By definition, ccTGA, with its subaortic RV and its particular tricuspid valve (TV) placement, supports the systemic circulation during neonatal life. Most newborns, infants, and young children with isolated ccTGA remain asymptomatic. The diagnosis may be made in adult life in asymptomatic patients, usually by identifying a systemic ventricle with RV morphology and its left-sided position; ventricular trabeculations, moderator band (trabecula septomarginalis, Leonardo band positioned between interventricular septum and musculus papillaris anterior), and by TV leaflet insertion at the ventricular septum as well as by the slightly more apical insertion of the septal leaflet of a morphologically tricuspid valve in comparison of the right side positioned mitral valve (Fig. 6.1a, b, Video 6.2a). Somerville et al. [9] reported a “natural and unnatural” history of ccTGA with two adequate ventricles managed over a 20-year period in survivors aged from 1 to 58 years (median 20); all but 10 % of these had additional anatomic abnormalities. Tricuspid valve abnormalities were more prevalent in patients with symptomatic heart failure (>50 % of patients) than those whose main problem was cyanosis (20 % patients); all dysplastic or Ebstein valves were at least moderately incompetent. Intra-cardiac repair of the lesion leaving the RV in a subaortic position was performed in the past with an early high mortality rate of more than 20 %; the risk factors for early death or a bad early outcome or poor result 6 months later related to a poor preoperative symptomatic status (especially from heart failure), impaired right ventricular function, heart block and younger age at surgery [10]. Patients with more than mild preoperative tricuspid regurgitation (TR), whose valves were not replaced, did very poorly [6, 10]. In addition, TR is the most significant independent predictor of outcome. However, TR strongly relates to RV dysfunction, raising the question whether TR leads to RV dysfunction or the other way around. By contrast, the course of patients, who were predominantly cyanotic, was more stable in early childhood and their surgical outcome was less compromised by a poor preoperative symptomatic status [9]. Considering the long-term outcome, RV systolic dysfunction might be the consequence of regurgitation in those with a malformed tricuspid valve as in Ebstein’s anomaly. It appears that the ventricular geometry and the design and function of the tricuspid valve are most important [6, 11]. However, the factors responsible for intrinsic failure of the systemic RV are not understood. It is possible that biventricular interactions are the fundamental basis for this pathophysiology [5]. Therefore, some associated lesions might have protective properties others promoting right ventricular failure. Obstructions at any part of the pulmonary outflow tract are in a wide range protective by decreasing the rate of early or the rate of late right ventricular failure due to an unloaded subpulmonary left ventricle. Our improved understanding of the pathophysiology of interventricular interaction (see also Chap. 7), has led to the abandonment of complete, gradient-free surgical resection of any pulmonary obstruction and alternative strategies for the patients with ccTGA are being developed. Pulmonary artery banding (PAB) is used to retrain the subpulmonary left ventricle in order to enable a double switch operation consisting of an atrial switch (Senning, Mustard operation) together with an arterial switch (Jatene—operation), or by creation of an interventricular tunnel (Rastelli-like operation), but also as a destination therapy to reverse the septal shift back to the subaortic RV with a restoration of the tricuspid valve competency and right ventricular function [11, 12]. The question still needs to be answered whether the strategy of PAB is limited to children or adolescents [12]. In agreement with Redington, the currently unsatisfactory results in adults after PAB are due to imperfect banding procedures rather than an intrinsic inability of “retraining” the more aged left ventricle [4]. Assuming the availability of a banding device that generates a graded outflow obstruction (adjustable banding) one can hypothesize, that the LV, weaned off systemic pressures even over decades, has the chance for retraining and recovery. New percutaneous or Hybrid surgical- (interventional) procedures are now feasible to delay heart or heart–lung transplantation (Video 6.2b, c). Regarding pathophysiological observations, reversible PAB is already considered as a prophylactic tool in newborns and infants with ccTGA [13]. Postnatal adaption of the subpulmonary left ventricle from fetal or immediate postnatal hypertension to a low-pressure circulation should be avoided or readapted, if the subpulmonary left ventricle is already unloaded. The risk of the procedure is low as younger the patient’s age (Fig. 6.2a, b). Recently, Thomas Karl [14] summarized nicely the role of surgical strategies including the Fontan circulation in the treatment of ccTGA (see also Chap. 8). He states that the unfavorable outcome for physiologic repairs (including VSD closure, conduit insertion, TV repair replacement, etc.) are well documented. The physiologic repair creates a situation similar to that of the ccTGA with intact ventricular septum without left ventricular outflow tract obstruction (LVOTO), but with the added potential burden of myocardial or conduction tissue injury and prosthetic material. However, the major factor of the unfavorable postoperative evolution is the structure of the tricuspid valve. The congenital or acquired abnormality of the TV tends to limit the long-term functional support of in the systemic circulation. In this context, Roger Mee at al. in Melbourne in the late 1980s was the first employed PAB for left ventricular retraining in both concordant and discordant TGA [15]. It was noted at the time that patients who had undergone PA banding alone often had a favorable septal shift, which in itself could reduce tricuspid insufficiency without additional surgical procedures. Mee et al. extended the developed concept of anatomic repair of TGA patients with failing Mustard or Senning operation to the primary repair of ccTGA. Additionally, Karl [14, 15] mentioned the strategy proposed by Mavrouidis et al. [16] for cases of ccTGA with a VSD and LVOTO, which is known as 1.5 ventricular repair. This approach may be an option that is somewhere in between the extremes of an anatomic and physiologic repair. In this regard, the 1.5 ventricle repair appears to be an effective solution for selected cases. The LV volume load is reduced by the use of the bidirectional cavopulmonary shunt (Glenn-shunt) limiting the LV to PA pressure gradient, which technically constitutes a physiologic repair, with a low mortality [16]. The general concept of the Fontan circulation in potentially septable biventricular hearts is also part of Chap. 8.

