Francis X Downey

Purely internal thoracic artery grafts: outcomes

BACKGROUND Most of our patients with coronary artery disease have undergone bypass exclusively with purely internal thoracic artery grafts (PITA). Our goal has been to lengthen the time a patient benefits from coronary bypass operations. The present report describes an 8.5-year study of outcomes including mortality and the need for reintervention in patients who have undergone bypass with PITA. METHODS We studied 897 patients who underwent PITA with a total of 3,784 internal thoracic artery (ITA) grafts (4.2 grafts per patient). Connecting ITA to ITA along with sequential anastomosis made the procedure possible. RESULTS Early mortality for the group was 2.3%. Freedom from death was 86% and freedom from reintervention was 94% at 5 years after the operation. CONCLUSIONS The acceptable early and late mortality and the 94% freedom from reintervention as long as 8.5 years after operation in this group of patients inspire us to continue choosing PITA for patients with three-vessel coronary artery disease.

Practical value of identifying antibodies to cryptic HLA epitopes in cardiac transplantation

BACKGROUND Identification of antibodies to human leukocyte antigens (HLA) by single antigen bead arrays has led to the common practice of virtual crossmatching. However, inappropriate assignment of anti-HLA specificities can lead to false-positive virtual crossmatching, resulting in the decline of potentially crossmatch-negative organ offers. In this study we describe identification of antibodies to cryptic HLA present on denatured forms of HLA on single antigen bead array and provide a reassessment of calculated panel-reactive antibody (CPRA) based on elimination of false-positive reactions due to antibodies to cryptic HLA epitopes. METHODS Sera from 96 patients with positive HLA antibodies detected on a standard single antigen bead platform were tested under denaturing conditions and with a new single antigen bead product (iBeads; One Lambda, Inc., Canoga Park, CA) to identify antibodies to cryptic HLA vs. native HLA. Flow cytometry crossmatching and complement-fixation assays were performed to assess clinical relevance. RESULTS Antibodies to cryptic HLA were present in approximately 21% of patients on our waiting list for cardiac transplantation. These antibody responses were not associated with factors commonly thought to be associated with antibody responses to HLA such as age, gender, transfusions or presence of circulatory support. CONCLUSIONS Antibodies to cryptic HLA can be reliably identified by iBeads technology, and usually do not fix complement nor produce positive flow cytometry crossmatches. Identification and removal of antibodies to cryptic HLA from the panel of unacceptable antigens may have dramatic and meaningful effects on CPRA and virtual crossmatch strategies.

Transsternal repair of coarctation and associated cardiac defects

Over a 13-year period, 20 infants and children underwent transsternal approach for repair of coarctation and associated cardiac defects. Fifteen patients (75%) were operated on in the last 6 years. Thirteen patients (group 1) had intracardiac shunts and 7 (group 2), intracardiac obstruction or valvular insufficiency. Group 1 had a mean age of 0.8 +/- 1.9 years versus 4 +/- 3 years for group 2 (p = 0.05). There were 12 patients (92%), 7 months old or less in group 1. Aortic arch hypoplasia was present in 6 patients in group 1. A large patent ductus arteriosus was present in 5 of these 6 patients versus no patent ductus arteriosus in patients without aortic arch hypoplasia (p = 0.006). The mean pulmonary blood flow to systemic blood flow ratio in group 1 was 3.8 +/- 2 and the mean right ventricular to left ventricular ratio, 0.8 +/- 0.2. The coarctation repair fell mostly into three types: side patch aortoplasty (8), ductal tissue excision and patch aortoplasty of the concavity of the aortic arch (6), and subclavian aortoplasty (4). There was one early death (5%) which was due to sepsis in a newborn. Another newborn who had subclavian aortoplasty needed a left carotid artery--descending aorta bypass conduit early because of aortic arch hypoplasia. All patients were followed to 12 years (mean follow-up, 4.3 +/- 3.5 years). There were no late deaths. Two patients had recurrent coarctation, 1 after an end-to-end repair and the other because of incomplete arch enlargement after a side patch aortoplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Transition from cardiopulmonary bypass to the HeartMate left ventricular assist device

