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Heart Failure Therapy: Potential Lessons Heart: First Published As 10.1136/Heartjnl-2015-309110 on 23 December 2016 Heart Online First, published on December 23, 2016 as 10.1136/heartjnl-2015-309110 Review ‘End-stage’ heart failure therapy: potential lessons Heart: first published as 10.1136/heartjnl-2015-309110 on 23 December 2016. Downloaded from from congenital heart disease: from pulmonary artery banding and interatrial communication to parallel circulation Dietmar Schranz, Hakan Akintuerk, Norbert F Voelkel ▸ Additional material is ABSTRACT reflected by the calculated transpulmonary gradient published online only. To view The final therapy of ‘end-stage heart failure’ is (TPG=mean PAP−LAP) and in particular the dia- please visit the journal online (http://dx.doi.org/10.1136/ orthotopic heart, lung or heart-lung transplantation. stolic PAP to LAP difference, the so-called diastolic heartjnl-2015-309110). However, these options are not available for many pressure gradient (DPG=diastolic PAP−LAP). Both patients worldwide. Therefore, novel therapeutical parameters become even more important in the Pediatric Heart Center, Justus Liebig University Giessen, strategies are needed. Based on pathophysiological setting of heart failure: pulmonary hypertension Virginia Commonwealth insights regarding (1) the long-term impact of an (PH) associated with an increased LAP, but normal University, School of Pharmacy, obstructive pulmonary outflow tract in neonates with TPG (<12 mm Hg) and in particular DPG Richmond, Virginia, USA congenitally corrected transposition of the great arteries, (<7 mm Hg)—labelled isolated postcapillary pul- — Correspondence to (2) the importance of a restrictive versus a non-restrictive monary hypertension may increase RV afterload Professor Dietmar Schranz, atrial septum in neonates born with a borderline left and negatively affect right (subpulmonary) ven- Pediatric Heart Center, Justus ventricle and (3) the significance of both, a patent tricular function. During the course of the disease Liebig University Clinic, foramen ovale and/or open ductus arteriosus for survival however there may be transition from purely Feulgenstr. 12, Giessen 30385, of newborns with persistent pulmonary hypertension, the passive pressure elevation to reactive pulmonary Germany; dietmar.schranz@ paediat.med.uni-giessen.de current review introduces some therapeutical strategies vascular disease. The transition from isolated to that may be applicable to selected patients with heart combined postcapillary pulmonary hypertension is Received 31 March 2016 failure. These strategies include (1) reversible pulmonary highly variable from patient to patient. Revised 28 September 2016 artery banding in left ventricular-dilated cardiomyopathy Non-reactive or fixed pulmonary arterial hyperten- Accepted 29 September 2016 with preserved right ventricular function, (2) the creation sion (PAH) is the result of a continuous vascular of restrictive interatrial communication to treat diastolic remodelling, while reactive PH is characterised by a (systolic) heart failure, (3) atrioseptostomy or reverse remodelled vasculature that can still dilate.3 Potts shunt in pulmonary arterial hypertension and (4) Chronically increased afterload forces the subpul- return to a fetal, parallel circulation by combining monary ventricle to adapt with appropriate hyper- atrioseptostomy and reversed Potts shunt with or trophy but ultimately the RV compensatory http://heart.bmj.com/ without placement of a bilateral pulmonary artery mechanisms are exhausted leading to RV failure. As banding. While still being experimental, it is hoped that usually RV and left ventricle (LV) are serially con- the procedures presented in the current overview will nected, advanced right heart failure may lead to a inspire future novel therapeutic strategies that may be paradoxical underfilling of the LV.4 Considering applicable to selected patients with heart failure. that the right and left hearts do not act in isolation and that LV may be responsible for more than 50% 5 of RV function under healthy conditions, the on September 29, 2021 by guest. Protected copyright. INTRODUCTION changes in right heart pressure and volume affect End-stage heart failure is the cause of death or the left side of the heart and vice versa. This need for heart transplantation (HTx) in many car- cardiac coupling, referred as ‘diastolic’ ventricular diovascular conditions.1 Heart failure represents a interaction,6 is illustrated in the online progressive disease with a wide symptom spectrum. supplementary video 1a–c. Despite existing myocardial damage, initially, In summary, left heart-dependent PH might be endogenous pathophysiological mechanisms will misinterpreted by focusing exclusively on TPG; the prevent cardiac decompensation and failing of the calculated