Echocardiography in Pediatric and Adult Congenital Heart Disease, 2nd Ed.

42. Eisenmenger Syndrome

The name “Eisenmenger” refers to Victor Eisenmenger, an Austrian physician who in 1897 described the clinical and pathologic features in a patient with a large ventricular septal defect (VSD). Dr. Eisenmenger described a “powerfully built man of 32 years” in whom cyanosis increased considerably on effort. The patient’s clinical course changed to one of cyanosis, clubbing, and a slow progressive decline in functional ability. This was followed by dyspnea and edema with a state of “heart failure.” His clinical exam revealed elevated venous pressure, liver distention, and extensive edema. The patient collapsed and died following a large hemoptysis. Autopsy revealed a 2.5-cm membranous VSD with pulmonary but not aortic atherosclerosis. This case demonstrates many salient points for the purpose of this chapter.

■Adult survival

■Pulmonary arteriopathy that includes changes similar to atherosclerosis

■Variable cyanosis, increasing with exercise

■Secondary erythrocytosis (white cells are low normal, platelets are low)

■Hemoptysis

■Thrombosis

■Late onset heart failure

■Sudden death

Eisenmenger syndrome (ES), as defined by Paul Wood in 1958, refers to any cardiac defect with initial left-to-right shunting that results in the development of pulmonary vascular changes with increased resistance and pulmonary hypertension. Initially one would think that this group would represent a very small minority of adult congenital heart cases and hopefully one day with early detection and correction, it will. But at the present time these patients comprise between 3% and 10% of patients seen at adult congenital heart disease clinics and as a group have one of the higher percentages of morbidity and mortality. ES was the largest group, representing 19% with sudden cardiac death in a recent report by Koyak that included 25,790 patients from the clinic databases of Canada, Belgium, and the Netherlands. Several factors, including ventricular dysfunction were associated with an increased incidence of sudden cardiac death. The other factors included supraventricular tachycardia, increased QRS duration, and QRS dispersion. But assessment of ventricular function remains the most challenging. The modality of assessment needs to be able to assess both the right and left ventricle, detect changes before clinical deterioration, and potentially show improvement with treatment modalities such as vasodilators. The right ventricle has been challenging to assess, especially the hypertensive or systemic RV. Echocardiography is the main modality for ventricular assessment.

This chapter applies to a group of congenital heart defects in which the development of systemic level pulmonary artery pressures is due to one or more nonrestrictive communications at the intracardiac or great vessel level. These can be classified as pre- or post-tricuspid valve and are outlined in Table 42.1. This classification has prognostic significance as well as containing important distinctions when using echocardiography for assessment. Van De Bruaene noted the difference in these two groups in a study of 58 patients with Eisenmenger syndrome. The pre-tricuspid group was older, had larger biatrial size as well as larger right ventricles. The post-tricuspid defects do not develop the right ventricular and pulmonary artery dilation. The reason for this is the onset of the volume and pressure overload. Nonrestrictive post-tricuspid defects result in immediate postnatal left-to-right shunting with both pressure and volume overload to the pulmonary vasculature. This results in the retention of features of the fetal heart, especially the right ventricle. It is the early adaptation of right ventricular function that contributes to the significantly improved outcome for this group of patients compared to all other forms of pulmonary hypertension.

When the defect is pre-tricuspid, the early stage is only volume overload on the pulmonary vasculature. This does not take place during infancy or childhood and may not do so for several years or decades. A nonrestrictive ASD of 2–3 cm in size with normal left ventricular compliance will not develop a significant left-to-right shunt (Qp/Qs >1.5:1) until LV compliance declines. This explains why the exam of an infant or child with a nonrestrictive atrial septal defect may not have the usual findings of increased pulmonary flow, including the fixed split second heart sound and pulmonary artery systolic flow murmur. As left ventricular compliance declines, the shunt increases and commonly exceeds a Qp/Qs of 3:1. With normal Qs of 4–5 L/min, the right ventricle and pulmonary artery are exposed to a Qp of 12–15 L/min. Again, this volume overload most commonly does not happen for several decades. It will then take several years to decades for this volume to trigger the hypertensive pulmonary arteriopathy changes that result in pressure overload.

