Peripheral Pulmonary Artery Stenosis Is Not a Contraindication to a Single-ventricle Pathway.

BACKGROUND: The presence of peripheral pulmonary artery stenosis (PPAS) involving lobar and/or segmental pulmonary artery (PA) branches might preclude proceeding to a single-ventricle pathway. We adopted a strict strategy for PA rehabilitation and surgical reconstruction in patients who are unable to progress to a single-ventricle pathway. METHODS: We conducted a retrospective review of 22 patients with single-ventricle physiology who underwent surgical reconstruction for PPAS from April 2008 to March 2020. Our surgical approach was single stage in 15 patients (68.2%) and 2 stage in 7 patients (31.8%) depending on the presence or absence of PA hypoplasia distal to the PPAS. RESULTS: The PPAS was type 3 (lobar) in 19 patients (86.4%) and type 4 (segmental) in 3 patients (13.6%). The mean number of PA angioplasties performed was 8 ± 5.6 per patient. There was no mortality in this series with a median of 52 months (range, 8-143) of follow-up. Twenty patients (90.9%) were able to progress in the single-ventricle pathway with 12 patients (54.5%) undergoing a Fontan operation and 8 patients (36.4%) achieving bidirectional Glenn shunt and awaiting a Fontan operation. Two patients (9.1%) were not suitable to progress to the single-ventricle pathway because of elevated PA pressure. All patients who achieved cavopulmonary connection were alive and asymptomatic with no signs of elevation of PA pressure. No patient required further reinterventions for the PA. CONCLUSIONS: PPAS is not a contraindication for single-ventricle palliation. With careful planning and aggressive early surgical reconstruction, most of these patients can successfully progress to cavopulmonary connections.

Late Outcomes After Pulmonary Arterial Reconstruction in Patients With Arterial Tortuosity Syndrome.

BACKGROUND: Surgical pulmonary artery reconstruction in patients with arterial tortuosity syndrome has excellent outcomes. In this study, we report our late outcomes after more than a decade of experience with such complex interventions. METHODS: We conducted a retrospective review of 33 arterial tortuosity syndrome patients who underwent pulmonary artery reconstruction. The mean preoperative right ventricular to left ventricular pressure ratio was 1.19 ± 0.2. Our surgical approach included either a single-stage complete repair through a median sternotomy (17 patients) or a two-stage repair through sternotomy/left thoracotomy (16 patients), depending on the degree of distal involvement in the left pulmonary artery. RESULTS: Median age was 36 months. All patients had distal segmental peripheral pulmonary artery stenosis. Thirty patients (90.1%) were symptomatic before surgery. There was one hospital death due to viral pneumonia 78 days after the surgery (in-hospital mortality 3%). The mean right ventricular to left ventricular pressure ratio decreased to 0.31 ± 0.07 early postoperatively (P < 0.001), representing a 74% reduction compared with preoperative values. Follow-up was 100% complete for all hospital survivors (32 of 33) with a mean follow-up of 70.42 ± 43.32 months (range, 2 to 143). There was no late mortality or need for reintervention (surgical or catheter based) after hospital discharge. In late postoperative catheterization, the mean right ventricular to left ventricular pressure ratio was 0.27 ± 0.05 (P = .003 compared with early postoperative value). All patients were asymptomatic on their most recent follow-up. CONCLUSIONS: A strategy of complete surgical reconstruction of all stenotic pulmonary artery segments in patients with arterial tortuosity syndrome is recommended for sustainable successful outcomes more than a decade later.

Late outcomes of surgical reconstruction of peripheral pulmonary arteries.

