Low cardiac output is the characteristic feature of the cavapulmonary circulation. Newer pharmacologic approaches to the problem include levosymendan ⁴⁷ and triodthyronine supplement ⁴⁸ , besides conventional postoperative administration of milrinone and dopamine, epinephrine. Implantation of a pacemaker can positively affect cardiac output in patients with the appropriate indications ⁴⁹ Ventricular assist devices are used as the bridge to cardiac transplantation ⁵⁰ Another effective option is external counterpulsation ⁵¹

Three main mechanisms contribute to the development of persistent pleural effusions after the Fontan procedure: inflammatory, hydrostatic and hormonal. The inflammatory response results mainly from exposure to CPB (cardiopulmonary bypass), causing increased capillary lekeage and subsequent fluid retention. Increased hydrostatic pressure in Fontan circulation results from factors increasing the pulmonary vascular resistance. Lack of atrioventricular synchrony also contributes to this mechanism. The hormonal mechanism involves activation of the rennin-angiotensin system ⁵² ; Mainwaring et al. ⁵³ , 1995 reported that the data demonstrated that patients who develop effusions following bidirectional Glenn and Fontan procedures have activation of their renin-angiotensin system. Thompson et al. ⁵⁴ , 2001 reported positive effect of perioperative administration of angiotensin converting enzyme inhibitors on the severity and duration of pleural effusions following bidirectional cavopulmonary anastomosis.

Several studies have evaluated the contribution of preoperative and intraoperative factors to post-Fontan pleural effusions and LOS (length of stay in the hospital). Factors found to be statistically related to reduced pleural effusions and shorter hospitalizations in these studies were creation of a fenestration, partial exclusion of the hepatic veins during completion of the Fontan procedure, and an extracardiac Fontan operation. The majority of studies have found, that most preoperative factors are not statistically related to prolonged pleural effusions and longer hospitalizations. The factors, evaluated in these studies were age; preoperative oxygen saturation, pulmonary artery pressure, or pulmonary vascular resistance; ventricular end-diastolic pressure; type of Fontan; previous bidirectional Glenn procedure; presence of branch pulmonary artery stenosis; degree of atrioventricular valve regurgitation; and decreased ventricular function. A fenestrated Fontan operation during the winter respiratory viral season in Wisconsin appeared to be associated with prolonged pleural effusions, longer hospitalizations, and an increased need for pleurodesis ⁵⁵ (Raymond T. Fedderly et al., 2001).

Gupta et al. ⁵⁶ , 2004 reported the following risk factors, associated with persistent pleural effusions after extracardiac Fontan: lower preoperative oxygen saturation, presence of postoperative infection, smaller conduit size, and longer duration of cardiopulmonary bypass.

Garofalo et al. ⁵⁷ , 2006 stated, that ventricular diastolic stiffness predicts perioperative morbidity and duration of pleural effusions after the Fontan operation. Tae-Jin Yun et al. ⁵⁸ , 2008 reported that low pulmonary vascular compliance is an important risk factor for prolonged pleural effusion drainage after the extracardiac Fontan procedure.

Frommelt et al. ⁵⁹ , 1995 concluded, that patients with an additional source of pulmonary blood flow after bidirectional cavopulmonary shunt have higher postoperative central venous pressures, have higher oxygen saturations, and are at risk for the late development of a chylothorax.

The performance of the baffle fenestration has been associated with the decreased pleural drainage, the fewer additional procedures and shorter hospital stay (Alphonso et al. ⁶⁰ , 2005). The management of the persistent postoperative pleural effusion is still considered difficult. Several methods have been reported: fenestration of diaphragm, pleuroperitoneal drainage, low fat diet, parenteral feeding, diuretics, ACE inhibitors, somatostatin (Octreotide) infusions .

