Electrocardiogram Findings Associated With Malignant Pericardial Effusion and Cardiac Tamponade

Mr T. was a 71-year-old Caucasian male admitted to the hospital with new-onset shortness of breath. The patient had no documented past medical history and had not seen a physician throughout his adult life. He was a nondrinker but admitted a history of cigarette smoking that began at age 10. Up until several weeks prior to admission, he continued to smoke 2 packs of cigarettes per day. Two to three weeks prior to admission, the patient, who was normally regularly active, noticed dyspnea on exertion. As the dyspnea with exertion worsened over the next several days, he became more concerned. He reported that “I figured I better stop smoking for this breathing problem to get better.” After a week of no smoking, the shortness of breath did not improve. At the urging of his wife, he reluctantly presented to a local urgent care center. A chest x-ray demonstrated a right perihilar mass with concern for pneumonia. The treatment plan included antibiotics, albuterol, and prednisone. He was advised to follow up with a primary care physician (PCP) for further evaluation of the perihilar mass. His wife’s PCP agreed to see Mr T. in the office 1 week later. Prior to that appointment, the patient’s dyspnea worsened, and he developed orthopnea. Mr T.’s wife called her PCP, who agreed to see the patient earlier than the previously scheduled appointment; the patient was directly admitted to the hospital from the office. A computed tomography scan of the chest and abdomen demonstrate a hilar mass suspicious for malignancy, a large pericardial effusion, a large right pleural effusion, a heterogenous mottled liver with potential for hepatic vein thrombosis, and abdominal and pelvic ascites. A transthoracic echocardiogram (TTE) was ordered by the primary team and cardiology was consulted.During the physical examination by the cardiology advanced practice nurse (APRN), the patient was resting comfortably in bed and noted that his dyspnea had improved since he had received intravenous diuretics. His blood pressure was 106/70 mm Hg, his heart rate was 106 beats per minute, and his respiratory rate was 18 breaths per minute. His oxygen saturation was 99% on room air. Positive physical examination findings included the presence of jugular venous distention (JVD) to the angle of the jaw with the head of the bed at 45°. Lung sounds were diminished over the right base, otherwise with no adventitious sounds. Auscultation of the heart revealed a regular rate and rhythm with a mild tachycardia. During cardiac auscultation, the cardiology APRN noticed no murmurs, rubs, or gallops but did recognize an auscultatory alternans, a finding that coincided with the pulsus alternans noted on assessment of peripheral pulses. Moderate abdominal ascites and 1+ lower extremity pitting edema were present. The cardiac monitor demonstrated electrical alternans (Figure). The cardiology APRN ordered a 12-lead electrocardiogram (ECG), which demonstrated tachycardia with low-voltage QRS complexes, most visible in the limb leads; normal but rightward QRS axis of 60°; and electrical alternans present in all leads. Leads V4 and V5 demonstrated alternating polarity (Figure). The cardiology APRN assessed the pulsus paradoxus and determined it to be 10 mm Hg.Pericardial effusions occur secondary to many causes including infectious disease; autoimmune disorders; trauma; metabolic syndromes such as uremia or myxedema; chest radiation; transudative fluid shifts; cancers; and after a myocardial infarction or cardiac surgery.1 The cancers most often associated with malignant pericardial effusions include breast, lung, esophageal, melanoma, leukemia, and lymphoma,2,3 with primary lung cancer being the most common cause, accounting for more than one-third of cases.4,5 Malignant pericardial effusion is seen in approximately 20% of all cancers.4 When first seen, 18% of patients with malignant pericardial effusions have not already had a malignant neoplasm diagnosed.6Cardiac tamponade, although rare in malignant pericardial effusions, is a life-threatening emergency that requires early recognition and prompt treatment. Large pericardial effusion with pericardial volumes greater than 500 mL are often associated with malignancies.7,8 Cardiac tamponade is a clinical syndrome that occurs when the pressure from the pericardial fluid impedes ventricular filling during diastole. The outermost layer of the fibrous pericardium is not easily distensible; pericardial content is forced to compress the heart thus preventing normal ventricular distention during diastolic filling. Cardiac output subsequently decreases, and ultimately diastolic collapse occurs.The presence of malignant cardiac tamponade is associated with