Thus, the pre-tricuspid defects allow the transformation of the fetal heart to the normal heart in infancy. This normal infant heart includes low pulmonary vascular resistance and pressure, as well as thinning of the right ventricular free wall to 3–5 mm with the normal septal configuration. This normal heart can then show the adaptive features to the low pressure, increased volume state associated with a pre-tricuspid defect. The post-tricuspid defect retains the crescent-shaped RV and LV size with the septum flat and midline. These are demonstrated in Figure 42.1Figure 42.2 shows the adaptive changes of the RV and PA to the longstanding volume overload and subsequent pressure overload as seen in ES. The RV and PA can become massively dilated. Right heart failure can develop as well as pulmonary artery thrombosis. These topics will be covered in subsequent sections of this chapter.

The reaction in the pulmonary vasculature called the Eisenmenger “reaction” by Hopkins results in pathologic changes called hypertensive pulmonary arteriopathy. These develop to alleviate the volume-overloaded pulmonary vasculature and resultant heart failure. The changes are progressive, become nonreversible and result in pulmonary pressures equal to systemic pressures with little to no ability to be lowered even when the physiologic demand would warrant it. The degree of pulmonary hypertension is severe enough to cause the reversal of shunting and subsequent systemic desaturation and central cyanosis. The anatomy and physiology of lesions which may develop pulmonary hypertension are covered elsewhere in this text. In addition, key chapters review echocardiographic tools in the assessment of pulmonary hypertension. This chapter will focus on the adult patient with Eisenmenger syndrome and expand upon those chapters dealing with specific problems in this group of patients.

Figure 42.1. The top is a short-axis view of RV and LV chamber configuration. A: Normal. B: Pre-tricuspid defect with volume overload without pulmonary hypertension. C: Post-tricuspid defect with pressure and volume overload. The bottom is the ventricular wall configuration with line thickness representing wall thickness. RV, right ventricle; LV, left ventricle.

Figure 42.2. Massive MPA dilation in an adult with Eisenmenger syndrome. This patient developed a thrombus on the posterior aspect of the proximal right pulmonary artery.

ANATOMIC AND HEMODYNAMIC FINDINGS

Adults with Eisenmenger syndrome, regardless of the cardiac defect, have similar pulmonary vascular pathology. The pathophysiologic mechanisms contributing to these changes include shear stress, flow, pressure, thrombosis, and inflammation. Heath and Edwards first described the grading of the changes. The sequence of these changes subsequently has been shown not to progress from stage I through VI but rather to have an inflammatory component as described in grade VI that occurs before grades IV and V. The pathologic changes result in elevated pulmonary vascular resistance (Fig. 42.3).

It is this abnormality and the presence of a systemic-to-pulmonary connection that result in the features of Eisenmenger syndrome. All patients will have central cyanosis, clubbing, and physical examination findings of pulmonary hypertension with a parasternal lift and loud P2 component of the second heart sound. However, without myocardial dysfunction, they should not have the murmur of a significant left-to-right shunt. In fact they are generally without murmur but may have mild pulmonary insufficiency, and a prominent jugular venous “a” wave. The typical echocardiographic findings are demonstrated in Figures 42.4 and 42.5. All patients will have systemic pressures in the pulmonary artery and right ventricle and their defect will be nonrestrictive, without a large gradient.

ROLE OF ECHOCARDIOGRAPHY

Echocardiography is the cornerstone imaging modality in the evaluation of patients with Eisenmenger syndrome and it is crucial in the evaluation of endocarditis, valvular disease, thrombosis, and ventricular dysfunction. Since the first edition of this textbook, there have been further developments in the assessment of ventricular performance before pump failure, which may aid in the detection and potential treatment of these patients. We will first describe the features of the fetal right ventricle and the transformation with normal anatomy and correlate this with echocardiographic assessment. During fetal development the right and left heart circulations have equal pressures throughout the cardiac cycle. The fetal right heart characteristics are outlined in Table 42.2 and are compared to normal and Eisenmenger syndrome.

