Vi amin C de iciency can lead o pulmona y hype ension:
a sys ema ic e iew o case epo s
Ha i Hemilä, MD, PhD 1), Angelique M.E. de Man, MD, PhD 2)
1. Depa men o Public Heal h, Uni e si y o Helsinki, POB 41, Helsinki, Finland
2. Depa men o In ensi e Ca e Medicine, Ams e dam Uni e si y Medical Cen e s, loca ion VUmc,
Ams e dam, The Ne he lands
[email p o ec ed]
h ps://o cid.o g/0000-0002-4710-307X
[email p o ec ed]
h ps://o cid.o g/0000-0001-8738-8295
SUPPLEMENT 1
2024-2-21
This is supplemen o a pape submi ed o
BMC Pulmona y Medicine
h ps://bmcpulmmed.biomedcen al.com
Con en s Page
Sea ch o case epo s on scu y and pulmona y hype ension 2
Fig. S1: Hea a e, espi a o y a e, and blood p essu e by he age o he pa ien 3
Fig. S2: Repo ed imp o emen in ca diac ou comes o e wo weeks a e he s a o i amin C 4
Fig. S3: Associa ion o scu y wi h TAPSE and he diame e o in e io ena ca a 5
Fig. S4: E ec o i amin C on ca diac ou comes in pulmona y hype ension pa ien s 6
Abb e ia ions used in he desc ip ion o he 32 cases 7
A case epo published a e he comple ion o he sys ema ic e iew 8
Desc ip ion o he 32 included case epo s 9
1
Sea ch o case epo s on scu y and pulmona y hype ension.
PubMed
On 2023-7-9, we ca ied ou a sea ch using he ollowing sea ch e ms:
("pulmona y hype ens*" o "pulmona y a e ial hype ension") and (" i amin c" o asco b*)
This ga e 46 eco ds
Scopus
On 2023-7-9. we ca ied ou he ollowing sea ch:
( TITLE-ABS-KEY ( "pulmona y hype ens*" OR "pulmona y a e ial hype ension" OR " igh
hea ailu e" ) AND TITLE-ABS-KEY ( " i amin c" OR asco b* ) )
This ga e 178 eco ds
Web o Science (Cla i a e)
On 2023-5-13, we looked a he ci a ions o he majo iden i ied case epo s and ca ied ou a sea ch
o ci ing publica ions. The epo s used in his sea ch we e he ollowing:
Dean T (2019) [82],
Du all MG (2013) [83],
F ank BS (2019) [85],
Gayen SK (2020) [86],
Ghulam Ali S (2018) [87],
Ichiyanagi S (2019) [89],
Kupa i M (2012) [90],
Meh a CL (1996) [92],
Me ens MT (2011) [93],
Penn EH (2019) [96].
This sea ch ga e 94 eco ds.
We also ead all he e e ence lis s o he iden i ied case epo s.
Toge he , hese app oached ga e us 32 case epo s abou scu y and pulmona y hype ension.
2
Fig. S1. Hea a e, espi a o y a e, and blood p essu e by he age o he pa ien . Da a we e
no a ailable o all cases. Fo he age ange <18 yea s, he blue con inuous line indica es he uppe
limi , and he ed dash line indica es he lowe limi o he he es ima ed 90% co e age o no mal
popula ion [106]. See ex ac ion o da a in Supplemen s 1 and 2.
3
Fig. S2. Repo ed imp o emen in ca diac ou comes o e wo weeks a e he s a o i amin
C. In he o dina y hospi al con ex , he e is no egula daily ollow-up by echoca diog aphy o o he
examina ions. Ins ead, epea examina ions a e usually ca ied ou a e ixed ime pe iods.
The e o e, his eco e y cu e is biased owa ds delayed documen ed eco e y. Ne e heless, his
analysis indica es ha abou hal o he cases demons a ed ca diac imp o emen wi hin 2 weeks.
The ca diac ou comes used in his igu e a e he e ogeneous, including measu es om
echoca diog aphy and ca he e iza ion, see Supplemen s 1 and 2. Time poin 0 indica es he s a o
i amin C adminis a ion.
4
Fig. S3. Associa ion o scu y wi h TAPSE and he diame e o in e io ena ca a.
A 25-yea -old emale in he USA [91]. Fou mon hs be o e admission o hospi al, TAPSE was 23
mm, and when scu y was diagnosed, i was 9.5 mm ( illed ci cles on le ). The e a e no TAPSE
da a a e i amin C was s a ed. In e io ena ca a was 23 mm when scu y was diagnosed, and 14
mm a e i amin C was adminis e ed (open iangles on igh ). The scale is di e en on he le -
hand side. Pe iod o scu y is a ound day 0, which is he day o admission o hospi al. The day
when i amin C was s a ed was no published.
5
Fig. S4. E ec o i amin C on ca diac ou comes in pulmona y hype ension pa ien s.
A. a 40-yea -old emale in Finland [90]. The RV + RV a ea wi h illed ci cles on he le -hand side,
and diame e o in e io ena ca a wi h open iangles on he igh -hand side.
B. a 6-yea -old male in he USA [98]. The RV sys olic o dias olic du a ion a io wi h illed ci cles
on he le -hand side, and RV a ea change wi h open iangles on he igh -hand side.
6
Abb e ia ions used in his Supplemen
ALP, alkaline phospha ase
ALT, alanine ans e ase
ASD, au ism spec um diso de
AST, aspa a e ans e ase
BNP, b ain na iu e ic pep ide
BP, blood p essu e
CT, compu ed omog aphy
CTA, CT angiog aphy
CXR, ches X- ay
DLCO, di using capaci y o ca bon monoxide
DVT, deep ein h ombosis
ECG, elec oca diog am
ECHO, ans ho acic echoca diog am
ESR, e y h ocy e sedimen a ion a e
FEV1, o ced expi a o y olume in 1 second
FVC, o ced i al capaci y
Hb, hemoglobin
HD, hospi al day
HR, hea a e
ICU, in ensi e ca e uni
INR, in e nalized no malized a io (measu e o blood clo ing and li e unc ion)
LV, le en icle/ en icula
LVEF, le en icula ejec ion ac ion
mPAP, pulmona y a e y mean p essu e (can be es ima ed om sPAP: mPAP = 0.61×sPAP + 10)
PAH, pulmona y a e y hype ension
PAP, pulmona y a e y p essu e; mPAP, mean PAP, sPAP, sys olic PAP
sPAP, pulmona y a e y sys olic p essu e (can be es ima ed om TRPG: sPAP = TRPG + 10)
PH, pulmona y hype ension
RA, igh a ium/a ial
RBBB, igh bundle b anch block
RHF, igh hea ailu e
RV, igh en icle/ en icula
SpO2, oxygen sa u a ion le el
SR, sinus hy hm
TAPSE, icuspid annula plane sys olic excu sion index
TR, icuspid egu gi a ion
TRV, TR eloci y (m/s)
TRPG, icuspid egu gi a ion p essu e g adien (= 4×TRV2; used o es ima e sPAP)
7
A case epo published a e he comple ion o he sys ema ic e iew
A e we ecei ed he e iewe epo s, we no ed a new epo (2024) on wo cases o PH induced by
scu y [1]. The wo cases a e consis en wi h he se we included in ou analysis, bu we did no append
hem o ou analysis. This is a b ie summa y o he cases.
Case 1 was a 2-yea -old boy p esen ed o hospi al wi h omi ing, dia hea, and e e . He had
hypo ension and was ans e ed o he pedia ic in ensi e ca e uni whe e he suddenly collapsed and
had con i med ca diac a es . The mPAP was 49 mmHg, based on peak TRV o 4.1 m/s. Th ee days
a e e e al, he igh ca diac ca he e iza ion showed mPAP 20 mmHg. Vi amin C le el was
unde ec able. The boy was adminis e ed 0.3 g/day i amin C. A e he was discha ged om he
hospi al, his symp oms g adually imp o ed and e u ned o his usual s a e o heal h wi hin 2 weeks. A
he one-yea ollow-up, he has been well wi h no mal PAP. P io o he episode, he boy had es ic i e
ea ing pa e ns. His die a y p e e ence we e ice, po k, eggs, and milk, wi h e y ew ege ables and
ui s.
Case 2 was a 6-yea -old boy wi h ASD. He had p og essi e dyspnea and low-g ade e e o 1 mon h
and e used o walk due o his swollen, pain ul le knee. Ches x- ay e ealed mild ca diomegaly wi h
p ominen pulmona y a e y unk. Echoca diog aphy showed enla gemen o RA, RV, and main
pulmona y a e y and mPAP was 36 mmHg (peak TRV o 3.4 m/s). Righ ca diac ca he e iza ion ound
mPAP 50 mmHg. His die a y in ake consis ed mainly o ice and egg wi h a oidance o milk,
ege ables, and ui . Vi amin C le el was unde ec able. Wi h a dose o 0.3 g/day i amin C, his
symp oms imp o ed g adually in 2 weeks, and he could walk in 1 mon h. His 2-yea echoca diog aphic
ollow-up was no mal wi hou signs o PH.
1. Sa awi iya M, Khongpha hanayo hin A, Limsuwan A.
Re e sible se e e pulmona y hype ension ela ed o scu y in child en.
BMC Ca dio asc Diso d. 2024;24(1):24.
h ps://doi.o g/10.1186/s12872-023-03629-6
h ps://www.ncbi.nlm.nih.go /pmc/a icles/PMC10765653
8
Desc ip ion o he 32 included case epo s
Abbas (2016) [76] h ps://pubmed.ncbi.nlm.nih.go /27682441
Pa ien 50 y woman, p e iously heal hy. Ne e smoked, d ank alcohol, o used
ec ea ional d ugs. No cu en medica ions.
