rm intermedia giunta giuliano
TRANSCRIPT
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EMOGLOBINOPATIE
E MIOT
il valore aggiunto
clinico diagnostico
e prognostico
del fare network nella
gestione del paziente con patologia rara
Palermo
27-28 novembre 2014
Multi-parametric Magnetic Resonance Imaging for
prediction of cardiovascular complications in Thalassemia
Intermedia: a prospective multicenter study
Dott. Pietro Giuliano Dott. Nicola Giunta
U. O Cardiologia
Arnas Civico Palermo
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Leonardo da Vinci
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B THALASSEMIA
Major (TM) / Intermedia(TI)
EMOGLOBINOPATIE
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COMPLICANZE CV NELLA TALASSEMIA
Scompenso cardiaco (accumulo Fe, alta
gittata, miocardite, CAD, PH, …)
Aritmie (prevalentemente SV)
Ipertensione polmonare (multifattoriale?)
Cardiopatia ischemica
Prima causa di mortalita’
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TALASSEMIA INTERMEDIA VS MAJOR:IPERTENSIONE POLMONARE
Ipertensione polmonare (eco*) Ipertensione
polmonare (cat. Dx)
0
2
4
6
8
10
TI
TM
9.3
4.81.6
1.1 TITM
Circulation 2014; 129:338-345* V. max IT ≥ 3,2 m/s
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TALASSEMIA INTERMEDIA VS MAJOR:ACCUMULO DI FERRO
Talassemia intermediaTalassemia major*
0
10
20
30
40
50
60
70
3.814.8
3.1
18.3
24.525.8
68,7%
41,2% MIO OmMIO Et < 20MIO Et > 20No MIO
* A. Pepe et al. – Multi-parametric magnetic resonance for prediction of cardiac complications in thalassemia major: a prospective multicenter study
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MULTI-PARAMETRIC CARDIAC MAGNETIC RESONANCE FOR PREDICTION OF CARDIAC COMPLICATIONS IN THALASSEMIA INTERMEDIA: A PROSPECTIVE MULTICENTER STUDY
12.2
28.235,1%
16.9
7.5
Età
<25 anni25-3535-4545-55> 55
48,2%51,8%
Sesso
MaschileFemminile
Pazienti n. 319 (+ 23 esclusi per eventi CV presenti)Follow-up 4,35 ± 2,1anni (30-6-2014)
Età media: 38 ± 11,7 anni
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58,9%
41,1%
Trasfusione-dipendenti
SiNo
20,8%
79,2%
Ferritina > 1500 ng/l
SiNo
Pazienti n. 302
Ferritina sierica media: 967 ± 985 ng/l
MULTI-PARAMETRIC CARDIAC MAGNETIC RESONANCE FOR PREDICTION OF CARDIAC COMPLICATIONS IN THALASSEMIA INTERMEDIA: A PROSPECTIVE MULTICENTER STUDY
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MULTI-PARAMETRIC CARDIAC MAGNETIC RESONANCE FOR PREDICTION OF CARDIAC COMPLICATIONS IN THALASSEMIA INTERMEDIA: A PROSPECTIVE MULTICENTER STUDY
6,9%
93,1%
Accumulo di Ferro: T2* globale < 20 ms
SiNo
68,7%24.5
3.13.8
Accumulo di Ferro miocardico (MIO)
No MIOMIO Et >20MIO Et <20MIO Om
Valore medio T2* globale: 36,7± 8,5MRI LIC: 8,8± 8,2 mg/gr dw (71,3% ≥ 3)
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MULTI-PARAMETRIC CARDIAC MAGNETIC RESONANCE FOR PREDICTION OF CARDIAC COMPLICATIONS IN THALASSEMIA INTERMEDIA: A PROSPECTIVE MULTICENTER STUDY
Ipertrofia ventricolare sx
Disfunzione ventricolare sx/dx
Dilatazione ventricolare sx/dx
Dilatazione atriale
Diabete mellito
HCV-RNA +
0 5 10 15 20 25 30 35 40 45
19,2%
16,9%
19,2%
39,4%
3,8%
27,3%
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MULTI-PARAMETRIC CARDIAC MAGNETIC RESONANCE FOR PREDICTION OF CARDIAC COMPLICATIONS IN THALASSEMIA INTERMEDIA: A PROSPECTIVE MULTICENTER STUDY
2,3%
97,7%
Ipertrofia ventrico-lare dx
SiNo
21,5%
78,5%
Fibrosi
SiNo
47/219 pz.
