patients who died of noncardiac causes, and 7 ventricular tissues that had been surgically resected from the origin of ventricular tachycardia. The history was reviewed to determine the presence (group 1A) or absence (group 1B) of spontaneous ventricular arrhythmias. Immunocytochemical staining for S100 protein, neurofilament protein, tyrosine hydroxylase, and protein gene product 9.5 was performed to study the distribution and the density of sympathetic nerves. The average left ventricular ejection fraction was 0.22+/-0.07. A total of 30 patients had documented ventricular arrhythmias, including ventricular tachycardia and sudden cardiac death. A regional increase in sympathetic nerves was observed around the diseased myocardium and blood vessels in all 30 hearts. The density of nerve fibers as determined morphometrically was significantly higher in group 1A patients (total nerve number 19.6+/-11.2/mm(2), total nerve length 3.3+/-3.0 mm/mm(2)) than in group 1B patients (total nerve number 13.5+/-6.1/mm(2), total nerve length 2.0+/-1.1 mm/mm(2), P<0. 05 and P<0.01, respectively). CONCLUSIONS: There is an association between a history of spontaneous ventricular arrhythmia and an increased density of sympathetic nerves in patients with severe heart failure. These findings suggest that abnormally increased postinjury sympathetic nerve density may be in part responsible for the occurrence of ventricular arrhythmia and sudden cardiac death in these patients.

Effect of prosthetic aortic valve design on the Doppler-catheter gradient correlation: an in vitro study of normal St. Jude, Medtronic-Hall, Starr-Edwards and Hancock valves.

To evaluate the normal range of Doppler-derived velocities and gradients, their relation to direct flow measurements and the importance of prosthetic valve design on the relation between Doppler and catheter-derived gradients, five sizes of normal St. Jude bileaflet, Medtronic-Hall tilting disc, Starr-Edwards caged ball and Hancock bioprosthetic aortic valves were studied with use of a pulsatile flow model. A strong linear correlation between peak velocity and peak flow, and mean velocity and mean flow, was found in all four valve types (r = 0.96 to 0.99). In small St. Jude and Hancock valves, Doppler velocities and corresponding gradients increased dramatically with increasing flow, resulting in velocities and gradients as high as 4.7 m/s and 89 mm Hg, respectively. The ratio of velocity across the valve to velocity in front of the valve (velocity ratio) was independent of flow in all St. Jude, Medtronic-Hall, Starr-Edwards and Hancock valves when the two lowest flow rates were excluded for Hancock valves. Although Doppler peak and mean gradients correlated well with catheter peak and mean gradients in all four valve types, the actual agreement between the two techniques was acceptable only in Hancock and Medtronic-Hall valves. For St. Jude and Starr-Edwards valves, Doppler gradients significantly and consistently exceeded catheter gradients with differences as great as 44 mm Hg. Thus, Doppler velocities and gradients across normal prosthetic heart valves are highly flow dependent. However, the velocity ratio is independent of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

A 6 year experience with the St. Jude medical valve: hemodynamic performance, surgical results, biocompatibility and follow-up.

After in vitro testing (confirmed in vivo) of three contemporary valve designs (St. Jude, Björk-Shiley and Carpentier-Edwards) demonstrated that the St. Jude valve possessed the most favorable hydrodynamic performance characteristics, a limited clinical trial was begun in high risk patients who might benefit from a prosthesis with improved hemodynamics. Between March 1978 and March 1984, 419 St. Jude prostheses (157 aortic, 156 mitral and 53 double aortic-mitral) were implanted in 366 patients. Ninety-six percent were in New York Heart Association functional class III or IV preoperatively. Early (30 day) mortality was 10.4% overall, and was lower after aortic (5.7%) or double (7.5%) than after isolated mitral valve replacement (16.0%). Forty-four prosthetic mitral valve recipients with severe ischemic mitral regurgitation experienced a 32% early mortality rate; without this group, mitral valve replacement carried a 10% early mortality rate (p less than 0.01). Multivariate logistic regression analysis confirmed that early death was strongly associated with three preoperative patient characteristics (p less than 0.05): ischemic mitral valve disease, depressed left ventricular function (ejection fraction less than 0.55) and advanced functional class (class IV). Late follow-up (7,055 patient-months, mean 22) was 99.7% complete (1 patient lost). Actuarial survival at 4 years was 80, 80 and 79% after aortic, mitral (nonischemic) and double valve replacement, respectively; in the subset with ischemic mitral regurgitation, actuarial survival was 34% (p less than 0.01). Eighty-six percent of survivors were in functional class I or II.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitral valve replacement early after myocardial infarction: attendant high risk of left ventricular rupture.

