Ethical dilemmas in pediatric cardiac interventions: Primum non nocere

Over the past few decades, structural cardiac interventions have become mainstream and routine modalities for treating a wide variety of congenital and structural heart defects. While device closure has now become the standard of care for most patent ductus arteriosus (PDA) and atrial septal defects (ASDs) with adequate rims, even more complex transcatheter interventions, such as ductal and right ventricular outflow tract stenting in infants, branch pulmonary artery stenting in older children, and coarctation stenting in adolescents and adults, have gradually gained widespread acceptance as the preferred treatment options at many tertiary pediatric cardiac centers.[1] However, concurrently in the past two decades, immediate and long-term surgical results have also improved dramatically; a recent study reported a pooled immediate surgical mortality of 5.84% for cardiac surgery for congenital heart disease in India,[2] and some of the best tertiary centers have achieved surgical mortality rates of <2.5%–3% while treating the entire spectrum of complex congenital and neonatal cases. As pediatric cardiac specialists, we know that routine transcatheter interventions are safe with excellent immediate and long-term outcomes. As we mature in our skill sets, many operators will be comfortable in pushing the envelope and designing and undertaking transcatheter interventions for conditions that are still routinely referred for surgical correction. This is how transcatheter pulmonary and aortic valve replacements were envisioned, developed, and made mainstream at the turn of the century, and also how transcatheter occlusion of sinus venosus defects has gained in popularity in the present decade as an acceptable alternative to surgery in adolescents and adults. Yet, whenever we deviate from the conventional, it is our duty as clinicians to weigh the potential benefits against the risks of the unknown and unexpected when attempting a challenging or rare procedure. As seen in many articles in the Annals of Pediatric Cardiology, complications can occur even with routine interventions, sometimes years after the primary procedure.[3–5] In all complex congenital or acquired structural cardiac defects, the clinician first needs to decide on two basic questions: surgery or transcatheter intervention and the timing of the procedure. And often, there is no right or wrong decision but rather one based on circumstances, experience, and recency bias. LIFESAVING INTERVENTIONS THAT ARE PROBABLY JUSTIFIED Catastrophic complications in the catheterization laboratory, including cardiac perforation and tamponade, are thankfully extremely rare. However, if this were to occur, even with optimum preparation and logistics, the realistic minimum time required to put the patient on crash cardiopulmonary bypass (CPB) is at least 20–30 min at most centers, with a significant risk of neurological and multiorgan sequelae even if the cardiac function and circulation recover after the emergency surgery. Hence, in such situations, it is logical to attempt a salvage intervention in the catheterization laboratory itself. Nema et al.[6] describe such a catastrophe, where there was inadvertent perforation of the aortic root during a transseptal puncture for the ablation of a left-sided accessory pathway, where the operators were able to successfully occlude the perforation with an 8 × 6 Konar multifunctional occluder while simultaneously carrying out pericardiocentesis and autotransfusion for the tamponade. As the authors stress, it is essential to continue preparing for simultaneous surgery in these situations, so that if the salvage procedure in the catheterization laboratory is unsuccessful, the patient can be temporarily stabilized and then transferred to surgery. WHEN SURGERY IS SAFE, AND INTERVENTION CARRIES UNKNOWN RISKS, WHY NOT PREFER THE ESTABLISHED OPTION? As interventionists, we often justify the preference for a transcatheter intervention with the argument that we can avoid subjecting the patient to CPB and for cosmetic avoidance of a scar. However, in the present era, we know that cardiac surgery is safe with excellent immediate and long-term outcomes. As pediatric cardiologists, we refer most of our patients for surgical repair or palliation with no reservations about the risks of CPB. Bypass strategies in the present era have been optimized for infants and children, and we seldom see bypass-related complications in our patients. Then why are we averse to referring some of our patients for cardiac surgery, where a transcatheter intervention is possible but perhaps carries unknown procedural or long-term risk? Shrutiraaj et al.