Systemic ventricular assist device support in Fontan patients: A report by ACTION.

BACKGROUND: The size of the Fontan population with end-stage heart failure is growing. In this population, heart transplantation has been the only option. This study sought to investigate the efficacy of ventricular assist device (VAD) support in Fontan patients. METHODS: We conducted a retrospective study of Fontan patients in the Advanced Cardiac Therapies Improving Outcomes Network. We evaluated patient characteristics, and the clinical and physiologic outcomes after VAD implantation. RESULTS: We identified 45 Fontan patients implanted with VAD. The average age of patients was 10 years (interquartile range: 4.5-18) and 30% were female. The majority had a morphologic right ventricle (69%), moderate or greater ventricular dysfunction (83%), and moderate or greater atrioventricular valve regurgitation (65%). The majority of implants were as a bridge to transplantation (76%), and the majority of patients were Interagency Registry for Mechanically Assisted Circulatory Support Profile 2 (56%). The most commonly employed device was the Medtronic HeartWare HVAD (56%). A total of 13 patients were discharged on device support, and 67% of patients experienced adverse events, the most common of which were neurologic (25%). At 1 year after device implantation, the rate of transplantation was 69.5%, 9.2% of patients continued to be VAD supported, and 21.3% of patients had died. Hemodynamically, VAD was effective in decreasing both Fontan and ventricular end-diastolic pressures in some individuals. CONCLUSIONS: VAD is effective in supporting patients with end-stage Fontan failure awaiting heart transplantation. Future research should focus on identifying clinical and physiologic characteristics predictive of a favorable response to VAD support.

Left main bronchus obstruction after patent ductus arteriosus ligation: an unusual complication.

This report discusses a premature complex newborn with persistent pulmonary difficulties following the clipping of the PDA. Bronchoscopy was critical in revealing a metallic clip obstructing the bronchus. Thoracothomy revealed that the clip had been placed across the bronchus. This case illustrates the importance of bronchoscopy in the face of persistent unexplained pulmonary symptoms as well as having clear intraoperative exposure of the anatomy in this region to assure accurate placement of PDA metallic clips.

Clostridium difficile colitis in children following lung transplantation.

Risk factors for Clostridium difficile diarrhea are antibiotic exposure, hospitalization, extreme ages, and immunodeficiency. Patients with CF have a high rate of colonization with C. difficile. We performed a retrospective chart review of patients at Texas Children's Hospital who underwent lung transplantation since the inception of our program in October 2002 until October 2008. There were 78 pediatric lung transplants performed at our institution during the study period. Four patients developed six total episodes of CDC for an overall incidence of 5.4%. CF was the underlying diagnosis in all four patients, leading to an incidence of 8.9% in patients with CF. Two patients developed colitis within the first four months following transplant, and the other two patients developed colitis more than three yr after transplantation. All four patients required hospitalization, and three patients were managed medically while one patient underwent diverting ileostomy. One experienced renal insufficiency and subsequently expired. Overall survival was 75% among patients with CDC following lung transplantation. CDC causes significant morbidity and mortality in children with CF who have undergone lung transplantation.

Mesenteric oxyhemoglobin desaturation improves with patent ductus arteriosus ligation.

Near-infrared spectroscopy was used to monitor cerebral and mesenteric regional oximetry in a preterm neonate undergoing surgical ligation of a patent ductus arteriosus. This patient initially demonstrated severe mesenteric oxyhemoglobin desaturation, which improved immediately following ductal ligation.

Pediatric mechanical circulatory support.

Over the past two decades clinicians and researchers have sought to bring mechanical circulatory support (MCS) to pediatric patients with heart failure. ECMO, IABPs, and VADs have all been used in infants and children as a bridge to myocardial recovery or as a bridge to transplant. However, until recently, a commitment by industry, government, and researchers towards the development of pediatric MCS has not been present, especially in the United States. Advancements in adult VAD design to smaller, quieter, and fully implantable pumps capable of complete outpatient support have sparked curiosity in the application of this technology to children. Also, the increasing success of palliating congenital heart disease is creating an ever-growing cohort of children and adolescents with heart failure. These changing demographics and technological advances have caused a refocus of attention. This is most clearly demonstrated by the international use of several established MCS pediatric and neonatal systems, by the FDAOs increasing proclivity to allow the use of international pediatric VADs in the USA, and by the recent National Heart, Lung, and Blood Institute funding of several institutions to develop pediatric VADs. This review describes the different aspects of pediatric MCS including indications, the features of the various VADs, and their current application in children worldwide.

Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device.

BACKGROUND: Support with a left ventricular assist device leads to normalization of left ventricular chamber geometry, regression of myocyte hypertrophy, alterations in left ventricular collagen content, and normalized expression of genes involved with excitation-contraction coupling in patients with heart failure. The objective of this study was to investigate the time course of these processes. METHODS: Passive left ventricular pressure-volume relationships were obtained from explanted hearts of 19 patients with heart failure undergoing transplantation without left ventricular assist device support, 25 patients with heart failure supported before transplantation (duration of support ranging between 8 and 155 days), and 5 normal human hearts not suitable for transplantation. Left ventricular size was indexed by the volume at which left ventricular pressure reached 30 mm Hg. Left ventricular tissue samples were probed for sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression and processed for analysis of myocyte diameter and relative myocardial collagen content. RESULTS: The volume at which left ventricular pressure reached 30 mm Hg was not significantly different between hearts without and with assist device support for less than 40 days. However, the volume at which left ventricular pressure reached 30 mm Hg in patients with assist devices supported for more than 40 days was significantly smaller than that of the hearts without assist devices but was larger than that of normal hearts. A similar pattern was observed for myocyte diameter. Sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression increased to normal levels by about 20 days of support with an assist device. Relative collagen content was significantly increased in hearts supported for more than 40 days. CONCLUSION: Maximum structural reverse remodeling by left ventricular assist devices is complete by about 40 days. Molecular reverse remodeling of sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression is quicker, being complete by about 20 days.

Recurrent remodeling after ventricular assistance: is long-term myocardial recovery attainable?

BACKGROUND: Long-term left ventricular assist devices (LVAD) have been used both as a bridge to heart transplantation and to recovery of native myocardial function. Despite much evidence for reversal of some of the structural and functional changes present in the failing heart during LVAD support, clinical evidence for sustained myocardial recovery is scant. We describe 2 patients in whom myocardial recovery during LVAD support led to device explanation only to have heart failure recur. This necessitated a second LVAD implantation, a process that we have termed recurrent remodeling. METHODS: The medical records of 2 patients with cardiomyopathy supported with HeartMate LVADs (Thermo Cardiosystems, Inc, Woburn, MA) were retrospectively reviewed. RESULTS: One patient was supported with an LVAD for 2 months, at which time the LVAD was explanted. Progressive deterioration of cardiac function followed, requiring a second LVAD 19 months after LVAD explanation. After 2 months of further LVAD support, a second episode of apparent myocardial recovery was observed during a period of device malfunction. The other patient was supported with an LVAD for 12 months, at which time the LVAD was explanted. The patient experienced progressive hemodynamic deterioration and required a second LVAD 6 months after LVAD explantation. Heart transplantations of both patients were successful. CONCLUSIONS: Our understanding of myocardial recovery in the setting of hemodynamic unloading with LVAD support has not yet progressed to the point where we are able to accurately predict successful long-term LVAD explantation. The evolution of reliable predictors of sustainable myocardial recovery will help to avoid further cases of recurrent remodeling requiring repeat LVAD implantation.

A randomized trial of antithrombin concentrate for treatment of heparin resistance.