4/176 pz.(RV mass index:22,3 ± 6,6 g/mq)
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MULTI-PARAMETRIC CARDIAC MAGNETIC RESONANCE FOR PREDICTION OF CARDIAC COMPLICATIONS IN THALASSEMIA INTERMEDIA: A PROSPECTIVE MULTICENTER STUDY
93,1%
6,9%
Eventi CV nel follow-up
No eventiEventi CV
Totale eventi CV: 22 pz./319
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MULTI-PARAMETRIC CARDIAC MAGNETIC RESONANCE FOR PREDICTION OF CARDIAC COMPLICATIONS IN THALASSEMIA INTERMEDIA: A PROSPECTIVE MULTICENTER STUDY
0,3% (1)
3,8% (12)
0,6% (2)
2,2% (7)
Eventi CV nel follow-up
Scompenso cardiacoAritmieInfarto miocardicoIpertensione polmonare
Totale eventi CV: 22 pz./319
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EVENTI CARDIOVASCOLARI TOTALI: ANALISI MULTIVARIATA DELLE VARIABILI SIGNIFICATIVE ALL’ANALISI UNIVARIATA
HR 95% CI P
Global heart
T2*<20 ms
0.98 0.11-8.47 0.976
Ventricular
dilation
1.81 0.44-7.43 0.413
RV
hypertrophy
12.39 2.16-
71.07
0.005
Myocardial
fibrosis
6.11 1.20-
30.98
0.029
Atrial
Dilatation
2.14 0.39-
11.49
0.375
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EVENTI CARDIOVASCOLARI TOTALI: VARIABILI PREDITTIVE ALL’ANALISI
MULTIVARIATA
HR CI P
RV
hypertrophy
24.12 5.09-
114.12
<0.0001
Myocardial
fibrosis
6.59 1.33-
32.67
0.021
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IPERTROFIA VENTRICOLARE DESTRA: PREDITTORE DI EVENTI
CARDIOVASCOLARI
4/4 pazienti con IVD sono andati incontro a complicanze CV!
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ARITMIE: ANALISI MULTIVARIATA DELLE VARIABILI SIGNIFICATIVE ALL’ANALISI UNIVARIATA
HR 95% CI P
Age 35-45
yrs
- - 0.945
Global heart
T2*<20 ms
- - 0.982
LV
hypertrophy
3.49 0.34-
36.22
0.296
RV
hypertrophy
0.93 0.04-
21.53
0.965
Myocardial
fibrosis
8.84 0.79-
98.84
0.077
Atrial
Dilatation
3.72 0.34-
41.08
0.284
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ARITMIE:VARIABILI PREDITTIVE ALL’ANALISI
MULTIVARIATA
HR CI P
RV
hypertrophy
33.83 6.07-188.74 <0.0001
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IPERTENSIONE POLMONARE: ANALISI MULTIVARIATA DELLE VARIABILI SIGNIFICATIVE ALL’ANALISI UNIVARIATA
HR 95% CI P
Ventricular
Dilation
(left/right)
3.12 0.25-39.09 0.377
RV hypertrophy 3.69 0.34-39.85 0.282
Myocardial
fibrosis
41.94 2.81-
626.76
0.007
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IPERTENSIONE POLMONARE: VARIABILI PREDITTIVE ALL’ANALISI
MULTIVARIATA
HR CI P
RV
hypertroph
y
73.33 10.00-
537.57
<0.0001
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
Ma perché i pz con ipertensione polmonare sono così pochi?
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PERCHE’ UNA COSI BASSA (2,2%) PERCENTUALE DI IPERTENSIONE POLMONARE?