Figure 42.3. Inflammatory process associated with smooth muscle cell (SMC) proliferation in pulmonary vascular obstructive disease. (Courtesy of Dr. Marlene Rabinovich.)

Figure 42.4. A: Transesophageal echocardiographic images demonstrating a large secundum atrial septal defect (ASD) with a Qp/Qs value of 1.8 and severe pulmonary hypertension. Left-to-right shunting during ventricular systole. B to D: Transthoracic echocardiography images of a large nonrestrictive ventricular septal defect (VSD) in an adult patient with double-outlet right ventricle. B: Two-dimensional image demonstrating large VSD. C: Laminar color Doppler flow representing left-to-right shunt through the VSD during systole. D: Spectral pulsed-wave Doppler sampled in the VSD showing low-velocity bidirectional shunting.

ASSESSMENT OF VENTRICULAR FUNCTION IN EISENMENGER SYNDROME

Until recently, assessment of RV function was limited to qualitative analysis as well as some global quantitative assessments that were predominantly developed for the left ventricle, such as ejection fraction (EF) and fractional shortening (Fig. 42.6). Other assessment tools used modalities that evaluated the longitudinal work of the RV such as tricuspid annular plane systolic excursion (TAPSE). However, as can be seen in Table 42.2, the post-tricuspid defect hypertensive RV takes on more of a circumferential contraction pattern but without the wringing-type twist characteristics of the LV. Thus, assessment of ventricular performance of the RV and LV may require different tools.

In the largest series to date, Moceri described echocardiographic variables in 181 consecutive patients with ES. In this study there was a heterogeneous mixture of patients: 16% pre-tricuspid ES, 41% with Down syndrome, 67% with functional NYHA Class 3 or 4 symptoms, and 41% who were receiving advanced pulmonary vasodilator therapy (bosentan and/or sildenafil). Predictors of mortality included TAPSE, peak systolic velocity, myocardial performance, RA area, and RA/LA area. They found the RV and RA to be significantly larger in the pre-tricuspid group but had no difference in longitudinal RV systolic function as assessed by TAPSE. However, the RV fractional area change (FAC) and tissue Doppler myocardial acceleration during isovolumic contraction were lower in patients with pre-tricuspid shunts, suggesting possibly abnormal circumferential function in the pre-tricuspid group. They also reported a marked increase in mortality (30% in 3 years) when TAPSE was <15 mm. The authors suggested a score based upon 1 point for each variable:

Figure 42.5. A, B: Continuous-wave spectral Doppler signals demonstrating typical tricuspid and pulmonary regurgitation velocity profiles obtained from an adult with Eisenmenger syndrome. C: Continuous-wave Doppler profile of pulmonary regurgitation demonstrating high early- and end-diastolic flow velocities consistent with pulmonary hypertension.

TAPSE

<15 mm

Ratio of RV effective systolic to diastolic duration

≥1.5

RA area

≥25 cm2

RA/LA area ratio

≥1.5

They suggested that such a composite score could be used to stratify risk in patients with ES and guide therapeutic decisions. It is interesting that all parameters indicative of a poor outcome involved the RV rather than the LV.

In the post-tricuspid valve patient, ventricular performance can be considered as a single unit; failure is biventricular. When one ventricle fails the other follows and deciding which parameter should be used to assess ventricular failure is a challenge. The parameters that assess longitudinal function of the RV may not be appropriate in patients with ES. This is especially true for the post-tricuspid group due to the retention of the fetal ventricular characteristics including the circumferential work type.

Kalogeropoulos and colleagues reported quantitative echocardiographic findings in 24 patients with ES and compared them to 25 patients with other forms of pulmonary hypertension as well as 25 normal control subjects. They found that long-axis function was comparable in both groups with pulmonary hypertension, but less than in the normal group. Parameters of long-axis function included global strain and global RV systolic strain rate. Short-axis RV function was significantly better in patients with ES versus those with primary PAH and was comparable to the control group. The parameter used for short-axis function was the RV fractional shortening by M-mode. Other conventional measures of RV function, such as FAC, were not different between these groups.

