© 2013, Wiley Periodicals, Inc. DOI: 10.1111/echo.12467
Echocardiography
Unexplained Double-Chambered Left Ventricle Associated with Contracting Right Ventricular Aneurysm and Right Atrial Enlargement Gherardo Finocchiaro, M.D.,* Daniel Murphy, M.D.,* Aleksandra Pavlovic, B.S.,* Francois Haddad, M.D.,* Hadas Shiran, M.D.,* Gianfranco Sinagra, M.D.,† Euan A. Ashley, M.R.C.P., D.Phil.,* and Joshua W. Knowles, M.D., Ph.D.* *Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California; and †Cardiovascular Department, Hospital Riuniti and University of Trieste, Trieste, Italy
In this article, we describe a double-chambered left ventricle (LV) associated with a functional right ventricular (RV) aneurysm and right atrial (RA) enlargement in an asymptomatic 24-year-old woman with a family history of sudden cardiac death. We will discuss the differential diagnosis, genetic testing and possible prognostic implications. (Echocardiography 2014;31:E80–E84) Key words: double-chambered left ventricle, congenital heart disease
A 24-year-old Caucasian female was referred to the Stanford Center for Inherited Cardiovascular Disease for evaluation of a murmur found on routine physical evaluation within the context of a positive family history of sudden cardiac death. Her paternal grandmother’s brother and the paternal grandmother’s father died suddenly at 40–50 years of age of “heart attacks.” The patient was asymptomatic except for a minimal reduction in exercise tolerance and for complaints of intermittent peripheral edema. Physical examination was significant for a 3/6 mid-systolic harsh murmur best heard at the 2nd and 3rd intercostal spaces at the left sternal border, but was otherwise normal. Electrocardiogram (ECG) revealed sinus rhythm and possible left atrial enlargement (Fig. 1). Resting transthoracic echocardiography (Fig. 2) (Philips iE33, Philips Medical Systems, Andover, MA, USA) revealed mild left ventricular (LV) hypertrophy, an abnormally configured LV with 2 distinct contracting chambers, a contractile aneurysm of the right ventricle (RV) and right atrial (RA) enlargement. The mitral apparatus was markedly abnormal with a single prominent papillary muscle and abnormal insertions into the mid-left ventricular wall. Biventricular ejection fraction (EF) was mildly reduced (LVEF 49%, RV fractional area change 31%), with a normal size Address for correspondence and reprint requests: Gherardo Finocchiaro, M.D., Division of Cardiovascular Medicine, Stanford University, Stanford, California, USA. Fax: (650) 725-1599; E-mail: [email protected]
E80
LV, a mildly dilated RV and mild mitral and moderate tricuspid regurgitation. Right atrial area and volume were, respectively, 29 cm2 and 115 mL by the single plane method of disks, and RV systolic pressure was estimated at 32 mmHg. The tricuspid valve was mildly displaced (5 mm/m2). Because of the subjective complaints of exercise intolerance, the family history of sudden death and the mildly decreased LVEF, an exercise echocardiogram and cardiopulmonary exercise testing were performed. Exercise echocardiogram demonstrated an increase in overall LVEF with exercise. The resting LV outflow tract (LVOT) gradient was not significant, whereas the postexercise LVOT gradient was 24 mmHg with a midcavitary gradient of 55 mmHg. Maximal oxygen consumption was 34 mL/kg per min (104% of predicted). A right heart catheterization was performed because of subjective complaints of swelling and concern for elevated RA pressures in the context of a mildly dilated RV. This demonstrated normal filling pressures (RA pressure: 5 mmHg, pulmonary arterial pressure: 28/15/10 mmHg, wedge pressure 12 mmHg) with a cardiac output of 5.58 L/min and no evidence of shunt. Cardiac MRI was performed to both get a better assessment of LV and RV morphology and to assess for presence of delayed gadolinium enhancement (Figs. 3, 4 and movie clip S1). The study was consistent with a double chamber LV. There was no hypertrabeculation to suggest LV noncompaction (LVNC) and no delayed
Double-Chambered LV and Contracting RV Aneurysm
I
aVR
V1
V4
II
aVL
V2
V5
III
aVF
V3
V6
II
VI
I
Device: ATP
Speed: 25 mm/sec
Limb: 10 mm/mV
Chest: 10 mm/mV
F 60- 0.5-100 Hz W
PH090A
P?
