Tetralogy of Fallot with coronary crossing the right ventricular outflow tract: A tale of a bridge and the artery.

A coronary artery crossing the right ventricular outflow tract is a subset of a larger pathomorphological cohort known as an anomalous coronary artery (ACA) in the tetralogy of Fallot (TOF). The best possible outcome in a patient with TOF and ACA is decided by judicious selection of optimum preoperative investigative information, the timing of surgery, astute assessment of preoperative surgical findings, and appropriate surgical technique from a wide array of choices. In most instances, the choice of surgical technique is determined by the size of the pulmonary annulus and the anatomical relation of ACA to the pulmonary annulus. In the present era, complete, accurate preoperative diagnosis and primary repair is a routine procedure with strategies to avoid a right ventricle-to-pulmonary artery conduit.

Where are we after 50 years of the Fontan operation?

First introduced in 1971, the Fontan procedure is the final common destination for all patients with a functional single ventricle. The procedure itself has evolved tremendously over the last five decades. This review traces this journey and presents the importance, outcomes and future outlook of the procedure in the current era.

Extracardiac Fontan With Direct Inferior Vena Cava to Main Pulmonary Artery Connection Without Cardiopulmonary Bypass.

We report the case of a six-year-old patient who underwent an extracardiac Fontan operation including bilateral bidirectional superior cavopulmonary anastomosis and direct inferior vena cava to main pulmonary artery connection that was performed without cardiopulmonary bypass.

Double Outlet Right Ventricle With Right-Sided Aorta From the Left-Sided Morphologically Right Ventricle in the Setting of Discordant Atrioventricular Connections.

We describe the anatomic findings in a 2-year-old patient with double outlet right ventricle with right-sided aorta in the setting of usual atrial arrangement and discordant atrioventricular connections, making comparison with a specimen from the pathological archive of the Birmingham Children's Hospital in the United Kingdom having this rare combination of anatomic features. We discuss the challenges involved in diagnosis and management.

Adipose tissue derived mesenchymal stem cells are better respondents to TGFß1 for in vitro generation of cardiomyocyte-like cells.

Mesenchymal stem cells (MSCs) are multipotent cells which hold immense potential in translational research as a novel treatment modality. In recent years, MSCs isolated from various tissues have been used in several clinical trials for the treatment of cardiac injury caused by permanent myocardial loss. However, a better MSCs source and an optimum inducer for in vitro cardiac differentiation are still far reaching and unexplored. The aim of the study was to compare the ability and efficiency of differentiation of MSCs isolated from bone marrow (BM-MSCs) and adipose tissue (ADSC) into cardiomyocyte-like cells to aid translational research. To fulfill this aim, freshly isolated BM-MSCs and ADSCs were differentiated into cardiomyocytes using 5-Azacytidine (6 µM) and TGF-ß1 (25 ng/ml). These two differentiation protocols were compared on the basis of morphological, transcriptional, translational and functionality analysis. Both tissue specific MSCs, ADSCs and BM-MSCs, have similar surface marker profile and population doubling time. In both the treatment regimes, BM-MSCs and ADSCs showed morphological changes like flattening of cells and myotube formation in concurrence with structure and multinucleation, with early sign of differentiation in ADSCs. Further, the expression of cardiac specific markers including myosin light chain-2v (Mlc-2v), cardiac troponin I (cTnI), and sarco/endoplasmic reticulum Ca2+-ATPase (SerCa2) were higher in AD-TGFß1 group, both at transcriptional and translational level. During functionality analysis by KCl stimulation, increased intracellular calcium fluorescence was observed in AD- TGFß1 group as compared to others. Thus, ADSCs proved to be a better choice for stem cell therapy in cardiovascular diseases when induced with TGF-ß1.

An alternative technique for completion of the total cavopulmonary connection.

