The so-called "one-and-a-half" ventricular repair: where are we after 40 years?

OBJECTIVES: The indications, timing, and results of the so-called "one-and-a-half ventricle repair", as a surgical alternative to the creation of the Fontan circulation, or high-risk biventricular repair, currently remain nebulous. We aimed to clarify these issues. METHODS: We reviewed a total of 201 investigations, assessing selection of candidates, the need for atrial septal fenestration, the fate of an unligated azygos vein and free pulmonary regurgitation, the concerns regarding reverse pulsatile flow in the superior caval vein, the growth potential and function of the subpulmonary ventricle, and the role of the superior cavopulmonary connections as an interstage procedure prior to biventricular repair, or as a salvage procedure. We also assessed subsequent eligibility for conversion to biventricular repair and long-term functional results. RESULTS: Reported operative mortalities ranged from 3% to 20%, depending on the era of surgical repair with 7% risk of complications due to a pulsatile superior caval vein, up to one-third incidence of supraventricular arrhythmias, and a small risk of anastomotic takedown of the superior cavopulmonary connection. Actuarial survival was between 80% and 90% at 10 years, with two-thirds of patients in good shape after 20 years. We found no reported instances of plastic bronchitis, protein-losing enteropathy, or hepatic cirrhosis. CONCLUSIONS: The so-called "one-and-a-half ventricular repair", which is better described as production of one-and-a-half circulations can be performed as a definitive palliative procedure with an acceptable risk similar to that of conversion to the Fontan circulation. The operation reduces the surgical risk for biventricular repair and reverses the Fontan paradox.

Therapeutic Approaches in Pulmonary Arterial Hypertension with Beneficial Effects on Right Ventricular Function-Preclinical Studies.

Pulmonary hypertension (PH) is a progressive condition that affects the pulmonary vessels, but its main prognostic factor is the right ventricle (RV) function. Many mice/rat models are used for research in PAH, but results fail to translate to clinical trials. This study reviews studies that test interventions on pulmonary artery banding (PAB), a model of isolated RV disfunction, and PH models. Multiple tested drugs both improved pulmonary vascular hemodynamics in PH models and improved RV structure and function in PAB animals. PH models and PAB animals frequently exhibited similar results (73.1% concordance). Macitentan, sildenafil, and tadalafil improved most tested pathophysiological parameters in PH models, but almost none in PAB animals. Results are frequently not consistent with other studies, possibly due to the methodology, which greatly varied. Some research groups start treating the animals immediately, and others wait up to 4 weeks from model induction. Treatment duration and choice of anaesthetic are other important differences. This review shows that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans. However, a uniformization of methods may increase comparability between studies and, thus, improve translation to clinical trials.

FHL-1 is not involved in pressure overload-induced maladaptive right ventricular remodeling and dysfunction.

AIMS: The cytoskeletal signaling protein four and-a-half LIM domains 1 (FHL-1) has recently been identified as a novel key player in pulmonary hypertension as well as in left heart diseases. In this regard, FHL-1 has been implicated in dysregulated hypertrophic signaling in pulmonary arterial smooth muscle cells leading to pulmonary hypertension. In mice, FHL-1-deficiency (FHL-1-/-) led to an attenuated hypertrophic signaling associated with a blunted hypertrophic response of the pressure-overloaded left ventricle (LV). However, the role of FHL-1 in right heart hypertrophy has not yet been addressed. METHODS AND RESULTS: We investigated FHL-1 expression in C57Bl/6 mice subjected to chronic biomechanical stress and found it to be enhanced in the right ventricle (RV). Next, we subjected FHL-1-/- and corresponding wild-type mice to pressure overload of the RV by pulmonary arterial banding for various time points. However, in contrast to the previously published study in LV-pressure overload, which was confirmed here, RV hypertrophy and hypertrophic signaling was not diminished in FHL-1-/- mice. In detail, right ventricular pressure overload led to hypertrophy, dilatation and fibrosis of the RV from both FHL-1-/- and wild-type mice. RV remodeling was associated with impaired RV function as evidenced by reduced tricuspid annular plane systolic excursion. Additionally, PAB induced upregulation of natriuretic peptides and slight downregulation of phospholamban and ryanodine receptor 2 in the RV. However, there was no difference between genotypes in the degree of expression change. CONCLUSION: FHL-1 pathway is not involved in the control of adverse remodeling in the pressure overloaded RV.

Bilateral pulmonary arterial banding results in an increased need for subsequent pulmonary artery interventions.