In summary, ccTGA is a highly problematic malformation. The right ventricle in ccTGA might be considered as a pure form of a systemic right ventricle [4]. Electrical disturbances, as congenital AV-block are already frequently observed in fetal life as well as life threatening supraventricular tachycardia. In addition to described coronary functional abnormalities [7], morphological coronary anomalies are found in 45 % of the heart specimens [17]. Any additional volume or pressure stress has to be considered as highly dangerous for the systemic RV. However, the reasons for the intrinsic myocardial right ventricular failure still need to be investigated. Unproportional stress forces are an increased afterload due to any aortic valve or arch obstructions or volume overload of the systemic RV. Important seems to be to differentiate between a volume workload caused by tricuspid valve regurgitation, aortic valve insufficiency, or a right ventricle dependent left-to-right shunt. Considering the data by Prieto et al. [6], those patients with trivial or only mild tricuspid incompetence might have virtually normal symptom-free survival. Improved knowledge of the mechanisms of systemic RV failure might also have a direct impact on the assessment of right ventricular dysfunction in an anatomically normal positioned RV (Chap. 5). Therefore, in the context of an unexplained or idiopathic precapillary pulmonary hypertension, it is hypothesized that a patient with a subpulmonary left ventricular might have a better long-term outcome, than a patient with a morphological normal subpulmonary RV. The left ventricular structure of the subpulmonary ventricle prevents early failure even in the case of suprasystemic pulmonary hypertension. Theoretically many of therapeutic options exist, but both ventricles have to be analyzed in concert and not as separate entities.

d-Transposition of the great arteries (d-TGA) accounts for 2.6–7.8 % of all cases of CHD [18] and is characterized by ventriculo-arterial discordance resulting in a parallel pulmonary to systemic circulation. During fetal life the parallel-connected circulations and the postulated higher right ventricular output of 55 % versus 45 % of the left ventricle seems to compensate for the relative lower oxygen saturation of the vital organs. Discussions are still ongoing whether the d-TGA dependent relative lower oxygen content of the fetal perfused coronary and in particular cerebral circulation has negative consequences. Postnatally uncorrected d-TGA is incompatible with life unless any communication at the venous, atrial, ventricular, or arterial level exists, followed by a surgical switch of the circulation either at the atrial or great artery, known as either physiologic or anatomic repair. The Mustard and Senning operations [19, 20] have first been performed over 50 years ago and have fundamentally changed the long-term perspective for these patients until Adib Jatene [21] in Brazil was the first to perform an anatomic repair of d-TGA in 1975. The arterial switch operation now represents the standard surgical procedure that restores ventriculo-arterial concordance [22]. However, the atrial switch operation was the first successful intervention allowing long-term survival of children with d-TGA. By creating atrioventricular discordance, this procedure turned the systemic and pulmonary circulation to work in series although the right ventricle remained in a systemic position (Fig. 6.3). The majority of adult d-TGA patients are at a higher risk of late RV dysfunction, arrhythmias, and tricuspid valve insufficiency. Moons et al. reported actuarial survival rates at 10, 20, and 30 years of 91.7 %, 88.6 %, and 79.3 %, respectively [18]. The main concern regarding the long-term prognosis for patients after an atrial switch operation relates to the function of the systemic RV. The systemic RV in atrial switch patients is characterized by impaired ventricular filling, a variable pattern of interventricular interaction, ventriculo-vascular uncoupling, and myocardial perfusion abnormalities resulting in progressive systolic as well as diastolic dysfunction [23–26]. Defining an RV ejection fraction of ≥50 % as normal, mild ventricular dysfunction can be detected in the majority of the patients after atrial switch operations, however, in up to 10–20 % of the total patient population RV dysfunction becomes severe [23]. Reversible and fixed myocardial perfusion defects with concordant regional wall motion abnormalities occur in the systemic RV 10–20 years after the Mustard repair for d-TGA. These may play an important role in the development of late right ventricular dysfunction in this patient group [24]. Derrick et al. [25] found a reduced stroke volume response to exercise and dobutamine stress in patients after the Mustard operation, despite appropriate responses in load-independent indexes of contraction and relaxation. The failure to augment stroke volume was caused by impaired right ventricular filling rates during tachycardia, presumably as a result of impaired atrioventricular