Du a ion o he
symp oms be o e hospi al
3 mon hs
Signs and symp oms P og essi ely wo sening sho ness o b ea h associa ed wi h ex eme
a igue, ano exia, abou 5 kg weigh loss, yellowing o eyes, hea y
mens ual bleeding, and a lowe ex emi y ash.
Main indings Neck eins we e dis ended o he ea lobes when si ing. Massi e
hepa omegaly.
A noncon luen , nonblanching pe echial ash on an e io legs, and a la ge
ecchymosis on he highs and bu ocks.
HR 92/min, BP 91/56 mmHg, espi a o y a e 20/min. SpO2 85% on
oom ai .
ECG showed SR wi h low ol age in he an e ioin e io leads.
CT showed pe ipo al edema wi h hepa o-splenomegaly, enla ged and
in e io ena ca a, po al ein, and splenic ein.
ECHO showed enla ged RA and RV, sep al la ening, igh en icula
mode a e hypokinesis, and mild- o-mode a e TR wi hou sys olic
e e sal in he hepa ic ein. No e idence o LV dys unc ion.
Hb 34 g/L, MCV 90 L, Fe 90 ug/L, e i in 147 ng/mL
AST 726 U/L, ALT 670 U/L, ALP 154 U/L, INR 2.2
BNP 347 pg/mL (no mal <100). Vi al hepa i is: nega i e.
B1 and ola e no mal
Vi amin C plasma le el 1 mg/L ( 5.7 µM)
D ugs in hospi al None
O he i amins and
mine als
Die be o e he e en Die a home was s ic ly limi ed o ce eal, eggs, and milk.
Vi amin C ea men Vi amin C dose and ou e no epo ed.
E ec o i amin C Symp oms imp o ed apidly and ema kably. Hea y mens ual bleeding
imp o ed and li e enzymes no malized.
A 4 weeks, ECHO was comple ely no malized wi h no e idence o RV
dys unc ion and no mal PAP.
NOTES To ask o u he de ails o he case, we con ac ed Fa ukh Abbas by
email on 2023-2-8 and 2023-2-23 bu did no ge a esponse.
9
Benhamed (2019) [80] h ps://doi.o g/10.3166/a mu-2019-0169
Pa ien 40 y male. Rheuma oid pu pu a in childhood.
Du a ion o he
symp oms be o e
hospi al
10 days.
Signs and symp oms Wo sening exe ional dyspnea. As henia, epis axis.
Main indings HR 130/min, BP 150/81 mmHg. SpO2 o 86% on oom ai . No signs o
hea ailu e.
ECG SR, no abno mali ies.
Angiog aphy excluded pulmona y embolism.
ECHO e ealed RV dila a ion, pa adoxical sep um. sPAP 100 mmHg.
Labo a o y esul s:
A e ial blood gass pH 7.55, PaCO2 21 mmHg, PaO2 58 mmHg, lac a e 3.7
mmol/l
D-dime 643 µg/L
Vi amin C le el unde ec able (<5 µM).
In addi ion, i amin K de iciency.
D ugs in hospi al Diu e ic he apy (no speci ied) “Ap ès ai emen diu é ique”
O he i amins and
mine als
Die be o e he e en Food alle gies. Exclusi ely dai y p oduc s o se e al yea s.
Vi amin C ea men Vi amin C dose and ou e no epo ed.
Au ho s w i e “F om a he apeu ic poin o iew, daily adminis a ion
o i amin C (1 g/d), di ided in o se e al doses daily o 15 days, emains
he his o ical e e ence” [ou ansla ion], bu hey do no s a e explici ly
ha 1 g/day was used o hei pa ien .
E ec o i amin C Day 2 sPAPs 70 mmHg and amelio a ion o symp oms.
Day 7 ECHO sPAP 28 mmHg.
“A e diu e ic ea men and i amin C supplemen a ion, he pa ien
p esen ed a ma ked imp o emen in symp oms, including a pa ial
eg ession o pu pu ic lesions and PAH (PAPs measu ed a 70 mmHg a 48
hou s). On he se en h day managemen , ul asound con ol in ca diology
measu ed PAPs a 28 mmHg” [ou ansla ion].
Time se ies In hei pape , au ho s epo ed [ ee ansla ion]:
[baseline sPAP du ing scu y] “sys olic pulmona y a e ial p essu e
(sPAP) measu ed a 100 mmHg… a ma ked imp o emen in symp oms,
including pa ial eg ession o pu pu ic lesions and PAH (sPAP was 70
mmHg a 48 hou s). On he se en h day o ea men , a epea ca diologic
ul asound measu ed sPAP o 28 mmHg.”
16
These igu es a e shown in ou g aph.
NOTES To ask o u he de ails o he case, we con ac ed D . Benhamed by email
on 2023-5-13 and 2023-5-23 bu did no ge a esponse.
17
Con e (2021) [81]
Lau en Ann Webe
h ps://pubmed.ncbi.nlm.nih.go /33960312
Pa ien 48 y emale. Gene alized anxie y and in e s i ial cys i is. Recen ly li e
inju y seconda y o polypha macy.
Du a ion o he
symp oms be o e
hospi al
2 weeks
Signs and symp oms Res and exe ional dyspnea. Lowe ex emi y edema, ea ly sa ie y,
inc eased abdominal gi h.
Main indings Anasa ca.
New sys olic and dias olic ca diac mu mu s.
NT-p oBNP ele a ed, no da a
Ca diac oponins no mal, no da a
CT angiog aphy and in asi e co ona y angiog aphy excluded pulmona y
embolism and co ona y a e y disease.
ECHO e ealed no mal LV sys olic unc ion, bia ial enla gemen ,
mode a e o se e e mi al egu gi a ion, mode a e ao ic insu iciency,
se e e TR, dec eased RV unc ion, and mode a e o se e e PH. The
es ima ed sPAP was 60 mmHg. Mic obubble s udy was nega i e o
in aca diac shun ing.
Righ hea ca he e iza ion demons a ed ele a ed le - and igh -sided
p essu es, wi h an RA p essu e o 20 mmHg, mPAP 35 mmHg, mean
pulmona y wedge p essu e 16 mmHg, and ca diac index o 2.1 L/min/m2
using he Fick equa ion. PVR no epo ed
Vi amins B1, B6, B12, D, E, ola e, Se, Zn no mal (Table 1 shows da a)
Vi amin C le el unde ec able.
D ugs in hospi al Diu e ic he apy (no speci ied) led o imp o emen
O he i amins and
mine als
Die be o e he e en Had been a oiding oods con aining i amin C o dec ease he in e s i ial
cys i is symp oms as pe in e ne guidance.
Vi amin C ea men “ i amin C eple ion” bu dose and ou e no epo ed.
E ec o i amin C 1 mon h la e , hype olemia and end o gan dys unc ion. Repea igh hea
ca he e iza ion demons a ed a ca diac index o 1.5 L/min/m2 using he
Fick equa ion. Vi amin C le els we e a he lowe no mal limi .
The pa ien was s a ed on mil inone and e e ed o al e su ge y. She
unde wen ao ic and mi al al e eplacemen and icuspid al e
annuloplas y while con inuing i amin C.
NOTES We we e able o con ac Lau en Ann Webe in 2023-2-23, wi h he
ollowing esponse: “I apologize I don’ ha e he in o ma ion any longe .”
18
Dean (2018) [82]
Paul Kim
h ps://pubmed.ncbi.nlm.nih.go /30351242
Pa ien 6 y boy.
Du a ion o he
symp oms be o e
hospi al
3 mon hs
Signs and symp oms Bila e al lowe ex emi y pain and e usal o bea weigh . Be o e
p oceeding wi h planned bone biopsy, he boy became acu ely achyca dic,
hypo ensi e, and pulseless.
Re u ned o spon aneous ci cula ion and a dopamine in usion was s a ed,
leading o s able blood p essu es.
Main indings BNP 850 pg/mL (no mal <100).
Pos -a es ECHO, pe o med while on a dopamine in usion and sho ly
ollowing epineph ine and phenyleph ine boluses, demons a ed
achyca dia 138 bpm wi h hype dynamic LV sys olic unc ion (sho ening
ac ion = 61%). Insu icien TR o es ima ion o RV p essu es, bu mild
sep al la ening was sugges ed.
A la e , e ospec i e e iew o he abo e ECHO demons a ed an
abno mal RV/LV diame e a io o 1.7 [>1 has been associa ed wi h
inc eased ad e se e en s in pedia ic PH]. LV eccen ici y index (LVEI)
was abno mal a 1.7 [LVEI > 1 in adul PH sugges s impai ed RV
unc ion]. The pulmona y a e y accele a ion ime (PAAT) in he pos -
a es ECHO showed an abno mal alue o 90 ms (no mal ≥ 100 ms).
Hospi al day 3
BNP 2716 pg/mL, and de eloped poo u ine ou pu and pe iphe al edema.
Hospi al day 5
ECHO showed significan RV dys unc ion wi h bo h RA and RV dila ion
and p ominen sep al bowing. The e was inc eased TR, wi h TR je based
p essu e g adien 68 mmHg (excluding RA p essu e).
Conce n o PH p omp ed a e ospec i e e iew o he o iginal pos -a es
ECHO and a mo e de ailed assessmen o he RV unc ion. The RV/LV
diame e a io had inc eased o 2.8, while he LVEI had inc eased o 2.85.
