Echocardiographic evaluation of patients with a left ventricular device.

Limited donor heart availability is primarily responsible for the renewal of interest in mechanical left ventricular assist devices (LVADs) as a bridge to transplantation. Donor availability is unlikely to increase significantly in the near future. Experience to date has shown that many patients can be maintained long enough to undergo transplantation, and LVADs may be acceptable as alternate therapy in some who may not be candidates for transplantation. However, criteria for noninvasive evaluation of patients on LVADs have not been developed. In a prospective study using serial echocardiography, we found that aortic valve opening, aortic forward flow, nonlaminar flow in the left ventricle, and mismatch of Doppler derived cardiac output at the pulmonic valve and device output are associated with device malfunction. Echocardiography was diagnostic in five of six patients with clinical instability unrelated to the device. These findings suggest that echocardiography is helpful in the routine evaluation of patients on LVADs.

Fluoroscopy and selective angiography of left ventricular assist system inflow cannula as a method of detecting cannula entrapment.

Left ventricular assist systems have become an important tool as a bridge to cardiac transplantation. Malfunction of these devices often leads to clinical and hemodynamic deterioration. One potential complication is the obstruction of the inflow cannula secondary to remodeling of the left ventricular cavity. We report two cases where fluoroscopy and selective angiography were used to visualize the orientation and obstruction of the inflow cannula when echocardiographic findings were indeterminant.

Activity of costal and crural diaphragm during progressive hypoxia or hypercapnia.

Because costal and crural diaphragm segments have different functional characteristics, ventilatory stimulation with hypoxia or hypercapnia may elicit differential segmental function. We report measurements of diaphragm segmental length, shortening, and electromyogram (EMG) activity from 11 canines that were chronically implanted with sonomicrometry transducers and EMG electrodes and then studied a mean of 18 days postimplantation while awake and breathing spontaneously during CO2 rebreathing and progressive isocapnic hypoxia. Ventilatory responses to hypercapnia and progressive hypoxia were moderate at 1.13 +/- 0.31 (SD) 1. min-1. mm-1 arterial Pco2 and -0.98 +/- 0.51 l. min-1.%arterial O2 saturation-1. When tidal values for breathing pattern and segmental function were compared at matching tidal volumes that correspond to mean CO2 of 49.4 arterial Pco2 and 77% arterial O2 saturation, there was no significant difference in resting length, tidal shortening, or tidal EMG of costal or crural segments. Intrabreath profiles of flow, shortening, and EMG activity at matched tidal volumes showed that 1) inspiratory flow during hypoxia was significantly greater during early inspiration, 2) crural EMG activity preceded costal EMG activity in early inspiration during both hypercapnia and hypoxia, 3) both segments showed increased postinspiratory inspiratory activity with stimulated ventilation, and 4) postinspiratory shortening and EMG were greatest for the crural segment during hypoxia. These results suggest that costal and crural diaphragm segments exhibit differential function during chemical stimulation, especially during postinspiration.

Use of the omentum in the management of sternal wound infection after cardiac transplantation.

Seven patients with deep sternal wound infection after orthotopic cardiac transplantation were treated at the Medical College of Virginia-McGuire Veterans Administration Hospitals over a 3-year period. Six patients had mediastinitis with pericardial abscess, and one patient had only sternal osteomyelitis. All patients underwent prompt sternal debridement. In the six patients with mediastinitis, the transplanted heart was surrounded by a large dead space after debridement. This space appeared to result from a size mismatch between the remaining enlarged pericardial sac and the new normal-sized transplanted heart. Wound closure was done at the time of debridement in all patients except one who was closed 3 days later. A pedicled omental flap based on the right gastroepiploic artery was used in five of the six patients with mediastinitis, and these five patients healed their wounds and resolved their infection. Three of these patients are alive and well and two died of later complications other than sternal infection. The patient with only sternal osteomyelitis healed uneventfully. When mediastinitis and intrapericardial infection is present after cardiac transplantation, the omentum appears to provide adequate bulk for obliteration of the large dead space that remains after debridement. This surgery, combined with antibiotic therapy and temporary reduction of immunosuppression, can treat sternal wound infection successfully after cardiac transplantation. Mortality from other complications can occur, however, and not all patients survive.

Noninvasive detection of transplant coronary artery disease by dobutamine stress echocardiography.