Although the exact mechanism of action of Octreotide remains to be clarified, it has been postulated that it could be beneficial to decrease post-Fontan pleural drainage. There are several data, describing its use after the Fontan surgery and other operations ⁶¹ (Aleo Lujon et al. 2004; Rimensberger et al., 1998).

Cava et al. ⁶² , 2005 reported successfull results after the clinical application of the standartized protocol, consisting of diuretics: furosemide 1 mg/kg every 8 hours on postoperative day, when taking liquids, an enteral combination of hydrochlorothiazide and spironolactone 1 mg/kg every 12 hours; afterload reduction using captopril was given at a maximum dose of 1 mg/kg/dose when enteral feeds were initiated; fluid restriction was limited to 80% maintenance; a minimum of 0.5 L of supplemental oxygen by nasal canula was used for its pulmonary vasodilatory effect, regardless of systemic saturation. All patients were on a low-fat diet consisting of 30% of daily calories from fat. Chest tubes were taken out when drainage decreased to 2 ml/kg/day. The duration of chest tube drainage, hospital stay, and the need for pleural sclerosis were significantly reduced, indicating that postoperative management plays an important role in reducing this morbidity.

Gradual loss of sinus rhythm is common after the all varieties of the Fontan procedures. Patients with the heterotaxy syndromes, particulary, polysplenia syndrome may also have congenital abnormalities of the sinus node independent of the effects of their surgical procedures (Triedman ⁶³ , 2002). Atrial arrhythmias have been reported between 22% and 50% of patients with an APC Fontan. (Weinstein , Chan ⁶⁴ , 2005). Alphonso ⁶⁵ , 2005 reported the following arrhythmias in desending order of appearance: supraventricular tachycardia, atrial flutter, bradyaritmia, atrial fibrillation and nodal rhythm.

A distinctive feature of atrial tachycardias in patients with the Fontan physiology is that they tend to be very organized, regular reentrant arrhythmias. At present, specific factors that appear to be relevant to arrhythmogenesis in the Fontan patient include abnormal size and anatomy of the atrium, myocardial hyperthrophy and fibrosis caused by cyanosis and chronic hemodynamic overload, surgical scarring, and bradycardia-mediated abnormalities of myocardial refractoriness. Frequently identified risk factors for atrial tachycardia include older age at operation and longer follow-up. (Triedman, 2002). Early tachyarrythmia is a predictor for late arrhythmia. Estimated risk factors for atrial flutter include older age at Fontan, longer follow up interval, prior atrial septectomy or pulmonary artery reconstruction, increased symptoms by NYHA class and sinus node dysfunction. Current effective medical therapies for the intraatrial reentrant tachyarrythmia include atrial stabilizing agents such as digoxin, amiodarone, flecanide and propafenone in conjunction with pharmacologic or DC cardioversion (O`Donnel, Lanzberg ⁶⁶ 2002). Electroanatomic mapping is the superior modality for arrhythmia mapping late after the Fontan procedure. Noncontact mapping is limited by a significant reduction in reconstructed electrogram correlation, timing, and amplitude >40 mm from the multielectrode array and cannot accurately define areas of scar and low-voltage endocardium ⁶⁷

Today it is not yet definitely proven, which Fontan modification is better in terms of reducing the incidence and the severity of the rhythm disorders. The newest modification of the Fontan procedure is the direct inferior vena cava to the pulmonary artery connection may be performed in selected patients with excellent results (McKay ⁶⁸ , Dearani, 2008). A good option for the patients with double inlet ventricles is the so-called septation procedure - an alternative to physiological repair anatomic approach (Ohuchi et al. ⁶⁹ , 2008).