poor outcomes, with an approximate 3-month median survival.5 According to 1 retrospective review of 43 patients with primary lung cancer who underwent a surgical pericardial window for malignant pericardial effusion, postsurgical survival rates were poor, with a reported median survival of 2.1 months, 40% survival at 3 months, 26% survival at 6 months, 15% survival at 1 year, and 8% survival at 2 years.3 Because of these poor survival rates, the primary treatment strategy is often symptomatic palliation. A TTE is considered the criterion standard diagnostic tool in identifying pericardial effusions and has a diagnostic accuracy nearing 100%.8,9 Transthoracic echocardiography also allows for assessment of the physiologic impact of the effusion and provides echocardiographic evidence of cardiac tamponade.Pericardial effusion without cardiac tamponade may be asymptomatic. When pericardial effusion is symptomatic, the most common reported symptoms are shortness of breath and chest pain.7,10-12 A wide range of clinical exam findings may also indicate cardiac tamponade. These findings are dependent on the volume of fluid in the pericardium and the speed at which the fluid accumulated. Malignant pericardial effusions tend to develop over days to weeks, allowing for larger accumulations. The fibrous pericardium, although not easily distensible, will distend over time with a slowly developing effusion allowing for larger accumulations of fluid and a more insidious development of symptoms. In a pooled analysis of 8 clinical trials, the most common clinical findings in pericardial effusion with cardiac tamponade found in the patients evaluated included dyspnea (82% sensitivity), tachycardia (77% sensitivity), elevated jugular venous pressure (76% sensitivity), and pulsus paradoxus (82% sensitivity), whereas hypotension (24% sensitivity) and diminished heart sounds (24% sensitivity) were insensitive to this disorder.13Three signs associated with cardiac tamponade—hypotension, muffled heart sounds, and elevated jugular venous pressure—were identified as the Beck triad by Dr Claude Beck in 1935.14 The Beck triad has been found to be more specific to the pericardial effusion with cardiac tamponade that develops rapidly, such as pericardial effusions seen after cardiac surgery, trauma, or myocardial rupture.11,14 In a meta-analysis evaluating 153 patients with pericardial effusions, Jacob and colleagues14 found that jugular venous distention was present in 54% of the cases, hypotension in 28%, and muffled heart sounds in 22%. Of 153 patients with pericardial effusion, including the 16 patients identified as having cardiac tamponade, none of them demonstrated all 3 components of the Beck triad.14 The presence of all 3 components of the triad in patients with pericardial effusion or cardiac tamponade is unlikely and only seen in a minority of the patients presenting with cardiac tamponade or impending cardiac tamponade.3,12 The presence of elevated jugular venous pressure is the most likely finding of the triad, with reports of 54% up to 100% in patients with pericardial effusion or cardiac tamponade.10,13,14Pulsus paradoxus is defined as an exaggeration of the normal inspiratory decrease in systolic blood pressure. In normal conditions, the systolic blood pressure can decrease up to 10 mm Hg during inspiration. A decrease of greater than 10 mm Hg is considered diagnostic of pulsus paradoxus.7,15 The finding of pulsus paradoxus is not exclusive to cardiac tamponade and can be noted in severe chronic obstructive pulmonary disease, shock, massive pulmonary embolism, constrictive pericarditis, right ventricular infarction, tension pneumothorax, morbid obesity, or tense ascites.10,15 Identifying pulsus paradoxus requires proper sphygmomanometer technique and is a useful clinical skill because the presence of pulsus paradoxus in a patient presenting with pericardial effusion is an important finding.12,13,15 In a review of 8 clinical trials, Roy and colleagues13 found that a pulsus paradoxus of greater than 10 mm Hg in the presence of pericardial effusion had a likelihood ratio of 3.3 with a sensitivity of 98%, and a pulsus paradoxus of greater than 12 mm Hg had a likelihood ratio of 5.9 with 98% sensitivity for cardiac tamponade; whereas a pulsus paradoxus of less than 10 mm Hg demonstrated a likelihood ratio of 0.03.Pulsus alternans is identified when an assessment of the arterial pulse reveals a large-amplitude strong pulse alternating with a low-amplitude weak pulse. This beat-to-beat variation occurs in the presence of a regular heart rate. The finding of pulsus alternans is rarely associated with cardiac tamponade but rather is seen with severe left ventricular dysfunction, heart failure, or valvular heart disease.16,17Auscultatory or acoustic alternans