BACKGROUND: Heparin resistance is an important clinical problem traditionally treated with additional heparin or fresh frozen plasma. We undertook a randomized clinical trial to determine if treatment with antithrombin (AT) concentrate is effective for treating this condition. METHODS: Patients requiring cardiopulmonary bypass who were considered to be heparin resistant (activated clotting time < 480 seconds after > 450 IU/kg heparin) were randomized to receive either 1000 U AT or additional heparin. RESULTS: AT concentrate was effective in 42 of 44 patients (96%) for immediately obtaining a therapeutic activated clotting time. This compared favorably to 28 of 41 patients (68%) treated with additional heparin (p = 0.001). All patients who failed heparin therapy were successfully treated with AT. The patients receiving AT required less time to obtain an adequate ACT but there was no difference in clinical outcomes among the groups. Study patients had deficient AT activity at baseline (56%+/-25%), which improved in those given AT concentrate (75%+/-31% versus 50%+/-23%, p < 0.0005). CONCLUSIONS: Heparin resistance is frequently associated with AT deficiency. Treating this deficiency with AT concentrate is more effective and faster for obtaining adequate anticoagulation than using additional heparin.

A technique of stapled gastrojejunostomy for open gastric bypass results in increased wound complication-rate.

BACKGROUND: Gastric bypass may be facilitated by a stapled gastrojejunostomy. This study compared two different techniques for performing this critical anastomosis in open surgery. METHODS: 67 consecutive patients were retrospectively studied for weight loss, hospital length of stay, anastomotic stricture, wound complication, and incisional hernia. 49 patients had a two layer hand-sutured gastrojejunostomy over a 34 Fr bougie via a laparotomy (sutured). 18 patients had a stapled gastrojejunostomy using the technique of Wittgrove and Clark via a laparotomy (stapled). All patients received prophylactic intravenous antibiotics preoperatively. RESULTS: Initial BMI, % of excess weight lost at 6 weeks and 6 months, and hospital length of stay were not statistically different between the groups. However, the rate of wound complication and incisional hernia rate were significantly higher in the stapled group when compared to the sutured group (p< 0.01). CONCLUSIONS: Based on these data we suggest that the technique of Wittgrove and Clark for performing the gastrojejunostomy should not be used in open gastric bypass as it results in increased rates of wound complication and incisional hernia.

Outpatient left ventricular assist device support: a safe and economical therapeutic option for heart failure.

The left ventricular assist device (LVAD), once considered for acute cardiac failure only when no other therapeutic option was available, is now used routinely at selected centers to allow the sickest patients to become self-sufficient and go home. This represents a dramatic change in the physician's perception of the LVAD in the early 1990s. The creation of these mechanical assist outpatient programs are possible for the following reasons: 1) confidence in the devices allow patients, their families, and health care providers to be more comfortable with outpatient therapy; 2) the devices are simplified and durable, allowing extended duration of support and more options for patients; and 3) a change in the perception of the LVAD from a last-resort therapeutic option to that of a safe and reliable bridge to recovery and transplant. With these general concepts in mind, programs have been created with specific safety nets, patient education goals, and discharge criteria. By using this construct, we have developed a successful outpatient LVAD program in which 70% of our vented electric LVAD patients were discharged with a 0% mortality and minimal morbidity. From our experience and studies, we believe that not only is an outpatient LVAD program safe and economical, but it is also socially, physically, and psychologically beneficial to the patient. In the current economic environment of cost containment, outpatient LVAD therapy is a necessary part of an LVAD program that should be sought by most cardiac mechanical assist programs.

Implantable left ventricular assist devices can successfully bridge adolescent patients to transplant.

BACKGROUND: Left ventricular assist devices (LVAD) have been used successfully as a life-sustaining bridge to transplantation in adults with end-stage heart failure. Long-term implantable cardiac assist devices for smaller adolescent patients are not yet available in the United States. METHODS: This study reviews the experience with patients less than 21 years old that received HeartMate LVADs (TCI) at our institution. Twelve patients were implanted with 13 LVADs. The patients ranged in age from 11 to 20 years (mean 16 years). Body surface area ranged from 1.4 to 2.2 m2 (mean 1.8 m2). Patients were selected for LVAD placement based on eligibility for heart transplant and evidence of end-organ dysfunction. Device placement in small patients was facilitated with prosthetic graft abdominal wall closure. No patient received systemic anticoagulation. RESULTS: The duration of LVAD support ranged from 0 to 397 days (mean 123 days). Seven of the 8 patients eligible for discharge from the hospital with a vented-electric LVAD were supported at home while awaiting transplantation. Outcomes of LVAD support were: LVAD explantation in 2 cases (15%), expiration with LVAD in place in 3 cases (23%), and successful transplantation in 8 cases (62%). Complications included 4 patients with systemic infection, 3 re-operations for hemorrhage, 1 embolic event, and 1 intraoperative air embolus that proved fatal. One explanted patient required a subsequent LVAD and the other expired 4 months after explantation. Six of the 8 transplanted patients are alive and well with follow-up ranging from 8 to 43 months. CONCLUSIONS: Adolescent patients with heart failure can be successfully supported on a long-term basis to heart transplantation with the HeartMate LVAD. The wearable device allows for discharge home while awaiting transplantation. Device explantation without subsequent transplantation can be unpredictable. The incidence of thromboembolism remains low despite the absence of systemic anticoagulation. The technique of prosthetic graft closure of the abdominal wall facilitates the use of this device in smaller patients.

