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Bhattarai, Anil (2013) One and a half ventricle repair: clinical and animal study. [Tesi di dottorato]

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Abstract (inglese)

SUMMARY
Since the first description of the so called “one and a half ventricle repair”, published by Billingsly et al. in 1989 1, this type of correction has been applied to several complex congenital cardiac anomalies. The rationale underlying this repair is twofold. On one hand the aim is to reduce the blood flow to, and therefore to downsize the pre-load of, a dysfunctional or hypoplastic right ventricle (RV), considered to be unable to sustain a biventricular correction. On the other hand the one and a half ventricle repair (1.5 VR) permits to maintain a complete and physiological separation of pulmonary and systemic circulations, avoiding blood mixing and desaturation. Furthermore it represents a valid alternative to the Fontan circulation in the setting of a less but still functioning RV, with the advantage to provide a pulsatile pulmonary blood flow and to prevent systemic venous hypertension 2,3. One and a half ventricle repair consists of bidirectional cavo-pulmonary shunt (BCPS) in addition to complete closure of intracardiac communications, associated or not with repair of other congenital heart defects. It can be appropriate for a wide spectrum of congenital anomalies, provided that the RV is large enough to manage the blood supply from the inferior vena cava. However, feasibility in adult population is being explored 1,4.
This study has divided in two parts:
1. Clinical study 2. Experimental study in animals.
In clinical study we have reviewed our institutional experience with 1.5 VR to evaluate early and long term results and explore the impact of associated cardiac malformations on outcomes of the one and a half ventricle repair. Animal study in rabbits was conducted to evaluate the effect of a pulsatile venous flow pattern in superior vena cava and to understand an immediate & after pharmacologically induced stress test the hemodynamic changes in superior vena cava, right atrium, right ventricle, pulmonary artery and inferior vena cava district.
A. Clinical study
Methods
All patients who underwent one and a half ventricle repair between March 1994 and January 2012 were included. All available clinical and operative data were reviewed. Patients were divided in: Group A - patients with right ventricle hypoplasia/dysfunction and malformations of tricuspid or pulmonary valves; Group B - patients with associated complex malformations involving other cardiac structures.
Results
This is an 18 years retrospective clinical review of 24 consecutive patients who underwent one and a half ventricle repair at our Institution. Mean age at repair was 11.9 years (range 4 months – 66.8 years). Mean TV annulus Z-score was -3.2 (range -6.2 to 3.6). Mean pulmonary vascular resistance was 1.75 U/m2 (range 1.0 to 3.0). Three patients had heterotaxy syndrome. Sixteen patients underwent previous cardiac operation, one of these had a Fontan operation.
There was no death at operation. Postoperative complications occurred in 19 patients (79 %), and were: chylothorax/chylopericardium (n=7), BAV III (n=2), arrhythmias (n=7), renal failure (n=4), heart failure (n=4), cardiac/pleural effusion (n=11), SVC syndrome (n=2), pulmonary infection (n=3), hemi diaphragm paralysis that required diaphragm plasty (n=1), SVC thrombosis with PE (n=1). Five patients required definitive PM implantation. All patients were discharged home alive and well, after a mean hospital stay of 32 ± 29 days. At a mean follow up of 8.3 years (range 1 month – 17.9 years, FU completeness: 96 %), there were 2 late deaths (1 non cardiac related). Among survivors, functional status was NYHA class I in 19 patients (90.4%). Late adverse events occurred in 10 patients (43 %) including: late reoperation (n=3), one of these was a biventricular conversion; haemodynamic procedures (n=6); arrhythmias (n=2); neurological event (n=1); other complications (n=5).
Overall freedom from adverse events, surgery and interventional procedures was 56.5 %, 87 % and 73,9 % respectively. Freedom from adverse event in Group A (n=12) was 83.3 % while in Group B (n=11) was 27.3 %. Statistical analysis demonstrated that Group B had a significantly lower freedom from adverse events than Group A (p = 0.015).
B. Animal Study
Methods
Experiment was performed in experimental Rabbits. Animal care has taken according to established standard for experiment in animals.
Experimental model: RABBIT
Strain: NEW ZEALAND
Total animal number: 30
Weigh of animals:4. 5-5.5 kg
Results
1. After cavapulmonary anastomosis- SVC and PA pressure has increased but RA pressure has decreased, which proves the decrease of the pressure in inferior vena cava district.
2. After pharmacologically induced stress test: increased the pressure in superior vena cava and also increased heart rate but right ventricular, right atrial & pulmonary artery pressures were remained as same as after cavopolmonary anastomosis, as it is in resting condition.
3. That means superior vena cava pressure is always higher after cavapulmonary anastomosis but venous pressure in inferior vena cava district is constant and even lower in comparison with preoperative pressure.
4. We found no any changes of right atrial pressure, after 1.5 ventricular repair and even after pharmacologically induced stress test which proves that the inferior vena cava return is ok and no hypertension in inferior vena cava district even after stress test(good exercise tolerance), which is a very positive finding in favour of one and a half ventricle repair in comparison to Fontan type procedure.
Conclusion
After having the result of both clinical study and experiment in animals we have concluded that the 1.5 VR is a safe and valid option for surgical repair of hypoplasic, borderline or failing right ventricles as an alternative to Fontan procedure. Most patients show good functional status at follow up. This repair provides a low pressure in the inferior vena cava district and allows good early and mid-term outcomes.