is identified when heart sounds alternate from loud to soft beat to beat. This finding is noted in the presence of a regular heartbeat. The presence of auscultatory alternans, although rare, is thought to be related to the “swinging heart” phenomenon that occurs with large pericardial effusions but may also occur in severe left ventricular dysfunction.18 The changes in the intensity of the auscultated heartbeat are secondary to the distance of the heart from the chest wall as the heart swings to and fro in the pericardia fluid.Changes on the 12-lead ECG are not diagnostic of pericardial effusion or cardiac tamponade.4,19,20 However, changes on the 12-lead ECG can point to cardiac tamponade in a patient with pericardial effusion. Common ECG changes include low QRS voltage, PR segment depression, and electrical alternans.In a study by Bruch and colleagues,19 low QRS voltage was seen in patients with cardiac tamponade but was not a recurrent finding in patients with pericarditis or large pericardial effusion without cardiac tamponade. Low QRS voltage was present in 61% (14 of 23) of patients with clinical evidence of cardiac tamponade. In this clinical study, low QRS voltage was defined as a maximum QRS amplitude of less than 0.5 mV in the limb leads.19 Considering the low sensitivity for low QRS voltage demonstrated in this study, the absence of this finding does not rule out cardiac tamponade. Eisenberg and colleagues20 defined low voltage QRS as a QRS amplitude less than 5 mm in all limb leads plus a QRS voltage less than 10 mm in all precordial leads. In this blinded evaluation of ECGs from 136 patients with pericardial effusions identified by echocardiogram, 12 had evidence of cardiac tamponade. The authors concluded that low voltage QRS was strongly associated with the presence of large and moderate pericardial effusion but most associated with cardiac tamponade, demonstrating high specificity but low sensitivity for low QRS voltage.20 The presence of low QRS voltage should result in further testing to confirm or rule out large effusions and tamponade; however, the absence of this ECG finding does not rule out these disorders.Argula and colleagues4 evaluated the diagnostic reliability of low QRS voltage, electrical alternans, and tachycardia on the ECG in identifying cardiac tamponade in 127 patients with malignant pericardial effusion. Low-voltage QRS complex was defined as QRS complexes less than 5 mm in all limb leads and less than 10 mm in all precordial leads. Of the 127 patients with malignant pericardial effusion, 66% had echocardiographic evidence of cardiac tamponade. Low-voltage QRS had an 81% positive predictive value in identifying those with cardiac tamponade in all sizes of pericardial effusions and a 96% positive predictive value in identifying those with cardiac tamponade in large pericardial effusion. However, the negative predictive value of both findings is low.4In an evaluation of 176 asymptomatic patients with pericardial effusion on echocardiogram, Kudo et al21 noted PR-segment depression on the 12-lead ECG in 40 (23%) patients. Of those patients, 15 (33%) were postpericardiotomy patients, 19 (40%) had malignant disease, and 6 (15%) had connective tissue disorders.21 PR-segment depression was defined in this study as least 0.5 mm of PR-segment depression from the TP segment in both the limb (more than 2 leads in leads I, II, aVL, and aVF) and precordial leads (more than 2 leads in leads V3 through V6). Patients in the trial with asymptomatic pericardial effusion and a diagnosis of primary heart disease, renal failure, nephrotic syndrome, or hypothyroidism did not demonstrate this ECG finding.21 Ang and colleagues22 evaluated the ECGs of 42 patients with documented cardiac tamponade and noted that PR-segment depression had a sensitivity of only 12% with only 5 of the 42 patients with known cardiac tamponade demonstrating this finding. Malignancy represented 40.5% of this population, which was the largest single group. However, of the 100 patients in the control group with normal echocardiograms, none demonstrated this finding on the ECG, making the specificity and positive predictive value of PR segment depression in cardiac tamponade both 100% in this study.22Electrical alternans is an ECG finding of beat-to-beat alternating amplitude of the QRS in any or all leads of the ECG.23 The interval between the alternating complexes is regular, and the impulse origination for each beat is from the same site of origin. Additionally, the finding is independent of respiratory activity.24 The alternans can be noted with any of the ECG complexes including the P wave, QRS complex, and the T wave but is most often seen only with the QRS complex.24 The term total electrical alternans is used when there is alternans of the