Coronary artery disease has emerged as the leading cause of late morbidity and mortality in heart transplant recipients. The incidence of allograft coronary artery disease has been reported to be as high as 40% to 50% by 5 years. Coronary angiography remains the standard approach for surveillance of coronary artery disease in this patient population. However, the detection and surveillance of allograft coronary disease by noninvasive methods remains a challenge. The purpose of this study was to determine the value of dobutamine stress echocardiography as a noninvasive screening test to rule out the presence of anatomically significant allograft coronary artery disease and to assess its prognostic power. Dobutamine stress echocardiography was carried out according to a standard protocol in which dobutamine was infused at 5, 10, 20, 30, and 40 micrograms/kg/min intravenously at 5-minute stages with 12-lead electrocardiogram and blood pressure monitoring. Left ventricular wall motion was analyzed at baseline and at peak dobutamine dose. Mean age (+/- standard error of the mean) of the study population was 50.5 +/- 1.5 years, and mean duration (+/- standard error of the mean) since transplantation was 57 +/- 5 months. The sensitivity, specificity, and positive and negative predictive accuracy of dobutamine stress echocardiography were 95%, 55%, 69%, and 92%, respectively. In the 12-month follow-up study 12 patients with abnormal dobutamine stress echocardiographic findings had 15 major cardiac events whereas no event occurred in patients with normal dobutamine stress echocardiograms.(ABSTRACT TRUNCATED AT 250 WORDS)

Costal and crural diaphragm function during panting in awake canines.

During natural panting for thermal regulation, the pattern of activation of the major respiratory muscles, including costal and crural diaphragm segments, is not known. We measured diaphragm segmental length, shortening, and electromyographic (EMG) activity in five chronically implanted canines awake and breathing spontaneously at rest and during a mild dry heat stress. During panting, minute ventilation increased fourfold from 5.07 l/min and respiratory rate increased from 16.9 to 192.8 breaths/min or 3.2 Hz. During panting, end-expiratory length of both costal and crural segments decreased, concurrent with significant increases in end-expiratory EMG. With the onset of panting, tidal costal shortening decreased significantly from 6.29% of end-expiratory length to 3.54%, whereas crural shortening decreased from 6.04 to 2.46%. Meanwhile, segmental EMG tended to increase during panting. During panting, intrabreath costal and crural segmental function revealed differential activation; the costal segment shortened in concert with inspiratory flow, whereas peak crural shortening occurred in expiration, almost 180 degrees out of phase with costal. The divergence in segmental shortening during panting was accompanied by a lesser shift in timing of segmental EMG. In the awake spontaneously panting canine, asynchronous costal and crural shortening may enhance gas mixing in a manner analogous to high-frequency ventilation.

Atrioventricular fistula: an unusual complication of endomyocardial biopsy in a heart transplant recipient.

Endomyocardial biopsy remains the primary method for diagnosis of cardiac allograft rejection. Generally, endomyocardial biopsy is considered a relatively safe procedure in heart transplant recipients. Complications that have been reported are related to catheter insertion and include carotid arterial puncture, prolonged bleeding, vasovagal reaction, ventricular tachyarrhythmias, and transient conduction abnormalities. Serious complications such as right ventricular perforation with cardiac tamponade may also occur. Most complications are usually without significant long-term sequelae. This report describes an unusual case of atrioventricular fistula between the right atrium and left ventricle that occurred during a routine endomyocardial biopsy in a heart transplant recipient. Sudden hemodynamic compromise developed in this patient soon after heart biopsy associated with hemodynamic picture of high-output heart failure. Right heart catheterization, including oximetry, peripheral venous contrast echocardiography, color flow Doppler studies, and transesophageal echocardiography confirmed the diagnosis of fistulous communication between the right atrium and left ventricle, most likely through the membranous interventricular septum. Conservative medical management resulted in striking clinical improvement within 48 hours commensurate with spontaneous closure of the right atrium-to-left ventricle fistula documented by hemodynamic and echocardiographic studies.

Prolonged survival after heart-lung transplantation in systemic lupus erythematosus.

Patients with multisystem involvement of connective tissue disorders are generally excluded from consideration for heart-lung and lung transplantation because of profound donor organ shortages. A 23-year-old woman with systemic lupus erythematosus (SLE) was referred for evaluation of severe, progressive pulmonary hypertension. She underwent an uneventful heart-lung transplant and received cyclosporine A, azathioprine, and prednisone on a long-term basis. Bronchiolitis obliterans resulted in the development of moderate airflow obstruction 18 months after transplantation, but the process was stabilized with augmented immunosuppression consisting of high-dose parenterally administered corticosteroids, and subsequently a course of antithymocyte globulin. Four years after transplant, despite the persistence of reduced complement levels, the patient remains functionally well without clinical manifestations of SLE. This patient's long-term successful outcome indicates that connective tissue disorders such as SLE do not necessarily represent absolute contraindications to heart-lung and lung transplantation.