value might be misinterpreted in consid- systemic, morphologically left, right or even single eration of the reversibility of PH or in the setting ventricle at rest. Additionally, it is commonly of decision-making for heart or heart-lung trans- observed that heart failure remains mostly compen- plantation. Therefore, as already emphasised by sated as long as right ventricular (RV) function is several other authors,7 DPG should be entered into preserved. Unfortunately, due to ventriculo- the analysis of PH, because DPG might be low, in ventricular interaction, systemic ventricular dys- spite of a calculated TPG above 15 mm Hg. function will generally have a detrimental impact Generally, the mean and, in particular, the systolic on the function of the subpulmonary ventricle pulmonary pressures are cardiac output To cite: Schranz D, during long term. Guazzi and Borlaug2 emphasise (CO)-dependent variables, but the diastolic pul- Akintuerk H, Voelkel NF. Heart Published Online First: the importance of the lung downstream pressure monary pressure remains quite independent from [please include Day Month (left atrial pressure, LAP) as an important contribu- CO changes.7 In addition, considering the margin Year] doi:10.1136/heartjnl- tor to pulmonary artery pressure (PAP). The rela- of error of CO measurements, in particular in con- 2015-309110 tionship between mean PAP and LAP is best genital heart disease with non-static left-to-right, Schranz D, et al. Heart 2016;0:1–6. doi:10.1136/heartjnl-2015-309110 1 Copyright Article author (or their employer) 2016. Produced by BMJ Publishing Group Ltd (& BCS) under licence. Review Heart: first published as 10.1136/heartjnl-2015-309110 on 23 December 2016. Downloaded from bidirectional or even right-to-left shunts, we emphasise to use form in infants and young children, while ischaemic DCM pre- the relationship of the diastolic pressure—pulmonary arterial dominates in adults. DCM is a myocardial disease with systolic pressure and systemic arterial pressure (PAPd/SAPd)—ratio as cardiac dysfunction and dilatation.8 very practical to compare the ‘true’ vascular resistance of both, Considering patients with a systemic RV, the long-term the pulmonary and systemic circulation. In addition, the preca- outcome is directly related to a balanced ventricular interaction pillary component of the pulmonary vascular circulation can and the competence of the systemic atrioventricular valve.9 additionally be assumed by analysing DPG. Dilatation of the systemic ventricle is prevented by subpulmon- In LV-dilated cardiomyopathy (DCM), stroke volume remains ary (left) ventricular outflow tract obstructions or even signifi- preserved by LV dilatation on the expense of a high-end systolic cant PH. Surgical rPAB may be used, if such an obstruction is volume; the physiopathology of a borderline left ventricle (BLV) absent.10 In congenitally corrected transposition of the great and even restrictive cardiomyopathy (RCM) is characterised by arteries (CCTGA), rPAB has been used for retraining of subpul- CpcPH; the precapillary pulmonary component prevents pul- monary LV-DCM,10 and as a preventative strategy in new- monary oedema. The properly adapted RV is able over quite borns.11 Considering favourable results of PAB in children with some time to maintain filling and pumping. Thus, systemic, or CCTGA, in Giessen12 we also applied surgical rPAB to treat sometimes suprasystemic, pulmonary artery pressures can LV-DCM with preserved RV-EF (figure 2 and online develop, which correspond to a pulmonary artery banding supplementary video 2a,b). The entry criteria for using rPAB in (PAB) effect that preserves RV systolic function, in particular in the setting of LV-DCM have been recently published.12 The pro- the setting of a congenitally restrictive LV-cardiomyopathy (see posed mechanisms of rPAB action are summarised in box 1:itis online supplementary video 1b). However, the disease process is postulated that the efficacy of rPAB correlates negatively with progressive and finally irreversible, resulting in LV, RV or biven- the patient’s age. The potential for myocardiocyte recovery and tricular (BV) failure with subsequent multi-organ failure. myocardiocyte repopulation may be greatest in infancy.13 Here we describe established and hypothetical novel percu- Hypothetically, even in adults an adjustable PAB might be able taneous interventional, surgical open chest and hybrid techni- to induce in certain patients a less rapid, but nevertheless signifi- ques that may palliate ‘end-stage’ heart failure, with the cant improvement of LV systolic impairment, but this remains potential to improve clinical symptoms and for bridging to unproven at present. Sufficient RV adaption to PAB seems to be transplantation; there can be also a chance for recovery, in par- age-dependent not at least
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