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Right arrow Congenital - cyanotic

Ann Thorac Surg 2006;82:1260-1266
© 2006 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Early Cavopulmonary Anastomosis After Norwood Procedure Results in Excellent Fontan Outcome

Robert D.B. Jaquiss, MDa,b,*, Stephanie L. Siehr, BSa, Nancy S. Ghanayem, MDb,c, George M. Hoffman, MDb,d, Raymond T. Fedderly, MDb,e, Joseph R. Cava, MD, PhDb,e, Kathy A. Mussatto, RN, BSNb, James S. Tweddell, MDa,b

a Division of Pediatric Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
c Division of Pediatric Critical Care, Medical College of Wisconsin, Milwaukee, Wisconsin
d Division of Pediatric Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin
e Division of Pediatric Cardiology, Medical College of Wisconsin, Milwaukee, Wisconsin
b Children's Hospital of Wisconsin, Milwaukee, Wisconsin

Accepted for publication April 27, 2006.

* Address correspondence to Dr Jaquiss, 800 Marshall St, Slot 677, Little Rock, AR 72202 (Email: rjaquiss{at}uams.edu).

Presented at the Forty-second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30–Feb 1, 2006.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 References
 
BACKGROUND: Children with univentricular hearts and aortic arch obstruction are treated sequentially with Norwood procedure, superior cavopulmonary anastomosis (SCPA), and Fontan operation. Early SCPA results in lower initial O2 saturation and longer hospitalization, but not increased mortality. We sought to determine the impact of early SCPA on Fontan candidacy and outcomes.

METHODS: Eighty-five consecutive patients undergoing Norwood operation between January 1998 and February 2003 were divided into group 1 (SCPA at less than 4 months, n = 33) and group 2 (SCPA at more than 4 months, n = 52). Of the original cohort, 69 have undergone Fontan operation, 7 await Fontan, 1 was transplanted, 3 are not Fontan candidates, and 5 died late after SCPA. Group 1 (n = 25) and group 2 (n = 44) patients who have completed Fontan operation were compared for preoperative and perioperative variables: age, size, O2 saturation, pulmonary artery pressure and size, prevalence of tricuspid regurgitation and ventricular dysfunction, extubation rate in operating room, duration of pleural drainage, hospital stay, and discharge O2 saturation. Late functional status and ventricular function were also compared. Survival was compared for original groups 1 and 2.

RESULTS: There were no differences for any preoperative or perioperative variable, or late functional assessment. Actuarial survival at 6 years was also not different (88% ± 5% for group 1 and 94% ± 4% for group 2, p= 0.72).

CONCLUSIONS: Although initially more cyanotic and hospitalized longer than older peers, younger SCPA patients achieve clinical equivalence by the time of Fontan operation and afterward. We conclude that both short- and long-term outcomes support performance of early SCPA.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Discussion
 References
 
The surgical management of children with univentricular hearts is directed toward creation of separated pulmonary and systemic circulations (series arrangement) whereby the single ventricle actively pumps systemic blood flow and pulmonary blood flow is passive, achieving so-called "Fontan physiology." For children with aortic arch obstruction and univentricular cardiac anatomy, surgical management is most commonly accomplished by an initial Norwood operation, with either systemic arterial or ventricular source of pulmonary blood flow, which is a parallel arrangement. That is followed some months later by conversion to a superior cavopulmonary source of pulmonary blood flow, resulting in the desired series circulation [1]. The operative staging is completed by the addition of inferior caval blood to the pulmonary inflow, completing the total cavopulmonary connection, often termed Fontan circulation [2, 3].

