This is Dr Kiran welcoming all to the new post of NH blog. I would like to know the usefulness of the segment on current evidences. I understand that it is quite dry and interspersed with so many strange-looking names and studies. But, that is how the evidence based analysis look like! Probably, this is one segment in medical practice which needs cosmetic lift-up to get better mass appeal!

This post, I am gathering evidence on the ‘Use of Sildenafil in post-op states in CHD’. This would be followed by our regular features on learning scenarios and Pearls.

Let us start with the evidence basis for ‘Use of Oral Sildenafil in Pediatric Patients with Congenital Heart Disease in post-operative setting’.

The current use of oral sildenafil in Pediatric population is largely an extrapolation of adult studies pertaining to pulmonary hypertension. However, the comparison is not that straight forward. The possible hemodynamic variants associated with congenital heart diseases are extensive. CHD may have absence of a crucial pulmonary valve, may come with serial and parallel circulations, pulmonary hypertension of high flow against high resistance, ala-carte designed surgical states to suit the anatomy and so on. So, unless the fundamentals are understood well, it may not be appropriate to use sildenafil as a knee-jerk response. Adding to the woes, there are no clearly definable outcome parameters to define the efficacy and results with treatment of sildenafil in the immediate post-op states.

Q1. Is sildenafil therapy logical in post-op CHD status?

In 1993, Celermajer et al showed that there is pre-existing pulmonary endothelial dysfunction caused by preoperative high flow pulmonary hemodynamics, which may alter the course in post-op states. In their article titled ‘Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics’ in the journal Circulation, they discussed this issue extensively. The same point was proved with simian experiments by Glavind-Kristensen in 2002 for post bypass status. Their article titled ‘Pulmonary endothelial dysfunction after cardiopulmonary bypass in neonatal pigs’ was published in Acta Anaesthesiology Scandinavia. In the same year, Lindberg et al published their article ‘How common is severe pulmonary hypertension after pediatric cardiac surgery?’ in JTCS. They found that iNO therapy is frequently indicated for the stabilization of pulmonary vascular reactivity, and decreased incidence of postoperative pulmonary hypertensive crisis. However, abrupt discontinuation of iNO was a major problem. In 1996 Atz et al had written on ‘Rebound pulmonary hypertension after inhalation of nitric oxide’ in ATS. Hence, there was a need for another treatment modality to prevent rebound PHT caused by abrupt discontinuation of iNO in post-extubation period. In 1999, Jackson et al showed the ‘Effects of sildenafil citrate on human hemodynamics’ in AJC. This was followed by another article by Atz et al titled ‘Sildenafil ameliorates effects of inhaled nitric oxide withdrawal’ in the journal Anesthesiology in the same year.

Q2. Is the supposed efficacy of Sildenafil proven?

In 2005, Karatza et al published the first study of Sildenafil in children in International journal of Cardiology, titled ‘Safety and efficacy of sildenafil therapy in children with pulmonary hypertension’. Here, they compared the efficacy and pharmacokinetics of Sildenafil with adult population as control and found equal efficacy. In 2007, in an article titled ‘Effects of escalating doses of sildenafil on hemodynamics and gas exchange in children with pulmonary hypertension and congenital cardiac defects’, Raja et al showed the efficacy of Sildenafil in the post-op CHD states by noticing a significant decrease in PA pressure compared with baseline values after starting sildenafil, without changes in CVP and systemic arterial pressure. In the same year, Peiravian et al published ‘Oral sildenafil to control pulmonary hypertension after congenital heart surgery’ in Asian Cardiovascular and Thoracic Annals. Here, they demonstrated the use of Sildenafil in post biventricular repair.

Q3. Is there a role of Sildenafil in Post-Fontan surgery?