The PAAT was inadequa ely assessed on HD5, in pa because he Dopple
flow pa e n in he pulmona y a e y was low a <50 cm/s (consis en wi h
low RV ou pu ).
Hospi al day 8
CT a e iog am o he ches , abdomen, and pel is did no ind e idence o
pulmona y embolus o asculi is.
Hospi al day 9
Ca he e iza ion confi med mild PH.
PVR index 3.5 Wood uni s × m2 (Table 1)
We assume body su ace a e 0.85 m2 which gi es PVR = 4.1 Wood uni s.
19
Wedge p essu e 4 mmHg.
mPAP 12-13 on iNO and mil inone.
Hospi al day 10,
Vi amin C le el unde ec able, <5 µM.
Vi amin A le el unde ec able.
Vi amins B1, B3, B6, B12, D, E, Zn no mal (Table 2 shows da a)
D ugs in hospi al Dopamine a e ca diac a es
Epineph ine
Phenyleph ine
iNO on HD5 and symp oms and ECHO imp o ed
Mil inone on HD5 and symp oms and ECHO imp o ed
Sildena il on HD10, and subsequen ly was weaned o iNO and mil inone.
O he i amins and
mine als
Vi amin A 10000 IU/day.
Die be o e he e en Die lacked ui , ege ables, i amins, o o ified oods, esul ing in
mul iple i amin deficiencies.
Vi amin C ea men HD10: Vi amin C 0.3 g/d in a enously.
E ec o i amin C By hospi al day 12, BNP had no malized and ECHO pa ame e s had
nea ly no malized (LV/RV diame e a io o 0.9, LVEI 1.11–1.18, PAAT
140 ms, TR je based p essu e g adien 19 mmHg (excluding RA
p essu e), mild sep al fla ening bu quali a i ely no mal RV unc ion).
A 6 mon hs, ECHO demons a ed no e idence o PH, and he was weaned
o sildena il.
A 12 mon hs, he emained asymp oma ic wi h a eassu ing ECHO.
NOTES To ask o u he de ails o he case, we con ac ed Paul Kim by email on
2023-2-8 and 2023-2-23 bu did no ge a esponse.
20
Du all (2013) [83] h ps://pubmed.ncbi.nlm.nih.go /24190688
Pa ien 9 y boy wi h ASD.
Du a ion o he
symp oms be o e
hospi al
4 mon hs
Signs and symp oms De eloped a limp. Neu ologic and o hopedic e alua ions did no e eal
an e iology. Symp oms wo sened despi e physical he apy.
Finally, en i ely unable o ambula e, and de eloped a d y cough and
labo ed b ea hing.
Main indings HR 135/min, BP 79/66 mmHg, espi a o y a e o 26/min. SpO2 o 96%
on oom ai .
Was gi en no mal saline, wi hou imp o emen in achyca dia, pe sis en
achyca dia con inued 140-170 bpm, espi a o y a e up o 56/min,
e ol ing hypoxia equi ed supplemen al oxygen by acemask.
Ea ly labo a o y es s
BNP 2019 pg/mL (no mal <100)
CRP 13 mg/L
ESR 23 mm/h (no mal <20).
CXR showed di use, nodula , ill defined ai space opaci ies h oughou
he igh lung g ea e han le lung (consis en wi h ca diogenic
pulmona y edema e sus pneumonia) and small igh pleu al e usion and
an enla ged main pulmona y a e y.
ECG showed sinus achyca dia wi h a le axis de ia ion, and igh hea
s ain pa e n wi h incomple e RBBB, and nonspecific ST and T-wa e
changes.
CT angiog am showed no mal pulmona y eins, a dila ed main
pulmona y a e y (3.2 cm), and no illing de ec s, excluding pulmona y
embolism.
Lowe limb Dopple ul asound excluded DVT.
ECHO showed a se e ely dila ed RV wi h mild o mode a ely dep essed
sys olic unc ion and a dila ed RA and pulmona y a e y. RV p essu es
de e mined by TRV sPAP 65 o 70 mmHg plus he igh a ial -wa e,
mPAP 45 mmHg, and end-dias olic p essu e o 30 mmHg plus he igh
a ial p essu e (no wa e) de e mined om he pulmona y egu gi an
eloci ies.
Se ial ECHOs on HD 2, 3, and 4 showed pe sis en se e e ele a ion o
RV p essu e as well as se e ely dila ed RV wi h mode a e dys unc ion.
Vi amin B1 55 nmol/L (no mal 70-180)
Vi amin B6 3.5 ng/mL (5-30)
Vi amin B12 <150 pg/mL (190-778)
Vi amin D 8.2 ng/mL (30-80)
21
Vi amin C le el unde ec able, <5 µM.
D ugs in hospi al No PH d ugs
An ibio ics o suspec ed pneumonia.
O he i amins and
mine als
Vi amins B1, B12 and D we e adminis e ed wi h a mul i i amin
p epa a ion.
A e 3 weeks, a mul i i amin p epa a ion, and calcium and i amin D
we e con inued.
Die be o e he e en Fo he pas 3 y, he boy had ea en chicken nugge s, c acke s, cookies,
and wa e . Re used milk, juice, ege ables, and ui s and was no on
i amin supplemen a ion.
Vi amin C ea men S a ing on HD 6, i amin C was adminis e ed in a enously, bu dose
was no desc ibed.
E ec o i amin C By HD 11 (5 days i amin C), espi a o y a e had dec eased o he
no mal ange.
By HD 15 (9 days i amin C), a epea ECHO showed RV p essu e less
han hal sys emic p essu e by sep al posi ion and esolu ion o RV
dila ion and no mal sys olic unc ion.
A he ime o discha ge, a 3 weeks, he was able o ambula e wi h
assis ance wi hou pain.
O e 18 mon hs, i amin le els emained no mal on i amin
supplemen s, and epea ECHO showed no mal RV p essu es and
unc ion.
NOTES To ask o u he de ails o he case, we con ac ed Melody Du all by
email on 2023-2-8 and 2023-2-23 and 2023-3-4 bu did no ge a
esponse.
22
Fe ei a (2020) [84] h ps://pubmed.ncbi.nlm.nih.go /32133311
Pa ien 51 y male. Pa anoid pe sonali y diso de , low socioeconomic s a us.
Du a ion o he symp oms
be o e hospi al
1 mon h
Signs and symp oms Dyspnea on minimal exe ion, lowe limb edema and pain ul b uises on
he lowe limbs.
Main indings Lowe limbs p esen ed pe i ollicula hemo hage, bila e al pi ing
edema and pain ul nodules and b uises.
Tachyca dia, espi a o y a e 20/min, SpO2 o 98%.
ECG showed ST-segmen ele a ion in leads DII, DIII and AVF
associa ed wi h in e ed T wa es in leads V1-V4.
Ches CT and pe usion/ en ila ion scan excluded pulmona y embolism.
Lowe limb Dopple ul asound excluded DVT.
ECHO showed enla ged RA and RV and RV sys olic dys unc ion: he
di e ence be ween he RV a ea du ing dias olic and sys olic s ages (14.5
– 17.5 cm2) was 15% (no mal 30%). Es ima ed sPAP 61 mmHg wi h
mild TR.
Ca diac ma ke s no mal, bu le els no epo ed.
Hb 51 g/l
Fe 23 µg/dL (no mal 59-158).
Folic acid 2.07 ng/mL (>5)
Vi amin B12 118 pg/mL (210-980)
Vi amin C le el 0.5 mg/L (2.8 µM).
D ugs in hospi al None
O he i amins and
mine als
Die be o e he e en Pa ien had been hinking ha someone in his house was poisoning his
meals, and he e o e es ic ed his in ake o ood, including ui and
ege ables.
Vi amin C ea men Vi amin C 1 g/day in a enously was ini ia ed in he hospi al.
A e discha ge, o al i amin C was con inued.
E ec o i amin C A 16 mon hs, epea ECHO did no show PH, and e ealed no mal RV
unc ion.
NOTES
23
F ank (2019) [85] h ps://pubmed.ncbi.nlm.nih.go /30738657
Pa ien 17 y male, who spen hou s indoo s playing ideo games.
De elopmen ally no mal, h i ing adolescen .
Du a ion o he symp oms
be o e hospi al
2 weeks
Signs and symp oms Leg pain, b uising wi hou auma, and ches pain.
Main indings Symme ic pedal edema, bila e al lowe ex emi y ende ecchymosis,
pe echiae, co ksc ew hai s.
Ca diac exam ound loud P2.
No unusual indings in X- ay o lowe ex emi y and ches , MRI o he
lowe ex emi ies, pel is, and abdomen, CT wi h angiog aphy o he
ches , bila e al lowe ex emi y ul asound, and ECG.
ECHO showed a s uc u ally no mal hea wi h PH wi h TRV 4.2 m/s.
NT-p oBNP 140 pg/ml
BNP <15 ng/L
Hb 111 g/L
MCV 76 L
Fe 25 ug/dL
Fe i in 76 ng/mL
CRP 57 mg/L
ESR 19 mm/h
Vi amin D 17.8 ng/mL
Vi amin C le el unde ec able.
D ugs in hospi al None
O he i amins and
mine als
Vi amin D
Fe
Die be o e he e en Die de oid o ui s and ege ables.
Vi amin C ea men Vi amin C supplemen dose was no epo ed; e m supplemen sugges s
o al adminis a ion.
E ec o i amin C A e 2 days, symp oms imp o ed and he was discha ged home.
A e 1 mon h, TRV 3.1 m/s and he symp oms had esol ed.
A e 6 mon hs, TRV 2.4 m/s, leg hai s had s aigh ened, and was
clinically well.