In a prior study examining the timing of SCPA, our group found that younger patients (defined as those less than 4 months of age at the time of SCPA) required slightly longer mechanical ventilation, experienced longer chest tube drainage, and were in the hospital longer [4]. We concluded that performance of SCPA at a younger age was safe, albeit associated with greater resource utilization. The present study was undertaken to extend the observation of the initial cohort and specifically to examine the impact of second stage timing on candidacy for and early outcomes after the Fontan procedure.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Discussion
 References
 
Patient Population
The original patient cohort consisted of 85 consecutive patients undergoing cavopulmonary anastomosis after an initial Norwood procedure (all were systemic to pulmonary artery shunts) between January 1998 and February 2003 at the Children's Hospital of Wisconsin. In the original study examining post-SCPA outcomes [4], the cohort was divided into those undergoing SCPA at less than 4 months of age (group I, n = 33; mean age at SCPA, 94 ± 21 days) and those over 4 months at second stage (group II, n = 52; mean age at SCPA, 165 ± 44 day). Timing of SCPA surgery was based on physician preference, and was not protocol driven [4]. For the present study, the medical records of the subset of the original cohort who have completed the Fontan procedure were reviewed (group I, 24 of 33; and group II, 44 of 52). The records of patients who did not undergo the Fontan procedure (those who received cardiac transplantation, died, or were not thought to be candidates for Fontan operation) were also examined. Patients were considered not to be Fontan candidates based on high transpulmonary gradients or elevated ventricular end-diastolic pressure. The remaining patients have not yet been evaluated for the third-stage operation. The timing of the Fontan procedure was at the discretion of the attending cardiologist and at the convenience of the family of the patient. By institutional preference, an attempt was made to avoid performance of the Fontan operation during the winter months [5]. The Institutional Review Board of the Children's Hospital of Wisconsin approved the study and waived the informed consent requirement because individual patients were not identified and the study was retrospective.

Cardiac Catheterization
All patients underwent pre-Fontan cardiac catheterization to assess suitability for Fontan operation and identify anatomic abnormalities requiring catheter-based or surgical intervention. Hemodynamic variables recorded included pulmonary artery pressure, ventricular end-diastolic pressure, arterial oxygen saturation (SaO2), and superior vena caval oxygen saturation. Branch pulmonary artery diameter was also measured. The Fontan procedure was usually not performed during the same hospitalization as the catheterization.

Operative Technique and Management
All operations were performed with moderately hypothermic (28°C to 32°C) cardiopulmonary bypass, direct vena caval cannulation, and cardiac venting through the atrial appendage. An extracardiac Fontan technique was employed for 61 (90%) of the patients, using expanded polytetrafluoroethylene conduits ranging in diameter from 18 to 22 mm. A fenestration (4.0 or 5.0 mm) was created in all patients.. The distal end of the conduit was beveled and anastomosed to the undersurface of the pulmonary artery. Pulmonary arteries were not routinely augmented, although the distal end of the conduit was occasionally placed to relieve focal stenosis. Bilateral pleural drains and one or two mediastinal drains were placed in all patients.

Anesthesia management typically consisted of a balanced inhaled/opiod technique, using fentanyl-equivalent dosing at 5 to 25 µg/kg and isoflurane at 1% to 2%. At the discretion of the attending anesthesiologist, regional anesthesia was additionally used (caudal block with bupivicaine and epidural morphine). Anesthesia was conducted with the intention of immediate postoperative extubation in the operating room. Hemodynamic monitoring consisted a radial or femoral arterial catheter, superior vena caval catheter, placed by either jugular or subclavian route, and a direct atrial pressure monitoring catheter, brought out through the chest wall. All patients received a milrinone infusion at 0.5 µg · kg-1 · min-1 after a loading dose of 50 µg/kg, administered while the patient was on cardiopulmonary bypass. All patients also received dopamine infusions (3 to 5 µg · kg-1 · min-1), and some received epinephrine infusions (0.02 to 0.1 µg · kg-1 · min-1) as dictated by hemodynamic status. All patients received intraoperative aprotinin.

Postoperative Management
Patients who were extubated in the operating room were maintained on supplemental oxygen to keep oxygen saturations greater than 80%. Patients who required mechanical ventilation were managed with the lowest possible mean airway pressure. Mechanical ventilation was weaned after recovery from neuromuscular blockade once spontaneous, comfortable breathing was assured with acceptable gas exchange and hemodynamic measurements.