Arginine vasopressin in the treatment of 50 patients with postcardiotomy vasodilatory shock.

BACKGROUND: The barroreflex-mediated secretion of arginine vasopressin has been found to be defective in a variety of vasodilatory shock states, such as postcardiotomy shock, and administration of the hormone markedly improves vasomotor tone and blood pressure. The high incidence of vasodilatory shock in patients undergoing left ventricular assist device (LVAD) implantation makes this population an ideal model in which to assess the risks and benefits of vasopressin. METHODS: The medical records of the 102 patients receiving LVADs at Columbia-Presbyterian Medical Center from January 1995 to August 1998 were reviewed. Fifty patients were eligible for study based on a history of arginine vasopressin administration in the operating room or intensive care unit within 24 hours of implantation. RESULTS: Despite LVAD implantation and the administration of vasopressors, patients were hypotensive with a mean arterial pressure less than 60 mm Hg. The administration of vasopressin (0.09+/-0.05 U/min) increased mean arterial pressure (58+/-13 to 75+/-14 mm Hg; p<0.001) while reducing norepinephrine administration (11.7+/-13 to 7.9+/-6.0 mcg/min; p = 0.023). There was no significant change in LVAD flow. The incidence of compromised regional perfusion was not different between LVAD patients who received vasopressin as compared to hemodynamically stable LVAD patients who did not receive vasopressin. CONCLUSIONS: We have demonstrated vasopressin at low doses to be a safe and an effective vasopressor in 50 patients with postcardiotomy vasodilatory shock.

Six-year experience of caring for forty-four patients with a left ventricular assist device at home: safe, economical, necessary.

OBJECTIVE: With increasing numbers of implantations, left ventricular assist device programs can put a financial strain on a hospital unless an efficient and safe outpatient program is developed. However, the left ventricular assist device is not widely recognized in the medical community as being reliable enough to support a patient at home. We reviewed our experience with these patients at home to assess the safety and the benefits of such a program. METHODS: Our institutional 6-year experience with 90 consecutive recipients of a wearable left ventricular assist device was analyzed. RESULTS: Forty-four (49%) of the 90 patients who received TCI vented-electric left ventricular assist devices (Thermo Cardiosystems, Inc, Woburn, Mass) were discharged, spending a total of 4546 days (12.5 years) at home with an average of 103 +/- 16 days of outpatient support (range 9-436 days). Of these 44 patients, all were successfully bridged to transplantation (42 patients, 96%) or planned explantation (2 patients, 4%). None of the outpatients died. The cumulative events per outpatient month were 0.020 for bleeding, 0.053 for device infection, 0.0068 for thromboembolus, and 0.020 for major malfunctions. Our estimated average cost to bridge a patient to transplantation or explantation once discharged is $13,200 and as an inpatient over the same length of time, including only room and board, is $165,200. Thirty percent of outpatients were able to return to work or school, 33% to sexual activity, and 44% to driving. All outpatients performed activities of daily living. CONCLUSION: Current left ventricular assist device technology provides effective and economical outpatient support and is associated with limited morbidity and a satisfactory quality of life.

Gender differences in patients undergoing coronary artery bypass surgery, from a mandatory statewide database.

