Noonan Syndrome and twin to twin transfusion

Transcription

1 Università degli Studi La Sapienza - Facoltà di Medicina e Chirurgia Roma Master di Terapia Intensiva Pediatrica Direttore Prof. Corrado Moretti Noonan Syndrome and twin to twin transfusion Neonatal outcome in extremely low birth weight premature with severe hypertrophic cardiomyopathy and right ventricular outflow tract obstruction Anno accademico Relatore Dott. Antonino Cutaia

2 Incidence twin to twin transfusion syndrome Twin gestation: 1-2% of all pregnancy Monozygotic twin: 1/3 of all twin pregnancy Monochorionic twin:2/3 of all monozygotic twin TTTS: up to 17,5% (5,5 17,5%) of monochorionic twin pregnancies 1/4.000 pregnancies

3 Type The number, size and type of vascular anastomoses play important roles in the etiologies of various forms of TTTS Chronic TTTS Acute perimortem TTTS Twin anemia polycythemia sequence Acute perinatal TTS Twin reversed arterial perfusion sequence

4 Chronic TTTS Most common form Clinically apparent during the second or early third trimester of pregnancy PROM preterm labor Recipient twin: rapid development of polyhydramnios (hypervolemia >>> polyuria) circulatory volume overload, fetal hydrops Donor twin: severe oligohydramnios (hypovolemia >>> oliguria) stuck twin, fetal hydrops

5 Pathogenesis of chronic TTTS new hypothesis Fetal RAS is reported to be upregulated in donor twins d/t hypovolemia and decreased renal perfusion Transfer of rennin and angiotensin through the vascular anastomoses from the donor into the hypervolemic recipient might increase the BP and aggravate cardiac dysfunction in the recipient

6 Diagnosis Inter twin birth weight discordance >20% Hb difference > 5g/dl

7 Neonatal morbidity Cardiovascular Renal Hematologic GI Neurology Others Donor Renal cortical necrosis/fibrosis Transient renal insufficiency Hematuria Acute renal failure Permanent tubular dysfunction d/t renal tubular dysgenesis Severe anemia - fetal hidrops NEC, intestinal atresia Equally at risk for cerebral injury (HIE, PVL, IVH..) Amniotic band syndrome Recipient Congenital heart disease Neonatal hypertension Hypertrophic cardiomyopathy RVOTO > > > fetal hydrops Cardiac hypertrophy polycythemia idem idem Lower limb necrosis

8 Cardiovascular morbidity 3.8% vs singleton 0.6% Mainly in recipient 1 theory: consequence of increased preload d/t chronic hypervolemia causing cardiac hypertrophy 2 theory: increased afterload induced by elevated levels of vasoconstrictive substances such as endothelin-1 found in recipients Congenital heart disease 12 times more frequent in TTTS than in the general population, mainly found in recipient twins. PPHN, TR, left chamber myocardial infarction, pulmonary artery calcification, RVOTO

9 Cardiovascular morbidity Biventricular hypertrophy with prevalent left ventricular hypertrophic cardiomyopathy may be present in % of the recipient twins. Fetal hypertrophic cardiomyopathy >>> hydrops fetalis Reversible in most cases after delivery. d/t removal of causal factors Cardiac hypertrophy >>>functional RVOTO (4-11%) may be progressive, require urgent treatment

10 Must be aware of the risk of RVOTO in recipient twins!!!

11 Neonatal Hypertrophic Cardiomyopathy Familial Idiopathic Hypertrophic Maternal disease Diabetes Myocarditis Infectious endotoxins Drugs /Iatrogenic Dexamathasone (BPD) ECMO Malformation syndromes Beckwith Wiedemann Noonan (case report) Leopard Downs Myocyte hypertrophy & disarray Increased mass & thickness Increased mass/volume ratio Poor diastolic chamber compliance Left ventricle High systolic pressure gradient

12 Case study Baby L is a 830-g female 1 born, delivered by emergency cesarean section at 27 weeks gestation following an uncomplicated monochorionic twin pregnancy until late in labor, when fetal heart rate decelerations were noted secondary to abruptio placentae. 2 born is a 600-g female, fetal demise ongoing the labor Weight discordance : 230-g 230 : 830 = x : 100 (28%) Parents no consanguineous (mother 43 y. o. gravida para 3, father 45 y.o.) and the other two children were reported to be heathy The week before a fetal echocardiography reported no problems

13 Initial evaluation Apgar scores were 1 at 1 minute and 6 at 5 minutes Phisical examination revealed a weak respiratory effort, therefore, positive pressure ventilation with 60% oxigen was given for approximately 15 seconds, followed by endotracheal intubation delivering sufficient positive pressure ventilation to barely move the infant s chest, because even brief periods of overdistension can cause lung injury and attenuate the benefits of surfactant replacement therapy. Cardiovascular examination was unremarkable

14 Following care Was transferred to a maximally humidified incubator Placed on a ventilator with an inspiratory pressure (IP) of 18 cm H2O, a positive end-espiratory pressure (PEEP) of 5 cm H2O, a synchronized intermittent mandatory ventilation (SINV) rate of 40, and an inspired oxigen concentration (FiO2) of 0,40-0,60. Surfactant was given UVC was placed The initial blood work demonstrated only high hemoglobin (20mg/dl) and creatinine (1,7 mg/dl) and low calcium (6 mg/dl) Head and abdomen ultrasonography were unremarkable

