What is the progression of a missed pulmonary embolism (PE) in a patient, particularly those with underlying risk factors such as cancer, recent surgery, or trauma?

Natural Progression of Missed Pulmonary Embolism

A missed pulmonary embolism carries a 25-30% mortality risk if left untreated, with death primarily occurring from recurrent embolic events, and the majority of fatal cases showing multiple pulmonary emboli of different ages at autopsy. 1, 2

Immediate to Early Progression (Days to Weeks)

Recurrent Embolization Risk

• The onset of massive PE is frequently preceded by smaller emboli in recent weeks that escape clinical detection, with autopsy studies revealing multiple PEs and infarcts of different ages in 15-60% of fatal cases 1
• Without anticoagulation, the risk of fatal or non-fatal recurrent PE is substantial, with historical data showing untreated patients face the highest recurrence risk during the first two weeks 1
• Successive emboli are the primary mechanism of death in untreated PE, and these deaths are potentially preventable with early diagnosis 1

Hemodynamic Deterioration

• Right ventricular afterload stress develops directly related to the size and number of emboli and pre-existing cardiopulmonary status 1
• Patients with pre-existing left ventricular failure or pulmonary disease are at highest risk for pulmonary infarction 1, 3
• Right ventricular dysfunction detected by echocardiography is a major determinant of short-term prognosis and mortality 1, 4

Short-Term Outcomes (Weeks to 3 Months)

Mortality Rates

• Untreated PE demonstrates 30-day all-cause mortality rates between 9-11% and three-month mortality ranging from 8.6-17% in registry data of unselected patients 1
• Advanced age, cancer, stroke, and cardiopulmonary disease are factors associated with higher mortality 1
• Anticoagulant therapy reduces mortality in patients with PE by 75% compared to no treatment 1

Recurrence Without Treatment

• Based on historical data, untreated proximal DVT carries significant risk of recurrence and PE complications in 40-50% of cases, often without clinical manifestations 1
• The cumulative proportion of patients with early recurrence amounts to 2.0% at 2 weeks, 6.4% at 3 months, and 8% at 6 months even with anticoagulation treatment 1
• Active cancer and failure to achieve therapeutic anticoagulation independently predict increased recurrence risk during the early period 1

Intermediate to Long-Term Progression (3-24 Months)

Incomplete Thrombus Resolution

• Pulmonary arterial patency is restored in the majority of PE survivors within the first few months, but lung perfusion abnormalities persist in approximately 35% of patients at one year 1, 2
• The degree of pulmonary vascular obstruction remains <15% in 90% of cases with persistent abnormalities 1, 2
• If acute PEs have not resolved within 1-4 weeks, embolic material becomes incorporated into the pulmonary arterial wall and begins remodeling into connective tissue 3

Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

• The incidence of CTEPH after unprovoked PE is approximately 1.5%, with most cases appearing within 24 months of the index event 1, 2
• CTEPH represents a rare but life-threatening obstructing vasculopathy that develops when thrombi fail to resolve and become organized 2
• If left untreated, CTEPH is usually fatal within 2-3 years following initial detection 1, 2

Critical Clinical Pitfalls

Missed Diagnosis Consequences

• In fatal PE cases, 59% of deaths result from PE that remained undiagnosed during life, and only 7% of patients who died early were correctly diagnosed before death 1
• Silent recurrent PE can present as investigation of dyspnea or chronic right heart failure disclosing severe pulmonary hypertension 1
• Dyspnea, tachypnea, or chest pain are present in 97% of patients with PE, making their absence a strong negative predictor 1

High-Risk Patient Populations

• Patients with cancer, recent surgery (especially orthopedic), major trauma, or immobilization face exponentially higher risk of progression and recurrence 5
• Inpatients have higher incidence of missed PE complications (4.8%) compared to outpatients (0.8%) 1
• Patients with congestive heart failure, chronic cardiopulmonary disease, or stroke with lower limb immobility are at particularly high risk for adverse outcomes 5, 4

Late Recurrence Risk

• After discontinuation of anticoagulation, the cumulative proportion of late VTE recurrence reaches 13% at 1 year, 23% at 5 years, and 30% at 10 years 1
• Recurrent VTE is likely to occur in the same clinical form as the index episode—if the first event was PE, recurrence will most likely be PE again 1

Prognostic Implications

Functional Outcomes

• Between 20-75% of patients report worse health status at 6-month follow-up than at PE diagnosis, with 47% demonstrating reduced maximal aerobic capacity at one year 2
• Even with treatment, long-term prognosis is largely determined by underlying conditions such as malignancy and cardiovascular disease 1