Birth of the Modern Era of CTEPH Diagnosis and Care

It was a Sunday morning. That was the only time Drs. Pat Daily or Walt Dembitsky could review cases before they operated on Monday. It was 1986, and I was a pulmonary fellow, so my presence at this meeting with Dr. Kenneth Moser (1929–1997) (Figure 1) was as an observer, not a participant. At this meeting, we discussed the history of a middle‐aged man who had experienced years of declining health. He had been labelled with various cardiopulmonary diagnoses, but none of the prescribed treatments seemed to help. An echocardiogram was eventually obtained, which showed enlargement of the right ventricle. When a carefully solicited history revealed that he had experienced a pulmonary embolus, the puzzle pieces fell into place. They led to a seldom diagnosed disease called chronic thromboembolic pulmonary hypertension (CTEPH).

Figure 1.

Dr. Kenneth Moser (1929–1997).

I knew nothing about CTEPH and soon I realized that I wasn't alone given the state‐of‐the‐art in the mid‐1980s. At that time, the worldwide clinical experience with CTEPH was very limited. CTEPH was rarely reported, the mortality rate was high, and pulmonary thromboendarterectomy (PTE) was considered by many to be “experimental” or “a last resort” [1].

I watched Dr. Moser and Dr. Daily review cut films of a pulmonary angiogram, carefully examining each vessel for signs of organized thrombus. It wasn't only about the diagnosis but also about determining if the surgeon could remove the clots. After an extended discussion, they concluded that PTE was possible, and without other options, they would offer this man an operation that seemed unimaginable. The patient and his family understood that the surgery was risky, and the postoperative course would likely be challenging. The whole thing seemed terrifying, yet hopeful at the same time.

A likely contributor to the obscurity of this disease was that only two university hospitals in the United States exhibited some expertise with the management of CTEPH, Duke University and the University of California, San Diego (UCSD). The two programs were distinctive in their approach to CTEPH. From my perspective, though, the most significant difference was that UCSD had Dr. Moser. His early contribution to the field consisted of the description of four patients undergoing PTE, an eloquently written manuscript published in 1965 [2]. Not only did he describe the value of a novel diagnostic technology, lung scintigraphy, but he also described lessons learned from the endarterectomy of organized thrombus, emphasizing the potential for this unique operation. It was in this article that he observed that “the exploration of any new area inevitably produces as many questions as answers”. This mantra set the tone for his approach to CTEPH patients and had a lasting influence on my entire career. At every step in our approach, the “state‐of‐the‐art” was challenged. Could lung perfusion scans or pulmonary angiography be safely performed in pulmonary hypertensive patients with severe right heart dysfunction? How did pulmonary angiographic findings correlate with what was observed at the time of surgery? Why was it that the degree of occlusive vascular disease poorly correlated with the level of pulmonary hypertension? What explained the observation that in some patients the degree of perfusion abnormalities underestimated the extent of organized thrombus observed on pulmonary angiography? Were there opportunities to “optimize” the clinical status in CTEPH patients with a poorly defined hypercoagulable status to reduce surgical risk? Could changes in surgical approach result in a more complete endarterectomy and mitigate postoperative complications such as hemidiaphragm paresis and the development of reperfusion lung injury? Were there opportunities with postoperative mechanical ventilation, anticoagulation protocols and arrhythmia management to improve outcomes? These questions…and many others…prompted us to develop a meticulous catheterization approach with our interventional cardiologists. We accompanied our surgical colleagues in the operating room to advance our interpretation of pulmonary angiograms. The pulmonary angioscope was developed to better assess the proximal extent of organized thrombi [3]. Procedural modifications and specifically designed surgical instruments resulted in significant advances in outcomes. And the focus on meticulous clinical research drew us closer to the answers to the many questions we faced each day. Dr. Moser was the champion for so many of these efforts. But his most significant influence on me was how important it was to seek out and foster collaboration with a team of talented surgeons, diagnosticians, and clinical research scientists.

The surgical experience at UCSD was published in 1987, describing the evaluation and surgical outcomes of 42 CTEPH patients over a 15‐year period (1970–1985), the largest patient series to date [4]. This group of very sick patients underwent PTE, resulting in a substantial PVR reduction and an improvement in functional status, results that were sustained over the long term. What drew the most attention, though, was the perioperative mortality rate of 16.6%. These results left the impression that surgically eligible CTEPH patients had a viable therapeutic, if not a curative, option at a more acceptable risk.

Soon after that publication, the volume of referrals dramatically increased. Caring for these patients was once only a slice of my day; it rapidly became a full‐time, all‐consuming job. The benefits of this rise in patient volume were an enhancement of our diagnostic and surgical expertise. It advanced scientific insight into CTEPH pathophysiology, and dramatically altered postoperative management as we were able to anticipate and treat commonly observed problems.

When you worked with Dr. Moser, it was apparent that his clinical acumen was often inspired, and I benefited tremendously from his mentorship. Truly though, the beneficiaries of his work are those with chronic thromboembolic disease and the many clinicians who care for this unique patient group. “The exploration of any new area inevitably produces as many questions as answers”…. truer words have never been spoken.

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