Case 2 -

Right Ventricular Infarction Secondary to Massive Pulmonary Embolism Carmela Tan, Cleveland Clinic, Cleveland, OH

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Clinical History A 72-year-old woman with history of dementia had been bedbound at home for the past six months. She was recently admitted for treatment of a urinary tract infection and discharged to a skilled nursing facility. Four days later, she was brought to the Emergency Department after having been found unresponsive. Postmortem examination revealed a thrombus within the pulmonary trunk extending into the right pulmonary artery. Case 2 - Figure 1 Nitroblue tetrazolium staining showing a right ventricular infarct. Case 2 - Figure 2 High-power view of right ventricular myocardium showing contraction band necrosis. Case 2 - Figure 3 High-power view of right ventricular myocardium showing polymorphonuclear cell infiltrates. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: The heart weighed 505 grams. There was mild dilatation of the left ventricle and concentric left ventricular hypertrophy. The right ventricle was not dilated and the free wall measured 0.4 cm. The ventricles were serially sectioned parallel to the atrioventricular groove. The slices were incubated for 30 minutes in 0.5% nitroblue tetrazolium solution to visualize signs of early infarction. As can be seen in Figure 1, nitroblue tetrazolium stains viable myocardium dark blue while infarcted myocardium without dehydrogenases appear unstained. Examination of the coronary arteries showed a focal 80% stenosis of the proximal right coronary artery without plaque rupture or thrombus formation. Histologic sections of the right ventricle (Figure 2 and 3) showed contraction band necrosis and polymorphonuclear infiltrates in focal areas. There was no evidence of left ventricular ischemia or infarction in this case despite the presence of coronary atherosclerosis. Differential Diagnoses: The differential diagnoses of unexpected death in the elderly include coronary atherosclerosis, stroke, aortic rupture and noncardiac causes. The risk of sudden death in adults closely reflects the incidence of coronary heart disease. In contrast, the common causes of sudden death in young adults include cardiomyopathies, coronary artery anomalies, arrhythmogenic disorders and drug abuse [1]. Most sudden deaths are secondary to ventricular tachyarrhythmias. Underling cardiac structural abnormalities that are potential substrates for ventricular arrhythmias include coronary thrombosis, myocardial scars, left ventricular hypertrophy, inflammation and interstitial fibrosis. Around 5-10% of patients who suffer from sudden cardiac death will have structurally normal hearts. The cause of death in this case was massive pulmonary embolism (PE). The patient's risk of developing PE was likely related to inactivity secondary to dementia. This catastrophic event usually results in acute right ventricular failure secondary to ischemia and necrosis. Final Diagnosis: Right Ventricular Infarction Secondary to Massive Pulmonary Embolism Case Discussion: Right ventricular infarction is most commonly associated with transmural posterior left ventricular infarction. On the other hand, isolated right ventricular infarction is found in less than 3% of cases of myocardial infarction in autopsy series [2]. The low incidence of right ventricular infarction is thought to be due to a lower myocardial oxygen demand/supply ratio compared to the left ventricle. The lower right-sided pressures require lower work load and consequently lower oxygen demand. Favorable coronary perfusion is related to the thinness of the wall, lower coronary vascular resistance, and collaterals from the left coronary circulation. The lower right ventricular wall tension results in minimal compression of the microvasculature, thereby allowing for coronary blood flow to occur continuously throughout systole and diastole. In massive PE, there is a sudden increase in right ventricular afterload. Acute right ventricular compensatory response is limited. Sympathetic stimulation result in an increase in systolic pressure which increases oxygen demand. The right ventricular response to outflow obstruction is predominantly ventricular dilatation to maintain stroke volume. Right ventricular oxygen consumption further increases due to increased enddiastolic volume. While oxygen demand increases, oxygen supply decreases because higher intracavitary filling pressures diminish transmural perfusion and limit coronary flow during diastole. Obstruction of the pulmonary arteries leads to a decrease in transpulmonary delivery of left ventricular preload. Furthermore, right ventricular dilation also causes the interventricular septum to shift to the left, which decreases left ventricular compliance contributing to inadequate left ventricular filling. A decrease in left ventricular output reduces coronary perfusion of the right ventricle. Systemic hypotension results once forward cardiac output can no longer be sustained. The imbalance in oxygen demand and supply, in combination of hypotension and hypoxia, produces right ventricular ischemia and dysfunction. The histologic features of right ventricular infarction are similar to those of left ventricular infarction. However, identification of very early myocardial infarcts (duration less than 6 hours) remains challenging as unequivocal gross pathologic changes are not recognizable until at least 24 hours of infarction. Diagnosis can be missed when only random sections are taken for microscopic examination. One method employed in this case was the use of