Time se ies “An echoca diog am … ( icuspid egu gi a ion [TR] eloci y o 4.2
m/s).
... ea ed wi h … asco bic acid …
One mon h la e , his TR peak eloci y was 3.1 m/s and he symp oms
had esol ed.
24
A e 6 mon hs, his TR peak eloci y had no malized (2.4 m/s)”
These igu es a e shown in ou g aph.
NOTES We we e able o con ac Benjamin F ank, who esponded 2023-2-9 o
ou ques ion abou i amin C dose and ou e as ollows:
“ i amin C supplemen was de ini ely gi en o ally, I don' emembe he
dose...”
Same day u he abou dose and echo da a:
“I would depend on inding he eco ds o ge he dose. The pa ien
p esen ed 5 o 6 yea s ago so I don’ hink memo y will hold.
We did no do a hea ca h in ei he case so he diagnosis o PAH was
empi ic based on he da a we had and wha is known abou i c e ec
on he lung.”
25
Ichiyanagi (2019) [89] h ps://pubmed.ncbi.nlm.nih.go /31567273
Pa ien 3 y wi h ASD.
Du a ion o he
symp oms be o e hospi al
No da a abou du a ion
Signs and symp oms Gene al a igue, sho ness o b ea h.
Acu e hea ailu e, dec eased deep endon e lexes, uns able gai .
Main indings CXR showed ca diac dila ion and an enla ged main pulmona y a e y.
ECHO showed a dila ed RV wi h a RV/LV basal diame e a io o 1.3,
TRV 4.1 m/s, and in e en icula sep al la ening.
P o-BNP 14,513 pg/mL (no mal <125).
Vi amin B1 20 ng/mL (21.3–81.9).
Vi amin B1 was ini ia ed.
Hospi al day 8
HR 135/min, BP 105/93 mmHg, espi a o y a e 36/min, SpO2 100% on
oom ai
Ca diac ca he e iza ion was scheduled unde gene al anes hesia.
Ci cula o y collapse occu ed in a ew minu es, and he p ocedu e was
cancelled, and ans e ed o pedia ic ICU.
Hospi al day 19
Ca diac ca he e iza ion:
mPAP 77 mmHg (PAP ange 98/64 mmHg).
PVR index 22.62 Wood uni × m2.
Below: BSA 0.55 m2 Thus, PVR = 41.1 Woods uni s
Ca diac index 2.98 L/min/m2
Tadala il was ini ia ed.
Hospi al day 21
The pa ien de eloped gingi al bleeding and was ound o ha e bila e al
hume al ac u es on X- ay.
Vi amin C le el unde ec able.
D ugs in hospi al Tadala il
O he i amins and
mine als
Vi amin B1
Die be o e he e en Fo 3 mon hs, only chicken and ice, wi hou ui and ege ables.
Vi amin C ea men Vi amin C in a enously 0.5 g/day, see NOTES.
E ec o i amin C A e 1 day, he hemo hagic dia hesis imp o ed and ECHO showed
imp o emen o he RV dila ion and TR (RV/LV basal diame e a io,
1.0; TRV 2.4 m/s).
“A e ini ia ing i amin C he apy, he indings o PH on [ECHO]
imp o ed he ollowing day and he clinical mani es a ions (ie, gingi al
bleeding, gene al a igue, sho ness o b ea h) imp o ed wi hin 2 weeks”
32
A e 6 weeks, epea ECHO showed sus ained imp o emen o PH on
i amin C he apy, wi hou adala il.
Ca diac ca he e iza ion:
mPAP 19 mmHg (PAP ange 26/12 mmHg).
PVR 2.32 Wood uni s.
Ca diac index 4.32 L/min/m2
Time se ies D . Ichiyanagi kindly p o ided us wi h he da a o ou ime se ies g aph,
see below.
NOTES We we e able o con ac Shogo Ichiyanagi, who esponded 2023-2-9 o
ou ques ion abou i amin C dose and ou e as ollows:
Wha was you dose o i amin C and was ha o ally o i ?
“The dose o i amin C was as ollow;
week 1: 250mg wice a day/ i. .
week 2: 250mg once a day/ i. .
week 3: 125mg once a day/ i. .
week 4-6: 40mg wice a day/ p.o.
week 7-: 40mg wice a day/ p.o.”
“We s ill ha e he echo da a.
The peak eloci y o TR a e 6 week was 2.0 m/s.”
Shogo Ichiyanagi sen mo e da a on 2023-2-20.
33
p e pos
TR eloci y 3.7m/sec 2.1m/sec
TRPG 56mmHg 17mmHg
TAPSE 13.0mm 17.5mm
e'/a'/s' 8.3/10.4/10.7 16.1/10.6/12.3
41.4/53.2 54.6/55.1
en icula sep um la ound
RV basal diame e / LV basal diame e >1.0 <1.0
eccen isi y index no app icable no app icable
RV-FAC 21% 49%
RVdiame e no app icable no app icable
RV-Tei index 0.53 0.03
RV sys o dia du a ion a io 1.8 1.1
accele a ion ime 40 130
PR eloci y no app icable no app icable
PA diame e 16.3 16.1
RA diame e 6 6.1
TMF e/a
See u he da a on he nex page.
Ichiyanagi sen u he da a abou ECHO and ca he e iza ion on 2023-2-24.
34
e en (p e echo)
1s . ca diac
ca he e iza io
n
(PH c isis)
2nd. ca diac
ca he e iza io
n
(Be o e)
Diagnosed
possible
scu y.
Vi .C
was
ini ia ed
da e 12/22 12/24 12/26 12/27 12/28 1/1 1/2 1/4 1/5 1/8 1/10 1/11
hospi al day 1 3 5 6 7 11 12 14 15 18 20 21
TR eloci y (m/s) 2,6 3,4 4,1 3,7 4,9 4,7 4,4 3,7 4,9 3,8 4,0
TRPG (mmHg) 27 46 67 56 97 87 77 56 97 58 64
TAPSE (mm) 13.0mm
e'/a'/s' 8.3/10.4/10.7
TMF e/a 41.4/53.2
en icula sep um la
RV basal diame e / LV basal diame e >1.0
eccen isi y index no app icable
RV-FAC 21 %
RVdiame e no app icable
RV-Tei index 0,53
RV sys o dia du a ion a io 1,8
accele a ion ime 40
PR eloci y no app icable
PA diame e 16,3
RA diame e 6
BSA (m2)0,55
Wedge p essu e (FiO2 1.0) (mmHg) 9,5
Wedge p essu e (FiO2 1.0 + NO20ppm) (mmHg) 11
e en
(pos echo)
App oxima el
y 6 weeks
a e he s a
o i C
adminis a io
n
3 d. ca diac
ca he e iza io
n
(A e )
en
da e 1/12 1/13 1/15 1/24 1/31 2/8 2/16 2/22 2/26 2/27 3/2
hospi al day 22 23 25 34 41 49 57 63 67 68 71
TR eloci y (m/s) 2,4 2,1 2,4 2,3 2,6 2,4 2,0
TRPG (mmHg) 22 18 24 21 27 23 17
TAPSE (mm) 16,1 19,8 17,3 17,3 17.5mm
e'/a'/s'
14.0/14.5/15.3
13.0/12.5/15.6
10.7/11.2/15.0
12.2/12.7/16.1
10.9/10.1/13.1
16.1/10.6/12.3
TMF e/a 54.6/55.1
en icula sep um ound
RV basal diame e / LV basal diame e
1,0 <1.0
eccen isi y index no app icable
RV-FAC 49 %
RVdiame e no app icable
RV-Tei index 0,03
RV sys o dia du a ion a io 1,1
accele a ion ime 130
PR eloci y no app icable
PA diame e 16,1
RA diame e 6,1
BSA (m2)0,56
Wedge p essu e (FiO2 1.0) (mmHg)
9
Wedge p essu e (FiO2 1.0 + NO20ppm) (mmHg) 11
Kupa i (2012) [90] h ps://pubmed.ncbi.nlm.nih.go /22796843
Pa ien 40 y woman wi h mild as hma and ood alle gies.
Du a ion o he
symp oms be o e hospi al
18 mon hs
Signs and symp oms Tende ed-bluish nodules, ecchymoses, and palpable pu pu a on legs 18
mon hs ea lie .
Acu e issue was anemia, inc easing b ea hlessness, and subcu aneous
bleeding.
Main indings The e we e la ge subcu aneous hema omas on he legs bu she was in no
acu e dis ess.
HR 105 bpm, BP 115/75 mmHg, SpO2 o 100% on ambien ai .
ECG showed fla ening o he T wa es in he igh p eco dial leads.
CXR no mal.
O al Fe adminis a ion was s a ed.
Because o a ague suspicion o asculi is, ea men wi h o al
p ednisone was ini ia ed.
Wi hin a ew days, he pa ien became inc easingly dyspneic and SpO2
d opped o 77-80% on ambien ai .
Oxygen was adminis e ed.
ECHO showed a dila ed and poo ly con ac ing RV, TRV 3.5 m/s, an
eccen ically de o med LV, pe ica dial e usion, and flow om igh o
le a ium h ough open o amen o ale.
Dila ed igh side o he hea and se e ely la ened LV.
CTA e ealed dila a ion o he pulmona y a e y bu no pulmona y
embolism.
A en ila ion-pe usion scan excluded pulmona y embolism.
Righ -sided hea ca he e iza ion, wi h he pa ien b ea hing oom ai ,
e ealed se e e p ecapilla y PH, RV ailu e, and a la ge igh - o-le
shun .
mPAP 48 mmHg (PAP ange 74/36 mmHg).