Atrial pressure monitoring catheters were typically removed on the first postoperative day, and superior vena caval catheters were removed once invasive hemodynamic monitoring was no longer considered necessary. Inotropic infusions were weaned and discontinued at the discretion of the supervising physician. Thoracic drainage catheters were typically left in until the establishment of enteral nutrition had been established without a corresponding increase in pleural drainage. Patients were routinely maintained on supplemental oxygen, and received both loop diuretics and thiazide diuretics. After leaving the intensive care unit, oral anticoagulation was begun with warfarin, adjusted to maintain an international normalized ratio of 1.5 to 2.0. The majority of patients were managed by an institutional protocol devised to minimize the duration of pleural drainage [6].

Statistical Analysis
All continuous data are expressed as group means ± SD. Categorical variables are expressed as counts or percents. Normally distributed clinical parameters were compared with t tests. The Fisher exact test was used for binary variables. Nonnormally distributed data were compared by Mann-Whitney test. Kaplan-Meier analysis was used to determine actuarial survival and achievement of the Fontan endpoint, with log-rank comparison of groups. The SPSS 13.0 software (SPSS, Chicago, Illinois) was used to perform the analyses.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Discussion
 References
 
Pre-Fontan Characteristics
Anatomic diagnoses in each group are demonstrated in Table 1. The majority of patients in each group had classic hypoplastic left heart syndrome, with approximately 20% in each group having other forms of univentricular anatomy with aortic arch obstruction at initial presentation. Data derived from the pre-Fontan cardiac catheterization and echocardiograms are shown in Table 2. At the time of Fontan operation, there was no difference in patient age or size between groups, and none of the variables determined at cardiac catheterization was different between groups. Of particular note, the sizes of the pulmonary arteries were the same, as were the pulmonary artery pressures and transpulmonary gradients (calculated as mean pulmonary artery pressure minus ventricular end-diastolic pressure at cardiac catheterization). In both groups, the left pulmonary artery was smaller than the right pulmonary artery. The prevalence of significantly impaired ventricular function and atrioventricular valve function was also not different between groups, with a small minority in each group having moderate or worse ventricular dysfunction or tricuspid regurgitation.


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  		Table 1. Original Diagnoses
 

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  		Table 2. Pre-Fontan Assessment
 
Fontan Completion
The proportions of each group achieving the various endpoints at the time of the present study are depicted in Figure 1. In each group, approximately 80% have progressed to Fontan operation. A similar and small fraction of each group have died, required cardiac transplantation, or are not considered to be candidates for proceeding to Fontan operation. At the time of the study, a slightly larger fraction of patients in group 1 was awaiting Fontan completion. The time course of proceeding to Fontan operation is depicted in Figure 2. The mean age at Fontan procedure in each group was approximately 2.5 years.


Figure 1
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  		Fig 1. Outcome by group.

 

Figure 2
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  		Fig 2. Proportion achieving Fontan operation with mean age at Fontan.

 
Operative and Postoperative Course
There were no operative or early deaths after Fontan in either group. In each group, the vast majority of patients were extubated in the operating room. The initial postoperative transpulmonary gradient and SaO2 were not different between groups, nor were length of intensive care unit stay, duration of pleural drainage, or total length of hospital stay. At the time of hospital discharge the SaO2 was slightly less in group 1 (83% ± 6% versus 86% ± 6%, p = 0.02). The patency of the fenestration was not assessed at the time of the measurement of hospital discharge oxygen saturation determination. Details of postoperative assessment are shown in Table 3.


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  		Table 3. Postoperative Assessment
 
Late Outcomes
For those patients who have completed the Fontan procedure, at a mean follow-up of more than 2.3 years, functional outcomes were excellent and did not differ between groups. For both groups, more than 90% of patients were in New York Heart Association class II or I at most recent follow-up. Echocardiographic evaluation at most recent follow-up showed a very small number in each group with moderate or worse tricuspid regurgitation (group 1, 17%; group 2, 26%; p = not significant), and an even smaller number with significantly impaired ventricular function (group 1, 4%; group 2, 5%; p = not significant). There have been 2 late deaths after Fontan operation, both in group 2 patients. Actuarial survival for both groups is shown in Figure 3.


