Michael was born at 23 weeks and 4 days after a pregnancy complicated by early gestational hypertension and premature rupture of membranes at 18 weeks. The mother of Michael is known for rheumatoid arthritis on a TNFalpha biologic and chronic NSAIDs use for severe arthritic changes. Mother was treated pre-natally with Adalat, labetalol, magnesium sulfate and betamethasone. She was hospitalized at 18 weeks of PPROM and covered with antibiotics. Serial ultrasound demonstrated severe oligohydramnios, with severe intra-uterine growth restriction (at <1st percentile). Doppler were worsening starting 20 weeks of gestation and it was decided to undergo a c-section at 23+4 weeks because arrest of fetal growth, maternal fever and reverse end-diastolic flow in the umbilical artery Dopplers.
Michael was born at 382 grams and intubated in the delivery room. Surfactant was administered and he was put on HFOV (M14) immediately after birth due to severe hypoxic respiratory failure. His pre-ductal saturation at 3 hours of life was 90% and post-ductul was 76%, despite 100% FiO2. He was initially quite unstable and required iNO for 3 days, broad-spectrum antibiotics were initiated but were stopped at 48 hours after cultures were negative. A UVL central is placed, as well as a UAL, confirmed by X-Ray. Chest radiography indicates a bell appearance of the chest with bilateral air-bronchograms and small lung volume. Areas of the lung that are aerated are black with absent vascular markings.
Echocardiography options, which one corresponds most to the clinical scenario:
a) Normal anatomical heart (SDS), large unrestrictive ductus left to right, dilated LV, dilated LA, LA/Ao 2.3, No VSD, normal LV and RV function. PFO Left to right. UVL seen at the entrance of the right atrium. Septum round in systole and in diastole. UAL seen in the descending abdominal aorta. How do we call this scenario? What are the risk factors? Treatment?
b) Normal anatomical heart (SDS), ductus has spontaneously closed, PFO is right to left strict, no VSD, markedly decreased RV function (TAPSE 2mm), TR of 65 for sBP of 45/22. Septum bowing in systole. UVL seen at the entrance of the right atrium. UAL seen in the descending abdominal aorta. How do we call this scenario? What are the risk factors? Treatment?
c) Normal anatomical heart (SDS), ductus arteriosus is large and right to left, hypertrophy of the RV, RV and LV systolic function preserved. Slight retrograde flow in sub-hepatic veins with RA dilation. PFO right to left. Septum bowing in systole. UVL seen at the entrance of the right atrium. UAL seen in the descending abdominal aorta. How do we call this scenario? What are the risk factors? Treatment?
d) Interrupted aortic arch, ductus arteriosus large and right to left, LV systolic function mildly decreased (EF 47% by Simpson’s), marked LV dilation, normal RV function. Septum flat in systole and round in diastole. PFO left to right with mean gradient of 10. UVL seen at the entrance of the right atrium. UAL seen in the descending abdominal aorta. What clinical element in the scenario indicates that this is not the compatible echocardiography with this patient.
His first arterial gaz is: 7.24/65/18/-4.2; Lactate 4.5. PaO2 28.
Calculate the oxygenation index:
Definition of pulmonary hypertension?
Cut-offs for pulmonary hypertension suspicion / diagnosis?
Mimickers of pulmonary hypertension?
Classification of pulmonary hypertension?
Complications of iNO, mechanisms of iNO?
Case – followup:
His course was complicated by:
a) Necrotizing enterocolitis with perforation requiring surgery at 10 days of life
b) Prolonged TPN with cholestasis
c) Prolonged antibiotics coverage (meropenem) due to Enterobacter bacteremia and absesses (intra-abdominal)
d) IVH grade 2 bilateral
e) Multiple attempts to extubation with exposure to 3 courses of post-natal steroids (Dexamethasone)
At 36 weeks Post-menstrual age, he is on bCPAP+8 with FiO2 35%. He is 1220 grams. He is fed by continuous gavage in gastric position and has an ileostomy. He is tolerating his full feeds at 120 mL/kg/day with EBM . He is on Hydro/spiro; hydrocortisone maintenance at 10 mg/m2/day (failed ACTH stim test), Calicum/phosphorus/iron/mulvitamins. An echocardiography is done and reads:
3 Scenarios possible to be understand the differences between these 3 presentations:
A) Echocardiography A: Ductus has spontaneously closed. Normal intra-cardiac anatomy, PFO stretched bidirectional, retrograde flow in the hepatic veins, dilated right atrium, dilated right ventricle with hypertrophy, TAPSE 5.2 mm, Tricuspid regurgitant Jet of 85 for sBP of 55/32 (M41). Septal curve bowing at end of systole in the LV cavity. Pulmonary veins at osteum visualized and bi-triphasic pattern maintained. PI jet (peak) of at least 30 mmHg. A large brightness of 1.5 x 2 x 3cm is seen at the entrance of the IVC to the RA with slight turbulence of low, likely secondary to previous position of the UVL.