BACKGROUND: Total Cavopulmonary connection (Fontan) is the final palliation for patients with a functionally univentricular heart. This is commonly accomplished after a prior bidirectional Glenn on cardiopulmonary bypass (CPB) with separate cannulation of the aorta, superior vena cava (SVC), and inferior vena cava. We describe an alternative technique of Fontan completion that eliminates the need for cannulation and dissection of the SVC, and pulmonary artery dissection. METHODS: Between January and October 2018, 17 patients underwent completion Fontan using an alternate technique at our institute. All operations were conducted on CPB at normothermia without cannulating the SVC RESULTS: Mean CPB time was 60 ± 16.8 minutes (range, 39-102 minutes). There were no early deaths. Mean postoperative Fontan pressures were 15.6 ± 1.2 mm Hg with no gradient between the SVC and IVC pressures. Mean duration of hospital stay was 15.6 ± 3.6 days (range, 10-22 days). No patient developed phrenic nerve paresis or palsy. CONCLUSIONS: Completion without cannulating the SVC is simple, reproducible, and easy to teach. It avoids the disadvantages associated with routine techniques.

Patch materials for right ventricular outflow reconstruction: past, present, and future.

In this review, we discuss various patch materials used for reconstruction of the right ventricular outflow tract. Their relative merits and demerits are discussed. Traditional patches and their results are detailed along with a brief description of newer developments in the field.

Comparison of del Nido and histidine-tryptophan-ketoglutarate cardioplegia solutions in pediatric patients undergoing open heart surgery: A prospective randomized clinical trial.

OBJECTIVES: We conducted a prospective randomized controlled trial to compare del Nido (DN) and histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution in pediatric patients undergoing intracardiac tetralogy of Fallot repair. METHODS: One hundred consecutive patients 12 years of age or younger, undergoing intracardiac repair of tetralogy of Fallot were randomized into DN (n = 50) and HTK (n = 50) groups. Cardioplegia strategy consisted of a single dose of DN (20 mL/kg) or HTK (6 mL/kg/min for 6 minutes). Primary outcome was cardiac index (CI). Secondary outcomes were ventricular arrhythmias post cross-clamp release, time to peripheral rewarming, duration of mechanical ventilation, inotropic score, intensive care unit and hospital stay, and serum levels of troponin-I, interleukin-6, and tumor necrosis factor-α. Ultrastructural changes in the myocardium were assessed. RESULTS: CI was significantly higher in the DN group compared with the HTK group at 6 (P = .005) and 24 hours (P < .001) after surgery. It was on an average 0.44 L/min/m2 higher in the DN group at any time point (P = .004). Time for complete cessation of electrical activity was longer in the HTK group (P = .01) and more patients in the HTK group had ventricular arrhythmias post cross-clamp release (P = .03). Duration of mechanical ventilation (P = .006), intensive care unit stay (P = .05), and hospital stay (P < .001) were lower in the DN group. Patients in the DN group had lower troponin I levels 24 hours after cardiopulmonary bypass (P < .001). Electron microscopic studies showed more myocardial edema (P = .02) and myofibrillar disarray (P = .04) in the HTK group along with lower glycogen stores (P = .04). DN cardioplegia was more cost-effective than HTK cardioplegia (P < .001). CONCLUSIONS: DN cardioplegia was associated with better preservation of CI, less duration of mechanical ventilation, shorter intensive care unit and hospital stays, lower inotropic scores, and less release of troponin-I. Electron microscopy showed less myocardial edema and better preservation of the myofibrillar architecture and glycogen stores in the DN group.

Oral thyroxin supplementation in infants undergoing cardiac surgery: A double-blind placebo-controlled randomized clinical trial.