Pettersen described systemic RV function in terms of longitudinal and circumferential myocardial shortening and ventricular torsion. They studied 14 patients who had the Senning procedure as infants. The analysis was performed an average of 18 years postoperative and included echocardiography as well as MRI. Longitudinal and circumferential shortening were measured using TDI measurements of peak systolic strain and strain rate, and torsion was evaluated by tagged MRI images and reported as the difference between basal and apical rotation. The systemic RV had opposite findings from the normal RV with the predominant function being circumferential not longitudinal, and there was an absence of torsion.

These studies would suggest the need for alternative modalities to assess the RV in patients with ES and especially those with post-tricuspid lesions. In this group an assessment of circumferential shortening may be more accurate for the RV. Parameters of longitudinal RV function such as TAPSE and RV FAC have been shown to have prognostic value in other forms of pulmonary hypertension but may not be appropriate when the RV has retained its fetal characteristics. For the post-tricuspid ES patient, assessment should include analysis of not only longitudinal but also circumferential shortening.

Figure 42.6. Parasternal short-axis two-dimensional (A) and M-mode (B) images demonstrating flattening of the interventricular septum consistent with pressure (systole) and volume (diastole) overload in Eisenmenger syndrome.

The assessment of ventricular function is increasingly important due to advances in potential therapy. Pulmonary vasodilators have shown promise for patients with ES. Therefore, the identification of patients for whom therapy may be indicated is important and assessment of ventricular function may be the critical element. Therapy is expensive, sometimes prohibitively. The appropriate time to initiate therapy is a critical question. The fate of the post-tricuspid ES patient is much better than with any other forms of pulmonary hypertension. One year, 3-year, and even 5-year survival rates exceed 90% for this group. Thus empiric therapy in ES may not be appropriate. But, heart failure and sudden death do occur and ongoing attempts to identify patients at risk is critical. Assessment of ventricular function before the onset of clinical heart failure may be beneficial and the echocardiographic assessment as outlined in this chapter will identify appropriate patients for early treatment. The analysis of vasodilator therapy with bosentan and sildenafil will be reviewed later in this chapter.

Sudden death unfortunately is common in patients with ES. Most are clinically considered to be arrhythmogenic in origin. However, patients may develop ventricular dysfunction, which is rapid in onset, occurring over just a few days and resulting in cardiogenic shock (Video 42.1). The description of this phenomenon was reported in abstract form at the Adult Congenital Heart Disease Program in June 2011. Eight patients with sudden onset and rapid deterioration of ventricular performance were studied and their data are shown in Table 42.3. All patients had qualitative ventricular failure with a combined EF of <20%, markedly reduced TAPSE of ≤10 mm and markedly increased RV effective systolic/effective diastolic ratio of greater than 2.5:1. This prolonged ratio correlates to markedly impaired diastolic filling. Coronary arteriography in this group of patients revealed reduced coronary perfusion without obstructive coronary artery disease. Patients had TIMI flow of I-II in at least one coronary artery. Those patients supported with an intraaortic balloon pump and/or vasodilator therapy survived (n = 5) with improved ventricular function. They were placed on standard systolic heart failure therapy with beta-blockers and ACE inhibitors as well as pulmonary vasodilators. At 6 months, EF remained normal, TAPSE improved to >15 mm and effective systolic/diastolic time ratio decreased to 1.3:1. Most patients described symptoms for 3 days to 2 weeks prior to presentation. This report stresses the importance of early and reliable assessment of ventricular function before the onset of cardiovascular collapse.

ASSOCIATED ISSUES IN PATIENTS WITH EISENMENGER SYNDROME

Bleeding and Thrombosis

The cyanotic patient with congenital heart disease is at risk for bleeding. Fatal hemoptysis was a common cause of death for these patients until the past two decades. In current practice, avoidance of phlebotomy has reduced the incidence of hemoptysis dramatically. These patients have thrombocytopenia, abnormal platelet function, activated coagulation cascade with increased fibrin degradation products, and deficiencies of clotting factors and von Willebrand factor.