OBJECTIVE: The ideal management of peripheral pulmonary artery stenosis is still controversial. We adopted a primary surgical approach to this complex lesion with excellent early outcomes. In this study, we analyzed our late outcomes. METHODS: We performed a retrospective review of 91 patients with biventricular anatomy who underwent peripheral pulmonary artery reconstruction from March 2008 to July 2020. Our surgical approach included either a single-stage complete repair through median sternotomy or a 2-stage repair through sternotomy/left thoracotomy, depending on the degree of distal involvement of the left pulmonary artery branches. RESULTS: Median age was 26 months. Syndromic etiology was established in 54 patients (59.3%) versus nonsyndromic etiology in 37 patients (40.7%). Single-stage repair was achieved in 68 patients (74.7%). There were 2 (2.2%) in-hospital mortalities. The mean right ventricular to aortic systolic pressure ratio decreased from 1.07 ± 0.20 preoperatively to 0.32 ± 0.07 immediately postoperatively (P < .001), representing a 70.1% reduction. At 1-year postoperative catheterization, the mean right ventricular to aortic systolic pressure ratio was 0.28 ± 0.05 (P < .001 compared with immediately postoperative value). With a median follow-up of 68 months (IQR, 39-117.5 months), there was no late mortality after discharge. All patients were active and asymptomatic on the most recent follow-up. There were no early or late reinterventions on pulmonary arteries. CONCLUSIONS: Late outcomes of surgical reconstruction of peripheral pulmonary arteries are excellent and durable in various pathologies (syndromic and nonsyndromic) with a significant reduction in right ventricular to aortic systolic pressure ratio, low mortality, and no reintervention.

Surgical experience in the rehabilitation and reimplantation of disconnected pulmonary arteries and its effectiveness in restoring pulmonary haemodynamics and function.

OBJECTIVES: We established a policy to restore disconnected pulmonary arteries (PAs), regardless of aetiology or cardiac pathology, using a protocol-based strategy. There are conflicting reports of the need to restore disconnected PA especially if severely hypoplastic with some groups advocating surgical repair of cardiac defects to single lung with moderate to high risk. METHODS: All patients referred to our PA reconstruction programme (2007-14) with complete separation of one branch PA were included. Our surgical strategy was based on the size of the PA. In patients with mild or no PA hypoplasia, we performed single-stage implantation of the disconnected PA and repair of intracardiac defects. Two-stage approach was used in patients with severe PA hypoplasia where the disconnected PA was retrieved inside the lung then connected to the aorta with a shunt to promote growth. After 6-12 months, the PA was implanted with simultaneous repair of intracardiac defects. RESULTS: Twenty patients were included (age range = 1 week to 8 years). Aetiologies were ductal origin of distal PA in 13 patients and iatrogenic in 7 patients. Group 1 (isolated lesion) consisted of 8 patients who presented with severe pulmonary hypertension. Group 2 consisted of 12 patients with associated intracardiac defects and was subdivided into Group 2a (biventricular hearts) 8 patients and Group 2b (univentricular hearts) 4 patients. Single-stage repair was achieved in 10 patients. Direct tissue-to-tissue connection was achieved in 18 (90%) patients. The follow-up was 100% complete (median = 53.8 months). All patients are alive and asymptomatic. Implanted PAs are patent with good growth demonstrated on serial echocardiography. Only two PAs required balloon dilatation for moderate restenosis at the anastomosis. No surgical reintervention was needed. All Group 1 patients had complete resolution of the pulmonary hypertension. Lung perfusion scans showed increased uptake (24-53% of the total uptake). CONCLUSIONS: Our study demonstrated that, in paediatric age group, disconnected PAs can be restored with low risk and excellent outcomes even in patients with severely hypoplastic PA. Strategies to repair intracardiac defects to a single lung might not be the optimal approach.

Surgical Reconstruction of Peripheral Pulmonary Arteries: Strategies, Outcomes, and New Classification.

BACKGROUND: Pulmonary artery stenosis (PAS) is classified as central (types 1 and 2) and peripheral (type 3 affects proximal part of lobar arteries, type 4 affects proximal part of segmental arteries, and type 5 affects distal part of segmental arteries). In this study, we examine the outcomes of surgical reconstruction of peripheral PAS. METHODS: We reviewed 31 patients with peripheral PAS who underwent surgical repair. Median age was 30 months. Patients with intact ventricular septum (24 patients) presented with severe right ventricular dilation and dysfunction and mean right ventricular to left ventricular pressure (RVSP/LVSP) ratio was 0.96 ± 0.25, 1.14 ± 0.23, and 1.43 ± 0.07 for types 3, 4, and 5, respectively (p = 0.03). Pulmonary artery reconstruction was achieved in single stage in 19 patients (61%). RESULTS: Six patients (19%) had type 3, 22 patients (71%) had type 4, and 3 patients (10%) had type 5. mean number of angioplasties per patient was 18 ± 8. There was no early mortality. Mean postoperative RVSP/LVSP ratio decreased to 0.27 ± 0.08, 0.36 ± 0.05, and 0.96 ± 0.06, for types 3, 4, and 5, respectively (p < 0.001). The median follow-up was 48 months. Patients with type 3 and 4 showed marked improvement in functional status after surgery. Patients with type 5 showed clinical evidence of improved cardiac output despite modest decrease in RVSP. No surgical re-intervention was needed, while balloon dilation was performed in 1 patient with type 5 lesions. CONCLUSIONS: Surgical reconstruction of diffuse peripheral PAS is feasible and associated with excellent hemodynamic and functional outcomes in patients where there is no involvement of the distal part of segmental arteries.