BACKGROUND: Decreases in serum total thyroxin and total triiodothyronine occurs after cardiopulmonary bypass, and is reflected as poor immediate outcome. We studied effects of oral thyroxin supplementation in infants who underwent open-heart surgery. METHODS: In this prospective study, 100 patients were randomized into 2 groups: 50 in the thyroxin group (TH) and 50 in the placebo group (PL). Patients in the TH group received oral thyroxin (5 µg/kg) 12 hours before surgery and once daily for the remainder of their intensive care unit (ICU) stay. Data on intraoperative and postoperative variables were recorded. Cardiac index (CI) was measured. Perioperative serum thyroid hormone levels and serum interleukin-6 and tumor necrosis factor-α were measured. Secondary analysis was performed by dividing patients into simple and complex subcategories. RESULTS: Results of the primary analysis indicated a higher CI in the TH compared with the PL. In the complex category, the mean duration of mechanical ventilation was 3.85 ± 0.93 and 4.66 ± 1.55 days in the TH and PL, respectively (P = .001). Mean ICU stay was 6.79 ± 2.26 and 8.33 ± 3.09 days (P = .03), and mean hospital stay was 15.70 ± 4.77 and 18.90 ± 4.48 days (P = .01) in the TH and PL, respectively. There were no significant differences between the TH and the PL in the simple category. CI was higher in the TH at all time points (P = .004). The average therapeutic intervention scoring system scores for the first 2 days were higher in the PL in the complex category. CONCLUSIONS: Oral thyroxin supplementation improves the CI and reduces the inotropic requirement. In addition, it reduces the duration of mechanical ventilation, ICU and hospital stay, and therapeutic intervention scoring system in infants after surgery for complex congenital heart defects.

Multiple saccular aortic aneurysms following the arterial switch operation.

We report a 3-month-old male presenting with multiple aortic aneurysms arising de novo 2 months following the arterial switch operation. Successful repair of the aneurysms was performed under total circulatory arrest and at seven years follow-up, the patient has no recurrence.

A prospective study of risk factors associated with persistent pleural effusion after total cavopulmonary connection with special reference to serum cortisol level.

OBJECTIVES: The Fontan operation is usually followed by significant pleural effusion. We aimed to study the factors associated with persistent pleural effusion with special reference to serum cortisol levels. PATIENTS AND METHODS: Thirty-eight patients undergoing the Fontan operation between September 2015 and November 2016 were prospectively studied. Parameters studied included age, weight, symptoms, atrio- ventricular valve regurgitation/stenosis/atresia, ventricular function, pulmonary artery pressures, oxygen saturation, aorto-pulmonary, and veno-venous collaterals, type of Fontan, duration of cardiopulmonary bypass, need for inotropes, duration of mechanical ventilation, conduit size, presence or absence of fenestration, and serum cortisol levels. The latter were measured before and after the Fontan operation and the co-relation between pleural effusion and change in serum cortisol levels was studied. RESULTS: Mean age at operation was 13.1 ± 5.6 years (median 13 years). Mean duration and amount of pleural drainage was 15.76 ± 13.2 days (median 11.5 days) and 9.15 ± 4.6 mL/kg/day (median 9 mL/kg/day) respectively. Statistically significant risk factors for prolonged pleural effusion were higher pulmonary artery (PA) pressures (r = 0.328, p = 0.003, odds ratio 1.30), higher inotropic score (r = 0.4, p = 0.01), lower rise in serum cortisol (p = 0.03),elevated superior caval venous pressure (CVP) at 6 h (r = 0.44, p = 0.005) and 12 h (r = 0.4, p = 0.01) and higher duration of mechanical ventilation (r = 0.45, p = 0.005). CONCLUSIONS: PA pressures > 15 mmHg, higher inotropic score, higher CVP and lower rise in serum cortisol levels following the Fontan operation were associated with persistent pleural effusion.

One and half ventricle repair: rationale, indications, and results.

Surgical strategies in patients with functionally or anatomically borderline right ventricles include a high-risk biventricular repair, a Fontan procedure, or a one and half ventricle repair (also referred to as the partial biventricular repair). One and half ventricle repair (1.5VR) circumvents the high early mortality of a biventricular repair and also the late morbidity of the Fontan. The two most common indications for a 1.5VR are a small pulmonary ventricle and a dilated poorly functioning pulmonary ventricle. Extension of 1.5VR to patients undergoing anatomical repair for congenitally corrected transposition of great arteries, straddling tricuspid valves, and severe Ebstein's anomaly has facilitated biventricular repair with decreased mortality. We reviewed the relevant literature on this subject in detail and describe its rationale, indications and its early and late results.

