Anjali Vaidya, MD, FACC, FASE, FACP Associate Director, Pulmonary Hypertension, Right Heart Failure,

and Pulmonary Thromboendarterectomy Program Advanced Heart Failure & Cardiac Transplant

Temple University Lewis Katz School of Medicine

Disclosures

• No disclosures relevant to this presentation

• Consulting/Speaking: United Therapeutics, Gilead, Actelion, Bayer

Pulmonary Hypertension

evolution

Pulmonary Hypertension

I: Pulmonary Arterial HTN (PAH) – Idiopathic/Familial – Portal HTN – Drugs/Toxins – Collagen vascular disease – HIV – Systemic-Pulm Shunt – Schistosomiasis – PPHN

II: Pulmonary Venous HTN (Left Heart Disease) – Left ventricular or atrial disease – Mitral or Aortic valve disease

III: Chronic Respiratory Disorders – Interstitial lung disease – COPD – Sleep disordered breathing (Who Group II?) – Chronic high altitude exposure – Alveolar hypoventilation disorders

IV: Chronic thromboembolic disease (CTEPH) V: Miscellaneous

– External compression, Tumor obstruction – Fibrosing mediastinitis – Langerhans cell histiocytosis – Lymphangiomatosis – Hematologic disorders – Sarcoidosis

J Am Coll Cardiol. 2013;62(25_S) – 5th WSPH Nice 2013

Hemodynamics: PAH = CTEPH

• Defined as:

– mPAP (mean pressure) ≥ 25 mmHg - HIGH

– PAWP (L heart pressure) ≤ 15 mmHg - LOW

– PVR (vascular resistance) > 3 Wood Units - HIGH

• PH Specific Medical Therapy approved for:

– WHO Group I (PAH) - all

– WHO Group IV (CTEPH) – riociguat

CTEPH Diagnosis

• PAH hemodynamics (PVR >3, PCW < 15)

• VQ with unmatched perfusion defects

• CTA Chest with vascular abnormalities

• Anticoag > 3-6 months

Kim, NH et al. J Am Coll Cardiol. 2013.62(suppl).D92-99.

Incidence of CTEPH after PE?

Pengo, V, et al. N Engl J Med 2004.350:2257-2264.

1% at 6 months

3.1% at 1 year

3.8% at 2 years

• Prospective • N = 314 • Median f/u 8 years • Risk predictors:

• Idiopathic • Young age • Large defect • Hx multiple PEs

Risk Factors for CTEPH

• PE specific: – Recurrent, ‘unprovoked’ – Young age at PE diagnosis – PASP > 50 mm Hg at time of PE

• Hypercoagulable:

– Lupus anticoagulant, antiphospholipid – Protein C, S deficiency – Beta 2 Microglobulin – Prothrombin gene mutation

• Medical conditions:

– Cancer – Indwelling pacemaker, ports – Splenectomy

Piazza G, Goldhaber SZ . N Engl J Med 2011;364: 351-360.

Risk Factors for CTEPH

• PE specific:

• Hypercoagulable:

• Medical conditions:

• Anatomic conditions:

– May-Thurner Syndrome

– Uterine fibroids

– Pelvic vein compression, stenosis

Lacharite-Roberge A, Vaidya A. CTEPH National Proceedings. 2017c

V/Q Scan

Fedullo PF. N Engl J Med 2001; 345:1455-1472.

CTEPH Evaluation

Left image courtesy of Dr Nick Kim, University of California, San Diego. Right image courtesy of the PTE Program at University of California, San Diego.

Treatment Evaluation

• Guidelines recommend referral to expert PTE/CTEPH Program

• Multidisciplinary care: Cardiology/PH, Chest Radiology, Cardiac Surgery, Interventional Cardiology

• Coordinators

Pulmonary Thromboendarterectomy

• First line treatment

• Similar to transplant, outcomes correlate with volume and experience

• Deep hypothermia (20° C)

• Extracorporeal circulation

• Circulatory arrest (20 minutes)

• ICU Perioperatively: – Reperfusion pulmonary lung injury – VV ECMO

– Bleeding

– Hemodynamics

– Neurologic; Sedation

– Arrhythmia

Jamieson SW, et al. Ann Thoracic Surg.2003;76:1457-1464. Galie N, et al. Eur Heart J. 2009;30:2493-2537

Post-Operatively

• Improvements in 6MW distance

• Improved RV function, TR

• Improved hemodynamics

• Improved quality of life

• Life-long anticoagulation

• Inoperable?

• Are you sure?? (expert center referral) – Distal disease

– Comorbidities

– PH out of proportion to thromboembolic burden

Kim NH, et al. J Am Coll Cardiol. 2013;62(suppl) D92-D99. Pepke-Zaba J, et al. Circulation. 2011;124:1973-1981

CTEPH treatment algorithm

Pulmonary Embolectomy

Pulmonary Thromboendarterectomy

Raza F, Vaidya A, Forfia P. J Cardiovascular Surgery. 2017 Sep 4.10188-6.

N = 108 PTEs Mortality = 3.7% Last year: 40 PTEs

Raza F, Vaidya A, Forfia P. J Cardiovascular Surgery. 2017 Sep 4.10188-6.

Raza F, Vaidya A, Forfia P. J Cardiovascular Surgery. 2017 Sep 4.10188-6.

Raza F, Vaidya A, Forfia P. J Cardiovascular Surgery. 2017 Sep 4.10188-6.

Raza F, Vaidya A, Forfia P. J Cardiovascular Surgery. 2017 Sep 4.10188-6.

• 68 yo M with hx NICM, EF 10%

• Progressive DOE • Remote PE 40 years ago • Referred to TUH for OHT • Severely elevated PVR

Balloon Pulmonary Angioplasty

PH: Medical Therapy • PDE-5 inhibitors

– sildenafil, tadalafil

• Guanylate cyclase stimulator – riociguat

• Endothelin receptor antagonists – bosentan, ambrisentan, macitentan

• Prostacyclin therapy – treprostinil, epoprostenol, iloprost

• Prostacyclin receptor agonist – selexipag

CTEPH!

Drug Pathways in PAH

CHEST-1

NEJM 2013

Improved: 6MW, PVR, NT-ProBNP, Functional Class

PH: Medical Therapy • PDE-5 inhibitors

– sildenafil, tadalafil

• Guanylate cyclase stimulator – riociguat

• Endothelin receptor antagonists – bosentan, ambrisentan, macitentan

• Prostacyclin therapy – treprostinil, epoprostenol, iloprost

• Prostacyclin receptor agonist – selexipag

CTEPH?

Drug Pathways in PAH

MERIT-1 Data - Macitentan

• Phase 2, DBRCT vs placebo, inoperable CTEPH

• N = 80; 16 weeks

Ghofrani HA, et al. Lancet. 2017.5(10):785-794.

Improved:PVR 16% reduction, 6MW distance (34 meters)

Thank You!

Pulmonary Hypertension, Right Heart Failure, and Pulmonary

Thromboendarterectomy Program P: 215-707-7636; F: 215-707-9977

Cell: 215-531-2297 anjali.vaidya@tuhs.temple.edu

9th Floor Parkinson Pavilion 3401 North Broad Street Philadelphia, PA 19140