Abstract (italiano)

RIASSUNTO
La prima descrizione della cosiddetta "correzione a un ventricolo e mezzo", fu pubblicato da Billingsly et al. nel 1989 1, Questo tipo di correzione è stato poi applicato in altri centri per correggere diverse anomalie congenite cardiache complesse caratterizzati da un ventricolo destro ipoplasico. La logica alla base di questa riparazione è duplice. Da un lato l'obiettivo è di ridurre il flusso di sangue, e quindi il pre-carico in, un ventricolo disfunzionale o ipoplasico destro (RV). D'altra parte la riparazione a un ventricolo e mezzo (1,5 VR) permette di mantenere una separazione completa e fisiologica della circolazione polmonare e sistemica, evitando mixing di sangue e desaturazione. Inoltre rappresenta una valida alternativa alla circolazione secondo Fontan nel contesto di una ipoplasia del ventricolo destro, fattore funzionale, con il vantaggio di fornire un flusso polmonare pulsatile e prevenire l’ipertensione venosa nel distretto della vena cava inferiore 2, 3. La correzione a un ventricolo e mezzo comprende la connessione della vena cava superiore all’arteria polmonare (shunt cavopolmonare bidirezionale), oltre a completare la chiusura di eventuali comunicazioni intracardiache, o meno alla riparazione di ulteriori difetti cardiaci congeniti associati. Questa metodica può essere applicata ad un ampio spettro di anomalie congenite, purché il ventricolo destro ipoplasico sia funzionalmente valido e pertanto in grado di gestire la portata di sangue della sola cava inferiore 1, 4.
Questo studio è diviso in due parti:
1. Studio clinico 2. Studio sperimentale negli animali.
In questo studio abbiamo valutato i risultati del nostro Istituto a lungo termine e non solo della circolazione polmonare bifocale ma anche l’impatto delle malformazioni cardiache associate. Lo studio sugli animali e stato condotto nei conigli per valutare l'effetto del “pattern” pulsatile del flusso venoso in vena cava superiore e di capire i cambiamenti emodinamici in vena cava superiore, atrio destro, ventricolo destro, arteria polmonare e vena cava inferiore, nell’immediato e dopo stress test formacologico.
A. Studio clinico
Metodi
Tutti i pazienti con correzione in uno ventricolo e mezzo tra il Marzo 1994 e Gennaio 2012 sono stati inclusi. Tutti i dati clinici disponibili e operativi sono stati valutati. I pazienti sono stati suddivisi in: Gruppo A - pazienti con ventricolo destro ipoplasico / disfunzioni e malformazioni delle valvole tricuspide e polmonare, Gruppo B - pazienti con associate malformazioni complesse che coinvolgono altre strutture cardiache.
Risultati
Si tratta di un esame clinico retrospettivo di 18 anni in 24 pazienti consecutivi sottoposti a correzione un ventricolo e mezzo presso il nostro Istituto. L'età media di correzione è stata di 11,9 anni (range 4 mesi - 66,8 anni). Il Z-score medio dell’ anello TV era -3,2 (range -6,2 a 3,6). Le resistenze vascolari polmonari medie erano 1,75 U/m2 (range 1,0 - 3,0). Tre pazienti erano affetti da sindrome eterotassica. Sedici pazienti erano stati sottoposti a precedenti interventi cardiaci, uno di questi aveva una deviazione atriopolmonare totale secondo Fontan.
