Joseph M. Forbess

Management of coronary artery fistulae: Patient selection and results of transcatheter closure

OBJECTIVES We report short-term findings in 33 patients after transcatheter closure (TCC) of coronary artery fistulae (CAF) and compare our results with those reported in the recent transcatheter and surgical literature. BACKGROUND Transcatheter closure of CAF has been advocated as a minimally invasive alternative to surgery. METHODS We reviewed all patients presenting with significant CAF between January 1988 and August 2000. Those with additional complex cardiac disease requiring surgical management were excluded. RESULTS Of 39 patients considered for TCC, occlusion devices were placed in 33 patients (85%) at 35 procedures and included coils in 28, umbrella devices in 6 and a Grifka vascular occlusion device in 1. Post-deployment angiograms demonstrated complete occlusion in 19, trace in 11, or small residual flow in 5. Follow-up echocardiograms (median, 2.8 years) in 27 patients showed no flow in 22 or small residual flow in 5. Of the 6 patients without follow-up imaging, immediate post-deployment angiograms showed complete occlusion in 5 or small residual flow in 1. Thus, complete occlusion was accomplished in 27 patients (82%). Early complications included transient ST-T wave changes in 5, transient arrhythmias in 4 and single instances of distal coronary artery spasm, fistula dissection and unretrieved coil embolization. There were no deaths or long-term morbidity. Device placement was not attempted in 6 patients (15%), because of multiple fistula drainage sites in 4, extreme vessel tortuosity in 1 and an intracardiac hemangioma in 1. CONCLUSIONS A comparison of our results with those in the recent transcatheter and surgical literature shows similar early effectiveness, morbidity and mortality. From data available, TCC of CAF is an acceptable alternative to surgery in most patients.

Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery

OBJECTIVES We previously reported that postoperative hemodynamics and developmental outcomes were better among infants randomized to a higher hematocrit value during hypothermic cardiopulmonary bypass. However, worse outcomes were concentrated in patients with hematocrit values of 20% or below, and the benefits of hematocrit values higher than 25% were uncertain. METHODS We compared perioperative hemodynamics and, at 1 year, developmental outcome and brain magnetic resonance imaging in a single-center, randomized trial of hemodilution to a hematocrit value of 25% versus 35% during hypothermic radiopulmonary bypass for reparative heart surgery in infants undergoing 2-ventricle repairs without aortic arch obstruction. RESULTS Among 124 subjects, 56 were assigned to the lower-hematocrit strategy (24.8% +/- 3.1%, mean +/- SD) and 68 to the higher-hematocrit strategy (32.6% +/- 3.5%). Infants randomized to the 25% strategy, compared with the 35% strategy, had a more positive intraoperative fluid balance (P = .007) and lower regional cerebral oxygen saturation at 10 minutes after cooling (P = .04) and onset of low flow (P = .03). Infants with dextro-transposition of the great arteries in the 25% group had significantly longer hospital stay. Other postoperative outcomes, blood product usage, and adverse events were similar in the treatment groups. At age 1 year (n = 106), the treatment groups had similar scores on the Psychomotor and Mental Development Indexes of the Bayley Scales; both groups scored significantly worse than population norms. CONCLUSIONS Hemodilution to hematocrit levels of 35% compared with those of 25% had no major benefits or risks overall among infants undergoing 2-ventricle repair. Developmental outcomes at age 1 year in both randomized groups were below those in the normative population.