Despite the predisposition to bleed, many patients with ES have pulmonary artery (PA) thrombosis. The thrombus is typically found in the proximal PA, which is dilated (Fig. 42.2). It has been suggested that pulmonary artery thrombosis is more common in females, as well as in those with lower systemic arterial oxygen saturations. More recently, Broberg et al. studied 55 consecutive patients with ES and found the incidence of detectable pulmonary thrombus to be 20%. Pulmonary thrombosis was associated with older age, lower RV and LV ejection fraction, large PA diameter, and lower peak systolic velocity in the PA. However, empiric anticoagulation is not recommended and has not been shown to be of benefit. Sandoval reported 48 anticoagulated and 44 nonanticoagulated patients with ES. Anticoagulation did not impact survival, and bleeding complications occurred exclusively in the anticoagulated group in 16%, with 2 fatalities. Mortality was associated with NYHA Class 3–4 symptoms, evidence of right heart failure, and an MCV of <80. Again, assessment of ventricular performance may be key to understanding morbidity, mortality, and potential treatment.

Endocarditis, Emboli, and Brain Abscess

All cyanotic patients with residual shunts should have filters on all intravenous lines to decrease the potential for paradoxical emboli. Based on the 2007 American Heart Association guidelines, these patients require endocarditis prophylaxis. Suspected endocarditis requires detailed echocardiographic evaluation, and TEE is indicated when TTE is nondiagnostic, patients have prosthetic valves, abscess is suspected, or with organisms with high likelihood for endocarditis such as staphylococcal aureus. Patients with an unrepaired VSD may be at highest risk for development of endocarditis.

Left Coronary Artery Compression

Compression of the proximal left coronary artery is a rare effect of the massive main pulmonary dilation that may occur in patients with ES. In 2007, Dubois and colleagues described this finding in a patient using angiography and adjunctive MRI (Fig. 42.7). In a patient with LV dysfunction or symptoms of angina, this associated problem should be evaluated.

UPDATE ON RECENT PULMONARY VASODILATOR TRIALS

The pulmonary vascular resistance in Eisenmenger syndrome is markedly elevated due to the development of hypertensive pulmonary arteriopathy. Endothelin-1, a potent vasoconstrictor, has been found to be elevated in these patients. Blockade of endothelin-1 with an endothelin receptor antagonist has been shown to improve the exercise capacity and hemodynamics in patients with ES. In the BREATHE-5 trial, 54 patients were randomized in a 2:1 ratio to bosentan or placebo for 16 weeks. Bosentan was shown to lower the pulmonary vascular resistance index and mean PA pressure while increasing exercise capacity. Kaya reported on 23 patients with ES (6 pre-tricuspid, 17 post-tricuspid) who were treated with bosentan. At 24 months they reported not only improved WHO functional class, 6-minute walk test, and PA systolic pressures, but also documented an improvement in RV MPI from 0.46 to 0.35. Measures of biventricular long-axis function using the tricuspid and lateral Sa and Ea also improved. No distinction was made between the pre-tricuspid and post-tricuspid patients. Sitaxsentan, another endothelin receptor antagonist but selective for endothelin-A, has been used in patients with ES including a 12-week hemodynamic study and a crossover trial with 7 patients between bosentan and sitaxsentan. In this study, Kopec used the 6-minute walk duration (6MWD) and magnetic resonance to assess LV and RV mass, volume, ejection fraction, and pulmonary flow. They reported an increase in LV mass and in LV ejection fraction from 55% to 65%, as well as increased pulmonary flow from 64 to 69 mL/min. The authors speculated that an increase in LVEF and pulmonary flow may have contributed to an improved systemic arterial saturation, 6MWD, and a decrease of NTproBNP. No Doppler data were reported, but this study demonstrates the exciting results being reported for this class of agents in patients with ES.