OBJECTIVE: To determine why women have a higher mortality rate than men when undergoing coronary artery bypass grafting. DESIGN: Retrospective analysis of patients entered in a mandatory state database. PARTICIPANTS: 19,224 patients who underwent coronary artery bypass grafting in New York State in 1995. METHOD: The authors evaluated data pertaining to 27 variables. They conducted univariate analysis using the Student t test for continuous variables and the chi-square test or the Fisher exact test for discrete data. They conducted multivariate analysis using a logistic regression model. RESULTS: Analysis of body surface area revealed that smaller size was a risk factor for both women and men. Analysis of age demonstrated increased risk for mortality in women in both older and younger subpopulations. Other significant variables included a lesser degree of revascularization and less frequent use of the internal mammary artery in women. CONCLUSION: Smaller size and advanced age alone do not explain why female gender is an independent risk factor for mortality from coronary artery bypass grafting. Increased mortality is probably due to the fact that women have more comorbid conditions than men at the time of referral, perhaps because they are not being evaluated aggressively enough.

Left ventricular assist device bridge-to-transplant network improves survival after failed cardiotomy.

BACKGROUND: Postcardiotomy cardiogenic shock has been reported to occur following 2% to 6% of cardiac surgical procedures. Both the mandatory New York state cardiac surgery database and a voluntary ventricular assist device registry have reported hospital discharge rates of only 25% in postcardiotomy patients supported with ventricular assist devices. Although many centers have access to short-term mechanical cardiac assist devices, most lack a dedicated team which can resuscitate these critically ill patients. Equally important, these centers do not have easy access to effective cardiac replacement options, including implantable left ventricular assist devices (LVADs) and heart transplantation. METHODS: A referral network based upon the use of implantable LVADs as a bridge to transplantation in patients with postcardiotomy heart failure was established in the New York City region. Cardiac surgery centers were encouraged to contact our center early following any failed cardiotomy. RESULTS: Forty-four patients entered our postcardiotomy network: 12 recovered without an implantable LVAD, 23 received implantable LVADs, and six expired without long-term LVAD support. Of the 44 referrals, 29 (66%) survived to hospital discharge. Of the 23 patients receiving implantable LVADs, two recovered myocardial function and underwent LVAD explant, 14 were bridged to heart transplant, one underwent an emergent heart transplant, and six expired. Of the 23 implantable LVAD patients, 17 (74%) survived to hospital discharge. CONCLUSIONS: Regional networks centered around bridge-to-transplant facilities that have an aggressive approach to implantable LVAD placement may substantially improve the survival rate of patients with postcardiotomy heart failure.

Development of an off bypass mitral valve repair.

BACKGROUND: The Bow Tie Repair (BTR), a single edge-to-edge suture opposing the anterior and posterior leaflets of the mitral valve (MV), has led to satisfactory reduction of mitral regurgitation (MR) with few re-operations and excellent hemodynamic results. The simplicity of the repair lends itself to minimally invasive approaches. A MV grasper has been developed that will coapt both leaflets and fasten the structures with a graduated spiral screw. METHODS: Eleven explanted adult human MVs were mounted in a mock circulatory loop created for simulating a variety of hemodynamic conditions. The MV grasper was used to place a screw in each valve, which was then continuously run for 300,000 to 1,000,000 cycles with a fixed transvalvular pressure gradient. At the completion of these studies, the valves were stressed to a maximal transvalvular gradient for ten minutes. In seven cases, MR was induced and subsequently repaired using the MV screw. In vivo, the MV screw was tested in nine male canines. Through a subcostal incision, the MV grasper entered the left ventricle, approximated the mitral leaflets and deployed the MV screw under direct visualization via an atriotomy. Follow-up transthoracic echocardiograms were done at postoperative week 1, 6, and 12 to identify screw migration, MV regurgitation/stenosis or clot formation. Dogs were sacrificed up to postoperative week 12 to allow gross and histologic assessment. RESULTS: In vitro, no MV screw detached from the valve leaflets or migrated during the durability testing period of 6.8 million cycles, including periods of stress load testing up to 350 mm Hg. The percent regurgitant flow used to assess MR statistically decreased with the placement of the screw from 72 +/- 7% to 34 +/- 17%; p = 0.0025. In vivo, seven dogs whose valves were examined within the first 48 hours revealed leaflet coaptation with an intact MV screw and no evidence of MR. Two dogs, followed for a prolonged period, had serial postoperative echocardiograms demonstrating consistent coaptation, no screw migration, no clot, and no regurgitation or stenosis. In the animal sacrificed at 12 weeks, the MV screw was integrated into the tissue of both leaflets. CONCLUSIONS: The MV screw has provided durable leaflet coaptation and has reduced regurgitation in human MVs. Initial data on the MV screw's biocompatibility and interactions with living valve tissue is promising. Our early success supports further efforts towards the maturation of this prototype into off bypass mitral valve repair technology.