The blind stump of the main pulmonary artery is the important source of thrombus formation. It should be oversewn as proximally as possible after the excision of the pulmonary valve to minimize this risk (Jonas ⁷⁰ , 2000; Madan ⁷¹ et al., 2002; Kammerad ⁷² et al., 2004). Either high and low molecular heparins have been used postoperatively with the further treatment with aspirin or warfarin. Alphonso ⁷³ et al., 2005 reported the following indications for warfarin: the arrhythmia, intracardiac thrombus, venous thrombus, pulmonary embolism, the right pulmonary artery stent, embolic cerebrovascular accident. And there has been only one nose bleed related to warfarin in his study. Probably, the combination of aspirin and clopidogrel may be more safe than warfarin and more effective than aspirin alone, but there is a lack of evidence to prove it.

Protein-losing enteropathy (PLE) is a disease with the significant morbidity and mortality seen after the Fontan operation. Mechanisms for the explanation of the pathophysiology of PLE include abnormal mesenteric vascular resistance and inflammation, conditions uniquely present after the Fontan operation. Patients with PLE present with bloating or the abdominal pain, diarrhea, edema, pleural effusion, ascites and distress. Laboratory findings usually include hypoproteinemia, low serum immunoglobulins and calcium levels and low lymphocyte count. The onset may occur from weeks to years after the surgical procedure. In a study by Mertens, this interval ranged from one month to 16 years (mean: 2.7 years). Some cases may present with no diarrhea and with slight hypoalbuminemia, despite the marked reduction in serum immunoglobulin levels and lymphocyte counts, especially of CD4. Subclinical gastrintestinal protein loss may occur with no evidence of the classical clinical findings and with normal serum protein levels. The diagnosis of PLE is confirmed by finding high fecal 1-antitrypsin levels in patients with no other causes of hypoalbuminemia, such as liver disease or malnutrition. The current treatment for PLE is associated with a very high mortality rate. It consists of the diet modification, albumin infusion, diuretics, inotropes, corticosteroids, high- and low-molecular heparin, calcium, spironolactone, gammagloubulin, sildenafil, pacemaker implantation, and surgery: baffle fenestration, intestinal resection and heart transplantation ⁷⁴ There is an evidence of the therapeutic effect of the octreotide in the patients with PLE with conditions other, than the cavapulmonary circulation ⁷⁵ , so it could be proposed as the treatment for the single ventricle patients, suffering the complications with the same pathogenesis.

Plastic bronchitis is a rare complication, in which bronchial casts of the lymphatic origin develop in the tracheobronchial tree and cause the airway obstruction. The main feature of the disease is the expectoration of bronchial casts ⁷⁶ Treatment modalities include mucolytics and chest physiotherapy and fenestration of the tunnel ⁷⁷ , aerosolized urokinase ⁷⁸ or r-TPA ⁷⁹ , postural drainage, thoracic duct ligation ⁸⁰ , inhaled heparin ⁸¹ , macrolide antibiotics, dornase alfa ⁸² , oral or inhaled corticosteroids ⁸³ , hydration (Madsen et al., 2005, Ishman et al., 2002) and in the most severe cases bronchoscopy ⁸⁴ to remove the casts. Stent implantation in the left pulmonary artery ⁸⁵ , positive effect of sildenafil ⁸⁶ and bosentan ⁸⁷ (dual endothelin receptor antagonist which has been used to treat increased pulmonary vascular resistance Votava-Smith et al., 2007). have been reported relatively recently.

Kiesewetter et al. ⁸⁸ , 2007 reported, that the liver injury, which may be extensive in this patient group, is related to Fontan duration and hepatic vein pressures. According to their opinion and the research data, in the Fontan circulation, central venous pressures are raised by the virtue of the absence of a subpulmonary pump, rendering the systemic and pulmonary circulations in series. The liver, wedged between the raised pressure of the central venous system and the portal venous circulation, superimposes an additional capillary bed and above the pulmonary and intestinal arterial capillary beds. Cardiac output is also frequently depressed, thereby providing the ideal substrate for hepatocyte hypoxia, congestion and stimulation of the fibrotic response. Additionally, during atrial contraction, there is marked flow reversal with the deep intrahepatic reflux with associated hepatic vein distention, causing stromal stretch and compression of adjacent hepatocyte cell plates. Mechanodestruction associated with stretch and compression may be a potent inducer and/or modulator of hepatic fibrosis. Their data suggest that the radiological appearances of the liver on a CT scan may aid in defining liver injury. Hepatic fibrosis and cirrhosis are common findings late in patients reffered for Fontan conversion surgery.