PVR 30 Wood uni s (2400 dyn/s/cm5).
Wedge p essu e 3 mmHg.
Echo:
RV+RA 52 cm2
Vena ca a in e io max diame e 27 mm
LV eccen ici y index 2.5
TAPSE 7 mm
Hb 74 g/L.
Fe 5.4 µM (no mal 9-34).
35
T ans e in sa u a ion 10% (17%-52%).
T ans e in ecep o 7.0 mg/L (1.9-4.4).
Vi amin C le el unde ec able, <10 µM.
D ugs in hospi al P ednisolon, apidly ape ing doses a e discha ge
Epop os enol
Sildena il was ini ia ed, bu discon inued 3 weeks la e .
O he i amins and
mine als
Fe, discha ged wi h Fe adminis a ion
Die be o e he e en Fo se e al yea s, die had been deficien o ui and ege ables, because
o p o en and p esumed ood alle gies.
Vi amin C ea men Vi amin C 1 g/day o ally.
Sildena il was discon inued 3 weeks la e . The e o e, we classi y he
ea men as i amin C alone.
E ec o i amin C In 2 days, she expe ienced elie o dyspnea and no maliza ion o SpO2.
A e 1 week, con ol ECHO showed no signs o PH.
A e 8 weeks (wi h 5 weeks o sildena il), she epo ed no mal exe cise
capaci y and had no mal Hb 140 g(L
Findings a ca he e iza ion and ECHO showed ha he PAP, flow, and
esis ance we e comple ely no mal, as was igh -sided hea unc ion.
Echo 1 week:
RV+RA 38 cm2
LV eccen ici y index 1.0
Vena ca a in e io max diame e 18 mm
TAPSE 20 mm
Echo 8 weeks:
RV+RA 28 cm2
LV eccen ici y index 1.0
Vena ca a in e io max diame e 5 mm
TAPSE 23 mm
Ca diac ca he e iza ion 8 weeks:
mPAP 15 mmHg (PAP ange 26/9 mmHg).
Wedge 6 mmHg
PVR 1.3 Wood uni s (107 dyn/s/cm5)..
E ec o i amin C on labo a o y alues:
Hb
a diagnosis 74 g/L
8 weeks: 140 g/L (+89%)
Time se ies Da a o ou g aph was published in Table 1, he da a a e ex ac ed
abo e.
NOTES
36
Ku nick (2023) [91] h ps://pubmed.ncbi.nlm.nih.go /37650076
h ps://doi.o g/10.1016/S0735-1097(23)02958-3 (mee ing abs ac )
Pa ien 25 y emale, USA
His o y o i on de iciency anaemia seconda y o meno hagia.
Du a ion o he symp oms
be o e hospi al
5 mon hs sho ness o b ea h and gene alized weakness. ECHO was
“un ema kable” (see below).
Signs and symp oms 2 weeks p og essi e weakness, sho ness o b ea h, myalgia, a h algia.
Main indings On admission, HR 123, BP 131/93 mmHg.
O2 sa u a ion 100% on oom ai .
ECG e ealed sinus achyca dia wi h igh axis de ia ion.
CT angiog am o he ches uled ou pulmona y embolism; bu e ealed
signi ican igh hea s ain.
ECHO showed sPAP 71.1 mmHg wi h se e ely dila ed RV and RA.
TAPSE 9.5 mm. Non-collapsible in e io ena ca a dila ed o 3.0 cm.
ECHO 4 mon hs p io o admission: no mal en icles and
papillae, no mal size RV. No mal TAPSE 23 mm.
HD4. ca diogenic shock, HR 45, BP 77/56 mmHg, O2 sa u a ion 69%
on oom ai .. Two episodes o ca diac a es wi h pulseless elec ical
ac i i y bu e u n o spon aneous ci cula ion.
HD5. Ca he e iza ion
mPAP 48 mmHg (63/43/48 mmHg)
Wedge p essu e 13 mmHg.
PVR 16
Ca diac ou pu 2.2 L/min
Ca diac index 1.6 L/min/m2.
HD14 Ca he e iza ion
mPAP 39 mmHg
Wedge p essu e 19 mmHg.
PVR 4.3 WU
Ca diac ou pu 4.6 L/min
Ca diac index 2.8 L/min/m2.
On admission
Hb 71 g/L
p o-BNP 330000 pg/mL
mildly ele a ed oponin
Vi amin B1 and D le el we e wi hin no mal limi s
HD5 AST 136, ALT 71
37
D ugs in hospi al No epineph ine , Dobu amine, Mil inone
O he i amins and
mine als
Die be o e he e en Se e ely es ic ed die lacking ui s and ege ables, mos ly consuming
chickpeas
Vi amin C ea men 2 g in a enous i amin C pe day.
Discha ged on o al i amin C 1 g daily
E ec o i amin C HD23 Repea ECHO e ealed he esolu ion o igh en icula
dila ion wi h comple e esolu ion o RHF and PH. Collapsible in e io
ena ca a measu ing 14 mm. TRPG 16 mmHg.
HD23 Ca he e iza ion
PAP 36/9 mmHg [we calcula e mPAP = 24 mmHg]
Wedge p essu e 9 mmHg.
Repea ECG showed esolu ion o igh axis de ia ion.
NOTES We con ac ed John Sabu o ask o mo e de ails (email 2023-3-15, 2023-
9-26 and 2023-9-29). We did no ecei e any esponse.
We we e able o con ac Adam Ku nick (email 2023-3-15) bu we we e
unable o ge any addi ional in o ma ion o he case.
The case was i s published as an abs ac (abo e), bu a inal epo
was published be o e we inished he manusc ip and de ails we e
ex ac ed om he epo (abo e)
38
Meh a (1996) [92] h ps://pubmed.ncbi.nlm.nih.go /8607903
Pa ien 40 y woman wi h ano exia ne osa. She had been in psychia ic ca e
and was on se aline. Ameno heic since he bi h o he 5 y child;
b eas ed his child un il 6 mon hs p io o p esen a ion.
Du a ion o he symp oms
be o e hospi al
3 mon hs
Signs and symp oms A h algia, myalgia, weakness, a igue o 3 mon hs.
1 week p io o p esen a ion, sho ness o b ea h and a pu pu ic ash on
he legs.
Main indings On he lowe ex emi ies, he e we e e y hema ous ende nodules,
di use pe i ollicula pu pu a, and an ecchymosis. Tende ness on
palpa ion in knees, ankles and ee . Ankles showed mode a e syno ial
swelling, wa m h, and pain on palpa ion.
Heigh 157.5 cm, and weigh 44 kg, BMI 17.7.
Hea sounds no mal
Hb 118 g/L.
ESR 12 mm/h.
CXR and CT showed di use in e s i ial p ominence and mul iple
in apa enchymal nodules wi h size <1 cm.
Pulmona y unc ion es ing showed DLCO 53% and i al capaci y o
70%.
B onchoscopic e alua ion led o se e e bleeding and hypo ension, and
luid esusci a ion he ea e led o se e e anasa ca.
A lung biopsy showed in e s i ial edema.
ECHO showed se e e PH, wi h a dila ed pulmona y a e y, and RA and
RV enla gemen .
Righ hea ca he e iza ion showed a PAP 55/35 mmHg.
Vi amin B 1178 nM (88-192)
Vi amin C le el 2 mg/L (11 μM).
D ugs in hospi al None
O he i amins and
mine als
Die be o e he e en Die consis ed o 2-4 bagels pe day.
P olonged b eas eeding migh also con ibu e o he decline in i amin
C le el in he mo he ’s body.
Vi amin C ea men Vi amin C supplemen a ion indica es o al adminis a ion, bu dose was
no epo ed.
In addi ion, “o he suppo i e he apies” which we e no desc ibed, bu
hey we e no co icos e oids o an ibio ics.
E ec o i amin C In 1 week, he musculoskele al, skin, and pulmona y symp oms
39
esol ed.
In 19 days, he CXR, ECHO, and pulmona y unc ion es esul s had
no malized.
NOTES
40
Me ens (2011) [93]
Case 3
Elie Ge ne
h ps://pubmed.ncbi.nlm.nih.go /21185063
Pa ien 74 y emale wi h no signi ican medical his o y, no smoking.
Du a ion o he symp oms
be o e hospi al
“Se e al mon hs”; we ansla e his o >3 mon hs
Signs and symp oms Wo sening exe ional dyspnea.
Main indings Bila e al e y hema ous and swollen ankles, and a pu pu ic ash along
he igh o ea m.
Ca diac auscul a ion showed g ade 2/6 sys olic mu mu .
Righ hea ca he e iza ion showed se e e PH wi h sPAP >80 mmHg.
A ches CT showed a 1.5-cm consolida ion in he le uppe lobe.
Pulmona y unc ion es showed mode a e es ic i e disease wi h FVC
65% and FEV1 63%, and DLCO 46% o p edic ed.
Hb 124 g/L
ESR 41 mm/h
Vi amin B6 and Zn le els no mal
Vi amin B1 sligh ly low, bu no da a
Vi amin C le el unde ec able, <0.12 mg/dL (<7 µM).
D ugs in hospi al Ni edipine, sel -discon inued a e 1 week.
O he i amins and
mine als
Die be o e he e en She had a numbe o delusions abou sensi i i ies o oods and o he
chemicals and limi ed he die o g ound bee , goa ’s milk, apioca,
sp ing wa e , and i amin B6 and i amin A supplemen s.
Vi amin C ea men Vi amin C supplemen a ion 1 g/day, bu ou e no de ined.