Figure 42.7. Left coronary compression (arrow) caused by a dilated hypertensive main pulmonary artery in a patient with Eisenmenger physiology. A, C: Coronary angiography before and after coronary stent (arrow) placement. B, D: Same anatomy with magnetic resonance imaging. (From Dubois CL, Dymarkowski S, Van Cleemput J. Compression of the left main coronary artery by the pulmonary artery in a patient with the Eisenmenger Syndrome. Eur Heart J. 2007;28:1945.)

Similar results have been demonstrated with sildenafil. Garg reported on 22 patients with ES and compared 8 pre-tricuspid patients with 14 post-tricuspid patients. While both groups improved, the pre-tricuspid patients showed a better response in both clinical and hemodynamic parameters.

Finally, not all patients with ES will be unoperated. Some patients will have had prior surgery that may have been palliative, such as a systemic-to-pulmonary shunt to enhance pulmonary flow. In a surgically palliated patient, pulmonary pressures may regress, remain unchanged, or progress. Meticulous assessment of ventricular function and pulmonary artery pressure and resistance are critical in defining prognosis and to guide response to therapy. If the “post-repair” patient still has significant pulmonary hypertension, this can result in critical elevations in RV systolic pressure and right heart failure when cardiac output increases in response to hemodynamic demands. Prior to repair, this increased cardiac demand with limited pulmonary vasodilation is handled by the congenital defect, providing a “pop-off” so that the excess flow during increased cardiac output is shunted to the systemic bed. Flow is dependent on the difference in resistance between the pulmonary and systemic beds. The systemic bed can undergo vasodilation while the pulmonary vasculature cannot. These patients experience dramatic episodes of systemic desaturation, but are not likely to have right heart failure. When the patient with fixed or nonreversible pulmonary vascular obstructive disease undergoes surgery, this “pop-off” is eliminated and the right ventricle is forced to pump the entire systemic venous return into the pulmonary vascular bed. These patients behave similarly to patients with primary or pre-tricuspid pulmonary hypertension. Survival may be shortened as a consequence of the right heart being unable to handle the increased demand in the setting of elevated pulmonary vascular resistance. However, advances in the treatment of pulmonary hypertension with specific pulmonary vasodilators such as endothelin antagonists and phosphodiesterase inhibitors may be of benefit in this scenario.

The decision of when to initiate vasodilator therapy and the specific agent to apply in patients with ES is a challenge. Care needs to be individualized for these patients and their management should occur at centers with expertise in the evaluation and management of adults with congenital heart disease.

SUGGESTED READING

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Hopkins W. The remarkable right ventricle of patients with Eisenmenger syndrome. Coron Artery Dis. 2005;16:19–25.

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Kaya M, OLam Y, Erer B, et al. Long-term effect of bosentan therapy on cardiac function and symptomatic benefits in adult patients with Eisenmenger syndrome. J Card Fail. 2012 May;18(5):379–384.

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Questions

1.Which of the following is an expected hematologic finding in a 32-year-old with Eisenmenger syndrome?

A.Elevated platelet count

B.Elevated white cell count

C.Elevated MCV

D.Elevated red blood cell count

2.Which of the following would NOT be expected in a 10-year-old with Eisenmenger syndrome?

A.Survival into adulthood

B.Cyanosis that increases with exercise

C.Sudden death

D.Premature coronary artery disease

3.Of the following lesions, which defect usually has onset of pulmonary hypertension in adulthood and not in infancy?

A.Large ASD

B.Large PDA

C.Complete AV septal defect

D.Truncus arteriosus

4.The shape of the ventricular septum in which of the following situations would be expected to be crescent-shaped towards the left ventricle?

A.Normal 20-week fetus

B.Normal 2-day-old

C.Large ASD with Eisenmenger Syndrome

D.Large PDA with Eisenmenger Syndrome

5.Which of the following lesions would be least likely to cause Eisenmenger physiology if left unrepaired into adulthood?

A.Complete atrioventricular septal defect

B.Tetralogy of Fallot

C.Truncus arteriosus

D.Common atrium

6.In a patient with Eisenmenger syndrome, which of the following physical exam findings would NOT be expected?