Coronary collateral circulation in the transplanted heart.

BACKGROUND: The concept that coronary collateral (CC) circulation can develop in cardiac transplant recipients (CTR) is controversial. Indeed, a decreased occurrence of CC in CTR has been previously reported. METHODS AND RESULTS: We reviewed 102 coronary angiograms in 73 CTR to evaluate the presence and significance of CC in denervated human hearts. These angiograms were compared with angiograms of 70 nontransplanted patients. Twenty-six CTR who had undergone at least two coronary angiograms, thus allowing comparative evaluations, form the basis for this study. Angiograms were analyzed using a modification of CC classification (Rentrop et al) from grade 0 for complete absence to grade 4 representing mature collateral with clear filling of epicardial vessels. Coronary artery disease was classified according to the scheme reported by Gao et al. For the purpose of this study, all type A lesions were grouped as large vessel disease (LVD), and types B1, B2, and C were collectively grouped as small vessel (epicardial) disease (SVD). The presence of CC circulation in all 73 CTR was grade 0, 7 (10%); grade 1, 41 (56%); grade 2, 33 (45%); grade 3, 30 (41%); and grade 4, 5 (7%). However, in control nontransplanted subjects grades 0, 1, 2, 3, and 4 were found in 47 (67%), 22 (31%), 4 (6%), 11 (15%), and 16 (20%) patients, respectively. The presence of mature collaterals (grade 4) in both groups were associated with type A lesions and was frequent in nontransplanted hearts. In contrast, grade 2 and grade 3 vascular channels probably representing CC with "myocardial blush" was more frequent in CTR and was mostly associated with small vessel coronary arteriopathy. CONCLUSIONS: These results suggest the presence of atypical CC in patients with cardiac allograft arteriopathy. It is speculated that this atypical form of CC with "blush pattern" may represent an angiogenic response to microvascular ischemia due to allograft coronary arteriopathy.

Costal and crural diaphragm function during CO2 rebreathing in awake dogs.

If costal and crural diaphragm segments can perform as separate muscles, then CO2-stimulated ventilation may elicit differential segmental function. We studied diaphragm segmental length, shortening, and electromyogram (EMG) activity in 10 awake dogs chronically implanted with sonomicrometer transducers and EMG electrodes. During CO2 rebreathing, segmental shortening and EMG activity per whole tidal breath progressively increased, but segmental responses could not be differentiated at any level of CO2. With increasing CO2, resting end-expiratory length of both diaphragm segments increased. During the complete intrabreath inspiratory-expiratory cycle, costal and crural diaphragm revealed distinctive segmental function. At rest, crural shortening exceeded costal shortening in earliest inspiration, costal and especially crural shortening persisted into early expiration, and EMG activity of the crural segment was greater than that of the costal segment in earliest inspiration and showed more end-inspiratory/early expiratory [post-inspiratory inspiratory activity (PIIA)] activity. During CO2-stimulated breathing, neither segment shortened during the inspiratory flow of earliest inspiration. During CO2 rebreathing, shortening of the crural segment exceeded that of the costal segment during early inspiration and outlasted costal shortening during expiration; for both segments, shortening persisted after termination of inspiratory airflow. With increased CO2, EMG activity of the crural segment preceded that of the costal segment in earliest inspiration and was dominant into expiration, whereas costal EMG activity terminated abruptly with inspiratory flow. Thus, costal EMG PIIA was not evident during hypercapnia, whereas crural EMG PIIA was significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac preservation by continuous perfusion of the University of Wisconsin solution.

Recent studies have shown that the University of Wisconsin (UW) solution may be superior to standard solutions in preserving the isolated heart before transplantation. The authors compared the UW solution with a modified Krebs-Henseleit solution in a continuous hypothermic coronary perfusion model. Hearts from mongrel dogs were rapidly excised after hyperkalemic arrest with standard cardioplegia and were mounted in a perfusion apparatus for 24 hours. Twelve hearts were perfused with the Belzer UW solution (group 1), and 15 hearts were perfused with a modified Krebs-Henseleit solution (group 2). The hearts were transplanted in a cross-circulation model, and parameters of function (developed pressure [dP] and rate of pressure development [+/- dP/dt]) were measured. Mean (+/- SEM) developed pressure was 80 +/- 7 mm Hg in group 1 and 56 +/- 9 mm Hg in group 2 (p less than 0.05). The +dP/dt was 1433 +/- 126 mm Hg/s in group 1 and 843 +/- 154 mm Hg/s in group 2 (p less than 0.005), and the -dP/dt was 958 +/- 110 mm Hg/s in group 1 and 676 +/- 106 mm Hg/s in group 2 (p less than 0.05). The UW-preserved hearts also required fewer defibrillations (0.75 +/- 0.13) to establish a stable rhythm than the control hearts (5.87 +/- 2.07, p less than or equal to 0.02). There were no significant differences in weight gain, coronary resistance or creatine phosphokinase levels between the two groups. The authors conclude that the UW solution provides better preservation of function than a modified Krebs-Henseleit solution for continuous coronary perfusion.