Vi amin C alone.
E ec o i amin C A e 5 mon hs, a epea ECHO showed nea comple e esolu ion o he
PH wi h i amin C supplemen a ion alone and she was asymp oma ic
o any ca diopulmona y symp oms.
NOTES To ask o u he de ails o he case, we con ac ed Elie Ge ne by email
on 2023-2-8 and 2023-2-23 bu did no ge a esponse.
41
Pe e sen (2019) [97] h ps://shmabs ac s.o g/abs ac /when-li e-doesn -gi e-
you-lemons-a- a e-case-o -acu e-hea - ailu e
Pa ien 5 y boy wi h ASD
Du a ion o he symp oms be o e
hospi al
2 mon hs
Signs and symp oms Fa igue, lowe ex emi y pain, pe echial ash, weigh loss,
Re usal o walk o 1 week.
Main indings HR 160 bpm, BP 93/68 mmHg, espi a o y a e 30/min.
SpO2 no mal on ambien ai .
Ca diac auscul a ion S3 gallop, no jugula enous
dis ension.
ESR 33 mm/h.
A e in a enous luids, he became acu ely hypo ensi e
and hypoxic necessi a ing oxygen ia a ace mask and
asop esso suppo .
Lowe limb Dopple ul asound excluded DVT.
CTA no mal.
ECHO indica ed PH, a se e ely dila ed RV wi h sys olic
dys unc ion, and ele a ed igh -sided p essu es.
E y h ocy e sedimen a ion a e 33 mm/h
Vi amin C le el unde ec able.
D ugs in hospi al Vasop esso
O he i amins and mine als
Die be o e he e en Ex emely es ic ed die due o o al a e sion, bu no
u he desc ip ion o he usual die is desc ibed.
Vi amin C ea men Vi amin C in a enously, bu dose no epo ed.
E ec o i amin C adminis a ion Immedia e imp o emen in PAP.
In 1 week, no maliza ion o s eng h and gai .
In 2 weeks, comple e e e sal o RV dys unc ion.
NOTES We we e able o con ac D . Liz Pe e sen, who esponded
2023-2-26 ha he da a we e no mo e a ailable.
48
Quinn (2022) [98]
Benjamin F ank
Moo e
h ps://pubmed.ncbi.nlm.nih.go /36389378
Pa ien 6 y boy wi h ASD
Du a ion o he symp oms
be o e hospi al
3 mon hs
Signs and symp oms 1-week p io o p esen a ion, inabili y o bea weigh on he le
leg. Pa en s b ough him o clinic in a s olle .
Weigh loss 5% in 3 mon hs.
Main indings Du ing uppe endoscopy he pa ien de eloped b adyca dia,
hypo ension, ca diac a es .
CT excluded pulmona y embolism.
Echo sho ly pos -a es showed signs o PAH including ele a ed
TRV and se e ely diminished RV unc ion, and signi ican RV
hype ophy, sugges ing ha PAH p eda ed he ca diac a es .
“O he diagnoses on he di e en ial o he ca diac a es ha
we e excluded included achya hy hmia (no e idence on ca diac
moni o du ing he e en ), ca diac amponade (no e idence on
echoca diog am o clinically), pulmona y embolism (no mal CT
scan), and unde lying p ima y neu ologic o gene ic/me abolic
diso de s. Gi en his, scu y-associa ed PAH was hough o be
he p ima y con ibu o o his a es .”
Vi amin B1 55 nM (70–180)
Vi amin A 15 µg/dl (19–77)
Vi amin D <3.5 ng/ml (30–96l)
e i in 16.6 ng/ml (>20)
Fe sa u a ion 12% (>20%)
Se 43 ng/mL (70–150)
Zn 0.39 µg/mL (0.6–1.2).
Vi amin C le el unde ec able, <0.1 mg/dL (<0.6 µM).
D ugs in hospi al iNO on HD9
Sildena il on HD9
O he i amins and mine als Vi amin B1 wi hin 24 h o admission o pedia ic ICU.
Mul i i amin wi hin 24 h o admission o pedia ic ICU.
Se s a ed on HD2.
Discha ged wi h mul i i amin, Zn, Fe.
Die be o e he e en Die had been es ic i e a e choking on a F ench y a 2 y o
age, and consis ed o a nu i ionally comple e supplemen al
be e age and candy. In 6 mon hs p io o p esen a ion, he u he
na owed die o only chocola e peanu bu e cups and wa e .
Vi amin C ea men Vi amin C wi hin 24 h o admission o he pedia ic ICU
E ec o i amin C
adminis a ion
HD9: Repea ECHO showed imp o emen in RV dila ion and TR.
A ollow-up 3 mon hs, no signs o symp oms o ca diac
49
dys unc ion, and no e idence o PAH on epea ECHO.
Sildena il was discon inued 6 mon hs a e he ca diac a es and a
ollow up ECHO 3 mon hs o sildena il emained s able: no mal
endsys olic sep al posi ion, no mal RV size, and no RV
hype ophy.
Time se ies D . F ank kindly p o ided us wi h he da a o ou ime se ies
g aph, see below.
NOTES We we e able o con ac Benjamin F ank, who esponded 2023-2-
9 o ou ques ion o he ECHO da a:
We we e also able o con ac Jaime Moo e, who esponded 2023-
3-21 o ou ques ion abou i amin C doses and he i als:
“1) Rega ding he de ails o ou pa ien 's sepa a e Vi amin C
supplemen a ion:
-Wi hin 24h o he admission, he ecei ed an ini ial dose o en e al
asco bic acid 250mg c ushed able deli e ed ia nasogas ic ube
-The ollowing day, he ecei ed bo h a dose o en e al asco bic
acid 250mg c ushed able ia nasogas ic ube and a dose o IV
asco bic acid 100mg
-Fo he nex 6.5 days, he ecei ed IV asco bic acid 100mg wice
a day
-Fo he nex 20 days, he ecei ed en e al asco bic acid 125mg
once a day
2) Baseline HR, BP, and espi a o y a e:
I was documen ed on mo e han one occasion ha because o he
pa ien 's (au ism- ela ed) beha io s, BP and HR we e di icul o
50
42 25
16.90% 33.80% 41.30%
0.4 1.5
1.6 1.2 1.1 1.1
2.3 1.1 0.9 1
Echo
Timing/Pa ame e s
Sho ly A e A es
on ECMO
9 Days Pos A es
~4 Weeks Pos A es
(Fig 1 B)
on sildena il
9 Mon hs Pos A es
o sildena il
Mean pulmona y
a e y p essu eK
K K
Addi ional Pa ame e s om Table 1 Below
E idence o
pe ica dial e usion
(Y/N) K
NK NK NK NK
Righ en icula
ac ional a ea changeK
K
T icuspid annula
plane sys olic
excu sionK
K K
T icuspid al e
egu gi a ionK
3.3 m/sK 2.6 m/sK 2.3 m/sK 2.3 m/sK
Eccen ici yK
RV sys olic o
dias olic du a ion
a ioK
impossible o ob ain du ing ou ine ou pa ien clinic isi s.
On he da e o his admission o he hospi al, he i s eco ded ull
se o i als we e:
HR: 138
BP: 118/89
RR: 28
I would in e p e hese cau iously as his likely e lec s some
deg ee o pa ien anxie y and hus, in la ion, compa ed o wha
hey migh be in an en i onmen whe e he was calm/ elaxed.”
51
Ra anachu-Ek (2003a)
[99]
h ps://pubmed.ncbi.nlm.nih.go /14700174
h ps://www. esea chga e.ne /publica ion/8938594
Pa ien 1 y 9 mon h boy. This is one o 28 cases epo ed, he nex case is one
om he same se ies.
Du a ion o he
symp oms be o e
hospi al
No da a
Signs and symp oms Fe e , limb pain and clinical igh -sided hea ailu e [we in e ha his
indica es edema in his con ex ].
Main indings “Did no ha e any neu ological signs o be ibe i and diu e ic e ec s om
hiamine ea men ” (p S738)
Pulmona y hype ension was diagnosed by ECHO (p S736)
“Mode a e pe ica dial e usion”
“Two cases o pulmona y hype ension and igh -sided hea ailu e
diagnosed by echoca diog am wi hou a ailable in es iga ion o i amin
B1 le el. Bo h cases o pulmona y hype ension did no ha e any
neu ological signs o be ibe i and diu e ic e ec s om hiamin ea men .
So he pulmona y hype ension migh no ela e o hiamin de iciency” (p
S738).
D ugs in hospi al None
O he i amins and
mine als
Vi amin B1, bu dose no men ioned
Die be o e he e en “In he p esen s udy, he die a y his o y e ealed ha in akes o esh
ege ables and ui o ui juice we e inadequa e” (p S737).
“ ed wi h well-cooked oods and small amoun s o no ege ables and
ui s” (p S734).
In all, he e we e 28 scu y cases, bu he abo e s a emen seems o apply
also o he 2 cases we include in ou s udy.
Vi amin C ea men 0.15-0.3 g/d i amin C.
This is one o 28 cases, wi h desc ip ion ha “unde weigh cases we e
supplemen ed wi h mul i i amins and i on was supplemen ed in cases
suspec ed o i on de iciency anemia” bu he e is no speci ic desc ip ion
o his case.
E ec o i amin C “Clinical signs o limb pain and hea ailu e imp o ed a e a ew days”
No mal ECHO was eco ded 1 week a e ea men (p S736).
“The esul o i amin C ea men in his s udy was d ama ic wi h g adual
imp o emen o all physical signs in a ew days” (p S738).