Figure 1. Electrocardiogram showing sinus rhythm and left atrium enlargement.
gadolinium enhancement. There was a significantly enlarged RA, mild tricuspid regurgitation, but no evidence of atrial or pulmonary venous level shunting. Finally, there was an abnormal contour of the RV with a contracting aneurysm at the lateral apical wall of the RV (RVEF: 50%). The patient had genetic testing at GeneDx Laboratories (Gaithersburg, MD, USA) because of concern that she could have a phenotypic variant along the spectrum of hypertrophic cardiomyopathy (HCM) or LVNC1 in which the MV pathology was predominant. The patient had significant concerns that she might have a condition that would be passed onto future children. The phenotypic characterization of her parents and siblings with echocardiogram had been advised, but was declined by her family members. The genetic testing included sequencing of 27 genes: ACTC1, DES, LAMP2, LMNA MTND1, MTND5, MTND6, MTTD, MTTH, MTTI, MTTK, MTTL1, MTTL2, MTTM, MTTQ, MTTS1, MTTS2, MYBPC3, MYH7, PLN, SGCD, TAZ, TNNI3, TNNT2, TPM1, TTR, and ZASP. No disease-associated variants were identified. Because of the mild decrease in EF on echocardiogram, the patient was treated with low dose ACE-inhibitor with caution to use appropriate methods of contraception. Double-chambered LV is a rare anomaly characterized by the presence of 2 chambers divided by abnormal muscular tissue. Double-chambered RV is more common and often presents with murmur and exertional dyspnea and is associated with other congenital abnormalities such as sep-
tal defects, tetralogy of Fallot, and transposition of the great arteries. Double-chambered LV could be caused by the presence of anomalous muscle bundles that provoke a progressive thickening of interventricular septum generating an intracavitary gradient and development of two-chambers.2–5 Double-chambered LV is more often asymptomatic without any findings at cardiac auscultation. Its origin remains unclear. While echocardiography is an important tool for identifying this rare condition, cardiac MRI can produce a better characterization of the anatomical relationships and it is useful in excluding other congenital abnormalities.6 The differential diagnosis includes a number of conditions. In our case, the abnormal papillary muscle and the presence of several attachments to the ventricular wall could be consistent with a form of LVNC, even if imaging criteria were not fulfilled.7 Lee et al.8 described a similar case of a 25year-old female symptomatic for palpitations and chest discomfort. In that case, a 12-lead ECG showed repolarization abnormalities and the echocardiogram showed a hypertrophied muscle band in the LV that ran toward the interventricular septum across the LV and divided the LV into apical and basal cavities with a mid-ventricular gradient associated. When considering the family history of early cardiac related death, another condition that has to be considered is HCM; in fact a mild increase in septal and posterior wall thickness was E81
Finocchiaro, et al.
Figure 2. Double-chambered left ventricle (LV) in echocardiography. A. Parasternal long-axis view showing the double-chambered LV and the hypertrophic papillary muscle and interventricular septum. B. Parasternal short-axis view focusing on the presence of two-chambers divided by abnormal muscular tissue. C. Apical four-chamber view focused on LV showing a normal size double-chambered LV. D. Apical four-chamber view focused on right ventricle representing a dilatation of both right atrium and right ventricle.
Figure 3. Cardiac MRI showed the size and shape of the double-chambered left ventricle. A. Two-chamber view. B. Short-axis view.