Figure 3
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  		Fig 3. Actuarial survival.

 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Discussion
 References
 
Based in part on the detection of sentinel events after the Norwood operation and in part on a desire to minimize the interval of parallel circulation, earlier performance of second-stage surgery has become more frequent in our practice [7]. The present study confirms that earlier surgery does not result in worse outcomes at the time of the Fontan procedure. The various putative effects of earlier second-stage surgery, which may not emerge until the Fontan operation, include reduced central pulmonary artery growth, higher pulmonary vascular resistance, altered ventricular function, and altered atrioventricular valve function. Other clinical indicators that may suggest an advantage of early or late SCPA include failure to achieve the Fontan circulation (as indicated by hemodynamics incompatible with the Fontan procedure) cardiac transplantation, or death before Fontan, and standard perioperative indices such as operative mortality, length of pleural drainage, and length of hospital stay, all of which may be influenced by age at time of SCPA [8].

It has been suggested that conversion from a pulsatile source of pulmonary blood flow (ventricular or systemic arterial inflow) to SCPA may result in decreased pulmonary artery cross-sectional area [9]. This concern has led some to advocate the preservation of additional (non–superior vena caval) sources of pulmonary blood flow at the time of SCPA for children with non-HLHS univentricular hearts, typically by leaving a tightly banded pulmonary artery or a small systemic to pulmonary shunt [10, 11]. In patients coming to SCPA after the Sano modification of the Norwood procedure, leaving the right ventricular to pulmonary conduit intact has been advocated for similar reasons [12].

A logical extension of this line of reasoning would be that early second-stage surgery would be associated with relative pulmonary vascular hypoplasia, manifestations of which might be expected immediately after second-stage operation in the form of elevated superior caval pressure or elevated transpulmonary gradient. We did not find such manifestation after early SCPA [4]. However, the effect would be less with only superior caval blood traversing the pulmonary circuit, whereas the Fontan arrangement is a more severe test by virtue of forcing a much larger volume of blood across the pulmonary bed.

In the present study, this question was examined in two ways. From an anatomic perspective at the time of pre-Fontan cardiac catheterization, the angiographically determined branch pulmonary artery sizes were found not to be different between groups. The left pulmonary artery was smaller than the right in both groups, as has been observed by others [9]. Multiple etiologies may explain this finding: favorable effect of the original modified Blalock-Taussig shunt on the right pulmonary artery, preferential flow from the SCPA to the right lung, compression or distortion by the enlarge neo-aorta on the left pulmonary, or simply the smaller size of the left lung. More important than the size of the arteries is whether there is a functional impact on the transpulmonary gradient of earlier second-stage operation, as this would likely translate into much less favorable and durable Fontan physiology. Such an effect was not found in the present study, as estimated by pre-Fontan hemodynamics in the catheterization laboratory and immediate postoperative hemodynamics. By both of these hemodynamic assessments, the groups were essentially identical.

Beyond the potential disadvantages of early second-stage surgery on the pulmonary bed, which we have not found, other potential deleterious effects were also sought in the present study, particularly since it has been suggested that even slightly younger patients at the time of SCPA are at a disadvantage with regard to survival and Fontan suitability [8]. We have previously demonstrated initial relative hypoxemia after second-stage surgery in younger patients (no longer apparent by the time of hospital discharge), as well as slightly prolonged durations of mechanical ventilation, pleural drainage, and hospital stay [4]. Comparison of the groups demonstrated no differences in the rates of post–second-stage death or transplantation, and similar rates of Fontan candidacy. A slightly higher proportion of the initial group I cohort was still awaiting Fontan surgery at the time of this analysis (15% versus 5%), which likely reflects the tendency toward more recent performance of early second-stage operation; simply put, the group I patients are younger than the group II patients. The timing of Fontan surgery is essentially identical between groups, as shown by Figure 2. As a function of age, the proportion of each cohort that has completed Fontan operation is the same at all time points. As to other perioperative outcomes at the time of Fontan surgery, there were no differences between groups in rate of intraoperative extubation, duration of pleural drainage, or hospital stay.

