Charles C. Canver

Safety, Tolerance, and Efficacy of Adenosine as an Additive to Blood Cardioplegia in Humans During Coronary Artery Bypass Surgery

Myocardial stunning after heart surgery is associated with increased morbidity and mortality in patients with severe multivessel disease and reduced myocardial function. The purpose of this study was to evaluate the safety, tolerance, and efficacy of adenosine as a cardioprotective agent when added to blood cardioplegia in patients undergoing coronary artery bypass surgery. Sixty-one patients were randomized to standard cold-blood cardioplegia, or cold-blood cardioplegia containing 1 of 5 adenosine doses (100 microM, 500 microM, 1 mM, 2 mM, and 2 mM with a preischemic infusion of 140 microg/kg/min of adenosine). Invasive and noninvasive measurements of ventricular performance and rhythm were obtained preoperatively, prebypass, and then at 1, 2, 4, 8, 16, and 24 hours postbypass. Use of inotropic agents and vasoactive drugs pastoperatively was recorded; blood samples were collected for measurement of nucleoside levels. High-dose adenosine treatment was associated with a 249-fold increase in the plasma adenosine concentration and a 69-fold increase in the combined levels of adenosine, inosine, and hypoxanthine (p <0.05). Increasing doses of the adenosine additive were also associated with lower requirements of dopamine (p = 0.003) and nitroglycerine (p = 0.001). The 24-hour average doses for dopamine and nitroglycerine in the placebo group were 28-fold and 2.6-fold greater than their respective high-dose adenosine treatment cohorts. Finally, the placebo- and 100 microM-adenosine group was associated with a lower ejection fraction when compared to patients receiving the intermediate dose or high-dose treatment. These findings are consistent with the hypothesis that adenosine is effective in attenuating myocardial stunning in humans.

Mechanical valves versus the Ross procedure for aortic valve replacement in children: propensity-adjusted comparison of long-term outcomes.

OBJECTIVEnWe aimed to identify characteristics differentiating children undergoing aortic valve replacement by using mechanical prostheses versus the Ross procedure and to compare survival and the need for aortic valve reoperation after each procedure.nnnMETHODSnFrom 1983 to 2004, 346 children underwent aortic valve replacement (215 underwent the Ross procedure and 131 underwent placement of a mechanical prosthesis). Factors associated with procedure choice were used to construct a propensity score for use as a covariate in regression models to adjust for potential confounding by indication.nnnRESULTSnPatients undergoing the Ross procedure were younger, more likely to have a congenital cause, and less likely to have a rheumatic or connective tissue cause. They had a lower frequency of regurgitation, required more annular enlargement, and had less concomitant cardiac surgery. Competing-risk analysis showed that 16 years after aortic valve replacement, 20% of patients had died without subsequent aortic valve replacement, 25% underwent second aortic valve replacement, and 55% remained alive without further replacement. After propensity adjustment, factors associated with early-phase death included mechanical valves and a nonrheumatic cause. Mechanical valves were also associated with constant-phase mortality. Repeated aortic valve replacement was associated with the Ross procedure and a rheumatic cause. Both factors were also associated with all-cause cardiac reoperation. In children receiving mechanical prostheses, younger age and smaller valve size were significant risk factors for death. Freedom from homograft replacement after the Ross procedure was 82% at 16 years of follow-up.nnnCONCLUSIONnResults from this study showed good outcomes and an acceptable complication rate with both valve choices. Given the significantly increased risk of early and late death in younger children receiving smaller mechanical valves, the Ross procedure confers survival advantage in this age group at the expense of increased reoperation risk, especially in patients with a rheumatic cause.

Aortic and mitral valve replacement in children: is there any role for biologic and bioprosthetic substitutes?