Cardiac transplantation: treatment for cardiogenic shock.

Eighty-six patients received orthotopic cardiac transplants at the Royal Victoria Hospital in Montreal between 1985 and 1989. Of these, 16 mortally ill, being sustained in hospital by the intravenous administration of inotropic agents (15 patients [94%]) or intra-aortic balloon counterpulsation (6 [38%]). There was one early death (at 7 days), for a death rate of 6.3% (versus 8.6% for the 70 "elective" transplants). Two others died of delayed infection: one of viral hepatitis at 6 weeks, and one of pneumonia due to Pneumocystis 4 months after transplantation. The other 13 patients are alive and well 12 to 66 months postoperatively. Nine have returned to their preoperative work, three have decreased activity levels but are functioning well, and one is retired.

Cardiac transplantation with corticosteroid-free immunosuppression: long-term results.

To assess the long-term safety of an immunosuppressive regimen without corticosteroids, we retrospectively evaluated 42 long-term (greater than 1 year) survivors of orthotopic cardiac transplantation. We determined the incidence of (1) conversion of the immunosuppressive regimen from cyclosporine and azathioprine alone (group I) to cyclosporine, azathioprine, and prednisone (group II), (2) late acute graft rejection (defined as occurring at greater than 1 postoperative year), and (3) major postoperative complications related to corticosteroids. Of the 42 patients who were started on cyclosporine and azathioprine, 48% remained in group I, and 52% converted to group II. Forty-five percent of group II patients were able to taper and discontinue prednisone in 15.6 +/- 2.2 months. Among the patients on long-term corticosteroid-free immunosuppression, the incidence of late rejection was 2.1% per endomyocardial biopsy. The incidence of late infectious episodes was not significantly different between the two groups of patients, although diabetes mellitus and hypercholesterolemia were more prevalent in group II than in group I. These data suggest that cardiac transplant recipients who chronically remain on corticosteroid-free immunosuppression represent a select group of patients with an acceptably low risk of late graft rejection and associated reduction of potential risk factors of accelerated coronary artery disease.

Pulmonary denervation in humans. Effects on dyspnea and ventilatory pattern during exercise.

The role of the pulmonary autonomic nerves in the mediation of respiratory sensation is unclear. Pulmonary neurogenic mechanisms may contribute to dyspnea either directly or indirectly via an influence on the pattern of ventilation. Using human heart-lung transplantation as a model of pulmonary denervation, we studied the ventilatory response, respiratory drive (P0.1), and sensation of breathlessness (modified Borg scale) during maximal incremental bicycle exercise. The subjects were four female heart-lung transplant recipients 3 to 9 months post-transplant and 10 age-matched control subjects. The ventilatory response to increasing CO2 output (VCO2) was higher (p less than 0.001) in transplant recipients than in control subjects, such that ventilation at peak exercise was similar in the two groups despite a lower peak VCO2 in transplant recipients. The ratio of tidal volume to inspiratory capacity increased with increasing ventilation in a similar fashion in both groups. Although the respiratory rate increased more quickly in transplant recipients, it was similar at peak ventilation in the two groups. Ventilatory timing and duty cycle at half-peak and peak ventilation were similar in transplant recipients and control subjects. Dyspnea ratings were not different between the two groups at similar levels of ventilation. Dyspnea as a function of P0.1 was also similar in transplant and control groups. These results indicate that pulmonary neurogenic mechanisms play a role in determining the level, but not the pattern, of ventilation during exercise. Furthermore, these pathways do not appear to contribute significantly to the perception of breathlessness in normal humans.

Coronary artery bypass profile in Canada and the United States.

This study compares computer registry data on coronary bypass surgery from several centres in Canada and the United States to assess current trends in patient profile, and looks at demand and resources available for this form of treatment. A computerized registry established at the Royal Victoria Hospital in 1982 was used to document the profile of patients undergoing coronary artery bypass graft. Comparing 1988 to the previous six years (1982-87), a significant increase was found in patients with unstable angina (P less than 0.001) and abnormal left ventricular function (P less than 0.015) among those operated. The incidence of emergency operations also increased (P less than 0.001). The patient profile was similar to that of the Toronto university hospital population and many major United States university hospitals. The incidence of coronary artery bypass graft per 100,000 population, however, is much greater in the United States than in Canada (120 versus 56). Resources in many Canadian centres appear to be insufficient to meet demand for this type of surgical intervention.

