pipeline problems: exploring the arterial tree

Clinical Cases

Cardiologists of Tomorrow Track

Pipeline problems: exploring the arterial tree

Acute cor pulmonale: don’t forget the pulmonary tumor thrombotic microangiopathy

Anna Patrignani, Francesca Calcagnoli, Nino Ciampani

Cardiology Department, – Area Vasta n°2 – Senigallia Hospital - Italy

http://www.escardio.org/communities/cardio-tomorrow/Pages/welcome.aspx

A 56-year-old man came to our attention because of a

two-day history of progressive dyspnoea

Medical history: arterial hypertension, dyslipidemia and

persistent atrial fibrillation

He was in therapy with warfarin, amiodarone, zofenopril

and atorvastatin

Before the present medical contact he showed normal

electrocardiographic and echocardiographic parameters

Physical examination: tachycardia, tachypnoea, few

basilar inspiratory crackles, swelling of multiple lymph

nodes in left sovraclavicular region

Blood pressure: 120/70 mmHg

Arterial gas analysis

Laboratory tests

Mild anaemia: Haemoglobin 12.7 g/dL

Myocardial injury: Troponin I 0.10 ng/mL (nv 0.00-0.06)

Cardiac dysfunction: BNP 591 pg/mL (nv 0-100)

INR in the therapeutic range (2.0)

Elevated plasma D-Dimer 5758 ng/mL (nv 0-300) ”ELISA assay”

The chest radiography showed no evidence of

parenchymal, interstitial or pleural disease

ECG Sinus tachycardia, QT interval prolongation and T wave

inversion in inferior leads and in V1-V5 precordial leads

TAPSE 11 mm PASP 65 mmHg

Right ventricle inflow tract 49 mm

First diagnostic hyphotesis Acute cor pulmonale due to

pulmonary thromboembolism

INR in the therapeutic range

Lower extremity Doppler ultrasound negative for

deep venous thrombosis

?

Computed tomography pulmonary angiogram negative for thromboembolism

It confirmed the absence of alveolar, interstitial or pleural disease

Multiple lymphadenopathy

A lymph node biopsy and a ventilation-perfusion

scintigraphy were planned

Recent onset of dyspnoea

Hypoxaemia / D-Dimer elevated

Acute cor pulmonale with pulmonary hypertension

Clear lung fields on chest radiography

CT scan negative for thromboembolism with

multiple lymphadenopathy

Microscopic

pulmonary

tumor

embolism ??

Patient’s condition progressively worsened, despite fluid,

oxygen and inotropic therapy

He presented a cardiac arrest due to ventricular asystole

and died three days after admission

A post-mortem examination was required

Macroscopic findings

absence of intraparenchimal lung lesions or visible

thrombo-emboli in the major branches of pulmonary vessels

swelling of abdominal and thoracic lymph nodes

enlargement of left adrenal gland

no macroscopic lesions in the remaining abdominal organs

Most of the small pulmonary arteries and arterioles were stenotic or occluded

by fibrocellular intimal proliferation or thrombo-emboli

Microscopic findings of the lung

No tumor cells invaded the vascular wall or the perivascular areas

Primary tumor site could not be confirmed due to the limitation on autopsy

Morfology of the neoplastic cells: poorly differentiated and some signet ring cells

Neoplastic cells were found in left adrenal gland and

in multiple lymph nodes

Surrenal cortex

Residual lymph node

Final diagnosis:

Acute cor pulmonale due to Pulmonary Tumor

Thrombotic Microangiopathy associated with

cancer of unknown origin

It should be distinguished from microscopic tumor embolism

Tumor cells might not only occlude the small arteries and arterioles,

but also activate the coagulation system and release inflammatory

mediators and growth factors resulting in thrombosis, fibrocellular

intimal proliferation and smooth muscle colonization

Pulmonary Tumor Thrombotic Microangiopathy (PTTM)

The reported incidence in patients with solid tumors varies from

0.9-3.3% in autopsy series

Very few cases have been diagnosed antemortem

Algorithm to improve PTTM antemortem diagnosis

Acute/Subacute “Breathless”

CT pulmonary angiogram

Negative for Thromboembolism

Echocardiogram: first evidence or new onset of pulmonary hypertension ± right ventricular dilatation/dysfunction

Diagnostic hypothesis: Pulmonary Thromboembolism

Hypoxaemia Normal Chest Radiography Laboratory tests

Pulmonary Thromboembolism

Right heart catheterization and blood aspiration

from the catheter in his wedged position

Lung biopsy: CT-guided, transbrochial, open lung

PTTM MPTE

Lung scintigraphy: normal ventilation and non

diagnostic, but atypical, perfusion pattern

Tumor Markers

Breathless differential diagnosis Gavin et al (53)

MPTE (microscopic pulmonary tumor embolism) – PTTM

At the present time, treatment targeting the primary

tumor remains the only therapeutic option

Unfortunately, the poor performance status of most patients at the

time of presentation usually precludes this treatment

Should be considered in the differential diagnosis of

acute/subacute cor pulmonale and pulmonary

hypertension in patients with carcinoma as well as in

noncancer patients

Pulmonary Tumor Thrombotic Microangiopathy

CONCLUSIONS

Clinical Cases

Cardiologists of Tomorrow Track

Thank you for your attention

Anna Patrignani, Francesca Calcagnoli, Nino Ciampani

Cardiology Department, – Area Vasta n°2 – Senigallia Hospital - Italy

http://www.escardio.org/communities/cardio-tomorrow/Pages/welcome.aspx








Right heart cahteterization and blood aspiration



PTTM MPTE



Tumor Markers










Right heart cahteterization and blood aspiration





(history of carcinoma / lymphadenopathy / laboratory tests, tumor markers…)



MPTE – PTTM

Lung scintigraphy: normal

ventilation and non diagnostic, but

atypical, perfusion pattern

It’s potentially dangerous in patients

with compromised capillary beds and

its sensitivity is unknown

Right heart catheterization and

blood aspiration from the catheter in

his wedged position

Distinguishing tumor cells from

pulmonary megakaryocytes and

endothelial cells is technically

challenging and the sensitivity and

specificity of such testing are

unknown







MPTE – PTTM


PTTM MPTE

Lung biopsy remains the diagnostic

gold standard, but there is little

information on the safety of these

procedures in acutely ill patients

with pulmonary hypertension


The vascular occlusive lesions seem to develop exclusively in the lung

The onset of symptoms and acute cor pulmonale can be very rapid

whereas the histological features of fibrocellular and fibromuscolar

proliferation take a relatively longtime to develop

Interesting points

Pathogenesis

Possible pathogenetic role of VEGF and TF (transmembrane

glycoprotein that is a major physiologic initiator of blood coagulation),

2A serotonin receptor, osteopontin, PDGF and many vasoactive

molecules.

Expression of TF and VEGF on tumor cells causes increased

coagulation as well as endothelial damage, after which impaired

endothelia produce various growth factors to induce intimal

proliferation

pipeline problems: exploring the arterial tree

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