[4] have presented a case of a 5-year-old child who developed erosion 2 years after an ASD device closure with an Amplatzer septal occluder (ASO) due to the right atrial (RA) disc eroding through the RA roof, traversing the transverse sinus, and eroding the noncoronary cusp (NCC) of the aortic root. The authors postulated that this erosion occurred due to intermittent systolic rubbing of the RA disc against the aortic root. They successfully occluded the erosion with a 5/4 Amplatzer duct occluder 2 (ADO-2), reasoning that the RA disc of the ADO-2 would now protect against the rubbing of the RA disc of the ASD device and prevent further erosion. They have reported a good 3-year follow-up with no further complications. The authors justify this strategy by stating that this approach obviates the patient’s exposure to the risks of open surgical intervention and related postoperative complications. By not extracting the ASO device, which caused the erosion in the first place, are we not subjecting this patient to lifelong unknown risks of possible future erosion at or adjacent to the site of the primary erosion? Surgery in this setting would have been a controlled procedure, as safe as all other cardiac surgeries under CPB, and would have predictably eliminated any future risks of device-related erosion. More importantly, how the parents were communicated about the uncertainty of the interventional outcome and how they accepted such uncertainty is difficult to understand. In another report, Issacs et al.[7] describe three cases of aortic obstruction following PDA device closure in infants with 4/6 Lifetech duct occluders requiring urgent surgical repair. The authors postulated that exaggerated recoil during the release led to unexpected device migration and aortic obstruction, neither of which was present on the postdevice deployment echocardiogram. As the authors have observed, using thinner, less rigid delivery cables (such as the ADO-2 cables) may help reduce recoil in these cases. We have also seen similar instances of recoil and embolization with the Lifetech 4/6 duct occluder,[8] which we postulated were due to inadequate splaying of the pulmonary end of the device and to the downward aortic systolic pressure wave acting on the device’s retention skirt. But again, as Isaacs et al.[7] have highlighted, having a low threshold for requesting surgical help during a complication in the catheterization laboratory often yields a predictable good outcome with a quick patient recovery. IMPORTANCE OF THE COMBINED CARDIAC TEAM MEETING IN DECISION-MAKING Perspectives on the best approach to treating a complex congenital or structural heart defect often vary among clinicians. The decision should not be based solely on the patient’s diagnosis but also on the available expertise at the treating center and the center’s immediate and long-term outcomes of transcatheter intervention versus surgery for that lesion. If a center has had good results with ductal stenting for pulmonary atresia, the clinicians would obviously continue to prefer this as the primary treatment option. Similarly, if a center has had good results with neonatal modified Blalock–Taussig–Thomas shunts, there may be no justification for establishing a ductal stenting program with its learning curve unless there are other logistical constraints. However, in the best centers of the world, such decisions are made through a heart team approach involving the pediatricians/neonatologists, pediatric cardiologists, cardiac surgeons, imaging experts, and intensivists, among others. In most Indian centers, such a formal decision-making process does not exist, or, if it does, it may be dominated by personal and financial factors. A similar argument holds for small-to-moderate perimembranous ventricular septal defects (VSDs) in proximity to the aortic valve. Many Indian operators are comfortable closing these VSDs with a device, with the plan to refer for surgery if the device’s left ventricular disc distorts the right coronary cusp (RCC) and causes new-onset aortic regurgitation.[9] However, we know of isolated cases in which RCC perforation and aortic regurgitation have occurred years after device closure. In retrospect, is it justified to close VSDs with aortic cusp prolapse with devices even if there is no significant aortic regurgitation on immediate and midterm follow-up in these patients? For rare conditions such as coronary arteriovenous fistulae, the decision should not be based solely on the feasibility of completing the procedure safely but also on the long-term physiological sequelae.[10] The principles of transcatheter occlusion for proximal coronary-cameral fistulae are fairly standardized and accepted. Distal coronary fistulae are, however, notorious for retrograde thrombus propagation into myocardial branches, and it is essential to delineate the anatomy and plan the postdevice anticoagulation before the procedure to prevent postdevice myocardial ischemia. Hence, the decision is not only whether to occlude the distal coronary fistula in the catheterization laboratory or the operating theater but also whether to occlude the fistula at all and subject the patient to long-term anticoagulation, versus leaving the patient on medical follow-up. NEED FOR LONG-TERM SURVEILLANCE It is general practice after an ASD or PDA device closure to discharge the patient from follow-up after 4–5 years postprocedure. Kumar et al.[5] reported a case of a large pseudoaneurysm detected 1 year after a PDA device closure with a 6/4 ADO device in a 2-year-old girl, which led to destruction of the left bronchus and left lung necessitating pneumonectomy during the surgery for the pseudoaneurysm. Such reports are scary and stress the importance of meticulous long-term follow-up for any intervention. Fortunately, such reports are extremely rare. These cases[3–5] also highlight the need for frequent review within the 1st year after any intervention or surgery, as well as the possibility that long-term sequelae can present years after the primary procedures. This implies that we may need to keep our transcatheter intervention patients on lifelong follow-up and mention this to parents during pre-procedure counseling. BALANCE BETWEEN INNOVATION AND PATIENTS’ RIGHTS As interventional pediatric cardiologists, we are good at improvising and innovating, and we can often deliver outstanding outcomes in the catheterization laboratory.