December 5, 2014

What Happens to Patients Who Suffer Pulmonary Embolus

Pulmonary embolism (PE) is a common and often fatal disease process whose clinical presentation and long term outcome is widely variable. The natural evolution of PE ranges significantly, with abrupt hemodynamic compromise and death within one hour for approximately 10% of all cases. In contrast, approximately one third of patients with deep venous thrombosis (DVT) present with asymptomatic PE . The pathophysiologic consequences of an acute PE are primarily hemodynamic and manifest when approximately 30-50% of the pulmonary bed is obstructed. When this obstruction approaches 75%, the right ventricle (RV) must acutely generate a systolic pressure above 50 mm Hg, which a normal ventricle cannot accommodate. This leads to RV ischemia and dysfunction, and in severe cases, septal shift resulting in left ventricular obstruction and significant hypotension . Early mortality is closely linked to the probability of recurrent PE with an associated death rate of approximately 25%. This cascade of events can progress rapidly, and if unrecognized and untreated, PE mortality approaches approximately 30%.

Although certain clinical signs and symptoms can help to guide the clinician towards the diagnosis of PE, these are often nonspecific and lack adequate positive or negative predictive value for conclusive diagnosis. Therefore, several objective measures should be employed to help risk stratify patients into massive (high), submassive (intermediate) and nonmassive (low) PE categories . A patient meets criteria for massive PE when they present with systolic blood pressure less than 90 mm Hg (or a systolic pressure decrease greater than 40 mm Hg from baseline) for greater than 15 minutes. Additional criteria for massive PE include persistent hypotension requiring pressor support, pulselessness or persistent bradycardia (less than 40 bpm). Submassive PE criteria include evidence of RV dysfunction, RV chamber dilation (either by echocardiogram or computed tomography), EKG changes or elevated biomarkers (troponin I or T, or brain naturietic peptide). Nonmassive PE do not meet criteria for either massive or submassive PE.

Early risk stratification for patients with PE is essential as mortality dramatically increases with escalating level of risk. Early mortality exceeds 15% for patients who meet criteria for massive PE. Within this subgroup, mortality approaches 70% for those who require cardiopulmonary resuscitation vs approximately 25% for patients who present with shock . Even within the submassive PE subcategory, RV dysfunction alone is associated with a 3 to 15% early mortality risk. An RV diameter/LV diameter ratio greater than 0.9 on chest CT is associated with an 82% thirty day adverse event rate (odds ratio 4.0) . This also portends to long term consequences as dysfunction that does not resolve at hospital discharge is associated with 13% risk of PE-related mortality at three years . In contrast there is a 4% three year mortality for patients with resolved RV dysfunction at hospital discharge. Other findings on echocardiogram can also indicate poor prognosis, including severe RV free wall hypokinesis with sparing of the apex (McConnell’s sign), pulmonary hypertension, tricuspid regurgitation, and RV thrombus. Cardiac biomarkers also assist with short term prognostication where the odds ratio for short term mortality is 5.9 for patients with elevated troponin , and is 9.5 and 5.7 for patients who present with elevated BNP or pro-BNP , respectively. Non massive PE carry significant less mortality burden, with <1% of patients experiencing early death. The long term all-cause mortality of acute PE is significantly linked to concurrent clinical parameters which include advanced age, malignancy, neurodegenerative disease, chronic renal disease and cardiovascular disease . Approximately one-third of all patients who suffer a PE will die within 5 years and the predominant cause of long term mortality is associated cardiovascular disease. Finally, it is important to consider longstanding pulmonary hypertension due to chronic thromboembolic disease, affecting approximately 0.5-3% of all patients who experience PE .

References

  1. Stein P, Matta F, Musani M, Diaczok B. Silent pulmonary embolism in patients with deep venous thrombosis: a systematic review. Am J Med. 2010 May; 123(5):426-31.
    Piazza G, Goldhaber SZ. Acute pulmonary embolism: part I: epidemiology and diagnosis. Circulation. 2006 Jul 11; 114(2):e28-32.
  2. Piazza G, Goldhaber SZ. Acute pulmonary embolism: part I: epidemiology and diagnosis. Circulation. 2006 Jul 11; 114(2):e28-32.
  3. Jaff M, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26; 123(16):1788-830.
  4. Kasper W, et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol. 1997 Nov 1; 30(5):1165-71.
  5. Quiroz R, et al. Right ventricular enlargement on chest computed tomography: prognostic role in acute pulmonary embolism. Circulation. 2004 May 25; 109(20):2401-4.
  6. Grifoni S, et al. Association of persistent right ventricular dysfunction at hospital discharge after acute pulmonary embolism with recurrent thromboembolic events. Arch Intern Med. 2006 Oct 23; 166(19):2151-6.
  7. Becattini C, Vedovati MC, Agnelli G. Prognostic value of troponins in acute pulmonary embolism: a meta-analysis.Circulation. 2007 Jul 24; 116(4):427-33.
  8. Sanchez O, et al. Prognostic value of right ventricular dysfunction in patients with haemodynamically stable pulmonary embolism: a systematic review. Eur Heart J. 2008 Jun; 29(12):1569-77.
  9. Ng A, et al. Long-term cardiovascular and noncardiovascular mortality of 1023 patients with confirmed acute pulmonary embolism. Circ Cardiovasc Qual Outcomes. 2011 Jan 1; 4(1):122-8.
  10. Piazza G, Goldhaber SZ. Chronic thromboembolic pulmonary hypertension. N Engl J Med. 2011 Jan 27; 364(4):351-60.