23 pz esclusi perché con patologia cardiaca presente al momento del primo esame RMN ( 8 con ipertensione polmonare).
27
EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
I pz non trasfusione dipendenti sono 124; se dovessimo valutare l’incidenza solo per questi la percentuale sarebbe del 5,64%
Se aggiungessimo gli esclusi ( 8 con ipertensione polmonare) alla popolazione studiata (tot 302) La percentuale sarebbe il 4,96%
….ampiamente in linea con i dati dei diversi database………
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
Che importanza dare alla fibrosi?
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SCAR IS SCARING?
29
EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
LA FIBROSI E’ UN FATTORE PREDITTIVO INDIPENDENTE DI EVENTI CARDIOVASCOLARI AVVERSI?
La fibrosi è prognosi
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
Quali opzioni terapeutiche abbiamo?
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JACC 2013Nice
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
Chronic Hemolytic Anemia
Chronic hemolytic anemia such as sickle cell disease, thalassemia, spherocytosis, and stomatocytosis are associated with an increased risk of PH.
The cause of PH is unclear and often multifactorial, including chronic thromboembolism, splenectomy, high cardiac output, left-heart disease, and hyperviscosity; the role of an inactivation of nitric oxide by free plasma hemoglobin due to chronic hemolysis iscontroversial .
The prevalence and characteristic of PH in chronic hemolytic anemia has been extensively studied only in sickle cell disease (SCD).Specific therapies approved for the treatment of PAH include prostacyclin derivatives, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors.
However, none of these agents is currently approved for the treatment ofPH associated with SCD due to the lack of data in this specific population…..
JACC 2013Nice guidelines PH
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Pulmonary hypertension (PH) is common in thalassemia and contributes to mortality. Advancing age and a history of splenectomy are major risk factors in this population.
The etiology of PH is multifactorial, involving a complex interaction of platelets, the coagulation system, erythrocytes, and endothelial cells along with inflammatory and vascular mediators.
The long-term effect of splenectomy, red cell membrane pathology, coagulation abnormalities, low nitric oxide (NO) bioavailability, excess arginase activity, platelet activation, oxidative stress, iron overload, and chronic hemolysis play a role.
The process of hemolysis disables the arginine-NO pathway through the simultaneous release of erythrocyte arginase and cell-free hemoglobin. Both NO and its obligate substrate arginine are rapidly consumed. The biological consequences of hemolysis on NO bioavailability ultimately translate into the clinical manifestations of PH.
Guidelines for the management of PH in thalassemia have not yet been established; however, clinical trials are ongoing in an effort to guide future therapy.
Ann. N.Y. Acad. Sci. ISSN 0077-8923ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
Cooley’s Anemia: Ninth SymposiumPulmonary hypertension in thalassemiaClaudia R. Morris and Elliott P. Vichins
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clin
take home message
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
Pill in the pocket…….1
Valutazione della massa del ventricolo destro in tutti i pazienti con TI
L’ipertrofia del ventricolo destro è segno precoce di ipertensione polmonare o espressione della stessa
Nei pazienti con emoglobinopatie flow chart per la valutazione dell’ipertensione polmonare che preveda:
STUDI NON INVASIVI:ecocardio ( IT con v max >/= 3,2 m / sec),six min walking test etc..STUDI INVASIVI: cateterismo cardiaco destro
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
Pill in the pocket…….2
La fibrosi miocardica è un fattore predittivo di eventi cardiovascolari ……
Attento follow-up dei pz con positività del delay enhancement nella cardiorisonanza
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clinico diagnostico e prognostico del fare network
nella gestione del paziente con patologia rara
Palermo 27-28 novembre 2014
Pill in the pocket…….3
Le linee guida per l’ipertensione polmonare non prevedono trattamenti specifici per la mancanza di studi clinici
Il network MIOT può iniziare uno studio clinico sulla prevenzione e sulla terapia dell’ipertensione polmonare
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EMOGLOBINOPATIE E MIOT:
il valore aggiunto clin
grazie