Cardiovascular Drug Therapy during Interstage After Hybrid Approach: A Single-Center Experience in 51 Newborns with Hypoplastic Left Heart

Abstract

Background Newborns with hypoplastic left heart (HLH) are usually palliated with the Norwood procedure or a hybrid stage I procedure. Hybrid is our preferred approach. Given the critical relationship between stage I, interstage, and comprehensive stage II or advanced biventricular repair, we hypothesized that appropriate drug treatment is a significant therapeutic cornerstone, especially for the management of the high-risk interstage. Methods We report a single-center observational study addressing the cardiovascular effects of, in particular, oral β-blockers and the additional use of angiotensin-converting enzyme (ACE) and mineralocorticoid inhibitors. Results In total, 51 newborns-30 with HLH syndrome (HLHS) and 21 with HLH complex (HLHC)-with a median bodyweight of 3.0 kg (range 1.9-4.4; nine with bodyweight ≤ 2500 g) underwent an uneventful "Giessen hybrid approach" using a newly approved duct stent. All patients were discharged home with a single, double or triple therapy consisting of ß-blockers, ACE and mineralocorticoid inhibitors; 90% of the patients received bisoprolol, 10% received propranolol, 72% received lisinopril, and 78% received spironolactone. Resting heart rate decreased from 138 bpm (range 112-172; n = 51) at admission to 123 bpm (range 99-139; n = 51) at discharge and 110 bpm before stage II/biventricular repair/ heart transplantation (range 90-140; n = 37) accompanied by favorable bodyweight gain. No side effects were evident. Conclusion In view of drug risk/benefit profiles, as well as the variable morphology and hemodynamics, the highly selective β1-adrenoceptor blocker bisoprolol is our preferred drug for treatment of HLHS/HLHC in the interstage. We avoid using ACE inhibitor monotherapy and exclude potential risks for coronary and cerebral perfusion pressure beforehand.

A word on netting of angiotensin-converting enzyme inhibitor therapy in hypoplastic left heart syndrome following stage-I

“…However, there is no monotherapy with an angiotensin-converting enzyme inhibitor. 5,15,17 This is consistent with the knowledge that infants with hypoplastic left heart syndrome may have adrenoreceptor genotypes associated with higher catecholamine release and sensitivity and then lower event-free survival after stage-I Norwood palliation. 30 Excessive catecholamine activation is postulated to an adverse affected cardiovascular adaption after the Norwood surgery.…”

“…The basic prerequisite for using the angiotensin-converting enzyme inhibitor is that there is no risk of obstruction of the aortic flow and that the coronary and cerebral perfusion pressure is not endangered. 17 As mentioned earlier, the clinical parameters to demonstrate the effectiveness of the treatment were a lowest effective heart rate, a normal respiratory rate, and body weight gain up to comprehensive stage II. The therapeutic goal was to achieve a heart rate of less than 120/min, better one of less than 110/min during sleep of the patient.…”

“…16 The highly sensitive and easily verifiable surrogate parameter heart rate, which reflects oxygen consumption and cardiac filling time, can best be monitored at least by the ratio of systolic-diastolic time interval. 17 At the Children's Heart Center in Giessen, a retrospective evaluation over a 5-year period demonstrated that all patients following a Hybrid stage-I Norwood palliation received ß-blockers. From a cohort of 51 newborns with hypoplastic left heart syndrome and variants, 90% of the patients received bisoprolol or 10% the non-specific ß-blocker propanolol, which was indicated for atrial tachyarrhythmias.…”

“…From a cohort of 51 newborns with hypoplastic left heart syndrome and variants, 90% of the patients received bisoprolol or 10% the non-specific ß-blocker propanolol, which was indicated for atrial tachyarrhythmias. 17 With regard to the risk-benefit ratio, but also taking into account the compliance of the parents, the long-acting, highly specific ß1-adrenoreceptor blocker bisoprolol has been the ß-blocker of our choice for more than a decade now, administered in a single dose of 0.1-0.2 mg/kg once per day. In 70% of the newborns, the similarly long-acting tissue angiotensin-converting enzyme inhibitor lisinopril was also prescribed, but in no patient without an additional ß-blocker therapy.…”

“…The clinical data were re-checked, and systolic and diastolic blood pressures values and SaO2 were measured by experienced nurses. Despite such a close and in generally effective surveillance, which included periodic echocardiographic examinations, 17,18 one patient suffered cardiogenic shock and died of neurological sequalae. From our point of view, zero mortality during the interstage is not achievable regardless of any drug treatment.…”