P wave, QRS complex, and the T wave.24,25 Total electrical alternans is less frequently seen and has been associated with significant pericardial disease and large pericardial effusions causing cardiac tamponade.24 Electrical alternans has traditionally been associated with moderately large pericardial effusions and is thought to be due a “swinging heart” as the heart moves back and forth in an anterior posterior motion in the fluid-filled pericardial space with each contraction.23Although electrical alternans has traditionally been associated with significant pericardial effusion and cardiac tamponade, this clinical finding can also be associated with many disorders related to significant right or left ventricular dysfunction including cardiomyopathies, aortic stenosis, coronary artery disease, pulmonary embolus, pulmonary hypertension, and pneumothorax.16 Electrical alternans may also be associated with conduction disorders such as ventricular tachycardia, supraventricular tachycardias, and bundle branch blocks.20,23,25Electrical alternans can be indicative of pericardial effusion, and more specifically, malignant pericardial effusion with a high likelihood of cardiac tamponade.4 In a study by Argula and colleagues,4 127 patients with malignant pericardial effusions were evaluated. Eighty-four patients had echocardiographic evidence of cardiac tamponade. In the patients with cardiac tamponade, the ECGs of 19 (22.5%) patients demonstrated electrical alternans. Argula et al4 found that electrical alternans in the presence of pericardial effusion carried a high specificity for cardiac tamponade, with a positive predictive value of 95% when a large pericardial effusion was present; however, they found that electrical alternans demonstrated a low sensitivity for the disorder. In an older review of 54 patients with cardiac tamponade and available 12-lead ECGs, 18 were diagnosed with malignant cardiac tamponade. Six of the 18 patients (33.3%) with malignancies demonstrated electrical alternans and 5 of the additional patients with cardiac tamponade without malignancy also demonstrated electrical alternans.10 Interestingly, the average volume of pericardial fluid drained from those demonstrating electrical alternans was 970 mL versus 515 mL in those without alternans.10The presence of electrical alternans in a patient presenting with pericardial effusion should raise suspicion for cardiac tamponade and result in a clinical evaluation of the patient and further diagnostic testing with TTE.4,25,26 However, poor specificity and a poor negative predictive value prevents the clinician from ruling out cardiac tamponade when this finding is absent.4,20,26Upon noting the elevated JVD, pulsus alternans, auscultatory alternans, sinus tachycardia, low-voltage QRS, and the electrical alternans, the cardiology advanced practice registered nurse (APRN) assessed for pulsus paradoxus and observed a 10 mm Hg inspiratory drop in systolic blood pressure. The APRN urgently reviewed the case with the rounding cardiologist. Review of the recently completed echocardiogram with the cardiologist identified early right ventricular collapse, indicating early echocardiographic evidence of cardiac tamponade. After discussion and evaluation by cardiothoracic surgery, the patient was taken immediately for a pericardial window. Just over 1 L of fluid was removed from the pericardial space. A chest tube was placed for drainage of large right-sided pleural effusions. Unfortunately, the patient was ultimately diagnosed with end-stage small cell lung cancer and after reviewing his options chose hospice as his treatment strategy.In the patient with a large pericardial effusion, the concern for the development of cardiac tamponade should be at the forefront. Transthoracic echocardiogram is the most reliable tool for definitive diagnosis of cardiac tamponade. However, this modality may not be readily available at a moment’s notice.Patients presenting with shortness of breath, especially in the presence of tachycardia, require the provider to move through many differentials quickly. The chest x-ray and 12-lead ECG are often initial diagnostic tools. Chest x-ray findings of an enlarged cardiac silhouette, or the water bottle sign, noted on the posteroanterior chest x-ray27 and ECG findings of low-voltage QRS, PR segment depression, or electrical alternans should alert the clinician to the possibility of a large pericardial effusion and subsequent tamponade.14 Although the absence of these findings does not rule out cardiac tamponade, their presence has been found to have high sensitivity and positive predictive values in cardiac tamponade in the presence of a large pericardial effusion and should prompt the provider to move quickly to transthoracic cardiac echocardiogram.14,20-22