Adenosine enhances left ventricular flow during 24-hour hypothermic perfusion of isolated cardiac allografts.

Left ventricular flow progressively decreases during preservation of ex vivo hearts by continuous hypothermic perfusion, according to previous studies. This study was done to determine whether left ventricular flow could be maintained during 24-hour hypothermic perfusion by the addition of adenosine to the perfusate. Isolated canine hearts were perfused with either a modified Krebs-Henseleit solution or with the control solution containing adenosine (20 mumol/L) for either 4 or 24 hours. On completion of the perfusion period, radioactive microspheres were injected into the arterial inflow of the hearts. Myocardial samples were then taken from the endocardial, midcardial, and epicardial portions of the free wall and papillary muscles of the right and left ventricles, as well as the interventricular septum. Concentrations of radioactivity were determined for each sample, summed, and averaged for each ventricle. The ratio of average concentrations (L/R ratio) was significantly increased in the 24-hour adenosine hearts compared with 24-hour controls (1.10 +/- 0.15 vs 0.64 +/- 0.21, p less than 0.005). The L/R ratio of 4-hour controls (1.30 +/- 0.48) was also greater than that of 24-hour controls (p less than 0.005). These results suggest that left ventricular flow decreases during continuous hypothermic perfusion. The tendency toward diminished left ventricular perfusion after 24 hours is reduced when adenosine is added to the perfusate. Adenosine may be beneficial in ex vivo heart preservation with hypothermic perfusion by improving left ventricular flow.

General surgical procedures after heart transplantation.

Seventy-eight cardiac transplantations were performed between July 1982 and March 1989. The perioperative death rate was 10%. Overall survival was 86%. Among the long-term survivors, 14 patients underwent 16 noncardiac surgical procedures. Seven of them required emergency laparotomy, four for biliary tract disease, one for ruptured abdominal aortic aneurysm, one for suspected abdominal sepsis and one for enterocolitis. Elective surgical interventions included repair of symptomatic abdominal wall hernia, treatment of hemorrhoids or perianal condylomas, total hip arthroplasty, maxillary sinus drainage and resection of a duodenal villous adenoma. Preoperatively, all patients received cyclosporine orally. Ten of the 14 patients were on triple-drug immunosuppression (cyclosporine, azathioprine and low-dose prednisone [less than 0.20 mg/kg daily]). The remaining four patients took cyclosporine with either azathioprine or prednisone. There were no deaths. Complications were limited to residual choledocholithiasis treated by percutaneous removal, two cases of wound infection and an incisional hernia. The authors' experience indicates that noncardiac surgical procedures may be safely performed in patients who have received a heart transplant.

Enhanced 24-hour in vitro heart preservation with adenosine and adenosine monophosphate.

Continuous hypothermic perfusion is an effective means of preserving ex vivo cardiac allografts. Using canine hearts, we assessed the ability of the high-energy phosphate precursors adenosine and adenosine monophosphate to enhance the protective effect of continuous hypothermic perfusion. Group 1 hearts (controls) were perfused for 24 hours with a modified Krebs-Henseleit solution. Group 2 hearts were perfused with control perfusate to which adenosine was added (20 mumol/L). Group 3 hearts were perfused with control perfusate with adenosine monophosphate (0.1 mmol/L). After perfusion heart weights increased similarly in all groups. Coronary vascular resistance increased during the preservation period in group 1 hearts, but decreased in groups 2 and 3 hearts. Developed pressures were 103 +/- 22 mm Hg in group 1, 163 +/- 27 mm Hg in group 2 (p less than 0.01), and 141 +/- 34 mm Hg (p less than 0.05) in group 3. The rate of pressure development in group 2 (2143 +/- 249 mm Hg) and group 3 (2059 +/- 395 mm Hg) hearts was significantly greater than in group 1 hearts (1434 +/- 363 mm Hg, p less than 0.01). Only group 3 myocardial adenosine triphosphate levels were significantly greater than controls (3.18 +/- 0.52 mumol/gm vs 2.12 +/- 0.74 mumol/gm, p less than 0.05) on completion of perfusion. Myocardial lactate levels at this time were significantly higher in group 1 hearts (7.48 +/- 3.96 mumol/gm) compared with groups 2 and 3 (0.34 +/- 0.58 mumol/gm and 1.50 +/- 0.91 mumol/gm, respectively, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)