B) Echocardiography B: Large ductus arteriosus Left to right (unrestrictive), the size of the left pulmonary artery. LA/Ao of 2.1. Dilated Left ventricle, dilated left atrium. Normal LV and RV function. TR of 85 for systemic pressure of 90/55. Increased velocity of flow in pulmonary veins with bi-triphasic pattern maintained. TAPSE 10mm. Septum is flat at end of systole. A large brightness of 1.5 x 2 x 3cm is seen at the entrance of the IVC to the RA with slight turbulence of low, likely secondary to previous position of the UVL.
C) Echocardiography C (sBP 100/50): Very small restrictive ductus seen by colour only, left to right (gradient max of 10 in systole), ASD left to right (0.4cm), TR not obtained, TAPSE of 9.5mm, no RV dilation. Peak PI of at least 20 mmHg. Pulmonary veins at ostum x 4 seen, with normal biphasic/triphasic pattern. A large brightness of 1.5 x 2 x 3cm is seen at the entrance of the IVC to the RA with slight turbulence of low, likely secondary to previous position of the UVL.
At 45 weeks post-menstrual age, Michael is still on CPAP (now 6) – 30%, with last gaz done earlier during the week at 7.34/58/32/4.5. A chest radiography done at the same time was strongly suspicious for aspiration pneumonia, with a right upper lobe consolidation. Overnight, he decompensated and was re-intubated due to: fever, numerous desaturations and a new pleural effusion. He is now on conventional mechanical ventilation: 7 mL/Kg; PEEP of 8, Ti 0.5, Rate of 30. FiO2 is 100%. You request an echocardiography:
Echocardiography done at bedside on patient unstable hemodynamically. Hydrocortisone 1mg/kg IV q8hr, epinephrine 0.08 mcg/kg/min, iNO 20 ppm started overnight. cBG results at beginning of echo: 7.01/42/10/-12 Lactate of 9.0. sBP 55/32 (for usual sBP 100/52). Severe RV dilatation, severe RV failure pancacking the LV (septum bowing in systole and diastole). TR of 110 with severe RA dilatation. PFO is not seen. LV systolic function is within normal limit, with very restrictive filling due to RV dilatation impending on LV cavity. PI peak jet of at least 45 mmHg. Dilatation of sub-hepatic veins. The clot previously seen in in the IVC is still present. Pulmonary veins not visualized.
A central venous line is placed and indicates a central venous pressure of 15 mmHg. What does the information tell you?
If the report said: The large clot in the IVC is now seen in the Right atrium, but smaller in size. What does that change in your assessment and differential diagnosis?
Management of PH crisis?
Management of chronic PH?
- Mechanism of action of each drugs, side effects and advantage of each drugs
o Treprostinil / Epoprostenol /
o Sildenafil / Tadalafil
o Bosentan / Macitentan /Ambrisentan
o Orenitram / Selexipag
- What about other modality of treatments:
Michael is now tracheostomized and 6 months of age. He is brought to the cath lab. The report mentions:
A) mPAP 45, severely stenosed LLPV, RLPV, RUPV and atretic RLPV. sPAP 100 for sBP 85. RV output decreased. What does it tell you, what are treatment to consider? What would be the findings on the X-ray of this patient? How do these patient present? Evolve? What type of PH?
B) mPAP 45, normal pulmonary veins, PVRI of 9.2 WU·m2 with PVR/SVR ratio of 0.5, no response to iNO, IV adenosine, and oxygen.
C) What about if the report tells you that the venous blood coming from the pulmonary veins was saturated at 92% - what does this tell you?
At 3 years of age, you decide to refer Michael to a geneticist. His maternal aunt died of pulmonary hypertension at 3 years of age, and he has been refractory to Treprostinil / Sildenafil combination, with iso-systemic pulmonary pressures and a deterioration of his RV function. He was recently started on Digoxin 5 μg/kg orally twice daily and Diltiazem 0.5 mg/kg orally 3 times daily after his last cath evaluation that indicated a positive response at Vasoreactivity testing. His last NT-proBNP is 8430 (compared to 3461 - 3 months ago). What are you suspecting. Please outline some of the genetical elements that you would like to rule out. What are other genetic disease that are PH mimickers in early infancy?
If your medical therapies fail, what are other options for Michael?
- Discuss: POTT / Fenestration / Transplant.
How would altitude impact the condition of Michael?