A.Clubbing

B.Parasternal lift

C.Narrowly split second heart sound with a loud P2

D.Systolic ejection murmur at the left upper sternal border

7.Which of the following agents has been documented to improve subjective symptoms, pulmonary artery pressures or pulmonary vascular resistance in patients with Eisenmenger syndrome?

A.Propranolol

B.Bosentan

C.Carvedilol

D.Disopyramide

8.In a patient who has Eisenmenger syndrome with hemoglobin of 18.9 gm/dL, phlebotomy is indicated when which of the following circumstances occurs?

A.The hemoglobin reaches 20 gm/dL

B.The patient has a neurologic deficit

C.The MCV is 90

D.Systemic oxygen desaturation is noted with exercise

9.In a patient with Eisenmenger syndrome, pulmonary artery thrombosis is associated with which of the following?

A.Younger age

B.Small branch pulmonary artery diameter

C.LV ejection fraction greater than 50%

D.Lower peak systolic velocity in the pulmonary artery

10.Increased mortality in patients with Eisenmenger syndrome has been demonstrated with which of the following?

A.TAPSE < 15 mm

B.Ratio of RV effective systolic/diastolic duration < 1.5

C.Right atrial area < 20 m2

D.RA/LA area ratio < 1.0

Answers

1.Answer: D. Patients with Eisenmenger syndrome have a secondary erythrocytosis due to chronic hypoxia. Elevated hemoglobin and red blood cell counts are typical. These patients usually have low normal leukocyte and low platelet counts.

2.Answer: D. Pulmonary artery atherosclerosis is expected with Eisenmenger syndrome. There has been no association with systemic hypertension or premature coronary artery disease. Survival into adulthood is typical. However, these patients face many challenges such as progressive cyanosis with exercise, late onset of congestive heart failure and sudden death due to arrhythmia.

3.Answer: A. Patients with atrial septal defect rarely develop irreversible pulmonary hypertension or pulmonary vascular disease in infancy or childhood. More commonly, if this occurs, it is later in adulthood. Some adults who have large ASDs, with large left to right shunts, never develop significant pulmonary vascular obstructive disease.

4.Answer: C. Pretricuspid shunts that may predispose the patient to Eisenmenger physiology will cause progressive right ventricular volume overload and a crescent shape of the interventricular septum towards the left ventricle. The other situations mentioned will result in either midline or flat septum (normal fetal and post tricuspid Eisenmenger lesions) or crescent shaped towards the right ventricle (normal postnatal heart).

5.Answer: B. Patients with Tetralogy of Fallot inherently have variable degrees of pulmonary valve and subpulmonary stenosis. This generally protects the patient’s pulmonary vascular bed from the excessive flow that may occur from the VSD. But, these patients would be cyanotic because of right to left shunting due to severe right ventricular outflow tract obstruction.

6.Answer: D. A pulmonary outflow murmur from excess pulmonary blood flow would not be expected in patients who have developed Eisenmenger physiology. Pulmonary artery pressures are elevated at this point in time because of elevated arteriolar resistance rather than increased pulmonary blood flow. As the excess pulmonary blood flow is reduced, the outflow murmur disappears.

7.Answer: B. The BREATHE-5 trial demonstrated in 54 patients with Eisenmenger physiology that Bosentan, an endothelial receptor blocker, improved exercise capacity and hemodynamics in these patients.

8.Answer: B. Phlebotomy is indicated for patients with Eisenmenger syndrome who have neurologic deficits. Phlebotomy tends to make these patients iron deficient and actually lowers the MCV, which may predispose them towards thromboembolic events. Phlebotomy is rarely performed in the modern era.

9.Answer: D. Pulmonary artery thrombosis in patients with Eisenmenger syndrome is associated with older age, lower right ventricular and left ventricular ejection fraction, larger pulmonary artery diameter and lower peak systolic velocity in the pulmonary artery consistent with sludging of blood in the pulmonary arteries.

10.Answer: A. Moceri and colleagues demonstrated an increased mortality to 30% in three years for patients whose TAPSE < 15 mm. They suggested a scoring system based on reduced TAPSE, elevated ratio of RV effective/diastolic duration, elevated right atrial area, and elevated right atrial/left atrial area ratio.