Between 1969 and 1983, 608 patients underwent mitral valve replacement surgery at Cedars-Sinai Medical Center. Perioperative rupture of the left ventricular myocardium complicated seven operations (1.2%), five of them in the 247 patients with concomitant ischemic heart disease. Six ruptures were fatal. Relative incidences of seven previously hypothesized predisposing factors were determined for patients with and without myocardial rupture. In addition, because of the apparent frequency of association with ischemic heart disease and because all ruptures were posterior or posterolateral, patients were also categorized by prior history of posterior myocardial infarction: 177 patients had none, whereas 49 patients had a remote and 21 patients a recent (less than or equal to 1 month) posterior wall infarct. Four ruptures (accounting for 57% of all ruptures) occurred in the 21 patients (19% incidence) with a recent posterior infarct, compared with only three ruptures in the 587 patients (0.5%) without a recent posterior wall infarct (p = 0.000). None of the factors of age, sex, valve pathology, etiology of valve lesion, concomitant coronary disease, valve substitute or intraoperative myocardial preservation were associated with perioperative rupture. These data establish a low overall incidence of ventricular rupture after mitral valve replacement, high fatality and possible etiologic association with recent posterior wall infarction.

Esmolol: a new ultrashort-acting beta-adrenergic blocking agent for rapid control of heart rate in postoperative supraventricular tachyarrhythmias.

Prompt control of heart rate is important for successful treatment of supraventricular tachyarrhythmias early after open heart surgery when sympathetic tone is high and ventricular response rates may be rapid. Esmolol, a new ultrashort-acting (9 minute half-life) beta-receptor blocking agent, was given by continuous intravenous infusion for up to 24 hours in 24 patients (21 with isolated coronary bypass surgery and 3 with valve replacement) 1 to 7 days after surgery. Atrial fibrillation was present in 9 patients, atrial flutter in 2 and sinus tachycardia in 13. Eleven patients had received intravenous digoxin (average dose 0.6 mg, average serum level 1.19 mg/100 ml) before esmolol infusion without adequate control of the supraventricular tachyarrhythmia. After a 1 minute loading infusion of esmolol (500 micrograms/kg per min), maintenance dose, titrated to heart rate and blood pressure response, varied from 25 to 300 micrograms/kg per min. After esmolol administration, at an average dose of 139 +/- 83 micrograms/kg per min, mean heart rate decreased from 130 +/- 15 to 99 +/- 15 beats/min. Within 5 to 18 minutes after initiation of therapy, all patients had achieved a 15% reduction in heart rate at a maintenance dose of 150 micrograms/kg per min or less. A 20% reduction in heart rate was attained in 19 of the 24 patients, and conversion to sinus rhythm occurred during esmolol infusion in 5 of the 11 patients with atrial flutter or fibrillation. Transient asymptomatic hypotension (less than 90/50 mm Hg) was seen in 13 patients, requiring cessation of esmolol therapy in 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Fascicular conduction disturbances and ischemic heart disease: adverse prognosis despite coronary revascularization.

In patients with ischemic heart disease, fascicular conduction disturbances are associated with increased mortality. This study reveals that increased mortality also exists for certain types of fascicular conduction disturbances after myocardial revascularization. In 227 consecutive patients undergoing bypass surgery, 24 had preoperative and an additional 52 developed at surgery a fascicular conduction disturbance. At 66 +/- 14 months of follow-up, 6 (4%) of 148 control patients without pre- or postoperative fascicular conduction disturbances had died from cardiac causes. Although right bundle branch block and left hemifascicular block were the most common form of fascicular conduction disturbance, only 1 of 55 of these patients died (p = NS). Mortality rates were much higher for patients with left bundle branch block or an intraventricular conduction defect; 8 (38%) of 21 died from cardiac causes (p less than 0.05). A high risk subgroup was identified by comparing 14 consecutive patients with left bundle branch block or an intraventricular conduction defect who survived more than 1 year postoperatively with 21 consecutive patients with these same conduction defects who died within 1 year of surgery. The following variables were significantly (p less than 0.05) different (survivors versus nonsurvivors): age (58 +/- 7 versus 65 +/- 9 years); class IV angina (2 of 14 versus 16 of 21), prior myocardial infarction (9 of 14 versus 21 of 21), left ventricular ejection fraction (53 +/- 18 versus 41 +/- 15%), three vessel disease (9 of 14 versus 20 of 21) and left ventricular aneurysm (2 of 14 versus 13 of 21).(ABSTRACT TRUNCATED AT 250 WORDS)

Fibrinolytic therapy of St. Jude valve thrombosis under guidance of digital cinefluoroscopy.