nitroblue tetrazolium staining. Nitroblue tetrazolium is an oxidation-reduction indicator that produces a dark blue formazan pigment visible in viable myocardium. The absence of pigment indicates substrate depletion during periods of ischemia and loss of dehydrogenases in necrotic myocardium. It also accurately outlines recent, healing and healed infarcts. Therefore, it facilitates three-dimensional mapping of the infarcted areas by incubating sequential slices of the ventricles. Using the nitroblue tetrazolium method, infarcts can be recognized as early as 2 hours after arterial ligation in dogs [3]. Studies with human hearts report detection of infarcts as early as 1 hour to 3 ½ hours of presumed clinical onset [4, 5]. False positive reactions can be seen with poor technique and in cases with autolysis (more than 72 hours) [6]. Review of the Literature/Treatment Options: Infarction of the right ventricle is usually a direct result of an occlusion of the right coronary artery by plaque rupture and/or thrombus formation. Occlusion of the proximal segment of a dominant right coronary artery can result in infarction of the right ventricular free wall with extension to the posterior interventricular septum and adjoining posterior wall of the left ventricle. Occlusion of the proximal left anterior descending artery or conus branch of the right coronary artery can result in an anterior right ventricular infarction [7]. Less commonly, right ventricular myocardial infarction has been reported secondary to right coronary artery dissection [8], anomalous origin of the right coronary artery [9] and side branch occlusion during stenting of the right coronary artery [10]. In the absence of significant coronary artery disease, right ventricular infarction has been reported in the setting of right ventricular hypertrophy. A relationship between right ventricular infarction and pulmonary hypertension has been observed in several studies [11, 12, 13]. Patients with chronic obstructive pulmonary disease may also be more susceptible to right ventricular infarction due to associated right ventricular hypertrophy [14, 15]. The increased right ventricular mass and elevated right ventricular enddiastolic pressure not only increases oxygen demand but also cause compression of flow to the right coronary system. Conclusion(s): Isolated right ventricular infarction is rare. In addition to proximal right coronary artery occlusion, right ventricular infarction may also occur secondary to acute pulmonary hypertension in the setting of massive PE. Cases of right ventricular infarction have also been reported in patients with right ventricular hypertrophy due to chronic pulmonary hypertension and chronic obstructive pulmonary disease. Early diagnosis of myocardial infarction can be challenging. One valuable method for macroscopic identification of early myocardial infarction is the use of nitroblue tetrazolium staining to delineate the location and extent of infarct. References: Adabag AS, Luepker RV, Roger VL, Gersh BJ. Sudden cardiac death: epidemiology and risk factors. Nat Rev Cardiol. 2010 Apr;7(4):216-25. Wartman WB, Hellerstein HK. The incidence of heart disease in 2,000 consecutive autopsies. Ann Intern Med. 1948 Jan;28(1):41-65. Nachlas MM, Shnitka TK. Macroscopic identification of early myocardial infarcts by alterations in dehydrogenase activity. Am J Pathol. 1963 Apr;42:379-405. Derias NW, Adams CW. Nitroblue tetrazolium test: early gross detection of human myocardial infarcts. Br J Exp Pathol. 1978 Jun;59(3):254-8. McVie JG. Postmortem detection of inapparent myocardial infarction. J Clin Pathol. 1970 Apr;23(3):203-9. Andersen JA, Hansen BF. The value of the nitro-BT method in fresh myocardial infarction. Frequency and location of fresh myocardial infarction in a consecutive series of autopsies. Am Heart J. 1973 May;85(5):611-9. Andersen HR, Falk E, Nielsen D. Right ventricular infarction: frequency, size and topography in coronary heart disease: a prospective study comprising 107 consecutive autopsies from a coronary care unit. J Am Coll Cardiol. 1987 Dec;10(6):1223-32. Atkinson JB, Barnhill J, Virmani R. Isolated right ventricular infarction: a rare complication of coronary artery dissection. South Med J. 1986 May;79(5):619-22. Saremi F, Gurudevan SV, Harrison AT.Isolated right ventricular infarction owing to anomalous origin of right coronary artery: role of MR and CT in diagnosis. J Thorac Imaging. 2009 Feb;24(1):34-7. Coosemans M, Koevoets R, Vydt T. A right ventricular infarction disguised as an anterior infarction due to an occluded isolated right ventricular branch. Acta Cardiol. 2008 Oct;63(5):641-5. Wade WG. The pathogenesis of infarction of the right ventricle. Br Heart J. 1959 Oct;21(4):545-54. Forman MB, Wilson BH, Sheller JR, Kopelman HA, Vaughn WK, Virmani R, Friesinger GC. Right ventricular hypertrophy is an important determinant of right ventricular infarction complicating acute inferior left ventricular infarction. J Am Coll Cardiol. 1987 Dec;10 (6):1180-7. Carlson EB, Reimer KA, Rankin JS, Peter RH, McCormack KM, Alexander LG. Right ventricular subendocardial infarction in a patient with pulmonary hypertension, right ventricular hypertrophy, and normal coronary arteries. Clin Cardiol. 1985 Sep;8(9):499-502. Kopelman HA, Forman MB, Wilson BH, Kolodgie FD, Smith RF, Friesinger GC, Virmani R. Right ventricular myocardial infarction in patients with chronic lung disease: possible role of right ventricular hypertrophy. J Am Coll Cardiol. 1985 Jun;5(6):1302-7. Middelhoff CJ, Büthker W, Becker AE. Pure right ventricular infarction. Eur Heart J. 1980 Oct;1(5):369-74.