Khambadkone et al in 2003 published ‘Basal pulmonary vascular resistance and nitric oxide responsiveness late after Fontan-type operation’ in the journal Circulation. They showed that PA pulsatility is crucial for endothelium-dependent pulmonary vasodilation. However, Fontan circulation takes away the PA pulsatility. In 2008, Rossi et al showed that ‘Sildenafil improves endothelial function in patients with pulmonary Hypertension’ in an article published in Pulmonary Pharmacology and Therapeutics. This finding extrapolated that any patient with Fontan procedure is likely to benefit from Sildenafil. Apart from this, in 2008 Giardini et al showed ‘Effects of silenafil on haemodynamic response to exercise and exercise capacity in Fontan patients’ in European Heart Journal, demonstrating the improvements found in the hemodynamic profiles in post-Fontan patients on Sildenafil. Earlier in 2006, Haseyama et al in JTCS had shown ‘Pulmonary vasodilation therapy with sildenafil citrate in a patient with plastic bronchitis after the Fontan procedure for hypoplastic left heart syndrome’ where they demonstrated an improvement in the plastic bronchitis. In the same year in ATS, Uzun et al had shown ‘Resolution of protein-losing enteropathy and normalization of mesenteric Doppler flow with sildenafil after Fontan’. However, it is well understood that in patients with Fontan procedure, improvement of tissue oxygenation and hemodynamic parameters are more important than mean PA Pressure decrement.

Overall, it can be concluded that, in the present level of evidence, Sildenafil can be used safely in postoperative pediatric patients with CHD. It appears to be effective, or at least protective, against rebound PHT caused by withdrawal of iNO.

With this, let us get back to our regular feature: interesting learning scenarios:

ACUTE SEVERE AND CHRONIC

In acutely compromised hearts, is better to accept a natural deterioration or to go on a high-risk endeavour? We had a 10-year-old with acute deterioration of a chronic MR with a very vague history. Although her LV function could be pepped up with inotropic support, her third spacing was enormous. She had bilateral massive pleural effusions, ascitis and trace pericardial effusion. Left alone, we felt she may not get any better with medical management. However, the surgical risks are multiple-fold high in such patients. The only saving grace was preserved LV function, which could give some hope to patient and surgeon! It was contemplated that the existing third spacing is likely to add on to the post-op woes. One suggestion was to use peritoneal dialysis for about 72 hours and slowly decongest the accumulations. This would presumably reduce the myocardial edema and improve contractility. However, this idea was not considered effective by the entire team. The questions are: Is the venturing into high risk surgery in such cases advisable? Should more time be spent on medical management? Is PD a choice for consideration? Please let me know your opinions.

ONE AV, TWO SEMILUNARS

Is there a situation in left heart which parallels tricuspid atresia 3C? We had an infant diagnosed as TAPVC from outside. However, on echo, we found an obstructed cardiac TAPVC with a barely visible LA cavity. The mitral valve was imperforate. The LV was smallish, fed only by a couple of muscular VSDs shunting R to L. The RA and RV were dilated. The LV gave rise to reasonable sized aorta (Z score of minus 1) and RV to well developed, dialted PA. The ascending and transverse aortae were normal sized. The baby was symptomatic largely due to obstructed TAPVC and unusually increased Qp. One of the possibilities we thought was repair of TAPVC, DKS with BT shunt. With aortic valve being reasonable, is there any other possibility? What would the natural history of VSDs in such situations? Please let me know your ideas on the management of such issues.

JUXTADUCT

This one has always remained elusive. I don’t know if I have discussed this issue earlier. It becomes very difficult to assess the status of coarctation in the presence of patent arterial duct. We had a 4-year-old who had undergone a balloon coarctoplasty in an outside hospital in her infancy. She was being followed up. When she came to us, we found a moderately restricted PDA with a narrow juxtaductal segment. There was only systolic gradient across the narrow segment with no diastolic spillage. The classical teaching is that the presence of duct interferes with evaluation of coarctation. In this instance, we are not sure of the significance of coarctation. There were no systemic clinical signs of CoA. We contemplated the unmasking of CoA once the duct is closed. The CT may help us in this issue by a 3D reconstruction. Even if there is no CoA on CT at baseline, would the large aortic disc of PDA device compromise the diameter of juxtaductal segment further, thereby creating a CoA? I felt it is better to subject the patient for surgical ligation of PDA. We can always check for the CoA after PDA ligation on table and take a call. What is the advice of readership? How would you like to tackle this case? Please let all know.