There was a slight difference between groups in SaO2 at the time of hospital discharge after Fontan operation, with group I patients being slightly more cyanotic (83% ± 6% versus 86% ± 6%, p = 0.02); it remains to be seen whether this small difference will persist and whether it will have any functional impact. While it might be argued that the lower saturations reflects more right to left shunting at the fenestration level, and therefore higher pulmonary vascular resistance, the impact of other factors such as fenestration size and pulmonary venous desaturation confound such a conclusion. At a time when more intensive hemodynamic monitoring was in place, namely, immediately after Fontan surgery, the saturations were actually not different between groups, nor was the measured transpulmonary gradient, suggesting that factors other than elevated pulmonary resistance are likely the explanation for the discharge SaO2 difference.

While there may be theoretical disadvantages to the pulmonary circulation of early second-stage surgery, which we have not found at either SCPA or Fontan operation in our cohort, there may be also be theoretical advantages for cardiac function by early relief of the volume load caused by parallel circulation. In particular, it might be postulated that the systolic and diastolic function of the single ventricle would be preserved by early reduction of volume loading. In the prior study of early SCPA, we did not identify such an effect [4]. In the present study, using such indices as preoperative ventricular end-diastolic pressure (at cardiac catheterization), postoperative atrial pressure (in the intensive care unit), and full echocardiographic analysis of systolic function before and after surgery, we found no differences between groups. Likewise, no impact of early surgery was found on atrioventricular valve function, with similar proportions of significant tricuspid valve dysfunction in the two groups.

Several limitations must be acknowledged in the present study. Most importantly, the groups were not randomly generated and the study was retrospective. Age was not analyzed as a continuous variable, because of the relatively small numbers of patient in each group, and thus no inflection point for risk may be discerned from our data. The decision in the original study to use four months as a cut-off age was admittedly arbitrary, but was considered to represent a significant departure from the then-popular 6-month target for second-stage operation. The group sizes are fairly small, and differences attributable to alternative timing of second stage may be infrequent enough or small enough to require much larger sample sizes for appropriate statistical power for detection. Some endpoints such as duration pleural drainage and hospital stays may be more reflective of physician behavior than patient physiology. Other analytical difficulties relate to the evolutionary nature of the care of children with single ventricle and arch obstruction, exemplified by relatively recently introduced modifications such as the right ventricle to pulmonary artery conduit [12], hybrid (partially catheter-based) approaches [13], as well as constantly improving postoperative care, both in and out of the hospital [7, 14].

Despite the limitations of the study as described, we believe the data suggest that there is no deleterious late effect of early performance of second-stage surgery, at least up to and early after the Fontan procedure. On balance, there is likewise no clear benefit of early surgery. However, for a particular child for whom early second-stage surgery may be considered necessary because of shunt stenosis, poor weight gain, or persistent hemodynamic instability, the present study may provide reassurance that the late outcome should be as good as if the second-stage surgery could have been delayed. Similarly, the study may provide support for institutions contemplating earlier elective second-stage surgery. As with most studies in congenital heart surgery, however, definitive conclusions will certainly require ongoing long-term follow-up, and ideally, confirmation by a prospective randomized trial.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
References
 
DR CHRISTOPHER KNOTT-CRAIG (Oklahoma City, OK): In my experience, most infants present between 3.5 and 4 months of age for the bidirectional Glenn, particularly after the Sano Norwood operation. Your early group was up to 4 months old. I would call that normal, not early. Did you actually look at the younger patients within that group and did that break out any differently?

DR JAQUISS: These are relatively small groups, and we didn't subset them particularly. I would agree with you that, I think that people come to Glenn, in the year 2006, at around 3 or 4 or 5 months of age. But compared with 5 years ago, that's actually younger. I think there has been a general move, certainly not provoked by this study or its predecessor, to do second-stage operation earlier. We did not look at the particularly youngest patients as a subset to see if they did worse.

