Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a progressive and life-threatening disease and a type of pulmonary hypertension, in which it is believed that thromboembolic occlusion (organized blood clots) of pulmonary vessels gradually lead to an increased blood pressure in the pulmonary arteries.
CTEPH is the only cause of severe pulmonary hypertension which is potentially curable without the need to resort to lung transplantation and typically is treated with anticoagulants.
But while we all have innate ability to break down clots, some patients don’t break down a clot that forms in their lungs, and instead of dissolving it turns to scar tissue that obstructs the blood vessels that go to the lungs. The pressure through the blood vessels to the lungs subsequently goes up and then the blood vessels that are still open experience higher blood pressure, causing disease and damage that becomes a progressive and potentially fatally is left untreated.
Results from a retrospective claims database study of pulmonary embolism (PE) patients published in the American Journal of Medicine indicate that U.S. physicians may be under-recognizing and under-diagnosing thousands of cases of this serious lung disease. The study found nearly half (45%) of patients who had a PE had no appropriate follow-up imaging tests performed in the two years following their diagnosis, even though 87% of them showed signs and symptoms of PH, such as breathlessness.
The INFORM (INvestigating the role oF disease monitORing in incident PE patients using a Managed care claims dataset) study, which Bayer sponsored, investigated the incidence of PH diagnoses following acute PE in 7,068 patients in the U.S. The researchers concluded that the two-year cumulative incidence of PH is 7.%, although 50% of these patients also had left heart disease diagnosed, suggesting that the incidence of CTEPH could be 3.8%.
CTEPH is a rare disease and is comparable in terms of population size to pulmonary arterial hypertension, though there are fewer diagnoses. CTEPH may evolve after prior episodes of acute pulmonary embolism, but the pathogenesis is not yet completely understood.
It is estimated that about 0.1% to 9.1% of people with symptomatic pulmonary thromboembolism (PTE or blood clot in the lungs) will develop CTEPH. This makes CTEPH one of the most common subsets of pulmonary hypertension (PH). However, despite this, CTEPH remains unrecognized and undiagnosed in most cases. This results in CTEPH being untreated, which is unfortunate given that CTEPH is potentially curable by a complete pulmonary endarterectomy (PEA).
“The exact prevalence and annual incidence of chronic thromboembolic pulmonary hypertension (CTEPH) are unknown, but recent data suggest that this condition may occur in ~5 individuals per million people per year,” explained Jason L. Guichard, MD, PhD, a cardiologist at The University of Alabama at Birmingham who specializes in advanced heart failure, pulmonary hypertension and heart transplantation.
People with CTEPH have symptoms similar to those of other more common conditions, such as asthma and chronic obstructive pulmonary disease, as well as other types of PH. However, unlike other types of PH, CTEPH is potentially curable with pulmonary thromboendarterectomy surgery. In part because of the nonspecific symptoms, CTEPH is underdiagnosed and often misdiagnosed as another disease.
“Symptoms of CTEPH are very nonspecific. Shortness of breath and fatigue are easily mistaken for more common diseases like asthma. It’s a very common scenario for the diagnosis of CTEPH to be delayed,” explained David Platt, MD, director, U.S. medical affairs, at Bayer Pharmaceuticals. “Physicians must have high awareness of this disease.”
The hallmark of CTEPH is fibrotic transformation of a PTE, leading to mechanical obstruction of the pulmonary arteries. The current understanding is that of an “inflammatory thrombosis.” This means that the PTE is modified by immunologic and inflammatory mechanisms that then trigger pathological remodeling of the pulmonary vessels. The pathological remodeling of the pulmonary vessels results in elevated pulmonary artery pressures and subsequent development of CTEPH.
The standard and potentially curative treatment for CTEPH is pulmonary thromboendarterectomy (PTE), a surgical procedure in which the blood vessels of the lungs are cleared of clot and scar material. However, a considerable number of patients with CTEPH (20%-40%) are not operable and in up to 35% of patients, the disease persists or reoccurs after PTE.
Specific risk factors for PTE have been identified as risk factors for CTEPH. Traditional risk factors for PTE include antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden, plasminogen deficiency, and anticardiolipin antibodies. Additionally, previous splenectomy, indwelling catheters and leads, thyroid replacement therapy, cancer, and chronic inflammatory disorders, such as osteomyelitis and inflammatory bowel diseases, are significantly associated with CTEPH and have a negative impact on survival.
Education of patients to be aware of CTEPH, physicians to determine the diagnosis of CTEPH, and surgeons to master the techniques of complete PEA is a complex and challenging endeavor but must be supported by all professional societies and health systems nationally and internationally.
“Between 300,000 and 600,000 Americans experience a pulmonary embolism every year, and our study shows that up to 4% of those patients may later go on to develop CTEPH,” said Victor Tapson, M.D., director of the Venous Thromboembolism and Pulmonary Vascular Disease Research Program at Cedars-Sinai Medical Center in Los Angeles, in a press release announcing the results of the study. “Furthermore, the results demonstrate that the risk of developing CTEPH after pulmonary embolism remains substantially under-recognized.”
Lack of Physician Awareness
The standard and potentially curative treatment for CTEPH is pulmonary thromboendarterectomy (PTE), a surgical procedure in which the blood vessels of the lungs are cleared of clot and scar material. A considerable number of patients with CTEPH (20%-40%) are not operable and in up to 35% of patients, however, the disease persists or reoccurs after PTE.
A 2015 survey sponsored by Bayer, however, revealed many physicians have a lack of familiarity with CTEPH. The survey of 604 primary care providers included approximately 200 cardiologists and 200 pulmonologists, and the results revealed a substantial under-recognition of surgery as a potential cure for CTEPH.
Additional education on the preferred diagnostic test to identify CTEPH is needed as well, said Richard Channick, MD, director of Massachusetts General Hospital’s Pulmonary Hypertension and Thromboendarterectomy Program.
“Because surgery can be an effective treatment for CTEPH, it is critical that physicians suspect and diagnose the condition. Unfortunately, as demonstrated by this survey, recognition of CTEPH among primary care physicians is inadequate,” Channick in the press release. “We very much need further education to identify and treat these patients as quickly as possible.”
More medical centers have begun performing PTE surgeries, meanwhile, and outcomes are improving6, but the number of physicians who recognize PTE as an option to cure CTEPH remains low, including only 20% of PCPs; 43% of cardiologists; and 64% of pulmonologists. Although surgery is the most effective therapy for CTEPH, 50% of PCPs would categorize it as a last resort, rather than a cure (14%) or treatment (33%).
Ultimately, specialists wish PCPs would refer patients with lung disease symptoms, including those of CTEPH, to them sooner. More than half (55%) of cardiologists and pulmonologists surveyed wish that general practitioners would better understand the specific signs and symptoms of CTEPH and pulmonary arterial hypertension (PAH), so that they can see patients sooner.
“Together with treating physicians, our goal is always to find ways to raise awareness about this misunderstood disease,” said Dario Mirski, MD, vice president and head, U.S. medical affairs at Bayer. “For patients with CTEPH, the benefits of surgery may be very positive, and we hope the results of this survey help drive conversations about optimal diagnostic tools and treatment among physicians and the patient community.”
Lindsey Nolen is a former staff writer.