DILATED PA

We recently had a 25-year-old referred for abnormal Chest radiograph from outside. She was otherwise asymptomatic. On examination, there was a click in the pulmonary area. Echo showed doming pulmonary valve leaflets with no gradient across. The MPA was significantly dilated. The estimated PA pressures were normal. How far are these pictures common? How frequently should such patients undergo repeat evaluations and what to look for? Is there a management plan for them? Is the supposed progress preventable by medications? There appears to be lot of data on bicuspid aortic valves. However, no such data seems to exist for this category. If anyone has any such instances in their follow up, please let us know.

SEPTOSTOMY Vs BTT SHUNT

This issue probably needs much more discussion in the professional circles. I have brought up this issue in the previous posts too. When it comes to mixing lesions, the capacitance chambers are much superior to contracting ones. That is the reason why a moderate sized ASD proves to be a superior option than a large VSD in TGAs. When a TGA with restrictive ASD gets desaturated, adding BTT shunt does no good. In fact, it may worsen the scenario. Extending the logic, this should be true for any d-malposed great artery situations, unless it is DILV! I came across one 11-year-old with 100% DORV saturating 56%. The PS was mild and the PAs were dilated. There was a subarterial VSD of about 40% of aortic annulus with a PFO. In this case, even the best of streaming cannot deliver a good amount of oxygenated blood into Aorta. How different the scenario is if there were to be a non-restrictive ASD? Please let me know your opinions on this.

PEDIATRIC CARDIOLOGY PEARLS

111. Neonates are more resilient to metabolic or ischemic injury. In fact, the neonate may be particularly capable of coping with some forms of stress. Tolerance of hypoxia in the neonate is characteristic of many species, and the plasticity of the neurologic system in the newborn is well described. (Lenn NJ. Plasticity and responses of the immature nervous system to injury. In journal Seminars in Perinatology in the year 1987 page 117)

112. The physiology of the PDA is secondary to overperfusion of the lung and possibly underperfusion of the systemic circulation. Infants' lungs are fully recruited at rest so that any increase in flow from left-to-right shunts predictably increases fluid filtration in the lung. (Alpan G, Scheerer R, Bland R, et al. Patent ductus arteriosus increases lung fluid filtration in preterm lambs. In journal Pediatric Research in the year 1991 page 616)

113. Elevated transpulmonary pressure gradient and elevated pulmonary vascular resistance have been identified as risk factors for early mortality after heart transplantation. (Kirklin JK, Naftel DC, Kirklin JW, et al. Pulmonary vascular resistance and the risk of heart transplantation. In Journal of Heart Transplantation in the year 1988 page 331)

114. Catheter therapy has now been applied to the cure or modification of most pediatric arrhythmias, including AV node re-entry tachycardia, ectopic atrial tachycardia, atrial re-entry/flutter, congenital junctional ectopic tachycardia, and some forms of ventricular tachycardia. (Kugler JD, Danford DA, Deal BJ, et al. Radiofrequency catheter ablation for tachyarrhythmias in children and adolescents. The Pediatric Electrophysiology Society. In New England Journal of Medicine in the year 1994 page 1481)

115. A release of nickel from the device with a peak at 1 month postimplantation has been described. However, its clinical significance is questionable, and reports of clinically significant allergic reactions to nickel after device implantation are rare. (Lai DW, Saver JL, Araujo JA, et al. Pericarditis associated with nickel hypersensitivity to the Amplatzer occluder device: A case report. In journal Catheterization and Cardiovascular Interventions in the year 2005 page 424)

This brings us to the end of another post. Please send your comments and suggestions to drkiranvs@gmail.com Hoping to add some features on to the existing segments. Please suggest if any novel ideas occur!

Regards

Kiran