DR KNOTT-CRAIG: Did you ligate the azygos vein in the younger kids?

DR JAQUISS: We ligate the azygos vein in all children at the second stage.

DR KNOTT-CRAIG: What about the accessory blood flow at the time of their Glenn? For instance, in the Sano-Norwood group, is that taken down or left in place?

DR JAQUISS: Well, this particular study included no children having a Sano operation. Speaking for myself and Jim Tweddell, I don't think either of us leave the Sano in place, although I know Dr Sano himself has said that he does.

DR MUHAMMAD A. MUMTAZ (Cleveland, OH): I'm sorry, I didn't hear the last comment. Did you say that none of these patients had a Sano operation?

DR JAQUISS: Right. This cohort was drawn from the era before the Sano modification.

DR MUMTAZ: That was what my question was going to be. Because I was just curious that at Fontan, by doing the Glenn earlier, you would have thought that maybe by that time you would get better ventricular function. But since in both groups there was really an outstanding ventricular function, you couldn't really show that difference. I was curious if you had any Sanos, and I guess you didn't.

DR JAQUISS: Not yet, no.

DR MARSHALL L. JACOBS (Philadelphia, PA): It's a lovely presentation and a terrific series and it addresses an important question. I think that Dr Bove's paper years ago about the early results of the very early bidirectional Glenn was similar in terms of low saturations with equal survival. And then, since all those patients went on to successful Fontans, it pretty much reverberates as the same kind of finding.

What struck me in your series of Fontans, who are nearly consistently, and I guess generously and successfully fenestrated, is that their discharge saturation, the mean statistically was the same. And perhaps, if one split hairs, was actually a millimeter of mercury, or a percentage lower, than their pre-Fontan catheterization saturation, which is fine and not surprising. But as you've had now several years follow-up on these patients, what happens to their saturations over time, do they remain in the mid 80s, or do they wind up in the low 90s?

DR JAQUISS: I wish I had been smart enough when I was putting together the data sheet to give to our medical student to abstract the data to ask her to draw that out. It didn't occur to me until I was doing the data analysis to come up with that very good question, so I don't have the answer to it.

My general impression, although being completely worthless statistically, is that their oxygen saturations do come up fairly nicely. We have closed the fenestrations in about 15% of these kids. It's inevitable that, as they grow, their fenestration to body surface area ratio is going to diminish dramatically, and I know that there are some who feel that fenestrations need not be closed ever. I doubt that the degree of right to left shunting that is present in a relatively recently operated on child is going to persist, so I would predict, but can't tell you based on data, that the saturations have come up into the low 90s.

DR THOMAS YEH (Dallas, TX): Doctor Jaquiss, I enjoyed your excellent presentation. Do you have any insight into the impact of prolonged low perioperative saturations on neurologic outcome?

DR JAQUISS: I think that's an excellent question, and the answer is that I don't. Based on our interest in the use of near infrared spectroscopy, we have some information about what we think to be the venous oxygen saturations in the brain are after surgery with early Glenns. The AVO2 difference tends to be normal, which we take as somewhat reassuring that the brain's efficient economy of oxygen extraction is making up for the fact that they're initially quite blue. But the answer to your question is I don't have an answer on the actual data or the impact long term.

DR YEH: Well, since you have a relatively large cohort, it would be interesting to study those kids, once they get old enough, to see if there is a difference between those two groups.

DR JAQUISS: I'm sure Dr Ghanayem will take that on.

DR CARL L. BACKER (Chicago, IL): What were the technical aspects of the bidirectional Glenn procedure? Did you use continuous cardiopulmonary bypass or circulatory arrest?

DR JAQUISS: Continuous cardiopulmonary bypass.

DR BACKER: What is your suture technique of choice— running suture, interrupted suture, absorbable suture, Prolene?