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Double-Chambered LV and Contracting RV Aneurysm
Figure 4. Cardiac MRI images show the abnormal left ventricular architecture and the right chambers enlargement focusing on the apical aneurysm. A. Four-chamber view. B. Inverted four-chamber view C. Inverted four-chamber view focusing on the apical RV aneurysm (white arrow) in diastole D. Inverted four-chamber view in systole.
observed and HCM is often characterized by hypertrophy and displacement of the papillary muscles.9 A disease-associated genetic variant finding could help in supporting a diagnosis of HCM or of LVNC. However, the absence of such a mutation does not completely exclude this possibility, as the yield for a positive genetic test in HCM probands is
Echocardiography
Unexplained Double-Chambered Left Ventricle Associated with Contracting Right Ventricular Aneurysm and Right Atrial Enlargement Gherardo Finocchiaro, M.D.,* Daniel Murphy, M.D.,* Aleksandra Pavlovic, B.S.,* Francois Haddad, M.D.,* Hadas Shiran, M.D.,* Gianfranco Sinagra, M.D.,† Euan A. Ashley, M.R.C.P., D.Phil.,* and Joshua W. Knowles, M.D., Ph.D.* *Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California; and †Cardiovascular Department, Hospital Riuniti and University of Trieste, Trieste, Italy
In this article, we describe a double-chambered left ventricle (LV) associated with a functional right ventricular (RV) aneurysm and right atrial (RA) enlargement in an asymptomatic 24-year-old woman with a family history of sudden cardiac death. We will discuss the differential diagnosis, genetic testing and possible prognostic implications. (Echocardiography 2014;31:E80–E84) Key words: double-chambered left ventricle, congenital heart disease
A 24-year-old Caucasian female was referred to the Stanford Center for Inherited Cardiovascular Disease for evaluation of a murmur found on routine physical evaluation within the context of a positive family history of sudden cardiac death. Her paternal grandmother’s brother and the paternal grandmother’s father died suddenly at 40–50 years of age of “heart attacks.” The patient was asymptomatic except for a minimal reduction in exercise tolerance and for complaints of intermittent peripheral edema. Physical examination was significant for a 3/6 mid-systolic harsh murmur best heard at the 2nd and 3rd intercostal spaces at the left sternal border, but was otherwise normal. Electrocardiogram (ECG) revealed sinus rhythm and possible left atrial enlargement (Fig. 1). Resting transthoracic echocardiography (Fig. 2) (Philips iE33, Philips Medical Systems, Andover, MA, USA) revealed mild left ventricular (LV) hypertrophy, an abnormally configured LV with 2 distinct contracting chambers, a contractile aneurysm of the right ventricle (RV) and right atrial (RA) enlargement. The mitral apparatus was markedly abnormal with a single prominent papillary muscle and abnormal insertions into the mid-left ventricular wall. Biventricular ejection fraction (EF) was mildly reduced (LVEF 49%, RV fractional area change 31%), with a normal size Address for correspondence and reprint requests: Gherardo Finocchiaro, M.D., Division of Cardiovascular Medicine, Stanford University, Stanford, California, USA. Fax: (650) 725-1599; E-mail: [email protected]
E80
LV, a mildly dilated RV and mild mitral and moderate tricuspid regurgitation. Right atrial area and volume were, respectively, 29 cm2 and 115 mL by the single plane method of disks, and RV systolic pressure was estimated at 32 mmHg. The tricuspid valve was mildly displaced (5 mm/m2). Because of the subjective complaints of exercise intolerance, the family history of sudden death and the mildly decreased LVEF, an exercise echocardiogram and cardiopulmonary exercise testing were performed. Exercise echocardiogram demonstrated an increase in overall LVEF with exercise. The resting LV outflow tract (LVOT) gradient was not significant, whereas the postexercise LVOT gradient was 24 mmHg with a midcavitary gradient of 55 mmHg. Maximal oxygen consumption was 34 mL/kg per min (104% of predicted). A right heart catheterization was performed because of subjective complaints of swelling and concern for elevated RA pressures in the context of a mildly dilated RV. This demonstrated normal filling pressures (RA pressure: 5 mmHg, pulmonary arterial pressure: 28/15/10 mmHg, wedge pressure 12 mmHg) with a cardiac output of 5.58 L/min and no evidence of shunt. Cardiac MRI was performed to both get a better assessment of LV and RV morphology and to assess for presence of delayed gadolinium enhancement (Figs. 3, 4 and movie clip S1). The study was consistent with a double chamber LV. There was no hypertrabeculation to suggest LV noncompaction (LVNC) and no delayed
Double-Chambered LV and Contracting RV Aneurysm
I
aVR
V1
V4
II
aVL
V2
V5
III
aVF
V3
V6
II
VI
I
Device: ATP
Speed: 25 mm/sec
Limb: 10 mm/mV
Chest: 10 mm/mV
F 60- 0.5-100 Hz W
PH090A
P?