BACKGROUND Safe transition from cardiopulmonary bypass to the HeartMate left ventricular assist device without periods of low output, air emboli, or injury to the right ventricle is vital to its successful implantation. A right atrial-to-left ventricular shunt has been developed to purge quickly and completely all air from the system and prevent its reentry, as well as to assist the right ventricle during the transition from cardiopulmonary bypass to the HeartMate. METHODS From January 1994 through July 1996, we used an extracorporeal membrane oxygenation right atrial-to-left ventricular shunt during 17 HeartMate implantations in 16 patients. The shunt consists of the existing right atrial two-stage cannula, the bypass circuit, and a separate aortic line that fills the left ventricle using a 21F cannula in the lateral ventricular wall. Air is monitored in the heart and aorta using transesophageal echocardiography. RESULTS Ten of the 16 patients are living and 8 have undergone transplantation. Two patients are still using the device and are awaiting transplantation. None of the patients have experienced postoperative neurologic events suggestive of air emboli. CONCLUSIONS The extracorporeal membrane oxygenation right atrial-to-left ventricular shunt is simple and inexpensive to construct. It provides for a smoother and safer transition from cardiopulmonary bypass to the HeartMate left ventricular assist device.

Enhanced store-operated Ca2+ influx and ORAI1 expression in ventricular fibroblasts from human failing heart

ABSTRACT Excessive cardiac fibrosis, characterized by increased collagen-rich extracellular matrix (ECM) deposition, is a major predisposing factor for mechanical and electrical dysfunction in heart failure (HF). The human ventricular fibroblast (hVF) remodeling mechanisms that cause excessive collagen deposition in HF are unclear, although reports suggest a role for intracellular free Ca2+ in fibrosis. Therefore, we determined the association of differences in cellular Ca2+ dynamics and collagen secretion/deposition between hVFs from failing and normal (control) hearts. Histology of left ventricle sections (Masson trichrome) confirmed excessive fibrosis in HF versus normal. In vitro, hVFs from HF showed increased secretion/deposition of soluble collagen in 48 h of culture compared with control [85.9±7.4 µg/106 cells vs 58.5±8.8 µg/106 cells, P<0.05; (Sircol™ assay)]. However, collagen gene expressions (COL1A1 and COL1A2; RT-PCR) were not different. Ca2+ imaging (fluo-3) of isolated hVFs showed no difference in the thapsigargin-induced intracellular Ca2+ release capacity (control 16±1.4% vs HF 17±1.1%); however, Ca2+ influx via store-operated Ca2+ entry/Ca2+ release-activated channels (SOCE/CRAC) was significantly (P≤0.05) greater in HF-hVFs (47±3%) compared with non-failing (35±5%). Immunoblotting for ICRAC channel components showed increased ORAI1 expression in HF-hVFs compared with normal without any difference in STIM1 expression. The Pearsons correlation coefficient for co-localization of STIM1/ORAI1 was significantly (P<0.01) greater in HF (0.5±0.01) than control (0.4±0.01) hVFs. The increase in collagen secretion of HF versus control hVFs was eliminated by incubation of hVFs with YM58483 (10 µM), a selective ICRAC inhibitor, for 48 h (66.78±5.87 µg/106 cells vs 55.81±7.09 µg/106 cells, P=0.27). In conclusion, hVFs from HF have increased collagen secretion capacity versus non-failing hearts and this is related to increase in Ca2+ entry via SOCE and enhanced expression of ORAI, the pore-forming subunit. Therapeutic inhibition of SOCE may reduce the progression of cardiac fibrosis/HF. Summary: The excessive collagen secretory phenotype found in failing human hearts is associated with ventricular fibroblast remodeling, caused by an elevated influx of intracellular calcium via SOC channels.

Pharmacological strategies for prevention of postoperative atrial fibrillation

Atrial fibrillation (AF) complicating cardiac surgery continues to be a major problem that increases the postoperative risk of stroke, myocardial infarction, heart failure and costs and can affect long-term survival. The incidence of AF after surgery has not significantly changed over the last two decades, despite improvement in medical and surgical techniques. The mechanism and pathophysiology underlying postoperative AF (PoAF) is incompletely understood and results from a combination of acute and chronic factors, superimposed on an underlying abnormal atrial substrate with increased interstitial fibrosis. Several anti-arrhythmic and non-anti-arrhythmic medications have been used for the prevention of PoAF, but the effectiveness of these strategies has been limited due to a poor understanding of the basis for the increased susceptibility of the atria to AF in the postoperative setting. In this review, we summarize the pathophysiology underlying the development of PoAF and evidence behind pharmacological approaches used for its prevention in the postoperative setting.

Many de novo donor-specific antibodies recognize β2 -microglobulin-free, but not intact HLA heterodimers.