Fibrinolytic therapy is an alternative to urgent reoperation for patients with St. Jude prosthetic valve thrombosis, but requires an accurate method for repeated assessment of prosthetic function. Since the St. Jude valve is not well visualized by conventional cinefluoroscopy, digital subtraction techniques were developed that improved visualization of the value and allowed assessment of leaflet separation and velocity. A 74 year old woman with prosthetic valve thrombosis 5 years after St. Jude aortic valve placement had an opening angle of 58 degrees (normal range 10 to 13; n = 8) with a maximal opening velocity of 1.37 degrees/ms (normal range 2.46 to 2.93). The closing angle was 125 degrees (normal range 120 to 127) with a maximal closing velocity of 1.38 degrees/ms (normal range 2.24 to 3.60). The patient received 250,000 U of streptokinase intravenously, then 100,000 U/h for 72 hours. Improvement in auscultatory findings occurred at 12 hours; repeat digital cinefluoroscopy showed an opening angle of 20 degrees with a maximal velocity of 2.77 degrees/ms, and a closing angle of 126 degrees with a maximal velocity of 1.91 degrees/ms. Digital cinefluoroscopy 4 weeks after discharge on warfarin and dipyridamole therapy was unchanged. There have been no thromboembolic complications after 6 months of follow-up. Thus, digital cinefluoroscopy is a new noninvasive technique that permits accurate measurement of normal and abnormal St. Jude leaflet function. Intravenous streptokinase dissolution of prosthetic valve thrombosis under digital cinefluoroscopic guidance may be an acceptable alternative to emergency reoperation. The frequency and significance of residual subclinical leaflet dysfunction after fibrinolytic therapy and the indications for elective reoperation require further evaluation.

Treatment of severe platelet dysfunction and hemorrhage after cardiopulmonary bypass: reduction in blood product usage with desmopressin.

Impairment of platelet function commonly occurs after cardiopulmonary bypass, and may result in substantial bleeding. Because desmopressin acetate (a synthetic analogue of vasopressin) shortens bleeding time in a variety of platelet disorders, a controlled clinical trial of intravenous desmopressin was performed in 39 patients with excessive mediastinal bleeding (greater than 100 ml/h) and a prolonged template bleeding time (greater than 10 minutes) more than 2 hours after termination of cardiopulmonary bypass. Twenty-three desmopressin recipients and 16 control patients (no desmopressin) were similar in surgical procedure, pump time, platelet count, template bleeding time and amount of bleeding before therapy (p = NS). Compared with the control group, the patients receiving desmopressin (20 micrograms; mean 0.3 micrograms/kg) utilized fewer blood products (29 +/- 19 versus 15 +/- 13 units/patient; p less than 0.05), especially platelets (12 +/- 9 versus 4 +/- 7 units/patient; p = 0.004), while achieving a similarly effective reduction in mediastinal bleeding (4.8- and 4.3-fold, p = 0.001 for both). Severe platelet dysfunction was partially corrected within 1 hour after desmopressin infusion, during which interval no blood products were administered: the template bleeding time shortened (from 17 to 12.5 minutes, p less than 0.05), whereas the platelet count remained unchanged (at 96 +/- 35 and 105 +/- 31 X 10(3)/mm3, p = NS). The plasma levels of two factor VIII components increased: procoagulant activity (VIII:C) from 0.97 +/- 0.43 to 1.52 +/- 0.74 units/ml (p less than 0.05) and von Willebrand factor (VIII:vWF) from 1.28 to 1.78 units/ml (p less than 0.05); these increases correlated with the shortening of the bleeding time (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic differentiation of pathologic and physiologic stenosis in mitral porcine bioprostheses.