Figure 1. Electrocardiogram showing sinus rhythm and left atrium enlargement.
gadolinium enhancement. There was a significantly enlarged RA, mild tricuspid regurgitation, but no evidence of atrial or pulmonary venous level shunting. Finally, there was an abnormal contour of the RV with a contracting aneurysm at the lateral apical wall of the RV (RVEF: 50%). The patient had genetic testing at GeneDx Laboratories (Gaithersburg, MD, USA) because of concern that she could have a phenotypic variant along the spectrum of hypertrophic cardiomyopathy (HCM) or LVNC1 in which the MV pathology was predominant. The patient had significant concerns that she might have a condition that would be passed onto future children. The phenotypic characterization of her parents and siblings with echocardiogram had been advised, but was declined by her family members. The genetic testing included sequencing of 27 genes: ACTC1, DES, LAMP2, LMNA MTND1, MTND5, MTND6, MTTD, MTTH, MTTI, MTTK, MTTL1, MTTL2, MTTM, MTTQ, MTTS1, MTTS2, MYBPC3, MYH7, PLN, SGCD, TAZ, TNNI3, TNNT2, TPM1, TTR, and ZASP. No disease-associated variants were identified. Because of the mild decrease in EF on echocardiogram, the patient was treated with low dose ACE-inhibitor with caution to use appropriate methods of contraception. Double-chambered LV is a rare anomaly characterized by the presence of 2 chambers divided by abnormal muscular tissue. Double-chambered RV is more common and often presents with murmur and exertional dyspnea and is associated with other congenital abnormalities such as sep-
tal defects, tetralogy of Fallot, and transposition of the great arteries. Double-chambered LV could be caused by the presence of anomalous muscle bundles that provoke a progressive thickening of interventricular septum generating an intracavitary gradient and development of two-chambers.2–5 Double-chambered LV is more often asymptomatic without any findings at cardiac auscultation. Its origin remains unclear. While echocardiography is an important tool for identifying this rare condition, cardiac MRI can produce a better characterization of the anatomical relationships and it is useful in excluding other congenital abnormalities.6 The differential diagnosis includes a number of conditions. In our case, the abnormal papillary muscle and the presence of several attachments to the ventricular wall could be consistent with a form of LVNC, even if imaging criteria were not fulfilled.7 Lee et al.8 described a similar case of a 25year-old female symptomatic for palpitations and chest discomfort. In that case, a 12-lead ECG showed repolarization abnormalities and the echocardiogram showed a hypertrophied muscle band in the LV that ran toward the interventricular septum across the LV and divided the LV into apical and basal cavities with a mid-ventricular gradient associated. When considering the family history of early cardiac related death, another condition that has to be considered is HCM; in fact a mild increase in septal and posterior wall thickness was E81
Finocchiaro, et al.
Figure 2. Double-chambered left ventricle (LV) in echocardiography. A. Parasternal long-axis view showing the double-chambered LV and the hypertrophic papillary muscle and interventricular septum. B. Parasternal short-axis view focusing on the presence of two-chambers divided by abnormal muscular tissue. C. Apical four-chamber view focused on LV showing a normal size double-chambered LV. D. Apical four-chamber view focused on right ventricle representing a dilatation of both right atrium and right ventricle.
Figure 3. Cardiac MRI showed the size and shape of the double-chambered left ventricle. A. Two-chamber view. B. Short-axis view.
E82
Double-Chambered LV and Contracting RV Aneurysm
Figure 4. Cardiac MRI images show the abnormal left ventricular architecture and the right chambers enlargement focusing on the apical aneurysm. A. Four-chamber view. B. Inverted four-chamber view C. Inverted four-chamber view focusing on the apical RV aneurysm (white arrow) in diastole D. Inverted four-chamber view in systole.
observed and HCM is often characterized by hypertrophy and displacement of the papillary muscles.9 A disease-associated genetic variant finding could help in supporting a diagnosis of HCM or of LVNC. However, the absence of such a mutation does not completely exclude this possibility, as the yield for a positive genetic test in HCM probands is