Cardiac cirrhosis with the risk of developing gastro-oesophageal varices and regenerative liver nodules, a precursor to hepatocellular carcinoma, is common in this patient group. Chaloupecky et al. ⁸⁹ , 2005, documented that almost half the patients after TCPC had laboratory signs of a mild cholestasis. Decreased liver synthesis of procoagulant factors was observed but overall coagulation homeostasis appeared to be in balance in this selected group of patients with a good clinical outcome.

Vasodilator treatment has the potential to reduce the transhepatic and transpulmonary gradient. Recently, sildenafil (phosphodiesterase inhibitor type 5) and bosentan, the non-selective endothelin receptor blocker, have been shown to favourably modulate pulmonary vascular resistance, and in the context of the Fontan circulation, may improve transhepatic perfusion pressures. Their effects on hepatic vascular resistance are unknown. Authors ⁹⁰ believe that patients, suffering the liver disease are likely to benefit from the creation of a fenestration, but this fact needs prospective evaluation before a general recommendation can be made.

Anne Premchand et al. ⁹¹ , 2008 reported the research data, revealing nephropathy with microalbuminuria which was resolved after the prescription of the ACE inhibitor. This unique investigation elucidates the concept of the total protein loss in Fontan patients (via bronchial tree, gastrointestinal and renal systems).

Hemidiaphragmatic paralysis after the modified Fontan operation is associated with an increase in early morbidity. Care should be taken to avoid the injury to the phrenic nerve. Early diaphragm plication may be favorable to optimize the Fontan circuit in patients with diaphragmatic paralysis ⁹²

In children with univentricular heart, intellectual and neurologic deficits, the syncope, the problems with learning are common. In the multiple linear regression model (Sarajuuri et al., 2007), diuresis the third day after the primary operation and cardiopulmonary bypass time in the bidirectional Glenn operation correlated significantly with the primary outcome of full-scale IQ, which was reported the lowest in HLHS patients. ⁹³

Cases of septic shock after the operations of physiological repair are reported rather rare, in single accidents. Both fungal and bacterial etiology of the systemic inflammatory response after the Fontan procedure occurs ⁹⁴ It is known, that such complications as the protein-losing enteropathy, plastic bronchitis and prolonged pleural effusions are associated with the development of the acquired immunodeficiency ⁹⁵ , increasing the vulnerability of the patient to the invading antigens. Probably, splenic dysfunction in heterotaxy patients may contribute to the problem.

Binotto et al. ⁹⁶ , 2005 concluded that the vascular endothelium plays a central role in the control of coagulation and fibrinolysis. The data suggest that patients with the Fontan circulation may have endothelial dysfunction, as indicated by raised levels of von Willebrand factor. Fibrinolysis seems to be relatively preserved, as suggested by the appropriate response to the venous occlusion.

Endothelial dysfunction is more prevalent in the Fontan patients, compared with the healthy controls, and the previous hypoxia is an independent factor. Although it is not statistically significant, those patients on treatment with ACE seem to have better endothelial function (Jin ⁹⁷ et al., 2007).

In case of Fontan operation failure, the histological modifications are subtle with a muscular extension of the distal pulmonary arterioles wall. Conversely, a marked increase of NO synthase and VEGF expression is observed which can witness of an endothelial dysfunction. (Levy et al. ⁹⁸ , 2004).

In Fontan patients, diminished exercise capacity was related to a reduced blood flow supply and an attenuated post-exercise oxygen resaturation of the working skeletal muscle, which also was related to the impaired endothelium-dependent vasodilation (Inai ⁹⁹ , 2004).