DR JAQUISS: I use a continuous Prolene interrupted at a few points, and I think Jim does a similar thing.

DR TWEDDELL: Similar thing, running 7-0 Prolene.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 References
 

  1. Bridges ND, Jonas RA, Mayer JE, Flanagan MF, Keane JF, Castaneda AR. Bidirectional cavopulmonary anastomosis as interim palliation for high-risk Fontan candidatesEarly results. Circulation 1990;82(Suppl 4):170-176.
  2. Forbess JM, Cook N, Serraf A, Burke RP, Mayer Jr JE, Jonas RA. An institutional experience with second- and third-stage palliative procedures for hypoplastic left heart syndrome: the impact of the bidirectional cavopulmonary shunt J Am Coll Cardiol 1997;29:665-670.[Abstract]
  3. McGuirk SP, Griselli M, Stumper OF, et al. Staged surgical management of hypoplastic left heart syndrome: a single institution 12-year experience Heart 2006;92:364-370.[Abstract/Free Full Text]
  4. Jaquiss RD, Ghanayem NS, Hoffman GM, et al. Early cavopulmonary anastomosis in very young infants after the Norwood procedure: impact on oxygenation, resource utilization, and mortality J Thorac Cardiovasc Surg 2004;127:982-989.[Abstract/Free Full Text]
  5. Fedderly RT, Whitstone BN, Frisbee SJ, Tweddell JS, Litwin SB. Factors related to pleural effusions after Fontan procedure in the era of fenestration Circulation 2001;104(Suppl 1):148-151.
  6. Cava JR, Bevandic SM, Steltzer MM, Tweddell JS. A medical strategy to reduce persistent chest tube drainage after the fontan operation Am J Cardiol 2005;96:130-133.[Medline]
  7. Ghanayem NS, Tweddell JS, Hoffman GM, Mussatto K, Jaquiss RD. Optimal timing of the second stage of palliation for hypoplastic left heart syndrome facilitated through home monitoring, and the results of early cavopulmonary anastomosis Cardiol Young 2006;16(Suppl 1):61-66.[Medline]
  8. Douglas WI, Goldberg CS, Mosca RS, Law IH, Bove EL. Hemi-Fontan procedure for hypoplastic left heart syndrome: outcome and suitability for Fontan Ann Thorac Surg 1999;68:1361-1368.[Abstract/Free Full Text]
  9. Mendelsohn AM, Bove EL, Lupinetti FM, Crowley DC, Lloyd TR, Beekman III RH. Central pulmonary artery growth patterns after the bidirectional Glenn procedure J Thorac Cardiovasc Surg 1994;107:1284-1290.[Abstract/Free Full Text]
  10. Yoshida M, Yamaguchi M, Yoshimura N, Murakami H, Matsuhisa H, Okita Y. Appropriate additional pulmonary blood flow at the bidirectional Glenn procedure is useful for completion of total cavopulmonary connection Ann Thorac Surg 2005;80:976-981.[Abstract/Free Full Text]
  11. Caspi J, Pettitt TW, Ferguson Jr TB, Stopa AR, Sandhu SK. Effects of controlled antegrade pulmonary blood flow on cardiac function after bidirectional cavopulmonary anastomosis Ann Thorac Surg 2003;76:1917-1921.[Abstract/Free Full Text]
  12. Sano S, Ishino K, Kawada M, et al. Right ventricle-pulmonary artery shunt in first-stage palliation of hypoplastic left heart syndrome J Thorac Cardiovasc Surg 2003;126:504-510.[Abstract/Free Full Text]
  13. Bacha EA, Daves S, Hardin J, et al. Single-ventricle palliation for high-risk neonates: the emergence of an alternative hybrid stage I strategy J Thorac Cardiovasc Surg 2006;131:163-171.[Abstract/Free Full Text]
  14. Tweddell JS, Hoffman GM, Mussatto KA, et al. Improved survival of patients undergoing palliation of hypoplastic left heart syndrome: lessons learned from 115 consecutive patients Circulation 2002;106(Suppl 1):82-89.



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