pH strategies and cerebral energetics before and after circulatory arrest

The pH-stat strategy compared with the alpha-stat strategy provides more rapid recovery of brain high-energy phosphate stores and intracellular pH after 1 hour of hypothermic circulatory arrest in pigs. Possible mechanisms for this difference are (1) improved oxygen delivery and homogeneity of brain cooling before deep hypothermic circulatory arrest and (2) greater cerebral blood flow and reduced reperfusion injury owing to extracellular acidosis during the rewarming phase. To identify which of these mechanisms is predominant, we studied 49 4-week-old piglets undergoing 1 hour of deep hypothermic circulatory arrest. Four groups were defined according to cooling/rewarming strategy: alpha/alpha, alpha/pH, pH/alpha, and pH/pH. In 24 animals cerebral high-energy phosphate levels and intracellular pH were measured by magnetic resonance spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 5). In 25 animals cerebral blood flow was measured by labeled microspheres, cerebral metabolic rate by oxygen and glucose extraction, and the redox state of cytochrome aa3 and hemoglobin oxygenation by near infrared spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 6). Cerebral blood flow was greater with pH-stat than alpha-stat during cooling (56.3% +/- 3.7% versus 32.9% +/- 2.1% of normothermic baseline values, p < 0.001). Cytochrome aa3 values became more reduced during cooling with alpha-stat than with pH-stat (p = 0.049). Recovery of adenosine triphosphate levels in the initial 45 minutes of reperfusion was more rapid in group pH/pH compared with that in the other groups (p = 0.029). Recovery of cerebral intracellular pH in the initial 30 minutes was faster in group pH/pH compared with that in group alpha/alpha (p = 0.026). Intracellular pH became more acidic during early reperfusion only in group alpha/alpha, whereas it showed continuous recovery in the other groups. This study suggests that there are mechanisms in effect during both the cooling and rewarming phases before and after deep hypothermic circulatory arrest that could contribute to an improved cerebral outcome with pH-stat relative to more alkaline strategies.

Total Cavopulmonary Connection Flow With Functional Left Pulmonary Artery Stenosis Angioplasty and Fenestration In Vitro

Background— In our multicenter study of the total cavopulmonary connection (TCPC), a cohort of patients with long-segment left pulmonary artery (LPA) stenosis was observed (35%). The clinically recognized detrimental effects of LPA stenosis motivated a computational fluid dynamic simulation study within 3-dimensional patient-specific and idealized TCPC pathways. The goal of this study was to quantify and evaluate the hemodynamic impact of LPA stenosis and to judge interventional strategies aimed at treating it. Methods and Results— Simulations were conducted at equal vascular lung resistance, modeling both discrete stenosis (DS) and diffuse long-segment hypoplasia with varying degrees of obstruction (0% to 80%). Models having fenestrations of 2 to 6 mm and atrium pressures of 4 to 14 mm Hg were explored. A patient-specific, extracardiac TCPC with 85% DS was studied in its original configuration and after virtual surgery that dilated the LPA to 0% stenosis in the computer medium. Performance indices improved exponentially (R2>0.99) with decreasing obstruction. Diffuse long-segment hypoplasia was ≈50% more severe with regard to lung perfusion and cardiac energy loss than DS. Virtual angioplasty performed on the 3-dimensional Fontan anatomy exhibiting an 85% DS stenosis produced a 61% increase in left lung perfusion and a 50% decrease in cardiac energy dissipation. After 4-mm fenestration, TCPC baffle pressure dropped by ≈10% and left lung perfusion decreased by ≈8% compared with the 80% DS case. Conclusions— DS <60% and diffuse long-segment hypoplasia <40% could be considered tolerable because both resulted in only a 12% decrease in left lung perfusion. In contrast to angioplasty, a fenestration (right-to-left shunt) reduced TCPC pressure at the cost of decreased left and right lung perfusion. These results suggest that pre-Fontan computational fluid dynamic simulation may be valuable for determining both the hemodynamic significance of LPA stenosis and the potential benefits of intervention.

Results with the freestyle porcine aortic root for right ventricular outflow tract reconstruction in children

