A 53-year-old man was referred to the pulmonary hypertension (PH) clinic for shortness of breath. He was in his usual state of health until 6 month before presentation, when he developed progressive shortness of breath that limited his daily activities. His symptoms occurred when walking less than 300 feet on flat surface, climbing one flight of stairs or doing minimal physical activity. He denied shortness of breath at rest, orthopnea, paroxysmal nocturnal dyspnea, syncope or chest pain. He did complain of lower extremity edema that was worse with exertion and got better with rest. During initial work up he was found to have bilateral pulmonary embolisms on a CT scan and was started on warfarin. He expressed minimal improvement in his shortness of breath after initiation of anticoagulation, but remained physically limited.

His past medical history was remarkable for systemic hypertension. He had no prior surgeries. His medications included warfarin titrated to an INR 2-3 and lisinopril 10 mg daily. He works in the post office, has a 10 pack/year smoking history but quit 5 years ago, denies illicit drug or alcohol use. He denies a personal history of stroke, deep venous thrombosis, prolonged flights, coronary artery disease, myocardial infarction, heart failure, interstitial lung disease or connective tissue disorders.

After six month of anticoagulation he was referred to the PH clinic due to persistence of symptoms. His vital signs were notable for a heart rate of 80 bpm, respiratory rate of 20 bpm, blood pressure of 163/75 mmHg, oxygen saturation of 92% on room air. His physical exam showed a well developed African American male in no distress, a regular rhythm with accentuated pulmonary component of second heart sound, no murmurs, normal PMI, clear lungs to auscultation, an estimated jugular venous pressure of 15 cm, 2+ lower extremity pitting edema, no clubbing or cyanosis.

An electrocardiogram showed sinus rhythm with a heart rate of 78 bpm, right bundle branch block, T wave inversion in V1-3 and RA enlargement. A trans thoracic echocardiogram was obtained showing a normal left ventricular (LV) function, mild right ventricular (RV) hypertrophy, tricuspid annular plane systolic excursion (TAPSE) of 15 mm, a dilated RV with a basal diameter of 48 mm, right ventricular systolic pressure (RVSP) of 50 mmHg, a dilated right atrium (RA) and inter ventricular septal motion consistent with RV pressure overload. A ventilation perfusion (V/Q) scan was obtained showing multiple perfusion defects in right upper, middle and lower lobe as well as lingual. Pulmonary function tests showed no obstruction or restriction and DLCO was 65% of predicted. During a 6 minutes walk test he was able to walk 213 meters.

After developing a high suspicion for chronic thromboembolic pulmonary hypertension (CTEPH), the decision was to proceed with a right heart catheterization which showed the following information: RA pressure 20 mmHg, pulmonary artery (PA) pressure of 78/34 mmHg with mean of 50 mmHg, left ventricular end diastolic pressure (LVEDP) of 14 mmHg, pulmonary vascular resistance (PVR) of 8.54 Woods units and cardiac index (CI) measure by Fick method of 2.16. A coronary angiogram showed normal coronary arteries. These studies were follow by a pulmonary angiogram that showed patent but moderately dilated right pulmonary artery, obliteration and pruning of distal basal segments of the right lower lobe with inhomogeneous parenchymal staining; patent but dilated left pulmonary artery, mild peripheral irregularities and pruning of the left lower lobe.

At this point, the diagnosis of CTEPH was made and it was decided that the patient should be considered for a pulmonary artery endarterectomy and his case was discussed with a cardiothoracic team at a high volume center with a perioperative mortality of less than 5%. He was ultimately belied to have disease that was too distal and thus not surgically accessible.

The patient now wishes to know what are his options for treatment for CTEPH.

Questions:

What is the preferred treatment for this patient with chronic thromboembolic pulmonary hypertension (CTEPH)?

A: The treatment of choice for CTEPH even in this case is pulmonary thromboendarterectomy (aka pulmonary endarterectomy or PEA). Operability assessment is subjective. Accordingly, the latest WSPH (5th) guidelines recommend obtaining a second opinion in cases deemed inoperable. Even in our center, our operability criteria have continued to evolve, with our group taking on cases we might have turned down few years ago. Without actually seeing and reviewing the imaging data directly, I am not convinced we have excluded PTE from his treatment option. Imaging quality and technique from center to center also varies greatly. What may seem like minimal disease on one study (suboptimal technique or a single view) may be interpreted differently in favor of surgery when performed at another center. The degree of PH and RV failure in this case should not necessarily preclude successful PTE. His PVR is also in the average range rather than in excess of 1000 or 1500 dynes used as cutoffs in prior reports as being high risk.

What are the treatment options if a patient cannot undergo surgery?

A: If he is ultimately deemed inoperable due to predominantly peripheral disease out of proportion to his hemodynamic derangement, there are several treatment options. First, riociguat is the first and only FDA approved medical therapy for this indication. CHEST-1/2 studies have demonstrated efficacy and safety in these patients treated with riociguat for inoperable CTEPH (or residual PH after surgery). Secondly, a percutaneous catheter based treatment, balloon pulmonary angioplasty (BPA), may be an option depending on center/expertise availability and patient's specific anatomic abnormalities on pulmonary angiogram. This is an emerging technique that requires dedicated training and experience with patient selection and management of complications. Lastly, lung transplantation may be an option if he does not respond to riociguat/medical therapy.

Do you see a role for pulmonary artery angioplasty in patients who are not surgical candidates at this point?

A: BPA is a promising technique that has been refined in the past 5 years by dedicated CTEPH treatment centers in Japan. Multiple centers, each employing different approaches to imaging and balloon sizing, have reported successful examples of treating non-operable CTEPH cases. In the US, the experience is lacking and requires careful and difficult decision to recommend between potentially curable PTE versus an approved medical therapy – or this novel invasive procedure. BPA has been associated with significant complications, including deaths related to the procedure. Accordingly, in most instances, BPA is not a realistic or best first line option.

References

1. Kim NH, Delcroix M, Jenkins DP et al. Chronic thromboembolic pulmonary hypertension J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D92-9. doi: 10.1016/j.jacc.2013.10.024

Keywords: African Americans, Alcohols, Angioplasty, Auscultation, Blood Pressure, Bundle-Branch Block, Cardiac Catheterization, Chest Pain, Connective Tissue, Coronary Angiography, Coronary Artery Disease, Cyanosis, Dyspnea, Edema, Electrocardiography, Endarterectomy, Heart Atria, Heart Failure, Heart Rate, Heart Sounds, Hypertension, Hypertension, Pulmonary, Hypertrophy, International Normalized Ratio, Lisinopril, Lower Extremity, Lung Diseases, Interstitial, Myocardial Infarction, Oxygen, Physical Exertion, Pulmonary Artery, Pulmonary Embolism, Respiratory Function Tests, Respiratory Rate, Smoking, Illicit Drugs, Stroke, Syncope, Systole, Vascular Resistance, Venous Pressure, Venous Thrombosis, Warfarin

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