OBJECTIVE: Despite increasing use of bilateral branch pulmonary artery banding (bPAB), both as a temporary stabilizing treatment and as part of comprehensive hybrid management of hypoplastic left heart syndrome, little is known about the long-term outcomes of the pulmonary arteries (PAs) in banded patients. PATIENTS AND METHODS: We conducted a retrospective review of all patients with ductal-dependent systemic circulation (2001-2013) undergoing bPAB placement at a single institution (bPAB, n = 50); patients who underwent a stage I Norwood procedure (Norwood, n = 53) were used for comparison. The need for PA interventions (surgical arterioplasty, balloon angioplasty, and stent implantation) and PA growth were assessed. RESULTS: Bands were in place for a median of 76 days. PA growth and size were similar between groups, but bPAB patients required more interventions (1.4 ± 2.9 vs 0.5 ± 1.2, P = .01). In competing risks analysis, only 20% of bPAB patients were alive and free from intervention at 5 years after bPAB removal. Multivariable Cox proportional hazards regression of operative interventions within the bPAB group demonstrated the following risk factors: subsequent 2-ventricle repairs (hazard ratio [HR], 2.2; 95% confidence interval [CI], 0.7-6.7), smallest band diameter (HR per additional millimeter, 0.059; 95% CI, 0.004-0.849), and duration of band placement more than 90 days (HR, 3.5; 95% CI, 1.0-12.6). Hemodynamics and Fontan candidacy did not differ between groups. CONCLUSIONS: Patients with bPAB require additional interventions at earlier time points than Norwood patients. Patients with smaller bands and longer duration of banding are at high risk. Despite stenoses requiring additional interventions, Fontan candidacy is maintained.

A comprehensive review: the evolution of animal models in pulmonary hypertension research; are we there yet?

Pulmonary hypertension (PH) is a disorder that develops as a result of remodeling of the pulmonary vasculature and is characterized by narrowing/obliteration of small pulmonary arteries, leading to increased mean pulmonary artery pressure and pulmonary vascular resistance. Subsequently, PH increases the right ventricular afterload, which leads to right ventricular hypertrophy and eventually right ventricular failure. The pathophysiology of PH is not fully elucidated, and current treatments have only a modest impact on patient survival and quality of life. Thus, there is an urgent need for improved treatments or a cure. The use of animal models has contributed extensively to the current understanding of PH pathophysiology and the investigation of experimental treatments. However, PH in current animal models may not fully represent current clinical observations. For example, PH in animal models appears to be curable with many therapeutic interventions, and the severity of PH in animal models is also believed to correlate poorly with that observed in humans. In this review, we discuss a variety of animal models in PH research, some of their contributions to the field, their shortcomings, and how these have been addressed. We highlight the fact that the constant development and evolution of animal models will help us to more closely model the severity and heterogeneity of PH observed in humans.

Spontaneous dissection of the arterial duct during continuous infusion of prostaglandin E1 in a neonate with aortic arch interruption.

We report a 3-day-old boy with double outlet of the right ventricle and interruption of the aortic arch who developed spontaneous dissection of the arterial duct (DA) despite use of continuous infusion of lipo-prostaglandin E1 (PGE1). Transthoracic echocardiography demonstrated the spontaneous dissecting aneurysm of DA, which was confirmed by histology at the modified Norwood procedure done at age of 18 days. This is the first report of spontaneous dissection of DA in a neonate receiving PGE1, suggesting a new closing mechanism of DA.

Rapid 2-stage Norwood I for high-risk hypoplastic left heart syndrome and variants.

OBJECTIVES: Preoperative comorbidities (PCMs) are known risk factors for Norwood stage I (NW1). We tested the hypothesis that short-term bilateral pulmonary arterial banding (bPAB) before NW1 could improve the prognosis of these high-risk patients. METHODS: From January 2006 to October 2011, 17 high-risk patients with hypoplastic left heart syndrome (defined as having ≥4 of the following PCMs: prolonged mechanical ventilation; older age; sepsis; necrotizing enterocolitis; hepatic, renal, or heart failure; coagulopathy; pulmonary edema; high inotropic requirements; anasarca; weight <2.5 kg; and cardiac arrest) were identified. In addition to conventional treatment of PCMs, they underwent bPAB before NW1. bPAB was undertaken with Silastic slings and secured with ligaclips to a luminal diameter of approximately 3.5 to 4.0 mm. The patency of the ductus arteriosus was maintained with prostaglandin. NW1 was performed using a modified, right Blalock-Taussig shunt at a median interval of 8 days after bPAB. The data from these patients were retrospectively reviewed, and the 30-day mortality and 1-year survival were compared with the hypoplastic left heart syndrome population who underwent primary NW1 with <3 PCMs in the same period. RESULTS: Of the bPAB patients, 5 (29.4%) died before NW1. All had ≥5 PCMs. Twelve patients (70.6%) survived to undergo NW1. One early death occurred after NW1 (8.3%). The 1-year survival rate for high-risk patients who underwent NW1 was 66.7%. The early mortality and 1-year survival for the 130 patients with <3 PCMs was 10% and 80%, respectively. CONCLUSIONS: Optimizing the balance between the pulmonary and systemic blood flow with a short period of bPAB and ductal patency can improve the perioperative conditions of high-risk patients before NW1. Those who survived bPAB and underwent NW1 had early mortality and 1-year survival comparable to the standard risk category, despite the severity of their initial condition. A rapid 2-stage NW1 strategy with bPAB and prostaglandin to maintain ductal patency can avoid the risks of suboptimal palliation and vascular injuries associated with hybrid procedures.