BACKGROUND The ideal choice for valved reconstruction of the right ventricular outflow tract (RVOT) in children is undetermined. This study explores the Freestyle porcine aortic root for these patients. METHODS From January 1998 to December 2002, 56 patients ages 1.6 to 29.9 years old (mean 11.8 years old) underwent RVOT reconstruction using a Freestyle porcine aortic root. The patients averaged 1.9 prior operations (range 0 to 5) for tetralogy of Fallot +/- pulmonary atresia (28 patients), critical pulmonary stenosis (10 patients), Ross procedure (5 patients), pulmonary atresia/intact ventricular septum (4 patients), complete atrioventricular septal defect +/- tetralogy of Fallot (4 patients), and others (5 patients). At time of RVOT reconstruction, 42 patients (75%) had additional procedures including the following: tricuspid or mitral repair (24 patients), pulmonary arterioplasty +/- Glenn (12 patients), ventricular septal defect closure (5 patients), aortic valve replacement (3 patients), placement of a cardioverter/defibrillator or pacemaker (3 patients), and others (8 patients). RESULTS One patient developed mediastinitis; another was treated for Candida endocarditis (his excised homograft unexpectedly grew Candida). All patients are well on follow-up from 2 to 60 months (mean 30 +/- 20 months) with no deaths. The patient with endocarditis underwent conduit replacement for recurrent pulmonary stenosis 3.5 years postoperatively. Echocardiography revealed mild or no pulmonary insufficiency in 93%. The calculated mean peak systolic RVOT gradient by echocardiography was 19.7 +/- 15.4 mm Hg. CONCLUSIONS These data demonstrate excellent results with the Freestyle bioprosthesis for RVOT reconstruction in children. This valve may serve as a readily available alternative to homograft valves in RVOT reconstruction, particularly since early insufficiency seems to be less problematic. Questions of long-term durability and significance of echocardiographic stenosis remain unanswered.

Effects of l-Arginine and l-nitro-arginine methyl ester on recovery of neonatal lamb hearts after cold ischemia: Evidence for an important role of endothelial production of nitric oxide

Myocardial ischemia and reperfusion results in both ventricular and endothelial dysfunction. We have found that the endothelial defect is a reduced vasodilator response to an intraarterial infusion of acetylcholine that is likely due to reduced nitric oxide release, and we have hypothesized that reduced endothelial nitric oxide production contributes to postischemic cardiac dysfunction. However, others report that nitric oxide is deleterious after ischemia. We therefore examined the effects of infusions of L-arginine (3 mmol/L), a precursor of nitric oxide, D-arginine (3 mmol/L), an inactive stereoisomer of L-arginine, L-nitro-arginine methyl ester (1 mmol/L); a competitive inhibitor of nitric oxide synthase, and L-nitro-arginine methyl ester (1 mmol/L) plus L-arginine (3 mmol/L) versus controls in isolated blood-perfused neonatal lamb hearts having 2 hours of cold cardioplegic ischemia. L-nitro-arginine methyl ester was given before reperfusion, and L-arginine and D-arginine were infused for the first 20 minutes of postischemic reperfusion. At 30 minutes of reperfusion, by comparison with the control group, the L-arginine group showed significantly better recovery (p < 0.05) of left ventricular systolic function (maximum developed pressure, developed pressure at V10 [balloon volume to produce an end-diastolic pressure of 10 mm Hg during baseline measurement], positive maximum dP/dt, and dP/dt at V10), diastolic function (negative maximum dP/dt), coronary blood flow, and endothelial function assessed by the coronary vascular resistance response to acetylcholine. The L-nitro-arginine methyl ester hearts showed a significantly poorer recovery (p < 0.05) in left ventricular function, coronary blood flow, and endothelial function than the control group. These effects of L-nitro-arginine methyl ester were reversed to equal control values by adding a 3 mmol/L concentration of L-arginine to L-nitro-arginine methyl ester. There were no significant differences in the recovery of any variables between the D-arginine and control groups. These results point to an important salutary role for the endothelial production of nitric oxide in cardiac recovery after hypothermic ischemia in neonatal lamb hearts. The mechanism of these beneficial effects of L-arginine after ischemia and reperfusion is likely due to enhancement of the endothelial production of nitric oxide.