Early outcomes of total pulmonary arterial reconstruction in patients with arterial tortuosity syndrome.

BACKGROUND: Arterial Tortuosity Syndrome (ATS) is an autosomal recessive connective tissue disease that can present with complex pulmonary arterial stenosis, causing right ventricular (RV) hypertension and dysfunction. In this study, we review our experience and early outcomes with single stage surgical repair. METHODS: From 2008 to 2010, 7 patients with ATS and severe bilateral pulmonary artery stenosis underwent surgical repair that involved extensive reconstruction of the pulmonary arterial tree bilaterally, including the central, lobar and segmental branches. The clinical records of these patients were reviewed for preoperative data, repair techniques and early clinical outcomes, including reinterventions and recent echocardiographic studies. RESULTS: All 7 patients had bilateral peripheral and central pulmonary artery stenosis with systemic to supra-systemic RV pressure and severe RV dysfunction. Median age at the time of operation was 72 months (range=7 to 120 months). All patients had low RV pressure (≤40% systemic) after the procedure with significant improvement in RV function to normal before hospital discharge. The mean right ventricular/left ventricular pressure ratio decreased from 1.27±0.19 to 0.31±0.06 postoperatively (p<0.001). There was no mortality. All patients continued regular follow-up at our institution for a mean follow-up period of 17.6±9.1 months. All patients were alive and asymptomatic with normal RV function and no evidence of elevated RV pressure on most recent echocardiography. CONCLUSIONS: Complete surgical reconstruction of the pulmonary arterial tree in advanced cases of ATS is a successful intervention with excellent early clinical and hemodynamic outcomes.

Successful surgical pulmonary artery reconstruction in arterial tortuosity syndrome.

The outcomes of surgical repair for diffuse pulmonary artery stenoses due to arterial tortuosity syndrome are unknown. We report a 1-year-old girl with tortuosity syndrome who presented with suprasystemic right ventricular pressure due to distortion and stenoses of the pulmonary artery branches. We describe the operative findings of this unique pathology and the surgical techniques used to completely reconstruct the pulmonary arterial tree, with normalization of the right ventricular pressure.

Repair of aortic arch atresia with diffuse hypoplasia of the descending thoracic aorta.

We report successful repair of a rare combination of aortic arch atresia and diffuse long-segment hypoplasia of the descending aorta in a 2-month-old infant with PHACES association. Intraoperative findings and surgical techniques are discussed.

Heterotopic heart transplant combined with postoperative Sildenafil use for the treatment of restrictive cardiomyopathy.

We report successful management of a 22-month-old child with restrictive cardiomyopathy and severe pulmonary hypertension using the heterotopic heart transplant technique. Additional lessons learned from postoperative management, including the novel use of Sildenafil (Viagra, Pfizer, NY) for controlling pulmonary arterial pressure are described.

Outcome analysis of donor gender in heart transplantation.

BACKGROUND: Several studies have shown a detrimental effect of female donor gender on the survival of solid-organ transplant recipients, including heart, kidney and liver. We evaluated our own experience in heart transplantation in the cyclosporine era, since 1980, to determine the effect of donor gender on survival. METHODS: We retrospectively reviewed 869 consecutive patients who underwent primary heart transplantation at Stanford University Medical Center between December 1980 and March 2004. Actuarial life-table data were calculated for survival and freedom from rejection and compared between groups. Multivariate Cox proportional hazard analysis was used to identify predictors of reduced long-term survival. RESULTS: One-year mortality in male recipients who received a female donor heart (24%) was higher than in male recipients who received male donor heart (13%) (p = 0.009). Actuarial survival rates for male recipients at 1, 5 and 10 years were 86%, 69% and 50% (with male donor), and 76%, 59% and 45% (with female donor) (p = 0.01), respectively. Donor gender had no effect on long-term survival in male recipients < 45 years of age and female recipients. Female donor gender was identified as an independent risk factor for death by multivariate analysis, with an odds ratio of 2.3 (95% confidence interval 1.5 to 3.4, p < 0.001). CONCLUSIONS: In heart transplantation the detrimental effect of female donor gender on recipient survival is significant but limited to male recipients > 45 years of age. These findings should be considered in the process of donor-recipient matching.