An unusual combination of discreet subaortic membrane, aortopulmonary window, severe aortic insufficiency and rheumatic mitral regurgitation.

We report a 15-year-old female patient with an unusual combination of discreet subaortic membrane, aortopulmonary window, severe aortic insufficiency and rheumatic mitral regurgitation.

Factors determining early outcomes after the bidirectional superior cavopulmonary anastomosis.

OBJECTIVE: The bidirectional Glenn (BDG) procedure is a step in multistage palliation of univentricular heart (UVH). We aimed to report the factors determining the outcomes following BDG. METHODS: Two hundred fifteen consecutive patients, 5.29 ± 5 years (range 1 month to 38 years, median 3 years) of age, weighing 13 ± 8.8 kg (range 2.6 to 51 kg, median 10 kg) with variable forms of UVH underwent BDG from 2003 to 2013. Their clinical records were reviewed retrospectively. RESULTS: The most common anatomic diagnoses were tricuspid atresia (n = 87, 40.5%) and double outlet right ventricle (n = 78, 36%). Dextrocardia was present in 21 (9.86%) patients. Median left pulmonary (PA) and right PA diameters were 6 and 7 mm, respectively. One hundred sixty-two (77%) patients received unilateral BDG, and 45 had bilateral BDG. The antegrade pulmonary blood flow was closed in 199 and was left open in 16 patients. Concomitant procedures were reconstruction of pulmonary arteries for non-confluent PA (n = 28), atrial septectomy (n = 15), atrioventricular valve repair (n = 12) and repair of partial anomalous pulmonary venous connection (n = 1). A total of 37% of patients (n = 80) had a mean post-operative saturation of 90 ± 3.2%. There were four (1.86%) early deaths. Mean Glenn pressure was 14.7 ± 3.5 mm Hg, and mean inotropic score and Vasoactive inotropic score (VIS) were 1.64 ± 0.96 and 2.77 ± 2.63, respectively. Mean intensive care unit stay was 24.1 ± 26.4 (range 10-240) h, and mean duration of hospital stay was 7.15 ± 3.2 days. Mean saturation at the time of discharge was 92.4 ± 2.2% and on follow-up was 82 ± 2.16%. Follow-up cardiac catheterization data was available in 123 (60.3%). Sixty-nine (33.8%) patients underwent completion Fontan, and 135 patients were in follow-up or waiting for Fontan completion. CONCLUSION: BDG procedure can be performed safely with acceptable mortality. Age at presentation, pulmonary artery size and VIS were not related to mortality. Younger patients had similar outcomes but a longer hospital stay. Patients with preserved antegrade pulmonary blood flow had higher saturations. Those undergoing BDG without cardiopulmonary bypass had lower inotropic scores.

Immediate and early post-operative sequelae of off-pump total cavopulmonary connection.

BACKGROUND: Extracardiac Fontan (ECF) is currently the final operation of choice for patients with a univentricular heart. Performing this procedure without cardiopulmonary bypass (CPB) carries potential benefits. In this study, we report the early results of ECF without CPB. PATIENTS AND METHODS: Between 2012 and 2015, 72 consecutive patients underwent Fontan without CPB. Their medical records were examined in detail. RESULTS: Mean age was 11.8 ± 5.2 (range 5 to 23, median 10) years. Intraoperative mean superior vena cava clamp time was 15.19 ± 3.8 min, and the inferior vena cava clamp time was 16.93 ± 3.31 min. There were three early deaths. No patient required conversion from off-CPB to CPB. Mean inotropic score was 4.73 ± 5.9 (range 0 to 25, median 2.5). Mean time to extubation was 9.5 ± 5.82 (range 3 to 29, median 8) hours. Pleural drainage in intensive care unit (ICU) was 551.57 ± 452.77 (median 470) ml, and mean ICU stay was 2.27 ± 3.09 (median 1.5) days. Mean daily pleural drainage after discharge from the ICU was 163.7 ± 88.01 (median 140) ml, and mean time to removal of pleural tubes was 15.76 ± 8.4 (median 14) days. Total hospital stay was 17.03 ± 8.62 (median 15) days. At an early follow-up of 2-40 (median 25) months, all survivors (n = 69) had a patent Fontan circuit with normal ventricular function on echocardiography. There were no late deaths or thromboembolic complications. CONCLUSIONS: Off-pump ECF is a low-risk procedure that avoids the harmful effects of CPB. Post-operative course of these patients is predictable with substantial savings in costs.