Experimental confirmation of effectiveness of fenestration in acute aortic dissection.

BACKGROUND: Aortic fenestration is used clinically to treat organ ischemia in acute descending aortic dissection. However, fenestration has not been studied experimentally. This study does so using an animal model. METHODS: Descending aortic dissection was created in six dogs, with subsequent fenestration of the infrarenal aorta. Blood flow (femoral, cephalic, and renal), blood pressure (femoral and carotid), and aortic distensibility were measured at baseline, after dissection, and after fenestration. Values were compared using paired t tests. RESULTS: Baseline femoral, cephalic, and renal arterial flows were 53+/-37, 78+/-65, and 83+/-52 mL/min, respectively. Baseline femoral and carotid pressures were 82+/-13 and 81+/-11 mm Hg, respectively. After dissection, femoral, cephalic, and renal arterial flow decreased to 20+/-21 (p < 0.05), 38+/-26, and 56+/-36 mL/min, respectively. Femoral blood pressure decreased to 28+/-17 mm Hg (p < 0.05). With fenestration, femoral, cephalic, and renal flows increased to 60+/-37 (p < 0.05), 78+/-51, and 80+/-48 mL/min, respectively. Femoral blood pressure increased to 85+/-28 mm Hg (p < 0.05). Carotid pressure remained unchanged with dissection and fenestration (77+/-17 mm Hg, 82+/-17 mm Hg, respectively). Baseline aortic distensibility (21%) decreased significantly after dissection (to 1.4%, p < 0.05) and increased after fenestration (to 12%, p < 0.05). CONCLUSIONS: Experimental aortic fenestration restored blood pressure and flow to hypoperfused organs in acute descending aortic dissection. The continued clinical application of fenestration is supported.

Results of coronary artery bypass grafting by a single surgeon in patients with left ventricular ejection fractions < or = 30%.

Despite the ominous prognosis of severe left ventricular (LV) dysfunction from coronary artery disease, coronary artery bypass grafting (CABG) in this setting remains controversial because of concerns over high operative risk and low likelihood of functional or survival benefit. We analyzed 135 consecutive patients (113 men, 22 women; age 42 to 87 years, mean 66.5) with LV ejection fraction (EF) < or =30% undergoing isolated CABG by 1 surgeon over an 8-year period. LVEF ranged from 10% to 30% (mean 23.6%). Preoperatively, 63% of patients had angina, 61% had heart failure (23% with pulmonary edema), and 24% manifested severe ventricular arrhythmia. The mean number of grafts was 2.7 per patient. The internal mammary artery was used in 103 of the 120 grafts (86%) to the left anterior descending coronary artery. Seven patients (5.2%) died in hospital. Only 2 of 99 patients (2%) not in intensive care preoperatively died in hospital. Angina class improved by 2.0 categories and congestive heart failure class by 1.5 categories. LVEF (assessed in 104 of 128 hospital survivors) improved from 24% preoperatively to 34% postoperatively (p <0.0001). At 1, 3, and 4.5 years respectively, all-cause survival was 87%, 81%, and 71%, and freedom from cardiac death was 90%, 85%, and 80%. CABG in patients with coronary artery disease and advanced LV dysfunction: (1) can be performed relatively safely, (2) achieves good long-term survival, (3) improves LVEF, (4) improves quality of life, and (5) can safely utilize the internal mammary artery as a conduit. The use of CABG is encouraged for patients with advanced LV dysfunction and may provide a viable alternative to transplantation in selected patients.