15 On day 2 Baby L responded poorly to respiratory therapy Despite no heart murmur was heard, a patent ductus arteriosus (PDA) with left-to-right shunting was suspected and then confirmed by color Doppler echocardiography. Since then, evidence of severe biventricular hypertrophy, but no obstruction yet in right and left ventricular outflow tracts A course of ibuprophen was administered, with resolution of the PDA

16 After PDA closure Baby L continued to improve, but she was unable to be estubated because of poor chest wall stability and apnea that was responsive to caffeine therapy Intravenous infusion of catecholamines resulted in a dramatic improvement in peripheral perfusion, acidbase balance, and urine output Dopamine 5 μg/kg/min - Dobutamine 5 μg/kg/min On day 5 ncpap 5 cm H2O FiO2 0.60

17 On day 7 Nadir weight loss Small amounts of breast milk were started On examination, she had a grade 3/6 systolic heart murmur heard best over the left upper chest, and generalized edema most marked in the face, hands, and feet. Echocardiogram indicated : worsenig bi-ventricular hypertrophy Inter Ventricular Septum IVS thickness: 5 mm (> 97 cent.) Left Ventricular Posterior Wall thickness: 8.5 mm (> 97 Cent.) and moderate pulmonic valvular stenosis

18 On day 15 Recovered birth weight At that time the infant was on ncpap and 40% oxigen During feeding or crying events she continued to have 10 to 15 second apnea episodes, accompanied by decrease in heart rate to 70 beats per minute. Echocardiogram showed: Dysplastic pulmonary valve with systolic doming Severe Right ventricular outflow tract obstruction showing increased flow velocity with a predicted maximum instantaneous gradient of approximately 75 mm Hg D/T dynanic compression of hypertrophieed muscle bundles. SIV deviated toward the left ventricle indicative of suprasystemic right ventricular systolic pressure.

19 Devo aggiungere videoclip Continuous wave Doppler demonstrated a double envelope caused by two velocities; the first is flow across the pulmonary valve and the second represents increased velocity across the subvalvar obstruction.

20 Rule out genetic causes of cardiomyopathy I step Expanded metabolic screening negative II step Chromosomal assessment Normal female chromosomal constitution (46,xx)

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22 Rule out genetic causes of cardiomyopathy If negative Noonan test IV step Evaluation of mutations in one of a number of genes that encode for one of the sarcomere proteines

23 On day 30 Despite aggressive medical support (dopamine, dobutamine, intravascular volume expansion, sodium bicarbonate) Baby L has gradually developed an increased need for respiratory support, with an oxigen requirement up to 75% Failure to thrive Laboratory studies ruled out infections The chest and abdomen examinations, as well as other exams were unremarkable But

24 A new echocardiogram showed Critical Right ventricular outflow tract obstruction conditioning increased flow velocity with a predicted maximum instantaneous gradient of approximately 135 mm Hg D/T dynanic compression of hypertrophieed muscle bundles. AND Moderate Left ventricular outflow tract obstruction conditioning increased flow velocity with a predicted maximum instantaneous gradient of approximately 55 mm Hg and mitral valve Systolic Anterior Motion (SAM) Therefore

25 Milestone switch-therapy No more Dopa/Dobu Start β-blockers Propanolol 1 mg/kg/die

26 Over the next several days Baby L demonstrated improved activity and vital signs stabilized was weaned from supplemental oxigen was feeding well and had a normal physical examination, except for mild jaundice Sensible improvement to thrive To support tissue oxigenation were infused packed RBCs to keep, as more as possible, a 45% Ht A 21-day tapering course of dexamethasone was instituted

27 Our target is: to gain weight until 1800-g This is the right weight, to performe confidently the pulmonary valvuloplasty by our referral baby heart team of CCPM in Taormina Hospital How small is too small a baby to be operated is their institutional choice

28 On day 84 Baby L was taken to the cath-lab where a pulmonary valvuloplasty was performed Partial success of procedure pulling down trans-valvular gradient from 135 to 40 mmhg but in the next few days increase of gradient to 100 mmhg Therefore it was planned a surgical procedure to relieve right ventricular outflow tract obstruction

29 A week later Enlargement of right ventricular outflow tract by a trans-annulapatch Post-procedure gradient became 40 mmhg, enough, at the moment, to hope a better future for our Baby L

30 On day 105 Baby L was discharged clinically well and thriving (2500-g), without dyspnea or noticeable cardiovascular symptoms, with this supportive Therapy: Reduce afterload Improve cardiac ejection Reduce catecholamine drive prolonging cardiac survival Relieve cholestasis D/T TPN Careful titration necessary ACE inhibitors : Captopril 2 mg per dose PO /Q8 β-blockers : Propanolol 0,5 mg per dose PO /Q8 Diuretics : Furosemide 2 mg per dose PO /Q24 Dihydroxy bile acid : Ursodeoxycholic acid 2 mg per dose PO /Q8

31 The prognosis for Baby L is not good, depending, once its cause is removed, on the desirable regression of her hypertrophic myocardiopathy Approximately a third of these children die during the first 2 years of life, and those that survive need : Implantable defibrillators Hemi-Konno procedure The narrow left ventricular outlet is approached through the right ventricle, the septum is cut open, and filled with a large patch in such a way as to enlarge the LV outflow If failure >>> Cardiac transplant

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