CORSO DI CLINICAL COMPETENCE SULLA MALATTIA TOMBROEMBOLICA VENOSA

Firenze 4-5 Novembre 2010

DALLA TROMBOSI VENOSA ALL’ EMBOLIAALL’ IPERTENSIONE POLMONARE

C. Marini, Dipartimento Cardio-Toracico e VascolareUniversità di Pisa, e Fondazione CNR/Regione Toscana“Gabriele Monasterio”, Pisa.

“Scintigrafia polmonare”

Background. 1

“Prior to 1960, physician diagnosed pulmonary

embolism (PE) by the identification of a

suspicious combination of symptoms, signs,

and non-specific laboratory tests.

After 1960, the diagnostic capabilities were

enriched by the development of angiographic

and radionuclide pulmonary imaging

techniques1,2.”

1. Williams JR, et al. JAMA 1963;184:473-4762. Wagner HN Jr, et al. N Engl J Med 1964;271:377-384

Background. 2“Although invasive, angiography became a “gold

standard” for a validation of any other technique in the

diagnosis of PE, even though it was reported that a

normal perfusion lung scan essentially excludes the

presence of PE1.

In the mid ‘70s, due to some limitations of pulmonary

angiography, ventilation scan (V) was added to

perfusion lung scan (Q) to increase diagnostic

capability for PE by non-invasive techniques2.”

1. Dalen JE, et al. Am Heart J 1971;81:175-1852. McNeal BJ, et al. JAMA 1974;227:753-756

Rapporto ventilazione/perfusione nellaembolia polmonare acuta (EPA)

1. De Nardo GL, Goodwin DA, Ravasini R, Dietrich PA. The ventilatory lung scan in the diagnosis of pulmonary embolism. N Engl J Med 1970; 282: 1334-6.

2. 2. McNeil BJ, Holman BL, Adelstein SJ. The scintigraphic definition of pulmonary embolism. JAMA 1974; 227: 753-6.

3. Miller RF, O’Doherty MJ. Pulmonary nuclear medicine. Eur J Nucl Med 1992;19:355-368.

La strategia diagnostica era basata sulla aspettativa (teorica) dei rapporti ventilazione/perfusione (V/Q) : -Ventilazione normale nelle zone con alterata perfusione (V/Q mismatch) 1,2 : EPA;-Ventilazione alterata nelle zone con alterata perfusione (V/Q match) 3: no EPA .

Background. 3

“Despite the availability of this new diagnostic tool

(V/Q lung scan), a retrospective clinical pathologic

correlative study published in the early ‘80s indicated

a frequency of only 10% of in vita successful PE

diagnosis1.

In other words, the PE diagnosis was still a problem,

and the use of V/Q lung scan did not increase the

diagnostic capability2.”

1. Goldhaber SZ, et al. Am J Med 1982;73:822-8262. Hull RD, et al. Chest 1985;88:819-828

The PIOPED studyProspective Investigation of Pulmonary Embolism Diagnosis( JAMA 1990;263:2753-2759)

Aim. To determine the sensitivity and specificity of ventilation-perfusion (V/Q) lung scan for acute pulmonary embolism (PE).

Methods. To evaluate, in patients with established angiographic diagnosis, the presence and % dimention of at least two or more perfusion defects with or without matching ventilation or chest radiographic abnormalities.

Results. V/Q lung scan: sensitivity 41%, specificity 97%.

Conclusion. V/Q lung scan established the diagnosis or exclusion of PE only for a minority of patients.

The PISAPED studyProspective Investigation Study of Acute Pulmonary Embolism Diagnosis.

(Miniati M, Pistolesi M, Marini C, et al. Am J Respir Crit Care Med1996;154:1387-1393)

Aim. To assess the value of perfusion lung scan (PLS) alone in the diagnosis of acute pulmonary embolism.

Methods. To detect on PLS the presence (PE+) or the absence (PE-) of at least one of wedge-shaped perfusion defect with or without matching roentgenographic lung parenchimal abnormalities in patients with established angiographic diagnosis.

Results. PLS alone: sensitivity 86%, specificity 93%.

Conclusion. Accurate diagnosis of PE is possible by PLS alone.

12

3

4

56

98

7

Right lung

apex

12

3

6

78 9

4

5

Left lung

apex

Normal pulmonary angiographyNormal lung scan

base

base

Anterior

Anterior

Right arterylateral view

Left arterylateral view

Left oblique posterior view

apex

Anterior

base

base

apex

Anterior

Left oblique posterior view

Acute pulmonary embolism

Left pulmonary artery angiogram(anterior-posterior view)

Left lung perfusion scan(left lateral view)

2

1

3

4

56

78 9

Anterior

Base

Apex

apex

apex

3

6

78

23

87

2

12

3

4

56

98

7

apex

12

3

6

78 9

4

5

apex

apex

base

apex

base

Normal lung scan Lung scan withwedge-shaped defects

[PE +]

Lung scan withoutwedge-shaped defects

[PE -] Right lung

Anterior

base base

Left lung

base

Anterior

base

Right oblique posterior

Left oblique posterior

Anterior

Anterior Anterior

1

4

56

9

1

4

5

Anterior

PIOPED versus PISA-PEDV/Q scan

High probability(PIOPED)

Q scansuggestive of PE

(PISA-PED)

Sensitivity (%) 41 86

Specificity (%) 97 93

Alterazioni radiografiche in PIOPED e PISAPED

* Worsley DF, et al. Radiology 1993;189:133-6

PIOPED: JAMA 1990;263:2753 1063 pazienti; 88% con alterazioni Rx toraciche*.Nelle embolie, atelettasie e densità parenchimaliin 99/219 pz. (45%) a dx e 93/183 pz. (51%) a sn.