OBJECTIVEnThe ideal valve substitute in children does not exist. Biologic and bioprosthetic valves do not require anticoagulation, however their use is complicated by accelerated degeneration and requirement for reoperation. We examine results following mitral (MVR) or aortic (AVR) replacement with biologic and bioprosthetic valves at our institution.nnnMETHODSnMedical records of children who underwent AVR or MVR from 1986 to 2006 were reviewed. Median follow-up duration was 10.5 years. Competing-risks methodology determined time-related prevalence and associated factors for three mutually exclusive end states: death, valve reoperation, and survival without subsequent reoperation.nnnRESULTSnOne hundred and ten children (age 15.6+/-2.6 years, 80% females) underwent 123 valve replacements with biologic and bioprosthetic substitutes including 87 MVR and 36 AVR (13 had both). Underlying pathology was mainly rheumatic fever (91%). Thirty-nine patients (35%) had undergone a previous cardiac surgery. Most common mitral substitute was Hancock (73%) and homograft (8%); most common aortic substitute was homograft (41%) and Carpentier-Edwards (39%). Competing-risks analysis showed that 15 years after valve replacement, 16% of patients had died without subsequent reoperation, 66% underwent valve reoperations, and only 18% remained alive without further reoperation. Factors associated with increased reoperation risk included younger age at surgery (p=0.005), AVR (p=0.005), male gender (p=0.02) and homograft use (p=0.007) especially in the mitral position (p=0.002). Fifteen-year freedom from endocarditis was 97% while freedom from bleeding and thrombo-embolic complications was 100%. Majority of patients (95%) were in NYHA functional classes I/II at last follow-up.nnnCONCLUSIONnWhile valve reoperation is inevitable following AVR and MVR with biologic and bioprosthetic substitutes; favorable results such as low valve-related morbidity rate, good long-term survival and functional status encourage their consideration as valid replacement alternatives in selected children especially females. Valve durability is higher in the mitral position and longevity of bioprosthetic valves is greater than that of homografts especially in the mitral position.

The Ross procedure in children: preoperative haemodynamic manifestation has significant effect on late autograft re-operation.

OBJECTIVESnThe Ross procedure is the aortic valve-replacement procedure of choice in children. Nonetheless, late autograft re-operation for dilatation and/or valve regurgitation is of concern. We examined whether preoperative haemodynamic manifestation (e.g., stenosis, regurgitation and mixed aortic valve disease) affected late re-operation risk.nnnMETHODSnMedical records of 227 children who underwent the Ross procedure (1991-2004) were reviewed. Competing-risks methodology determined time-related prevalence and associated factors for two mutually exclusive end-states after the Ross procedure: (1) death prior to subsequent autograft re-operation and (2) autograft re-operation, with the remainder of patients being alive and free from subsequent autograft re-operation.nnnRESULTSnThere were 162 male patients (71%) in this study. Median age at surgery was 12.1 years (range: 1 week-18 years). The haemodynamic aortic valve dysfunction was primarily stenosis (n=40, 18%), primarily regurgitation (n=109, 48%) and mixed disease (n=78, 35%). Underlying pathology was rheumatic fever (n=104, 46%), congenital heart disease (n=113, 50%) and endocarditis (n=8, 3%). Competing-risks analysis showed that, at 10 years following the Ross procedure, ∼5% of patients had died, 16% had undergone autograft re-operation with aortic valve replacement and 79% were alive and free from autograft re-operation. Ten-year freedom from autograft re-operation for patients with preoperative stenosis, regurgitation and mixed disease was 97%, 69% and 93%, respectively, (p<0.001 for regurgitation vs others). Risk factors for increased risk of autograft re-operation were rheumatic fever (parameter estimates (PEs): 2.09 ± 0.75, p=0.006), and earlier year of surgery (PE: 0.20 ± 0.06, p=0.001). Ten-year freedom from homograft replacement was 81% and was not dependent on haemodynamic manifestation (PE: -0.16 ± 0.38, p=0.68). Significant factors for homograft replacement included fresh homografts (PE: 2.2 ± 0.63, p=0.01) and annular enlargement (PE: 1.11 ± 0.3, p=0.01). Ten-year freedom from cardiac re-operation other than auto-/homograft was 85%, higher in patients with preoperative aortic regurgitation (PE: 1.01 ± 0.42, p=0.02). Concomitant cardiac surgery was a significant factor for late cardiac re-operation other than auto-/homograft replacement (PE: 1.79 ± 0.39, p<0.001).nnnCONCLUSIONSnThe Ross procedure in children is associated with excellent survival. Late autograft re-operation may be required; however, it is more common in children with preoperative aortic regurgitation, especially those with rheumatic fever. Better patient selection in later era has mitigated the risk of autograft re-operation. Continued improved candidate selection, along with modifications in autograft implantation and root/sinotubular stabilisation techniques, may further decrease late autograft failure.

