Cardiovascular Effects of Pulmonary Embolism

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Lisa Motavalli, M.D.

Annually in the US, there are at least 600,000 episodes of pulmonary embolism (PE) leading to more than 100,000 deaths.(1) In the International Cooperative Pulmonary Embolism Registry (ICOPER), designed to measure overall mortality in patients presenting with PE, 3 month mortality rate was noted to be 11.4% at 14 days and 17.4% at 3 months.(2) Despite modern methods for diagnosis and treatment, the mortality rate can be as high as 30% in patients presenting with massive PE.(1) The initial evaluation of patients is critical to allow for rapid diagnosis. In addition to the current recommended diagnostic strategy, many of these patients undergo cardiac testing including EKG, cardiac biomarkers and echocardiography. The interpretation of these tests plays a role in early diagnosis, risk stratification, and management.

Pulmonary emboli usually arise from the lower extremity deep venous system, but they may also arise from the renal veins, pelvic veins, upper extremities as well as from the right heart. When venous thrombi detach from their sites of formation, they flow toward the pulmonary arterial circulation. Depending on the size of the embolus, and the site at which it lodges, the clinical consequences may range from minimal to massive saddle embolism with sudden death.

When a clot lodges in the pulmonary arterial circulation, various pathophysiologic effects occur. Pulmonary vascular resistance increases from anatomical obstruction and from the release of vasoconstricting factors, and impaired gas exchange results from the redistribution of blood flow leading to impaired ventilation/perfusion units and increased alveolar dead space. Reflex stimulation of irritant receptors, increased airway resistance and decreased lung compliance also has a role in the pathophysiology of pulmonary embolism.(3)

Right ventricular dysfunction can develop in this setting, as a consequence of increased pulmonary vascular resistance. The extent of pulmonary vascular obstruction and the presence of underlying cardiopulmonary disease determine the degree of RV dysfunction. With massive PE, the increase in right ventricular wall tension caused by the rise in pulmonary artery pressure leads to impaired right ventricular function and dilatation of the RV, RV ischemia and ultimately impaired LV filling with compromised cardiac output and systemic hypoperfusion. This cycle can lead to shock, circulatory collapse and death.(4)

The clinical evaluation of these patients is of paramount importance to establish early diagnosis. The most common patient complaint noted in the ICOPER registry was dyspnea (82%) and the most common finding on exam was tachypnea (60%).(2) Several abnormalities on the physical exam which suggest RV dysfunction include systemic arterial hypotension, right sided S3, accentuated P2, parasternal lift, tricuspid regurgitation murmur, elevation of JVP and cyanosis.(4)

The electrocardiogram is a frequently performed test in patients with suspected PE. Despite its lack of sensitivity and specificity, the EKG may have some value in determining the extent of the clot burden. In the PIOPED database, 30% of patients were noted to have a normal EKG, with the most common EKG finding noted to be non- specific abnormalities of ST segment or T wave in 49% of their population.(5)

An anterior ischemic pattern (negative T waves in leads V1-V4) has been described in the literature and is one of the more common findings, especially in the setting of massive PE. In one study, the anterior ischemic pattern was shown to correlate with severity of PE, and was a strong marker of severity when it appears on the first day.(6) The S1Q3T3 pattern, sinus tachycardia, low voltage in the limb leads, new complete or incomplete RBBB and pulmonary P wave are other EKG patterns suggesting PE.(7) EKG scoring systems have been designed and have been demonstrated to correlate with percentage perfusion defect on V/Q scanning and severity of pulmonary hypertension from PE.(8,9)

Cardiac biomarkers (BNP, cardiac troponin) are also being performed more frequently in patients with PE, especially when the presenting complaints mimic that of cardiac ischemia. At this time, they are not yet included in formal guidelines for treatment decision but they are emerging as promising tools for risk assessment.