transport, intimately related to the abnormal intra-atrial pathway morphology (baffle). As a consequence of these findings it has to be considered that atrial switch patients have chronotropic incompetence because stroke volume decreases proportionally with increasing heart rate, and this despite the use of an inotropic drug, like dobutamine. In this context, it is mandatory to discriminate between heart failure caused by systolic and/or diastolic myocardial dysfunction and the incompetence to adequately increase cardiac output because of filling limitations as by an atrial baffle or due to decreased diastolic compliance as observed in the Fontan circulation (Chap. 8). Inability to increase systemic flow in the absence of ventricular dysfunction is also noted in large shunt defects and in patients with a reduced pulmonary capillary bed (Chap. 5). However, such fundamental pathophysiological differences as the inability to increase cardiac output despite near normal cardiac function have to be considered with regards to pharmacological studies. Otherwise well-designed and methodologically sound, placebo-controlled, double-blind, randomized trials can lead to misinterpretation. In the study by Dore et al. [26] the effect of angiotensin receptor blockade on exercise capacity in adults with systemic right ventricles was investigated and the authors found that losartan did not improve exercise capacity or reduce NT-proBNP levels. Subsequently, the author’s general conclusion was that the systemic RV seems to be resistant to the effect of angiotensin-converting enzyme inhibition or angiotensin receptor blockade. Regarding the inclusion criteria of this study, patients had been selected that did not have a great chance to benefit from losartan therapy. The study results rather support the pathophysiology of Mustard patients with a functional class of < NYHA III; in these patients altering the afterload (because of the mentioned impaired atrioventricular inflow characteristics) cannot adequately increase the cardiac output. Therefore, it remains unknown whether a severely compromised systemic RV might benefit from angiotensin receptor blockade. Comparable studies were undertaken in patients with a single ventricle circulation (Chap. 8), where pathophysiologically non-phenotyped patients were randomized; again, ACE-inhibitors were found to be not effective [27]. However, beneficial effects of ACE-inhibitors were reported in the treatment of children affected by ventricular volume overload due to valvular regurgitation resulting in the regression of LV volume overload and reduction of LV hypertrophy [28]. In evaluating the impact of ACE-inhibitors in patients with inflow limitations, important differences in the pathophysiology of heart failure in congenital versus acquired heart disease can be defined. However, if drugs such as ACE-inhibitors reduce ventricular hypertrophy, improve systolic and diastolic function, then should ventricular size, mass and function, as well as AV-valve regurgitation should become important study endpoints. Considering the gene expression profile of the systemic right ventricle, pharmacological therapy with ACE-inhibitors and angiotensin receptor blockers should be effective as reported in the treatment of the systemic left ventricle, but less effective in the subpulmonary ventricle, regardless whether theirs is a left or right morphology (see Chap. 5). The atrial switch of the venous connection to the right and left atria might reverse the metabolic profile of the mal-connected ventricles. The anatomical left, subpulmonary ventricle shows the expression of cytochrome P450 genes normally found in the RV [29]. Emphasizing the importance of the subpulmonary ventricle and pulmonary circulation for detoxication of drugs and for the diminished expression of cytochrome P450 genes in the systemic ventricle [29]. Based on the available published data, whether the right ventricle is the wrong target, in congenital heart diseases [30] remains presently unclear. This is particularly true, if pharmacological studies are analyzed with a direct myocardial focus on mind and neglecting the influence of preload and afterload [31]. Patients with systemic right ventricle treated with eplerenone showed an improvement of an altered baseline collagen turnover biomarker profile, suggesting that reduction of myocardial fibrosis might be a therapeutic target in these patients. In addition to the pharmacological strategies to support the systemic right ventricle, mechanical intervention as described above in the context of the patients with ccTGA is an additional option. Ventriculo-ventricular interaction may improve the function of the subaortic RV and this may allow left ventricular retraining in order to prepare the subpulmonary left ventricle for a double switch operation. The option “to retrain” the subpulmonary left ventricle in adolescents and young adults in comparison to newborns and infants is probably limited [11], but retraining may be feasible in adult patients by using novel adjustable pulmonary banding technique [4].