[1,11] As some of the articles in this issue[12–15] demonstrate, skilled operators can plan and execute a wide variety of challenging, rare, and interesting interventions with excellent results, often by making minor variations in routine procedures. However, most innovations may not have adhered to strict ethical standards.[11] The challenge is to protect patients’ rights without hampering innovation. KEY PRINCIPLES AND SOLUTIONS We, the physicians, take the risk, and the patient often pays the price. More importantly, in pediatric cardiology, we usually treat patients in their first decade of life, where long-term implications can span 6–7 decades. The key focus should be on shared decision-making and a heart team approach. Most problems stem from a lack of evidence-based decision-making in pediatric cardiology.[16] Still, whenever we, as interventional pediatric cardiologists, are unsure of a predictable procedure with reliable long-term outcomes, the decision between transcatheter intervention and surgery should be made after detailed discussion and introspection by the combined cardiology and surgical team. As pediatric cardiologists, we decide in the same fashion when deciding to close a moderate ASD and a small VSD with a device. A clear distinction has to be made between on-label and off-label indications for a device or procedure. Off-label procedures should mandate more discussion with the family and among the team. It should be approved by a team, preferably not led by the primary interventionist. We must take a leaf from how fetal procedures are decided by a fetal board,[17] which may not include the physician who intends to intervene in making the final decision. Ethical approval and clearance should be mandatory for reporting, even for a retrospective series of interesting off-label procedures, which is not strictly adhered to in our field. More importantly, the patient should not bear the cost of procedures involving newer off-label devices, like some earlier reported cases.[18] This is fairly established in Western developed economies; however, it is often not followed in countries like India, where vulnerable patients frequently arrange their own finances for procedures.[19] In pediatric cardiology, off-label and on-label procedures depend not only on the indication but also on timing and patient/procedure characteristics, such as weight and device size. The indications and timing of common cardiac procedures in Indian settings are well established.[20] Yet, these guidelines are not strictly adhered to in practice. The guidelines themselves state that they need not be adhered to in every individual case. Yet, whenever such deviations occur, they must be documented and discussed in detail with the patient and family, as well as with the heart team. The reported PDA device-related aortic obstruction[7] may have been avoided if the intervention had been deferred by a few months. However, as fear of missing out is ubiquitous in modern life, it is also among pediatric cardiologists in India. Unlike in developed countries, patients in India have full freedom to choose the center where they receive treatment. Hence, there is always a fear that the patient may have the procedure performed at another center if given some time, leading to unnecessary early interventions. A combined cardiac team meeting to discuss and plan patient management should be mandatory for all complex and rare cardiac cases. The patient and family are integral to the decision-making process. Thus, truly a shared, informed, and combined team decision is made. The heart team approach has evolved as the core philosophy of decision-making in other structural and coronary interventions. As pediatric cardiologists, we have worked well with our cardiac surgeons over the years in collective decision-making for our patients. Of late, as pediatric cardiac interventions have exploded, pediatric cardiologists are first deciding and intervening for patients, leaving only the remaining patients for a combined decision-making process. We cannot forget or undermine the fact that immediate and long-term surgical results for most complex cardiac lesions are excellent, and whenever we plan and perform a complex cardiac transcatheter intervention, the efficacy and safety of the procedure are paramount.[21] It is unacceptable to achieve a suboptimal result compared to the surgical alternative. We must keep the patient as the top priority. Then, profession, institution, and individual interests should follow in that order. In India, we must move away from individual brilliance-based efforts toward a system-driven approach to improve our children’s overall outcomes in resource-limited settings. CONCLUSIONS A patient-centric approach, shared decision-making, and a heart team approach should address most ethical dilemmas in choosing an off-label pediatric cardiac intervention. While it may not always be possible to anticipate or prevent complications, adherence to the principle of “Primum non nocere” allows us to thoughtfully minimize unnecessary variables and adverse outcomes in the management of complex and challenging pediatric cardiac cases.