Serum troponin levels have been shown to be elevated in 30 to 40 percent of patients with a moderate to large pulmonary embolism.(10) The likely explanation for troponin release in PE is development of micro-infarcts from abrupt increase in PA pressure with an elevation in RV wall tension.(11) Troponins have been shown to be a risk factor for poor outcome in acute pulmonary embolism and elevation of troponin T has been related to more frequent prolonged hypotension/shock, need for ionotropic support, cardiopulmonary resuscitation, mechanical ventilation and death.(10) The negative predictive value of troponin has been shown to be high (92%) for predicting major clinical events, suggesting that a normal troponin level may identify a group of patients at low risk in the acute setting.(12)

BNP (brain natiuretic peptide), a plasma neurohormone released from the cardiac ventricules in response to increased pressure and stretch, has been shown to correlate with left ventricular dysfunction and is frequently elevated in setting of congestive heart failure. RV dysfunction in patients with pulmonary embolism can also result in an elevation of serum BNP levels and the magnitude of BNP elevation has been shown to predict adverse outcome.(13) In one study of 73 patients with acute PE, pts with BNP >90 pg/ml had lower blood pressures, higher heart rates, and 88% of pts with moderate-severe RV dysfunction on echo had BNP >90 pg/ml.(14)

Echocardiography is another diagnostic tool that may be useful for risk stratification in the setting of acute PE. Transthoracic echo is of limited diagnostic value and in one study, TTE failed to identify 50% of pts with angiographically proven PE.(15) Therefore, echo should not be used as a screening test for PE but may be useful for identifying pts who may have a worse prognosis such as those with PFO, free floating right heart thrombus and right heart dysfunction. In patients with major PE (with associated RV dysfunction), detection of right to left shunt through a PFO signifies a higher risk of death and arterial thromboembolic complications. Patients with a PFO also had a significantly higher incidence of ischemic stroke and peripheral arterial embolism.(16)

Floating right heart thrombi is a rare phenomenon, but tends to carry a dismal prognosis (45% mortality in one series).(17) Approximately 4% of patients in the ICOPER were found to have right heart thrombi by echo and these patients were more hemodynamically compromised, with lower SBP, higher HR, had more frequent RV hypokinesis on echo and had increased overall mortality.(18) Echocardiography is helpful for identifying patients with RV dysfunction who may have a poor prognosis. The most frequently used qualitative standards for diagnosing RV dysfunction are RV/LV end diastolic diameter >1 in apical 4 chamber view, RV end diastolic diameter >30 mm and paradoxical RV septal motion.(19) A distinct echocardiographic pattern of RV dysfunction, with akinesia of RV free wall but normal motion at apex, has been shown to occur in acute PE and has been coined “McConnel'’s sign”.(20)

Analysis of several registries has demonstrated that a finding of RV dysfunction on echo predicts an adverse outcome.(2,21,22) A systematic review of seven studies found that the incidence of right ventricular dysfunction ranged from 40-70 % of patients with PE, and that this finding was associated with a doubling of the risk of adverse outcomes in patients with hypotension.(23) Until recently, the data were less convincing in hemodynamically stable patients. A recent review of ICOPER demonstrated that among patients with PE presenting with SBP > 90mmHg, echocardiographic RV hypokinesis is an independent predictor of early death.(24) Hemodynamically stable patients with RV dysfunction on echocardiography constitute a current study group of interest for possible use of more aggressive treatment.

Heparin/LMWH followed by oral anti-coagulation constitutes the main treatment for pts with non-massive PE and without contraindications for anti-coagulation. For patients with hemodynamic instability, the guidelines suggest the use of thrombolytics int the absence of contraindications.(25) However, for patients with normal blood pressure and clinical, hemodynamic or echo evidence of RV dysfunction, the benefit of thrombolytics is less clear. A 24 hour improvement in RV wall motion in patients receiving thrombolytics has been demonstrated but several trials have revealed conflicting findings regarding mortality benefit.(26,27,28) In one trial of patients with normal BP and RV dysfunction, TPA minimized escalation of therapy (need for pressors, mechanical ventilation, CPR or open-label thrombolysis) without a statistically significant change in mortality alone.(29) Based on these results, thrombolytic therapy remains controversial in patients with stable blood pressure despite RV dysfunction.

PE is a common condition requiring rapid diagnosis and accurate risk stratification. Massive PE and RV dysfunction carry substantial morbidity and mortality and cardiac testing that is frequently performed in these pts can be important in suggesting the diagnosis, and distinguishing groups at increased risk. The EKG may help raise suspicion or confirm the diagnosis of PE in patients with right heart strain. Cardiac biomarkers (BNP, troponin) may be helpful in identifying low risk PE patients. Echocardiography should not be used for diagnosis, but is useful for risk stratification. Further studies are needed before thrombolytic use in RV dysfunction in stable patients is incorporated into guidelines.


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