Solid‐phase single antigen bead (SAB) assays are standard of care for detection and identification of donor‐specific antibody (DSA) in patients who receive solid organ transplantation (SOT). While several studies have documented the reproducibility and sensitivity of SAB testing for DSA, there are little data available concerning its specificity. This study describes the identification of antibodies to β2‐microglobulin‐free human leukocyte antigen (β2‐m‐fHLA) heavy chains on SAB arrays and provides a reassessment of the clinical relevance of DSA testing by this platform. Post‐transplant sera from 55 patients who were positive for de novo donor‐specific antibodies on a SAB solid‐phase immunoassay were tested under denaturing conditions in order to identify antibodies reactive with β2‐m‐fHLA or native HLA (nHLA). Antibodies to β2‐m‐fHLA were present in nearly half of patients being monitored in the post‐transplant period. The frequency of antibodies to β2‐m‐fHLA was similar among DSA and HLA antigens that were irrelevant to the transplant (non‐DSA). Among the seven patients with clinical or pathologic antibody‐mediated rejection (AMR), none had antibodies to β2‐m‐fHLA exclusively; thus, the clinical relevance of β2‐m‐fHLA is unclear. Our data suggests that SAB testing produces false positive reactions due to the presence of β2‐m‐fHLA and these can lead to inappropriate assignment of unacceptable antigens during transplant listing and possibly inaccurate identification of DSA in the post‐transplant period.

Obligatory Glenn shunt in fenestrated fontan

Five high-risk patients undergoing the Fontan operation required large fenestration (1 cm) because of high central venous pressure and low cardiac output. Because of major arterial desaturation, obligatory Glenn shunts were performed. Three patients had pulmonary atresia, 1 had tricuspid atresia 1-B, and the fifth had single ventricle with subaortic stenosis. The age ranged from 16 to 40 months (mean age, 25 +/- 9 months) and weight from 7.9 to 14.6 kg (mean weight, 11 +/- 2 kg). One patient had single and 3 had bilateral subclavian pulmonary artery shunts. The fifth patient had pulmonary artery banding and coarctation repair followed by an aortopulmonary window and central shunt. The first 2 patients repeatedly had to go back on cardiopulmonary bypass for a larger fenestration and subsequently had an obligatory Glenn shunt because of arterial desaturation. The last 3 patients had planned obligatory Glenn shunt and large fenestration. The first patient died on the second postoperative day of a combination of prolonged operation, repeated cardiopulmonary bypass, and periods of hemodynamic instability. Three patients had closure of the adjustable fenestration under local anesthesia at 4, 5, and 8 weeks postoperatively. The last patient is awaiting closure. We believe that in certain high-risk patients, a large fenestration combined with an obligatory Glenn shunt should be considered to minimize repeated cardiopulmonary bypass and urgent tightening or closure of fenestration in the immediate postoperative period.

Reoperation in patients with closed SVG and patent LITA—LAD graft: T-graft approach

Selection of the bypass graft that the patient has demonstrated will remain patent and free from critical atherosclerosis is a most important part of coronary artery bypass reoperations. Sixteen patients in whom a patent left internal thoracic artery-left anterior descending coronary artery bypass graft and obstructed or closed saphenous vein grafts to other coronary arteries were visualized underwent reoperation. To reach the inadequately perfused circumflex and right coronary arteries, the right internal thoracic artery was anastomosed to the left internal thoracic artery as a T graft and then was attached to the circumflex and right coronary artery branches. All patients survived the procedure and are free from angina. There were no perioperative myocardial infarctions, and there was no suggestion of hypoperfusion by the grafts. We believe this technique may reduce the incidence of graft failure in patients undergoing reoperative coronary artery bypass grafting.

Acute pulmonary hypertension complicating the arterial switch procedure

Two neonates undergoing arterial switch procedure developed life-threatening pulmonary hypertension intraoperatively. In one patient, bradycardia, hypotension, and electrocardiographic (ECG) evidence of myocardial ischemia suddenly occurred 20 minutes after uneventful weaning from cardiopulmonary bypass. Lifting a palpably hypertensive main pulmonary artery (MPA) resulted in reproducible hemodynamic improvement. Because the patient was already on full ventilatory support and a nitroglycerin infusion, the MPA was suspended onto the anterior chest wall. In the other patient, after removal of intraoperative drapes, severe generalized swelling and cyanosis were noted. The central venous pressure had risen to 25 mmHg, and the PO2 had dropped to 52 mmHg on 100% FIO2. The systolic arterial pressure and ECG remained normal. Immediate reexploration revealed a palpably hypertensive MPA. The coronary arteries implanted more laterally on the neoaorta were uncompromised. Amrinone loading and infusion produced immediate improvement. We believe that surgeons should be aware that pulmonary hypertension can cause coronary artery compression and right heart failure in neonates undergoing the arterial switch procedure. Lateral placement of the coronary artery and aggressive use of pulmonary vasodilators can minimize the problem.