Morgan et al. ¹⁰⁰ , 1998, have found the higher shear stress, acting on the wall of the vessels in the patients, having a bicaval tunnel, which may alter the endothelial function and affect the longevity of the repair.

Altered levels of endothelial markers in the plasma, in the presence of normal levels of d-dimer, suggest that endothelial dysfunction may precede the occurrence of intravascular coagulation and thrombosis in patients with functionally univentricular physiology. These observations may have therapeutical implications (Binotto et al. ¹⁰¹ , 2007).

In children with univentricular circulation after Glenn or Fontan operations, the increased central venous pressure may induce recanalization of embryologically preformed and obliterated vessels. Finally, such venous collaterals can result in systemic desaturation and reduction in ventricular function (Usta ¹⁰² et al., 2008).

Aorto-pulmonary collaterals are among etiology of pulmonary hemorrhage and hemoptysis together with pulmonary hypertension, pulmonary venous congestion, pulmonary arteriovenous malformations, and dilated bronchial arteries (Deisenberg ¹⁰³ , 2005). Bleeding gastric varix due to the development of collaterals from high-pressure systemic vein to low-pressure portal vein can be a late complication of total cavopulmonary shunt . (Furuse ¹⁰⁴ et al., 1993).

Because the hepatic venous return in left atrial isomerism patients is not directed to the lungs, the portal venous pressure is lower than the systemic venous pressure. Thus, there would seem to be a risk for the late development of collaterals and fistulous communications between the systemic venous and hepatic venous system leading to progressive systemic desaturation (Usta ¹⁰⁵ et al., 2008).

The prevalence of collaterals is considered as a common complication after cavopulmonary connection and varies between 20.2% to 31% of the patients. A late manifestation is rare. While Fontan completion is one choice of treatment, the other therapeutical option to eliminate such collaterals consists of percutaneous coil embolisation. Non-cardiac surgery as the favoured therapeutical choice for occlusion of such massive venous collaterals may be beneficial in selected patients with impaired ventricular function and rather complex collateral anatomy, who otherwise were high-risk Fontan patients (Vettukattil et al. ¹⁰⁶ , 2000)

Detailed angiographic evaluation on a routine basis allows identification of the vascular sites of origin of aortopulmonary collateral vessels and systemic venous collaterals potentially developing during long-term follow-up. Transcatheter interventions, including fenestration occlusion and occlusion of venous collaterals and aortopulmonary collaterals should be performed to maintain and improve the Fontan circulation in clinically symptomatic and asymptomatic patients. During long-term follow-up after Fontan-type operations, a regular postoperative cardiac catheterization protocol is recommended (Kaulitz ¹⁰⁷ et al. 2002, Stumper ¹⁰⁸ et al., 1995).

Autonomic nervous control of the heart can be studied by analysing variability in heart rate. In patients with the Fontan circulation, routine ambulatory electrocardiographic monitoring including analysis of variability in heart rate, detects over time a progressive sympatovagal imbalance and reduction of HRV (Rydberg ¹⁰⁹ et al., 2005).

Elevated neurohumoral activity and an abnormal cardiopulmonary response to exercise are well-established characteristics in patients after the Fontan operation. Angiotensin-converting enzyme inhibitor administration does not change this abnormality (Ohuchi et al., 2002) ¹¹⁰

Surgery on the caval veins and the atria alters the intracardiac ganglia that are abundant at the cavo-atrial junction and in the myocardium of the right atrium. Abnormalities of HRV in Fontan patients may act as a co-factor in the initiation of arrhythmia in these patients (Butera ¹¹¹ et al., 1999).

The impaired ventricular relaxation, compression and obstruction of conduit are associated with the occurence of the severe fatal pancreatitis. Toxicities of drugs and the adverse effects of cardiopulmonary bypass contribute to the pathogenesis of this devastating disease ¹¹²