“The e was no p e ious epo on pulmona y hype ension in scu y bu
wo cases in he p esen s udy esponded o i amin C ea men ” (p S738).
NOTES We we e able o con ac Sun a ee Ra anachu-ek, who esponded 2023-3-
31:
“I did no ha e any ecollec ion abou 2 cases o pulmona y hype ension
in 28 pa ien s in 2003, and all p e ious eco ds we e des oyed.”
52
Ra anachu-Ek
(2003b) [99]
h ps://pubmed.ncbi.nlm.nih.go /14700174
h ps://www. esea chga e.ne /publica ion/8938594
Pa ien 2 y 10 mon h boy. This is one o 28 cases, see p e ious case.
Du a ion o he
symp oms be o e
hospi al
No da a
Signs and symp oms Fe e , limb pain and clinical igh -sided hea ailu e [we in e ha his
indica es edema in his con ex ].
Main indings “Did no ha e any neu ological signs o be ibe i and diu e ic e ec s om
hiamine ea men ” (p S738)
Pulmona y hype ension was diagnosed by ECHO (p S736)
“Hype ension” bu no da a
“Two cases o pulmona y hype ension and igh -sided hea ailu e
diagnosed by echoca diog am wi hou a ailable in es iga ion o i amin
B1 le el. Bo h cases o pulmona y hype ension did no ha e any
neu ological signs o be ibe i and diu e ic e ec s om hiamin ea men .
So he pulmona y hype ension migh no ela e o hiamin de iciency” (p
S738).
D ugs in hospi al None
O he i amins and
mine als
Vi amin B1, bu dose no men ioned
Die be o e he e en “In he p esen s udy, he die a y his o y e ealed ha in akes o esh
ege ables and ui o ui juice we e inadequa e” (p S737).
“ ed wi h well-cooked oods and small amoun s o no ege ables and
ui s” (p S734).
In all, he e we e 28 scu y cases, bu he abo e s a emen seems o apply
also o he 2 cases we include in ou s udy.
Vi amin C ea men 0.15-0.3 g/d i amin C .
This is one o 28 cases, wi h desc ip ion ha “unde weigh cases we e
supplemen ed wi h mul i i amins and i on was supplemen ed in cases
suspec ed o i on de iciency anemia” bu he e is no speci ic desc ip ion
o his case.
E ec o i amin C “Clinical signs o limb pain and hea ailu e imp o ed a e a ew days”
No mal ECHO was eco ded 1 week a e ea men .
“The esul o i amin C ea men in his s udy was d ama ic wi h g adual
imp o emen o all physical signs in a ew days” (p S738).
“The e was no p e ious epo on pulmona y hype ension in scu y bu
wo cases in he p esen s udy esponded o i amin C ea men ” (p S738)
Hype ension was slowly imp o ed in 2 weeks.
NOTES We we e able o con ac D . Ra anachu-ek, who esponded 2023-3-31:
“I did no ha e any ecollec ion abou 2 cases o pulmona y hype ension
in 28 pa ien s in 2003, and all p e ious eco ds we e des oyed.”
53
Sakamo nchai 1
(2022a) [100]
O apo n
Dum ongwongsi i
h ps://pubmed.ncbi.nlm.nih.go /36337659
Pa ien 6y boy wi h ASD. The same epo published 2 cases, see also he nex .
Du a ion o he
symp oms be o e
hospi al
2 mon hs.
Signs and symp oms P og essi e bila e al knee swelling and e used o walk o 2 mon hs.
P og essi e dyspnea o 1 day.
Main indings He was pale and had espi a o y dis ess.
Le leg was swelling and limi ed mo emen due o pain.
Co ksc ew hai s we e p esen ed o e he body.
HR 130 bpm, BP 107/78 mmHg, espi a o y a e 48/min.
SpO2 90% on oom ai , co ec ed wi h 10 L/min oxygen ia ace mask.
ECHO showed TR wi h TRPG o 80 mmHg and D-shape LV.
He was diagnosed wi h se e e PAH, bu wedge p essu e and PVR we e
no published.
“No e idence o o he causes o PAH such as congeni al hea disease,
pulmona y embolism, and malignancy was ound”, bu no u he
examina ions a e desc ibed o exclude hem.
Hb 70 g/L
MCV 60 L
Fe 14 µg/dL (no mal 50-120)
T ans e in sa u a ion 4.4% (>16%)
Fe i in 41.5 ng/mL (7-140)
25-OHD 16.2 ng/mL (20-100)
Fola e 4.6 ng/mL (4-20)
Vi amin C le el unde ec able
D ugs in hospi al Ino opics
Pulmona y asodila o (no speci ied)
O he i amins and
mine als
Mul i i amins, i amin D, Fe, ola e and “o al nu i ional supplemen ”
we e con inued a e discha ge.
Die be o e he e en Meals consis ed o ice po idge and boiled eggs. Some biscui s we e
p o ided as a snack. Ne e d ank milk o 2 y and e used ed mea , ui ,
and ege ables.
Vi amin C ea men 0.3 g/day o i amin C was gi en ia o al ou e since he 1s day o
admission.
E ec o i amin C G adually eco e ed om espi a o y dis ess and could be discha ged in
13 days.
1-mon h ollow-up isi a e discha ge showed ha he was able o
mobilize bo h lowe ex emi ies wi hou pain and had no dyspnea while
doing he ac i i y.
54
ECHO a 2 mon hs a e discha ge showed no e idence o PAH and he
pulmona y asodila o could be weaned o .
NOTES To ask o u he de ails o he case, we con ac ed O apo n
Dum ongwongsi i by email on 2023-2-8 and 2023-2-23 bu did no ge a
esponse.
55
Sakamo nchai 2
(2022b) [100]
O apo n
Dum ongwongsi i
h ps://pubmed.ncbi.nlm.nih.go /36337659
Pa ien 5 y boy wi h ASD, alle gic hini is, and sno ing.
The same epo published 2 cases, see also he p e ious.
Du a ion o he
symp oms be o e
hospi al
2 weeks
Signs and symp oms P og essi e dyspnea and e used o walk.
Main indings Limi ed ange o mo ion o join s due o pain.
No sco bu ic osa y and no co ksc ew hai s.
HR 136 bpm, BP 110/60 mmHg, espi a o y a e 50/min.
Ches X- ay showed ca diomegaly, no mal pulmona y blood low and no
pulmona y conges ion.
ECG showed igh axis de ia ion and low QRS ol age.
ECHO showed mode a e o se e e TR wi h TRPG 80 mmHg, RA and RV
enla gemen wi h D-shape LV, impai ed RV sys olic unc ion, no e idence
o in a-ca diac shun .
“PAH was diagnosed”, bu wedge p essu e and PVR we e no published.
Hb 99 g/L
MCV 54.2 L
Fe 20 µg/dL(no mal 50-120)
T ans e in sa u a ion 4% (>16%)
Fe i in 7.5 ng/mL (7-140)
25-OHD 6.02 ng/mL (20-100)
Vi amin B1 49.2 µg/L(28-85)
Fola e 3.2 ng/mL (4-20)
Vi amin C le el unde ec able
D ugs in hospi al Pulmona y asodila o (no speci ied)
O he i amins and
mine als
A single dose o 100 mg i amin B1 in a enously.
10 l/Mul i i amins, Fe, ola e supplemen we e gi en and con inued a e
discha ge.
Die be o e he e en Only ice po idge wi hou any mea o 1 y, and he jus s a ed ha ing
some amoun o boiled egg o 1 week. He usually d ank 2 L/day o plain
UHT milk. Re used ui and ege ables and did no ecei e any i amin o
mine al supplemen a ion.
Vi amin C ea men 0.3 g/day o i amin C o ally.
E ec o i amin C Symp oms imp o ed d ama ically he nex day a e i amin C, and he was
able o wean himsel o espi a o y suppo , and an ECHO e ealed ha
his PH had imp o ed.
Discha ged on HD5.
56
ECHO a 3 mon hs a e admission showed no PH.
NOTES To ask o u he de ails o he case, we con ac ed O apo n
Dum ongwongsi i by email on 2023-2-8 and 2023-2-23 bu did no ge a
esponse.
57
On 2023-3-30 we ecei ed u he da a om Leong Ming Che n:
##################
I ha e ex ac ed hese da a om ou echoca diog am eco dings.
Column1 15/10/2019 21/10/2019 31/10/2019 04/02/2020
Dominan RV Yes Yes No No
Peak TR g adien 75 60 40 12
LV eccen ici y 2.05 1.4 1.02 1.01
RV FAC 18.7 11.9 52.7 51.1
Pe ica dial
e usion Yes Yes No No
Thank you.
MC Leong
##################
64
Ueki (2022) [104] h ps://pubmed.ncbi.nlm.nih.go /35942728
Pa ien 11 y boy wi h ASD
Du a ion o he
symp oms be o e
hospi al
3 mon hs
Signs and symp oms Fa igue, myalgia, a h algia o he knees, di icul y ambula ing.
Weigh loss 4.4 kg in 5 mon hs
Main indings D y skin, mild swelling o he knees, and limi ed ange o mo emen a
he knees and pel is because o se e e muscula pain.
CXR, ECG, and ECHO demons a ed RV olume o e load (% o RV
end dias olic olume index; 136.5) wi h mild PH and TRV 2.9 m/s
HR, BP, and SpO2 sa u a ion we e wi hin no mal anges.
Hb 68 g/L
MCV 67 L
Fe 250 μg/L (no mal 400–1880)
BNP 26.9 pg/mL (<18)
CRP 34 mg/L
D-dime 3.77 mg/L (<1.0)
Vi amins B1, B12, ola e, Se, Zn all wi hin no mal ange
Vi amin C le el unde ec able, <0.2 μg/ml (<1 μM).