PISA-PED: Am J Respir Crit Care Med 1996;154:1387 1100 pazienti; nelle embolie, infarti in 74/440 pz. (17%), atelettasie in 123/440 pz. (28%), elevazionediaframma in 185/440 pz. (42%) e versamento pleurico in 198/440 pz. (45%).

sensitivity

specificity

The PIOPED study

PIOPED

83%

96%

PISAPED

86%

93%

Radiation burden for commonly used imaging

techniques

Technique Dose(mSv) Equivalent no. of chest radiographs

Ultrasonography 0 0

Chest radiography 0.02 1

Lung scintigraphy 1 50

Spiral CTPA 7 350

Costs of imaging techniques for pulmonary

embolismTechnique Cost (Euros)

Ultrasonography 72

Chest radiography 21

Lung scintigraphy (Q) 68

Lung scintigraphy (V) 198

Spiral CTPA 206

Miniati M. et al. Medicine (Baltimore) 2006;85(5):253-262

Follow-up scintigrafico ed emogasanalitico in pazienti con APE

Management of suspected acute pulmonary embolism in the era of CTAngiography: A statement from the Fleischner Society.

Remy-Jardin M, et al. Radiology 2007;245:315-329

“If scintigraphy is used, elimination of the ventilation scan can reduce

cost and radiation. Although this is not common practice in most

centers, there is evidence from two studies1,2 that ventilation scan

can be eliminated without compromising diagnostic accuracy……

In addition, better sensitivity was achieved when the scans of the

PIOPED I study were reread by a blinder observer using the

perfusion images alone2.

Accordingly, scintigraphy can be considered as a preferred altenative

chest imaging technique for patients who cannot undergo

CTAngiography.”

1. Stein PD, et al. Am J Cardiol 1992;69:1239-1241

2. Miniati M, et al. Am J Respir Crit Care Med 1996;154:1387-1393

CONCLUSIONE

La scintigrafia polmonare da perfusione da sola nella diagnosi di embolia polmonare acuta:

VANTAGGI:- alta accuratezza diagnostica;- bassa esposizione radiante;- basso costo;- facile da ottenere;- facile da leggere;- innocua per il paziente;- utile per il monitoraggio del paziente .

LIMITI:- Nessuno

Consolidation(infarction)

Consolidation(no infarction)

Oblique posteriori destre

Oblique posteriori sinistre

giugulo

base

giugulo

base

giugulo

base

giugulo

base

giugulo

base

giugulo

base

Scan Normale Scan di EP Scan di non EP

Radiation burden for commonly used imaging techniques

Technique Dose(mSv) Equivalent no. of chest radiographs

Ultrasonography 0 0

Chest radiography 0.02 1

Lung scintigraphy 1 50

Spiral CTPA 7 350

Costs of imaging techniques for pulmonary embolism

Technique Cost (Euros)

Ultrasonography 72

Chest radiography 21

Lung scintigraphy (Q) 68

Lung scintigraphy (V) 198

Spiral CTPA 206

Expected versus observed PE (583 patients)

12/1872PE-Low

108/8113PE-Intermediate

7115/2158PE-High

5910/1758PE+Low

9259/6493PE+Intermediate

99212/21399PE+High

(%)PE /no. ptsExpected PE (%)ScanClinical probability

Miniati et al: Am J Respir Crit Care Med 1999

119/583 = 20% need further investigation to reach diagnosis

Clinical probability combined with CTA results (PIOPED , 477 patients)

Clinical probability CTA PE/No. of pts %

High + 22/23 96

Intermediate + 93/101 92

Low + 22/38 58

High - 6/15 40

Intermediate - 15/136 11

Low - 6/164 4

189/477 = 40% need further investigation to reach diagnosis

Predictors of pulmonary embolism

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Pisa Model 2. AUC: 0.88

Miniati M, et al. Am J Respir Crit Care Med 2008;178:290-294

Le Gal, et al. Ann Intern Med 2006;144:165

Wells PS, et al.Thromb Haemost 2000;83:413

Clinical models: predictors of PE

AUC: 0.78 AUC: 0.74

Angiografia polmonare con “Stop Flow”

Management of suspected acute pulmonary embolism in the era of CTAngiography: A statement from the Fleischner Society.

Remy-Jardin M, et al. Radiology 2007;245:315-329

“If scintigraphy is used, elimination of the ventilation scan can reduce

cost and radiation. Although this is not common practice in most

centers, there is evidence from two studies1,2 that ventilation scan

can be eliminated without compromising diagnostic accuracy……

In addition, better sensitivity was achieved when the scans of the

PIOPED I study were reread by a blinder observer using the

perfusion images alone2.

Accordingly, scintigraphy can be considered as a preferred altenative

chest imaging technique for patients who cannot undergo

CTAngiography.”

1. Stein PD, et al. Am J Cardiol 1992;69:1239-1241

2. Miniati M, et al. Am J Respir Crit Care Med 1996;154:1387-1393