Surgical Strategy to Establish a Dual-Coronary System for the Management of Anomalous Left Coronary Artery Origin From the Pulmonary Artery

BACKGROUNDnOptimal repair of anomalous origin of left coronary artery from pulmonary artery (ALCAPA) relies on the creation of a dual-coronary system. If the anomalous coronary arises at a long distance from the aorta, we use various coronary extension techniques to facilitate tension-free implantation.nnnMETHODSnThirty patients underwent ALCAPA operations using direct coronary transfer (n = 11) or coronary extension techniques (n = 19). Surgical outcomes were analyzed.nnnRESULTSnMedian age and weight were 5.7 months (range, 46 days to 5.45 years) and 5.35 kg (range, 3.3 to 15.9 kg). Five patients had concomitant mitral annuloplasty. Mean cardiopulmonary bypass and ischemic times were 108 +/- 38 and 57 +/- 25 minutes. Two patients required intraoperative revision of the implantation. There were three hospital deaths (10%) and no late deaths. Follow-up echocardiograms demonstrated significant improvement postoperatively vs preoperatively in shortening fraction (35% +/- 2% vs 16% +/- 2%, p < 0.00001), ejection fraction (64% +/- 3% vs 32% +/- 4%, p < 0.00001), and mitral regurgitation (11% moderate vs 70% moderate or severe, p = 0.0002). Left ventricular end-diastolic dimension Z-score decreased from 9.1 +/- 0.9 to 1.2 +/- 0.5 (p < 0.00001). Both techniques were equally effective. Two patients underwent reoperation 1 and 12 years postoperatively (coronary artery bypass grafting, 1; mitral repair with coronary angioplasty, 1). Surviving patients remain asymptomatic (p < 0.00001).nnnCONCLUSIONSnDual-coronary system can be established in patients with ALCAPA. Coronary extension implantation techniques have acceptable operative mortality and excellent cardiac recovery and late survival. Although the rate of late coronary occlusion is low, continual ventricular or mitral dysfunction should trigger evaluation of persistent coronary compromise.

Results after mitral valve replacement with mechanical prostheses in young children

OBJECTIVEnWe examined outcomes after mitral valve replacement in children younger than 8 years.nnnMETHODSnMedical records of patients who underwent mitral valve replacement from 1990 to 2006 were reviewed. Competing-risks methodology determined time-related prevalence and associated factors for death, repeated valve replacement, and survival without reoperation.nnnRESULTSnIn total, 79 patients, median age 24 months (40 days-8 years) underwent 91 mitral valve replacements (10 had repeated procedures). Underlying pathology was congenital heart disease in 95% of cases. Forty-six patients (58%) had undergone previous operations. Operative mortality was 18%, 30% for those 2-years old and younger and 6% for those older than 2 years. Competing-risks analysis showed that 10 years after initial mitral valve replacement, 40% of patients had died without repeated replacement, 20% had undergone a second replacement, and 40% remained alive without further replacement. Factors associated with death included higher prosthesis size/patient weight ratio (P < .0001) and longer crossclamp time (P < .0001). Second replacement 6 +/- 4 years after initial replacement was necessary for 10 survivors. At second replacement, larger prostheses were implanted (mean 24 mm vs 19 mm initially). Repeated MVR was associated with younger age at surgery (p = .006). Permanent pacemaker implantation was eventually needed by 11% of hospital survivors.nnnCONCLUSIONSnMortality and repeated valve replacement are common after mitral valve replacement in children younger than 8 years, especially younger patients with significantly oversized valves. At valve reoperation, larger prostheses could be implanted, suggesting continued annular growth.