Effect of administration of allopurinol on postoperative outcomes in patients undergoing intracardiac repair of tetralogy of Fallot.

OBJECTIVE: To determine effects of allopurinol administration on outcomes following intracardiac repair of tetralogy of Fallot (TOF). MATERIALS AND METHODS: Fifty patients undergoing TOF repair were randomized to 2 groups of 25 each: the allopurinol group (n = 25) and the placebo group (n = 25). Postoperatively, inotropic score, rhythm, duration of mechanical ventilation, cardiac output, intensive care unit (ICU) stay, and hospital stay were assessed. Plasma troponin-I, superoxide dismutase (SOD), interleukin (IL) 1-ß, IL-6, and malondialdehyde were measured serially. RESULTS: Inotropic score was lower in the allopurinol compared with placebo group (11.04 ± 5.70 vs 17.50 ± 7.83; P = .02). Duration of ICU and hospital stay was lower in the allopurinol group. Plasma levels of SOD preoperative were (2.87 ± 1.21 U/mL vs 4.5 ± 2.08 U/mL; P = .012), immediately following release of crossclamp (2.32 ± 0.98 U/mL vs 5.32 ± 2.81 U/mL; P < .001), and after termination of CPB (2.18 ± 1.0.78 U/mL vs 3.44 ± 1.99 U/mL; P = .003) between the placebo versus allopurinol group, respectively. Postoperative levels of IL1-ß and IL-6 were lower in the allopurinol group. Malondialdehyde levels following CPB were lower in the allopurinol group (11.80 ± 2.94 pg/mL in the placebo vs 9.16 ± 3.02 g/mL in the allopurinol group; P < .001). CONCLUSIONS: Allopurinol administration in patients undergoing intracardiac repair of TOF is associated with reduced inotropic scores, duration of mechanical ventilation, ICU stay, and hospital stay and favorable biochemical markers of inflammation. Further studies in multiple setups are needed before recommending it as a routine practice.

Evaluation of differential pulmonary perfusion using 99mTc macroaggregated albumin after the Fontan procedure.

OBJECTIVES: The Fontan procedure [total cavopulmonary connection (TCPC)] is the final palliation for patients with univentricular physiology. We studied differential perfusion ratio and percentage uptake of a radiotracer in different zones of each lung following TCPC. METHODS: Between July 2015 and June 2017, 45 patients underwent 99mTc macroaggregated albumin lung perfusion scan at a mean follow-up period of 49.3 ± SD 26.1 days following TCPC. Differential perfusion ratio and percentage uptake of the radiotracer in the upper, middle and lower zones of each lung were calculated. RESULTS: Post-foot injection [inferior vena cava (IVC) injection], preferential flow to the lungs was as follows: left lung (n = 13, 30.2%), right lung (n = 13, 30.2%) and uniformly to both lungs (n= 17, 39.6%). Post-arm injection [superior vena cava (SVC) injection], preferential flow to the lungs was as follows: left lung (n = 13, 30.2%), right lung (n = 22, 51.2%) and uniformly to both lungs (n= 8, 18.6%). The middle zone was perfused the most in both lungs. Total lower zone mean perfusion was higher than the upper zone following both SVC injection and IVC injection (34.1 ± SD 5.3% vs 17. ± SD 4.1% and 33 ± SD 5.0% vs 17.5 ± SD 4.1%, respectively). In patients with bilateral SVC, post-IVC injection, 6 (75%) patients had preferential flow to the right lung, whereas post-SVC injection, preferential flow to the left lung was visualized in 7 (87.5%) patients. CONCLUSIONS: Following TCPC, IVC blood was distributed uniformly in both lungs. SVC blood preferentially perfused the right lung. The middle zone was perfused the most in both lungs.