An institutional experience with second- and third-stage palliative procedures for hypoplastic left heart syndrome: The impact of the bidirectional cavopulmonary shunt

OBJECTIVES The aim of this study was to perform a retrospective analysis of an institutional experience with a consecutive series of patients with post-stage I palliation for hypoplastic left heart syndrome (HLHS). BACKGROUND In a recent review of 212 consecutive patients who underwent stage I operations for HLHS at our institution between 1983 and 1993, we identified risk factors related to stage I mortality. We sought to examine the outcome for these patients at subsequent palliative procedures. METHODS All patients who underwent stage I reconstruction between January 1983 and June 1993 and also underwent subsequent palliation at our institution were included. Seventy patients underwent palliative procedures and two underwent heart transplantation. Patient-specific factors and features of the stage II operation were analyzed for impact on stage II mortality and actuarial survival. RESULTS The only independent risk factor for stage II mortality was the performance of a nonfenestrated Fontan operation (p < 0.001). There were nine in-hospital deaths (69%) in the 13 patients undergoing the nonfenestrated Fontan procedure at stage II. Fifty patients underwent intermediate superior vena cava to pulmonary artery anastomosis at stage II, with 4 (8%) early deaths. Pulmonary artery augmentation was performed in 19 patients (38%) at stage II, without increased operative risk. Hypoplastic left heart syndrome anatomic subtype did not influence stage II mortality. The modified fenestrated Fontan procedure has been performed as a third stage in 32 patients whose median age was 28.7 months, with one early death at a median follow-up of 24.5 months. CONCLUSIONS A second-stage bidirectional cavopulmonary anastomosis for HLHS reduces second-stage mortality and improves intermediate survival. The modified fenestrated Fontan operation may then be performed as a final palliative stage with low operative risk.

Result of biventricular repair for double-outlet right ventricle.

The choice of optimal repair for many patients with double-outlet right ventricle continues to challenge the heart surgeon. We present the results of a 10-year surgical experience with the biventricular repair for double-outlet right ventricle with situs solitus and atrioventricular concordance. Preoperative anatomic findings within this population of 73 patients are detailed. These morphologic features are correlated with type of anatomic repair and clinical outcome. Patients were classified by ventricular septal defect location. Normal coronary anatomy was found in the majority of patients with subaortic and doubly-committed ventricular septal defects. Patients with subpulmonary and noncommitted ventricular septal defects had a wide variety of coronary anatomy. Patients with subpulmonary and noncommitted ventricular septal defects also had a considerably higher prevalence of aortic arch obstruction. A tricuspid-to-pulmonary annular distance equal to or greater than the diameter of the aortic annulus was found to indicate the possibility of achieving a conventional ventricular septal defect-to-aorta intraventricular tunnel repair. Tricuspid-to-pulmonary annular distance sufficient for intraventricular tunnel repair predominates in those patients with a right posterior or right side-by-side aorta. Five types of repair were used during the study period: intraventricular tunnel repair, arterial switch with ventricular septal defect-to-pulmonary artery baffle, Rastelli-type extracardiac conduit repair, Damus-Kaye-Stansel repair, and atrial inversion with ventricular septal defect-to-pulmonary artery baffle. Overall actuarial survival estimate at 8 years is 81%. The presence of multiple ventricular septal defects and patient weight lower than the median were nearly significant risk factors for early mortality (p < 0.06). Nineteen patients (26%) required 24 reoperations. Patients with subaortic ventricular septal defects were significantly reoperation free (p < 0.05). Patients with noncommitted ventricular septal defects were at significantly higher risk for reoperation during the study period (p < 0.05). The prevalence of late right or left ventricular outflow obstruction in the nonsubaortic groups is concerning. The median age at repair in this series was 0.76 years, and there was a nonsignificant trend (p = 0.13) for early mortality in patients younger than 1 year of age. These patients tended to have other serious cardiac anomalies associated with double-outlet right ventricle that necessitated early operation. On the basis of these data, we favor early repair for double-outlet right ventricle if possible.