The Rastelli Procedure for Transposition of the Great Arteries: Resection of the Infundibular Septum Diminishes Recurrent Left Ventricular Outflow Tract Obstruction Risk

BACKGROUNDnThe Rastelli procedure is the standard surgical treatment of d-transposition of great arteries (d-TGA), ventricular septal defect (VSD), and pulmonary stenosis. Late morbidity is significant due to recurrent left ventricular outflow obstruction (LVOTO), early conduit obstruction, and arrhythmias, with troublesome late mortality. To avoid recurrent LVOTO, we routinely enlarge the VSD and resect the infundibular septum before LV baffling to the aorta. We examined the efficacy of this approach in mitigating recurrent LVOTO risk.nnnMETHODSnLate echocardiographic and time-related clinical results of patients undergoing the Rastelli procedure were examined. Demographics and operative variables affecting outcomes were analyzed.nnnRESULTSnThe Rastelli cohort comprised 36 patients with d-TGA, VSD, and pulmonary stenosis. Median age at operation was 2.4 years (range, 0.3 to 8.3 years). Pulmonary stenosis was present in 31 and atresia in 5. Twenty-two patients had undergone a previous aortopulmonary shunt, and 6 had an atrial septectomy. No operative or late deaths occurred. Time-related freedom from permanent pacemaker implantation, recurrent LVOTO on echocardiogram, and conduit replacement at 10 years was 82%, 100%, and 49%, respectively. Systolic function was normal in all but 3 patients and 92% were in New York Heart Association functional class I and II. None of the patients had late arrhythmias or required heart transplantation.nnnCONCLUSIONSnEarly and midterm survival after the Rastelli procedure is satisfactory. Aggressive resection of the infundibular septum to enlarge the VSD has mitigated the risk of LVOTO recurrence. Late conduit obstruction remains an important source of morbidity and frequently requires reintervention.

Intermediate results following complex biventricular repair of left ventricular outflow tract obstruction in neonates and infants

OBJECTIVESnAlthough the majority of infants with severe left ventricular outflow tract obstruction (LVOTO) can be managed with balloon or surgical aortic valvotomy, a more complex biventricular repair may be required in a subset of infants with multi-level obstruction, failure of or complication to prior intervention. In the presence of normal left ventricle size and inflow, the Ross procedure is applied in patients with/without ventricular septal defect (VSD), while the Yasui procedure is applied only in those with VSD. We report mid-term outcomes in a single institution.nnnMETHODSnThirty-five consecutive infants with severe LVOTO underwent complex biventricular repair using the Ross (n=21) or Yasui (n=14) procedure. Outcomes were studied using univariate and multivariable parametric models.nnnRESULTSnThe Ross procedure was done at a median age of 88 days (8-353 days), in 8/21 (38%) neonates. As many as 12/21 (57%) had prior catheter and/or surgical intervention. Concomitant procedures included arch reconstruction (n=4/21, 19%) and mitral valve repair (n=6/21, 29%). In addition, 14/21 (67%) had annular enlargement (modified Ross-Konno). Haemodynamic manifestation was isolated obstruction (n=10/21, 48%) or mixed obstruction/regurgitation (n=11/21, 52%). Survival was 81% at 1 month, 70% at 1 year and 63% at 5 years. In multivariable regression models, factors associated with increased risk of mortality included neonatal surgery (p=0.007), mitral valve repair (p=0.02), longer cross-clamp time (p=0.003), and postoperative extracorporeal membrane oxygenator (ECMO) (p=0.004). Freedom from any cardiac re-operation was 86% at 5 years. The Yasui procedure was done at a median age of 36 days (7-207 days), 6/14 (43%) in neonates. As many as 13/14 procedures (93%) were primary and one procedure followed a prior single-stage Norwood palliation. A total of 10/14 (71%) had critical aortic stenosis and 4/14 (29%) had atresia. All patients had VSD, and 11/14 (79%) required concomitant arch reconstruction. Survival was 79% at 1 month and 5 years while 5-year freedom from re-operation was 57%.nnnCONCLUSIONSnComplex biventricular repair can be performed in neonates and infants with severe LVOTO with mid-term survival that is equivalent to that published following balloon or surgical aortic valvotomy. Associated lesions are significant factors that influence outcome and proper patient selection may further improve survival. In neonates with concomitant arch obstruction and VSD, the Yasui operation may be associated with lower early mortality risk. Neonates with concomitant mitral valve pathology may be better served with single ventricle palliation strategy.