Successful repair of blunt injury of aortic arch branches in the setting of bovine arch.

Intrathoracic great vessels injuries are usually fatal and represent a special surgical challenge. We report a successful surgical repair for blunt disruption of the three aortic arch branches in the setting of bovine arch anatomy. The repair was achieved without the use of cardiopulmonary bypass or arterial shunts. There was no clinical or radiologic evidence of neurologic abnormality after the repair.

New directions in cardiac transplantation.

More than three decades of clinical experience in cardiac transplantation resulted in the spread of the procedure worldwide with a wealth of knowledge and advancements. Developments included liberalization of recipient and donor selection criteria, improved surgical techniques, novel immunosuppressive drugs and protocols, new rejection surveillance techniques, and better understanding of the pathophysiology of cardiac allograft vasculopathy to direct interventions for prevention and treatment.

Thoratec ventricular assist devices in pediatric patients: update on clinical results.

Particularly in pediatric patients, mechanical circulatory support remains a clinical challenge. We analyzed the Stanford experience with use of the Thoratec ventricular assist device (VAD) in children and adolescents and data from the company's voluntary database. Through January 2005, 209 patients up to 18 years of age have been supported with the Thoratec VAD worldwide. Mean age was 14.5 years (range 5-18 years), mean weight was 57 kg (range 17-118 kg), and mean body surface area was 1.6 m2 (range 0.7-2.3 m2). The majority of patients were supported for cardiomyopathies (55%) and acute myocarditis (25%). A minority (6%) was treated for end-stage congenital heart disease. Average duration of support was 44 days (0-434 days). Overall survival to transplantation or weaning off the device was 68%. Survival rates were higher for patients with cardiomyopathies (74%) and acute myocarditis (86%) compared with patients with congenital heart disease (27%). We performed a subanalysis in small children with a body surface area of less 1.3 m2. This subgroup had a higher incidence of congenital heart disease and a slightly lower survival (52%). Aspects of the particular risks and device management in these small patients are discussed.

Successful single-lung fontan operation in an adult: 5-year follow-up.

We report a case of a 20-year-old man with a functional single left ventricle who underwent a successful Fontan operation into a single left pulmonary artery, the right pulmonary artery being atretic. The literature of a single-lung Fontan procedure is also reviewed.

Left ventricular unloading in a patient with end-stage cardiomyopathy and medically unresponsive pulmonary hypertension.

Severe, medically unresponsive pulmonary hypertension (PHT) is considered to be a contraindication for orthotopic heart transplantation (OHT). Chronic left ventricular (LV) unloading using a left ventricular assist device (LVAD) might result in reversal of the elevated pulmonary vascular resistance (PVR), allowing successful OHT in such patients. In this study, we present a patient with end-stage ischemic cardiomyopathy and fixed, elevated PVR (7.1 Wood units) who underwent implantation of a Novacor LVAD (Baxter Healthcare Corp., Deerfield, IL, U.S.A.), with a subsequent reduction in PVR to 1.2 Wood units and successful OHT eleven months post-LVAD implantation. Three years after heart transplant, the patient still leads an active life with no right heart failure. In conclusion, OHT is not contraindicated in patients with end-stage heart failure and medically unresponsive PHT in the presence of elevated left atrial pressure. Left ventricular unloading should be considered in these patients to allow reversal of the elevated PVR before OHT.

Mobilization and homing of bone marrow stromal cells in myocardial infarction.