Porcine bioprostheses are physiologically stenotic valves. Degenerative calcification leading to pathologic stenosis is an increasingly recognized serious late complication of mitral valve replacement with a porcine bioprosthesis. Hemodynamic differentiation of pathologic from physiologic stenosis is important for identification of porcine bioprosthetic valve dysfunction. In 42 patients with a normal Hancock porcine bioprosthesis (standard model, sizes 27 to 33 mm), mean diastolic flow (65 to 461 ml/s), mean gradient (2.0 to 13.4 mm Hg) and effective orifice area (1.1 to 4.4 cm2) were determined at rest, during epicardial pacing (90, 110 and 130/min) and with isoproterenol infusion. A statistically significant increase in mean gradient occurred with increases in flow and decreases in valve size (p less than 0.05). Effective orifice area increased significantly as flow rate increased and as valve size increased (p less than 0.05). These measurements were compared with those in 16 patients with pathologically confirmed porcine bioprosthetic valve stenosis: 8 patients with reoperation (1.1% per patient-year) 3 to 8.5 years after mitral valve replacement and 8 previously reported abnormal cases. Stenotic failure rate was inversely related to valve size (2.1, 1.4, 0.5 and 0% per patient-year for sizes 27 to 33 mm). Stenotic and normal bioprostheses were not accurately differentiated on the basis of a single value for gradient or effective orifice area. A mathematical model that related flow to the square root of the mean gradient allowed complete separation of stenotic from normal prosthetic valve function, after valve size was accounted for and normal confidence limits were established (r = 0.74 to 0.94, sizes 27 to 33, p less than 0.0001). The effective orifice area-flow relation did not provide accurate differentiation of abnormal from normal function. Thus, normal mitral bioprostheses have significant transvalvular gradients whose magnitude depends on flow. Risk of stenotic failure is increased in the smaller valves, which have a larger gradient at implantation. Differentiation of pathologic from physiologic stenosis cannot be made on the basis of a single value for gradient or effective orifice area. Accurate hemodynamic differentiation is achieved by relating mean gradient to mean diastolic flow rate and valve size.

Atrial emptying with orthotopic heart transplantation using bicaval and pulmonary venous anastomoses: a magnetic resonance imaging study.

OBJECTIVES: We hypothesized that orthotopic heart transplantation with bicaval and pulmonary venous anastomoses preserves atrial contractility. BACKGROUND: The standard biatrial anastomotic technique of orthotopic heart transplantation causes impaired function and enlargement of the atria. Cine magnetic resonance imaging (MRI) allows assessment of atrial size and function. METHODS: We studied 16 patients who had undergone bicaval (n = 8) or biatrial (n = 8) orthotopic heart transplantation without evidence of rejection and a control group of 6 healthy volunteers. For all three groups, cine MRI was performed by combining coronal and axial gated spin echo and gradient echo cine sequences. Intracardiac volumes were calculated with the Simpson rule. Atrial emptying fraction was defined as the difference between atrial diastolic and systolic volumes, divided by atrial diastolic volume, expressed in percent. All patients had right heart catheterization. RESULTS: Right atrial emptying fraction was significantly higher in the bicaval (mean [+/- SD] 37 +/- 9%) than in the biatrial group (22 +/- 11%, p < 0.05) and similar to that in the control group (48 +/- 4%). Left atrial emptying fraction was significantly higher in the bicaval (30 +/- 5%) than in the biatrial group (15 +/- 4%, p < 0.05) and significantly lower in both transplant groups than in the control group (47 +/- 5%, p < 0.05). The left atrium was larger in the biatrial than in the control group (p < 0.05). Cardiac index, stroke index, heart rate and blood pressure were similar in the transplant groups. CONCLUSIONS: Left and right atrial emptying fractions are significantly depressed with the biatrial technique and markedly improved with the bicaval technique of orthotopic heart transplantation. The beneficial effects of the latter technique on atrial function could improve allograft exercise performance.

Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy: role of increased fibrosis in the generation of reentry.

OBJECTIVES: We sought to evaluate the characteristics of wave fronts during ventricular fibrillation (VF) in human hearts with dilated cardiomyopathy (DCM) and to determine the role of increased fibrosis in the generation of reentry during VF. BACKGROUND: The role of increased fibrosis in reentry formation during human VF is unclear. METHODS: Five hearts from transplant recipients with DCM were supported by Langendorff perfusion and were mapped during VF. A plaque electrode array with 477 bipolar electrodes (1.6-mm resolution) was used for epicardial mapping. In heart no. 5, we also used 440 transmural bipolar recordings. Each mapped area was analyzed histologically. RESULTS: Fifteen runs of VF (8 s/run) recorded from the epicardium were analyzed, and 55 episodes of reentry were observed. The life span of reentry was short (one to four cycles), and the mean cycle length was 172 +/- 24 ms. In heart no. 5, transmural scroll waves were demonstrated. The most common mode of initiation of reentry was epicardial breakthrough, followed by a line of conduction block parallel to the epicardial fiber orientation (34 [62%] of 55 episodes). In the areas with lines of block, histologic examination showed significant fibrosis separating the epicardial muscle fibers and bundles along the longitudinal axis of fiber orientation. The mean percent fibrous tissue in these areas (n = 20) was significantly higher than that in the areas without block (n = 28) (24 +/- 7.5% vs. 10 +/- 3.8%, p < 0.0001). CONCLUSIONS: In human hearts with DCM, epicardial reentrant wave fronts and transmural scroll waves were present during VF. Increased fibrosis provides a site for conduction block, leading to the continuous generation of reentry.