What is the current epidemiology and management of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) in India?

Epidemiology and Management of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) in India

While specific epidemiological data for CTEPH in India is limited, the global incidence of CTEPH is estimated at 3-5 cases per million population per year, and this likely applies to the Indian population as well, requiring a structured approach to diagnosis and management.

Epidemiology of CTEPH

Global Epidemiology (Relevant to India)

• CTEPH has been reported with a cumulative incidence of between 0.1% and 9.1% in the first 2 years after a symptomatic pulmonary embolism (PE) event 1, 2
• The wide range in reported incidence is due to referral bias, absence of early symptoms, and difficulty differentiating acute PE from symptoms of pre-existing CTEPH 1, 2
• Recent data from a prospective multicenter study suggests a more precise CTEPH incidence of 3.7 per 1000 patient-years following PE, with a 2-year cumulative incidence of 0.79% 1
• In Germany, the incidence of CTEPH in 2016 was estimated at 5.7 per million adult population 1
• A recent European study reported an incidence rate of 3.96 per million adults per year 3

Risk Factors Relevant to Indian Population

• Thrombophilic disorders, particularly antiphospholipid antibody syndrome and high coagulation factor VIII levels 1, 2
• Non-O blood groups 1, 2
• History of splenectomy 1, 2
• Inflammatory bowel disease 1, 2
• Ventriculo-atrial shunts 1, 2
• Infection of chronic intravenous lines and devices 1, 2
• Cancer 1
• Inadequate anticoagulation, large thrombus mass, and residual thrombi 1, 2

Diagnosis of CTEPH

Diagnostic Approach

• The diagnosis of CTEPH should be considered in patients with unexplained dyspnea, especially after a history of PE 1
• Diagnosis is based on findings obtained after at least 3 months of effective anticoagulation to differentiate from "subacute" PE 1
• Diagnostic criteria include:
  • Mean pulmonary arterial pressure ≥25 mmHg with pulmonary arterial wedge pressure ≤15 mmHg 1
  • Mismatched perfusion defects on lung scan 1
  • Specific diagnostic signs for CTEPH seen by multidetector CT angiography, MR imaging, or conventional pulmonary angiography 1

Diagnostic Algorithm

1. Initial Screening: Ventilation/perfusion (V/Q) lung scan is the recommended first-line imaging modality with 96-97% sensitivity and 90-95% specificity 1, 2
2. Secondary Evaluation: If V/Q scan shows mismatched perfusion defects, proceed with:
   • Echocardiography to assess right ventricular function 1
   • CT pulmonary angiography to evaluate the extent of disease 1, 4
3. Confirmatory Testing: Right heart catheterization to confirm pulmonary hypertension 1
4. Operability Assessment: Conventional pulmonary angiography is the best method to assess anatomical extent of CTEPH for surgical planning 4, 5

Management of CTEPH

Treatment Algorithm

1. Referral to Expert Center: All patients with suspected or confirmed CTEPH should be referred to a pulmonary hypertension/CTEPH expert center for comprehensive evaluation 1, 6

2. Anticoagulation: Lifelong therapeutic anticoagulation is recommended for all CTEPH patients 7, 4

   • Novel oral anticoagulants (NOACs) are increasingly used (58.3% of patients in a recent registry) 3
   • Vitamin K antagonists remain an alternative option (30.8% of patients) 3

3. Definitive Treatment Options:

   • Pulmonary Endarterectomy (PEA): First-line treatment for patients with surgically accessible CTEPH 4, 5

     • Performed via median sternotomy on cardiopulmonary bypass with deep hypothermia 4
     • Excellent functional results that are generally sustained over time 4
     • 3-year survival rate of about 80% and long-term survival rates of 75-92.3% after 6 years 4

   • Balloon Pulmonary Angioplasty (BPA): Alternative for patients with inoperable disease 3

     • Used in 50% of patients in a recent registry 3
     • Often combined with targeted pharmacotherapy (48.1% of patients) 3

   • Medical Therapy: For inoperable CTEPH or persistent/recurrent pulmonary hypertension after PEA or BPA 4, 3

     • Riociguat is the approved medication for inoperable or persistent/recurrent CTEPH 7
     • Other pulmonary arterial hypertension-specific medications may be considered 4

Treatment Outcomes

• Combined treatment approaches (PEA, BPA, and/or medical therapy) are increasingly common 3
• Persistent CTEPH was present in 46% of PEA patients and 65% of patients after completion of BPA 3
• The use of PEA or BPA is associated with better survival than medical treatment alone 3

Challenges in CTEPH Management in India

• Delayed diagnosis due to non-specific symptoms and signs in early CTEPH 1
• Median time of 14 months between symptom onset and diagnosis even in expert centers 1
• Limited awareness and recognition among healthcare providers 6
• Variable clinical practices in acute PE follow-up and CTEPH diagnosis 6
• Suboptimal referral practices to expert centers 6

Follow-up Recommendations

• Routine clinical evaluation 3-6 months after acute PE episode 1, 7
• Further diagnostic evaluation in patients with persistent or new-onset dyspnea/exercise limitation after PE 1
• Integrated model of patient care involving hospital specialists, qualified nurses, and primary care physicians 1
• Lifelong anticoagulation and regular monitoring for all CTEPH patients 7, 4