D ugs in hospi al None
O he i amins and
mine als
O al Fe daily o 10 days. The ea e “i on supplemen a ion o 3.5
mon hs” bu doses we e no epo ed.
Die be o e he e en Selec i e die , including pancakes, apple juice, milk, bananas, and boiled
eggs a home. A e y minimal amoun o ege ables, mea , and ish om
his school lunches and had ne e aken any nu i ional supplemen s
Vi amin C ea men “1 g in a enous i amin C o 10 days. The ea e , o al 0.3 g/day i amin
C o 3.5 mon hs. Then i amin C was s opped, bu plasma le el
dec eased below de ec ion and he ea e 0.2 g/day was con inued”.
See NOTES.
E ec o i amin C A discha ge ( ollowing 10 days o in a enous i amin C ea men ),
he e was almos comple e esolu ion o pain, and he pa ien was able o
ambula e wi hou assis ance”
Abno mali ies associa ed wi h pulmona y hype ension on ECG and
ECHO imp o ed ollowing 3.5 mon hs o o al i amin C
E ec s o i amin C on labo a o y alues:
Hb
a diagnosis 68 g/L
A discha ge: 97 (+43%)
4 mon hs: 141 (+107%)
BNP
a diagnosis 26.9 pg/mL
65
A discha ge: 15.8 pg/mL (-41%)
4 mon hs: 6.0 pg/mL (-78%)
CRP
a diagnosis 34 mg/L
A discha ge: 2.8 mg/L (-92%)
4 mon hs: 0.4 mg/L (-99%)
D-dime
a diagnosis 3.77 mg/L
A discha ge: 0.72 (-81%)
4 mon hs: <0.25 (-93%)
IL-6
a diagnosis 38.08 pg/mL
A discha ge: 11.08 (-71%)
4 mon hs: 7.61 (-80%)
IL-8
a diagnosis 15.53 pg/mL
A discha ge: 12.53 (-19%)
4 mon hs: 201.67 (+1200%)
IL-18
a diagnosis 104.70 pg/mL
A discha ge: 155.29 (+48%)
4 mon hs: 201.94 (+93%)
NOTES We we e able o con ac Masahi o Ueki and ecei ed he ollowing eply
on 2023-3-8.
“In ou pa ien , he was ea ed wi h 1000mg o i amin C in a enously
o ini ial 10 days. Following esolu ion o muscle pain and
in lamma ion, 300mg o i amin C was adminis e ed o ally.
A 3.5 mon hs, abno mali ies associa ed wi h pulmona y hype - ension
on ECG and UCG imp o ed.
I s opped i amin C supplemen a 6 mon h, whe eas his se um i amin
C le el dec eased below de ec ion wi hou any symp oms ollowing 3
mon hs. A e his e en , He con inues 200 mg o i amin C supplemen .”
We ecei ed he ollowing addi ion on 2023-3-10.
“We e alua ed PH by icuspid al e egu gi a ion.
A diagnosis, eloci y o T was 2.9 m/s.
A 3.5 mon h, eloci y o T educed o 2.5 m/s.
I'm so y ha TAPSE was measu ed only a 3.5 mon hs.
TAPSE a 3.5 mon h was 21mm.
Righ en icula ou low ac diame e (RVOTD) was measu ed
66
sequen ially.
RVOTD a diagnosis was 23.6mm (he is su e ed om mild
dehyd a ion), and 26mm a 3.5 mon h.
On 2023-3-23:
“Changes in i al signs we e no signi ican du ing he ea men .
A diagnosis/ hospi al admission
HR 85 BP 89/52 RR 18
A discha ge
HR 97 BP 100/59 RR 18
A 3 mon hs
HR 93 BP 107/59 RR 16”
67
Valencia (2022) [105]
Melody Du all
h ps://pubmed.ncbi.nlm.nih.go /35969659
Pa ien 19 y male.
C ohn's disease, p ima y scle osing cholangi is, au oimmune hepa i is,
decompensa ed ci hosis had p og essed o e 6 y o end-s age li e
disease.
The pa ien unde wen li e ansplan a ion.
An ECHO pe o med a ano he hospi al 1 y be o e ansplan a ion
showed RV p essu e >½ sys emic, no mal bi en icula size and sys olic
unc ion, and no mal al ula unc ion.
Du a ion o he
symp oms be o e
hospi al
Signs and symp oms Pos ope a i e ECG no mal.
24 h a e ans e o he wa d (pos op day 2), he pa ien de eloped
pe sis en sinus achyca dia ( a e, 110–130 bea s/min) and hypoxia wi h
escala ion o his oxygen suppo o 4 L/min o oxygen ia nasal cannula.
Main indings CXR demons a ed e oca diac opaci ica ion, mild in e s i ial edema,
ace pleu al e usions.
Became p og essi ely mo e achyca dic, achypneic, and hypoxemic,
equi ing 5 L/min o nasal cannula oxygen o main ain SpO2 > 90%.
Hospi al eme gency call o pedia ic ICU- eam bedside assis ance was
ac i a ed on pos op day 3. Upon a i al o he ICU eam, he pa ien
de eloped b adyca dia, loss o consciousness, and pulselessness and was
in pulseless elec ical ac i i y a es .
ECMO eam was eme gen ly ac i a ed.
Echo ob ained p io o comple ion o ECMO cannula ion demons a ed
mildly dep essed LV unc ion, se e ely dep essed RV unc ion, RV
dila ion, and RV hype ension (RV p essu e 2/3 sys emic; RV p essu e
~55 mm Hg plus he RA -wa e, while nonin asi e sys olic blood
p essu e 80 mmHg). No pe ica dial e usion, no e idence o pulmona y
embolism a he bi u ca ion o he main o p oximal b anch pulmona y
a e ies. TRV 4.84 m/s
A e 220 min esusci a ion, an adequa e ci cula ion was achie ed.
Labo a o y esul s p io o ca diac a es
Hb 93 g/L
Pla ele 65
pos ope a i e day 2
Hb 79 g/L
Pla ele 6
Ca diac ca he e iza ion:
mPAP 77 mmHg ( igh ) and 75 mmHg (le ) (in hei Supplemen )
PVR 536.6 dynes/s/cm-5 = 6.7 Wood uni s (in hei Supplemen )
Wedge p essu e 30 mmHg ( igh ) and 31 mmHg (le ) (in hei
Supplemen )
68
On day 12 o ECMO, a e 72 hou s wi hou any bleeding, he was gi en
IV epop os enol... On day 15 o ECMO, epop os enol was discon inued.
O he medical he apies included use o low-dose epineph ine and
maci en an, a an en e al dose o 5 mg daily.
“A he ime, we also conside ed he possibili y o i amin C de iciency
as an associa ed causal ac o in he de elopmen o se e e PAH, since
i amin C de iciency is a complica ion o C ohn's disease, e en in
pa ien s wi h disease emission. We did p esc ibe i amin C in his
pa ien : we used high dosing ia pa en e al nu i ion and e en ually
en e ally.” (p e446)
The blood le el o i amin C was measu ed 7 weeks a e he ca diac
a es e en , and i was se e ely low (<5 μM).
D ugs in hospi al Epop os enol
Mil inone
Sildena il
Epineph ine
Maci en an
O he i amins and
mine als
Die be o e he e en No desc ibed, and may be a seconda y issue o his pa icula pa ien
Vi amin C ea men Vi amin C ini ially in a enously and he ea e o ally. Day o s a ing is
no desc ibed, and doses no desc ibed (only “high dosing ia pa en e al
nu i ion and e en ually en e ally”)
E ec o i amin C “The pa ien unde wen ECMO decannula ion a e 29 days and was
solely suppo ed by he pa aco po eal lung-assis de ice. I should be
no ed ha p io o emo ing he pa ien om ECMO, agg essi e, se ial
b onchoscopies we e equi ed o ensu e pa en ai ways o gas exchange.
Addi ionally, a PA ca he e was placed o e alua ion o eadiness o
decannula ion om he pa aco po eal lung-assis de ice. PA p essu es
anged om 35/25 o 45/30 mm Hg (mPAP, 30–35 mm Hg) (<½
sys emic)”
He was weaned om sildena il 5 mon hs la e and om maci en an 12
mon hs la e . Follow-up echoca diog am a 21-mon h pos - ansplan
demons a ed low RV p essu e and quali a i ely no mal RV unc ion. His
ollow-up i amin C le el a he ime o pulmona y hype ension
esolu ion had no malized.
NOTES The epo is con using.
“The blood le el o i amin C was measu ed 7 weeks a e he ca diac
a es e en ” (p e446), which co esponds o 49 days.
69
On he o he hand, “The pa ien unde wen ECMO decannula ion a e 29
days and was solely suppo ed by he pa aco po eal lung-assis de ice…
decannula ed om he pa aco po eal lung-assis de ice a e 15
days (3-d pos -ECMO decannula ion). TTE he ea e
demons a ed mild RV hype ension (<½ sys emic)
and no mal bi en icula sys olic unc ion.”
I is no clea how he 49 day i amin C measu emen ela es o he 32
day (=29+3) decannula ion om pa aco po eal lung assis de ice.
The ime o s a ing i amin C is no desc ibed.
The e o e he ole o i amin C in he eco e y om PH emains obscu e
in he epo .
To ask o u he de ails o he case, we con ac ed Melody Du all by
email on 2023-2-8 and 2023-2-23 and 2023-3-4 bu did no ge a
esponse.
70