Le complicanze postoperatorie si sono verificate in 19 pazienti (79%): chilotorace/chylopericardium (n = 7), BAV III (n = 2), aritmie (n = 7), insufficienza renale (n = 4), insufficienza cardiaca (n = 4), cardiaca / versamento pleurico (n = 11), la sindrome di SVC (n = 2), infezione polmonare (n = 3), paralisi emi-diaframma che ha richiesto plastica diaframmatica (n = 1), trombosi SVC con PE (n = 1). Cinque pazienti hanno richiesto l'impianto definitivo di PM. Tutti i pazienti sono sopravissuti e dopo una degenza media di 32 ± 29 giorni. Ad un follow up medio di 8,3 anni (range 1 mese - 17,9 anni, la completezza FU: 96%), ci sono stati 2 morti tardive (1 non cardiaca). Tra i sopravvissuti, lo stato funzionale prevalente era NYHA classe I in 19 pazienti (90,4%). Eventi avversi tardivi si sono verificati in 10 pazienti (43%) tra cui: un nuovo intervento(n = 3), uno di questi era una conversione biventricolare; procedure emodinamiche (n = 6), aritmie (n = 2), eventi neurologici
(n = 1 ); altre complicazioni (n = 5).
La libertà totale da eventi avversi, la chirurgia e le procedure interventistiche sono state 56,5%, 87% e 73,9% rispettivamente. La libertà da eventi avversi nel gruppo A (n = 12) è stata 83,3%, mentre nel gruppo B (n = 11) è stata pari al 27,3%. L'analisi statistica ha dimostrato che il Gruppo B ha avuto una libertà significativamente più basse di eventi avversi rispetto al gruppo A (p = 0,015).
B. Studio degli animali
Metodi
Esperimento è stato eseguito in conigli. La cura degli animali e stata svolta secondo lo standard stabilito per gli studi sperimentali.
Modello sperimentale: CONIGLIO
Strain: NUOVA ZELANDA
Numero totale Animali: 30
Peso di animali: 4. 5-5,5 kg
Risultati
1. Dopo anastomosi cavopolmonare- la pressione in SVC risultava aumentata ma la pressione in RA invece diminuiva, il che dimostra la diminuzione della pressione nella vena cava inferiore.
2. Dopo lo stress indotto farmacologicamente: la pressione nella vena cava superiore e la frequenza cardiaca aumentavano, mentre la pressione del ventricolo destro, atrio destro e la pressione in arteria polmonare rimanevano simili come in condizione di riposo dopo un’anastomosi cavo polmonare.
3. Ciò significa che la pressione della vena cava superiore è sempre più elevata dopo anastomosi cavapulmonare ma la pressione venosa nella vena cava inferiore è costante e ancora più bassa se confrontato alla pressione preoperatoria.
4. Non abbiamo trovato alcuna modifica della pressione atriale destra, dopo correzione ad un ventricolo e mezzo; anche dopo stress test farmacologico viene dimostrato che il ritorno dalla vena cava inferiore è adeguato e non esiste ipertensione in vena cava inferiore, (buona tolleranza fisica). Questo è un risultato molto positivo a favore della correzione a un ventricolo e mezzo ventricolo rispetto all’ intervento di Fontan.
Conclusione
Si conclude che la correzione 1,5 VR è una scelta sicura e valida per la riparazione chirurgica dell’ipoplasia del ventricolo destro associato o meno ad altre malformazioni cardiache come alternativa alla procedura di Fontan. La maggior parte dei pazienti mostrano un buono stato funzionale al follow-up. Questa riparazione mantiene una bassa pressione nella vena cava inferiore e permette buoni risultati precoci e a medio termine.

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Tipo di EPrint:Tesi di dottorato
Relatore:Stellin, Giovanni
Dottorato (corsi e scuole):Ciclo 25 > Scuole 25 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > SCIENZE CARDIOVASCOLARI
Data di deposito della tesi:24 Gennaio 2013
Anno di Pubblicazione:24 Gennaio 2013
Parole chiave (italiano / inglese):uno, mezzo, ventricolo/ one, half, ventricle
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/23 Chirurgia cardiaca
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari
Codice ID:5461
Depositato il:16 Ott 2013 10:36
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