OBJECTIVE: Marrow stromal cells (MSCs) contain multipotent cells, which may participate in the repair of damaged organs. We tested the hypothesis that MSCs are recruited to the heart upon myocardial infarction (MI), and play pathophysiological roles in the healing and adaptation process. METHODS: Donor MSCs from isogenic Lewis rats were harvested, multiplied and labeled with Lac Z reporter gene. Ten million labeled cells were injected intravenously into the recipient rats (n=30). One week later, 10 rats were killed to examine the distribution of the labeled MSCs. Other rats underwent either coronary artery ligations (n=14) or sham operations (n=6). The hearts were removed at various time points (1-8 weeks) and stained for beta-galactosidase activity. Phenotypes of labeled cells were identified with immunohistochemical stains. RESULTS: In rats killed at 1 week, labeled cells had homed into the bone marrow of the recipients, and none found in their hearts. In the coronary ligated hearts, labeled cells were seen in and near the infarct at all time points studied (14/14), but none in the sham operated hearts (6/6). There was evidence for myogenic differentiation. Some of these labeled cells showed positive staining for cardiomyocyte specific troponin I-c at 4 weeks, while others appeared in the vascular walls expressing smooth muscle alpha-actin. CONCLUSIONS: Following myocardial infarction, MSC's are signaled and recruited to the injured heart, where they undergo differentiation, and may participate in the pathophysiology of post-infarct remodeling, angiogenesis, and maturation of the scar. Therapeutic implantation of MSCs thus may further enhance such effects.

Therapeutic angiogenesis using autologous bone marrow stromal cells: improved blood flow in a chronic limb ischemia model.

BACKGROUND: We evaluated the effect of autologous marrow stromal cells (MSCs) on neovascularization and blood flow in an animal model of chronic limb ischemia. METHODS: Chronic hind limb ischemia was created by ligating the left common iliac artery of male Lewis rats. Three weeks after ligation, 5.0 million LacZ+MSCs (n = 10) or culture medium (n = 10) were injected into the anteromedial muscle compartment of the left thigh. At 4 and 6 weeks after injection, half the animals (n = 5) from each group underwent femoral artery ultrasonic blood flow measurements of the ischemic and nonischemic limbs to obtain a flow ratio. The animals also underwent angiography and measurements of blood vessel density and arteriolar density. Qualitative histologic assessment of the limb muscles was performed. RESULTS: LacZ+MSCs were found to differentiate into endothelium (F VIII+), vascular smooth muscle (positive a-smooth muscle actin), skeletal muscle (positive desmin), and adipocytes. Ischemic hind limbs where MSCs were implanted had greater vascular density and arteriolar density than control limbs (p < 0.001). Femoral artery flow index (left femoral artery flow/right femoral artery flow) was 0.89 +/- 0.12 and 0.90 +/- 0.06 for rats injected with MSCs measured at 4- and 6-weeks, respectively, compared with 0.50 +/- 0.15 and 0.50 +/- 0.10 for the control rats (p < 0.001). Angiography demonstrated reconstitution of the left femoral artery in rats that received MSC implantation through pelvic and abdominal wall collateral formation. CONCLUSIONS: Local MSC implantation induces a neovascular response resulting in a significant increase in blood flow to the ischemic limb. Marrow stromal cells are also capable of spontaneously regenerating the various components of muscular tissues.

In vitro preprogramming of marrow stromal cells for myocardial regeneration.

BACKGROUND: We have previously reported that marrow stromal stem cells (MSCs), when implanted into myocardium, can undergo milieu-dependent differentiation to express phenotypes similar to the cells in the immediate microenvironment. We tested the hypothesis that by in vitro preprogramming of MSCs, we may be able to guide their differentiation to express a therapeutically desirable phenotype that is different from those in their microenvironment. METHODS: MSCs were isolated from isogenic Lewis rats, culture expanded, and labeled with beta-gal using retrovirus carrying the lac-Z gene. A subset of the transfected MSCs was then treated with 5-aza-2'deoxycytidine (5-aza). Three weeks after the left ventricles were cryoinjured, either 5-aza-pretreated (n = 10) or untreated (n = 8) MSCs were injected into the myocardial scar. The hearts were harvested 4 to 8 weeks later and stained immunohistochemically for phenotypic markers. RESULTS: The labeled MSCs within the scars that were 5-aza pretreated appeared to be morphologically distinct from the untreated ones. The treated cells (8/10 rats) appeared more myotube-like, with elongated nuclei, linearly aligned with one another, and stained positive for the cardiomyocyte-specific marker troponin I-C. Untreated MSCs (5/8 rats), in contrast, were poorly differentiated, and some appeared to express other phenotypes seen in the scar tissue. CONCLUSIONS: Our findings indicate that in cellular cardiomyoplasty using MSCs, one may select different strategies to achieve specific therapeutic goals. By milieu-dependent differentiation, unmodified MSCs may augment myocardial angiogenesis and myogenesis, whereas converting scar into myogenic tissue may be facilitated by preprogramming of MSCs before implantation.