Right Ventricular Responses to Massive and Submassive Pulmonary Embolism
Section snippets
Clinical case
A 67-year-old man with a history of hypertension presented to the emergency room with 3 days of dyspnea. He denied leg swelling or pain, chest pain, palpitations, hemoptysis, lightheadedness, or syncope. He also denied any known risk factors for venous thromboembolism (VTE), except for his age. Physical examination revealed an anxious man who easily became dyspneic with minimal exertion. He was afebrile; his heart rate was 88 beats/min, blood pressure 130/92 mm Hg, and respiratory rate 21
Epidemiology
Every year, there are as many as 300,000 deaths in the United States from acute PE.1, 2 Unfortunately, the diagnosis is often not made until autopsy.3, 4 The case fatality rate for PE in the first 3 months after diagnosis has been reported to be about 15% to 18%, exceeding the mortality rate for acute myocardial infarction.5, 6 In fact, a prior study of PE demonstrated that sudden death was the initial clinical manifestation in nearly 25% of patients.7 Acute PE survivors may have sequelae that
Risk factors
Certain risk factors increase the likelihood of VTE, including a previous history of VTE. Trauma, major surgery (particularly hip and knee replacement and hip fracture), cancer, and hospitalization for acute medical illnesses (such as pneumonia and congestive heart failure)8 confer significant risks for thromboembolism. Immobility or markedly reduced mobility also imparts an increased risk. Prolonged air9 or ground travel appears to increase the risk for VTE, as do advanced age, obesity, and
Classifications of acute PE
Small to moderate PE commonly occur and are characterized by normotensive patients with preserved RV function.5 These patients appear clinically well and have an excellent prognosis with therapeutic anticoagulation alone.5
Massive PE is a life-threatening condition. The criteria that define massive PE include cardiogenic shock and systemic arterial hypotension. Shock leads to tissue hypoperfusion, hypoxia, and ultimately, multi-organ failure.10 The emboli are usually bilateral and widespread,
Hemodynamics
The RV response to massive and submassive acute PE is dependent on a few factors: the extent of the emboli, the patient's underlying cardiopulmonary status, and the release of vasoactive and bronchoactive agents such as serotonin from platelets.12, 13, 14 The extent of pulmonary arterial obstruction to blood flow plays a critical role in compromising physiology and predicting the degree of RV dysfunction.12, 15, 16 In addition to physical obstruction, there is an increase in pulmonary vascular
Experimental PE and the RV response
Murine experimental models have been used extensively to study the pathophysiology of RV dysfunction in acute PE. Sullivan and colleagues20 published a study in 2001 looking at biventricular dysfunction in the ex vivo perfused hearts of rats induced with acute massive PE via thrombus infusion. Their data (through examination of Starling curves) support the idea that the intrinsic mechanical function of both ventricles can become depressed in response to an acute massive PE (reduced RV systolic
Clinical Manifestations
It is critically important to prevent diagnostic and management delays when it comes to acute PE, particularly when the emboli are submassive or massive. Thus, having a clinical suspicion of PE is crucial in guiding diagnostic testing. Dyspnea, tachypnea, and tachycardia are the most common symptoms and signs of PE. In massive PE, severe dyspnea, syncope, and cyanosis can accompany hypotension, portending a poor prognosis.5, 13 Interestingly, significant pleuritic chest pain often signifies the
Massive PE
Given its poor prognostic implications, it is imperative to act quickly whenever massive PE is suspected. Intravenous unfractionated heparin (weight-based protocol) should be bolused immediately, followed by continuous infusion of unfractionated heparin targeting an activated partial thromboplastin time (aPTT) of at least 80 seconds.5, 10, 26 Although low-molecular-weight heparin can be used, the shorter half life of standard heparin may be advantageous if thrombolytic therapy, with its
Summary
It is critically important to quickly recognize and treat acute PE. Submassive and massive PE are associated with RV dysfunction and may culminate in RV failure, cardiac arrest, and death. The normally thin-walled right ventricle is a conduit that acutely cannot hold up to the abrupt increase in RV afterload following an extensive PE, and the resultant high RV pressure overload is crucial in appreciating the clinicopathologic progression of this disease. Ultimately, a rapid and coordinated
Clinical case (continued)
Several hours after admission to the hospital ward, the patient became hypotensive (BP 82/46). This hypotension did not respond to a normal saline bolus (1000 mL). His clinical deterioration further progressed and oxygen requirements increased; he ultimately required a 100% non-rebreather mask to maintain his oxygen saturation above 90%. Pressors were initiated, and the medical team agreed to treat with thrombolytic therapy. Recombinant t-PA was infused for 2 hours, and during this time his
References (51)
- et al.
Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER)
Lancet
(1999) - et al.
Double trouble for 2,609 hospitalized medical patients who developed deep vein thrombosis: prophylaxis omitted more often and pulmonary embolism more frequent
Chest
(2007) - et al.
Activation of coagulation system during air travel: a crossover study
Lancet
(2006) Pulmonary physiology during pulmonary embolism
Chest
(1992)- et al.
The acutely decompensated right ventricle
Chest
(2005) - et al.
Right ventricular dysfunction after acute pulmonary embolism: pathophysiologic factors, detection, and therapeutic implications
Am Heart J
(1995) - et al.
Quantitative two-dimensional echocardiography in massive pulmonary embolism: emphasis on ventricular interdependence and leftward septal displacement
J Am Coll Cardiol
(1987) Right ventricular involvement in myocardial infarction and cardiogenic shock
Lancet
(2003)- et al.
Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease
Chest
(1991) - et al.
Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review
J Thromb Haemost
(2007)
Cardiac troponin T monitoring identifies high-risk group of normotensive patients with acute pulmonary embolism
Chest
Cardiac troponin I elevation in acute pulmonary embolism is associated with right ventricular dysfunction
J Am Coll Cardiol
Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism
Am J Cardiol
Pharmacologic hemodynamic support in massive pulmonary embolism
Chest
Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism
Chest
Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Chest
Thrombolytic therapy for acute pulmonary embolism: a critical appraisal
Chest
Relation of duration of symptoms with response to thrombolytic therapy in pulmonary embolism
Am J Cardiol
Interventional therapies for venous thromboembolism: vena caval interruption, surgical embolectomy, and catheter-directed interventions
Clin Chest Med
Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study
Arch Intern Med
Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US
Blood
Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis?
J R Soc Med
A 30-year survey of pulmonary embolism verified at autopsy: an analysis of 1274 surgical patients
Br J Surg
Pulmonary embolism
The epidemiology of venous thromboembolism in the community: implications for prevention and management
J Thromb Thrombolysis
Cited by (0)
Dr Castillo has nothing to disclose. Dr Tapson has consulted with companies active in the field of venous thromboembolism, including sanofi Aventis, Bayer, Johnson & Johnson, EKOS, Pfizer, and Boehringer Ingelheim.