Comparison of del Nido and St Thomas Cardioplegia Solutions in Pediatric Patients: A Prospective Randomized Clinical Trial.

We conducted a prospective randomized trial to compare del Nido (DN) cardioplegia with conventional cold blood cardioplegia (St Thomas [STH]) in pediatric patients. We randomized 100 pediatric patients aged ≤12 years undergoing elective repair of ventricular septal defects and tetralogy of Fallot to the DN and the STH groups. In the DN group, a 20 mL/kg single dose was administered. In the STH group, a 30 mL/kg dose was administered, followed by repeated doses at 25- to 30-minute intervals. The primary outcome was cardiac index that was measured 4 times intra- and postoperatively. Troponin-I, interleukin-6, and tissue necrosis factor-alpha were measured. Myocardial biopsy was obtained to assess electron-microscopic ultrastructural changes. Cardiac indices were significantly higher in the DN group than in the STH group 2 hours after termination of cardiopulmonary bypass (P = 0.0006), after 6 hours (P = 0.0006), and after 24 hours (P ≤ 0.0001). On repeated measure regression analysis, the cardiac index was on an average 0.50 L/min/m2 higher in the DN group than in the STH group at any time point (P = 0.002). Duration of mechanical ventilation (P = 0.01), intensive care unit stay (P = 0.01), and hospital stay (P = 0.0007) was significantly lower in the DN group. Patients in the DN group exhibited lower troponin-I release 24 hours following cardiopulmonary bypass (P = 0.021). Electron microscopic studies showed more myofibrillar disarray in the STH group (P = 0.02). Use of long-acting DN cardioplegia solution was associated with better preservation of cardiac index, lesser troponin-I release, and decreased morbidity. Ultrastructural changes showed better preservation of myofibrillar architecture.

Synergistic Effect of BDNF and FGF2 in Efficient Generation of Functional Dopaminergic Neurons from human Mesenchymal Stem Cells.

To understand the process of neurogenesis, generation of functional dopaminergic (DAergic) neurons from human mesenchymal stem cells (hMSCs) is important. BDNF has been reported to be responsible for inducing neuronal maturation and functionality. Previously, we have reported the efficient generation of neurons from human bone marrow derived MSCs using FGF2 alone. We hypothesize that hMSCs from various tissues [(bone marrow (BM), adipose tissue (AD) and dental pulp (DP)], if treated with BDNF on 9th day of induction, alongwith FGF2 will generate functional DAergic neurons. Hence, cells were characterized at morphometric, transcription and translational levels for various markers like MAP2, TH, NGN2, PITX3, DAT, synaptophysin, Kv4.2 and SCN5A. Functionality of in vitro generated neurons was studied by calcium ion imaging. Result analysis depicted that BDNF has effect on expression of dopaminergic neuronal markers at gene and protein levels and functionality of neurons. Among these hMSCs, DP-MSC showed significantly better neuronal characteristics in terms of morphology, expression of neuronal markers and foremost, functionality of neurons. From the present study, therefore, we concluded that i) BDNF has additive effect on neuronal characteristics and functionality ii) DP-MSC are better MSC candidate to study DAergic neurogenesis and perform future studies.

An alternative technique of atrial septectomy during bidirectional superior cavopulmonary anastomosis.

An atrial septectomy is often required to create or enlarge a pre-existing restrictive atrial septal defect in patients with univentricular hearts undergoing the bidirectional superior cavopulmonary anastomosis. We describe an alternative surgical technique through the transected cardiac end of the superior vena cava without a right atriotomy successfully performed in 26 patients.