Adenosine reduces postbypass transfusion requirements in humans after heart surgery.

OBJECTIVEnThe objective of this study was to determine the effect, if any, of adenosine blood cardioplegia on blood component usage after heart surgery.nnnSUMMARY BACKGROUND DATAnThe most common cause of nonsurgical postcardiopulmonary bypass bleeding is platelet dysfunction. For this reason, pharmacologic agents are under investigation in an effort to reduce the need for transfusion in this setting.nnnMETHODSnA posthoc analysis of blood product usage was performed in data obtained from a Phase I, single center, open label, randomized study performed in 63 patients. The trial was designed to test the safety and tolerance of adenosine when added to blood cardioplegia in increasing doses to enhance myocardial protection. The database provided information regarding the effect of adenosine cardioplegia on venous plasma adenosine concentrations, the amount of platelets, fresh frozen plasma and packed erythrocytes used, and the association between the adenosine dose and postoperative thoracic drainage.nnnRESULTSnThe postoperative thoracic drainage at 6 hours, 24 hours, and at the time of chest tube removal in the high-dose adenosine cardioplegia group was 68%, 76%, and 75% of the placebo and low-dose adenosine cardioplegia group (p < 0.05). The highest dose of adenosine studied increased baseline adenosine venous plasma levels 360-fold, from 0.17 +/- 0.09 mumol/L to 42.30 +/- 11.20 mumol/L (p < 0.05). This marked increase was associated with a 68%, 56%, and 58% reduction in platelet, fresh frozen plasma, and packed erythrocyte usage, respectively (p < 0.05).nnnCONCLUSIONSnIn addition to enhancing the hearts tolerance to ischemia, adenosine-supplemented cardioplegic solution also may reduce bleeding after cardiopulmonary bypass.

Hybrid Management Strategy for Percutaneous Fontan Completion Without Surgery: Early Results

BACKGROUNDnWe report early results of surgical preparation and subsequent percutaneous Fontan completion strategy for the treatment of single-ventricle defects.nnnMETHODSnTwo hundred twenty-seven patients underwent bidirectional cavopulmonary connection (BDCPC) between 2002 and 2007. Thirty-four patients had lateral tunnel created at time of BDCPC, fenestrated with 10 to 14 mm openings with the cardiac superior vena cava end patched to maintain BDCPC physiology. At second stage, Fontan circulation was established by superior vena cava patch perforation, tunnel dilatation, and stenting plus fenestration device closure.nnnRESULTSnThirty-four patients underwent Fontan preparation with BDCPC. Median age was 7.7 months (5 to 51) and 29 patients (85%) had previous palliation. Mean bypass and ischemic times were 141 and 72 minutes, respectively. Median ventilation, intensive care, and hospital stay durations were 1, 5, and 10 days, respectively. There was one early death and two take-downs. Twenty-eight patients underwent Fontan procedure: surgical (n = 3), percutaneous (n = 25). None of the patients who underwent percutaneous Fontan completion required inotropes, chest tube insertion, or mechanical ventilation. Median intensive care and hospital stay durations were 1 and 6 days, respectively. There were no early mortalities after percutaneous Fontan but one late death and one surgical revision. Overall survival after BDCPC with Fontan preparation was 77%.nnnCONCLUSIONSnDespite longer bypass and ischemic times, Fontan preparation at time of BDCPC is feasible and associated with encouraging early outcomes. Percutaneous Fontan completion is associated with short recovery, low morbidity and excellent early dynamics, and echocardiographic and clinical outcomes. Further follow-up is needed to confirm those favorable results.