Management of Single‐Ventricle Patients With Berlin Heart EXCOR Ventricular Assist Device: Single‐Center Experience

There are minimal data regarding chronic management of single-ventricle ventricular assist device (VAD) patients. This study aims to describe our centers multidisciplinary team management of single-ventricle patients supported long term with the Berlin Heart EXCOR Pediatric VAD. Patient #1 was a 4-year-old with double-outlet right ventricle with aortic atresia, L-looped ventricles, and heart block who developed heart failure 1 year after Fontan. She initially required extracorporeal membrane oxygenation support and was transitioned to Berlin Heart systemic VAD. She was supported for 363 days (cardiac intensive care unit [CICU] 335 days, floor 28 days). The postoperative course was complicated by intermittent infection including methicillin-resistant Staphylococcus aureus, intermittent hepatic and renal insufficiencies, and transient antithrombin, protein C, and protein S deficiencies resulting in multiple thrombi. She had a total of five pump changes over 10 months. Long-term medical management included anticoagulation with enoxaparin, platelet inhibition with aspirin and dipyridamole, and antibiotic prophylaxis using trimethoprim/sulfamethoxazole. She developed sepsis of unknown etiology and subsequently died from multiorgan failure. Patient #2 was a 4-year-old with hypoplastic left heart syndrome who developed heart failure 2 years after bidirectional Glenn shunt. At systemic VAD implantation, he was intubated with renal insufficiency. Post-VAD implantation, his renal insufficiency resolved, and he was successfully extubated to daytime nasal cannula and biphasic positive airway pressure at night. He was supported for 270 days (CICU 143 days, floor 127 days). The pump was upsized to a 50-mL pump in May 2011 for increased central venous pressures (29 mm Hg). Long-term medical management included anticoagulation with warfarin and single-agent platelet inhibition using dipyridamole due to aspirin resistance. He developed increased work of breathing requiring intubation, significant anasarca, and bleeding from the endotracheal tube. The family elected to withdraw support. Although both patients died prior to heart transplantation, a consistent specialized multidisciplinary team approach to the medical care of our VAD patients, consisting of cardiothoracic surgeons, heart transplant team, hematologists, pharmacists, infectious disease physicians, psychiatrists, specialty trained bedside nursing, and nurse practitioners, allowed us to manage these patients long term while awaiting heart transplantation.

Effects of Endothelin-1 and Endothelin-A Receptor Antagonist on Recovery After Hypothermic Cardioplegic Ischemia in Neonatal Lamb Hearts

BACKGROUND Prior studies suggest an important role for coronary endothelium in ischemia/reperfusion (I/R) injury. Decreased endothelial release of the vasodilator nitric oxide occurs after I/R, but the role of the endothelium-derived vasoconstrictor endothelin-1 (ET-1) in I/R is unknown. METHODS AND RESULTS We measured plasma ET-1 concentrations by radioimmunoassay in isolated blood-perfused neonatal lamb hearts before and after 2 hours of 10 degrees C cardioplegic ischemia and examined the effects of ET-1 and the endothelin-A (ET-A) receptor antagonist BE-18257B on the postischemic recovery of isolated hearts. ET-1 levels in coronary sinus blood before ischemia and at 0 and 30 minutes of reperfusion in 8 control hearts were constant (2.2 +/- 1.2 fmol/L, 2.2 +/- 1.3 fmol/L, and 2.5 +/- 1.0 fmol/L, respectively). In group 2 (n = 6), 10 mumol/L of BE-18257B was given just before reperfusion. In group 3 (n = 8), 10 pmol/L ET-1 was given just before the start of reperfusion. At 30 minutes of reperfusion, the ET-A antagonist hearts had significantly greater recovery of LV systolic (positive dP/dt and dP/dt at V10) and diastolic function (negative dP/dt), coronary blood flow (CBF), and MVo2 compared with controls (P < .05). The ET-1 hearts showed significantly reduced recovery of LV systolic (positive maximum and volume-normalized dP/dt) and diastolic (negative maximum dP/dt) function, CBF, and myocardial oxygen consumption compared with controls (P < .05). CONCLUSIONS These results, combined with prior studies, suggest that I/R causes reduced production of endogenous vasodilators (eg, nitric oxide), leaving unopposed the vasoconstriction that is caused by the continued presence of ET-1. This imbalance may contribute to I/R injury. ET-A receptor antagonists may be useful therapeutic agents in reducing the injury that results from I/R.