Background
Left ventricular noncompaction (LVNC) is commonly associated with complex congenital anomalies. The association of LVNC with less complex but more frequent anomalies, such as bicuspid aortic valve (BAV), is not well described in the literature. The aims of this study were to (1) determine the incidence of association of LVNC with the most common congenital anomaly, BAV, in an echocardiographic database and (2) describe clinical and imaging characteristics of these patients.
Methods
An echocardiography database was retrospectively interrogated to identify 109 patients who fulfilled the echocardiographic criteria for BAV from July 1, 2011, to March 31, 2013. Echocardiograms were carefully evaluated to identify patients with concomitant LVNC.
Results
Twelve patients (11.0%) with BAV fulfilled the criteria for LVNC. The mean age at diagnosis was 33 ± 16.9 years; nine of 12 were men. Eight patients (66.7%) had symptoms during initial presentation. The most common BAV morphology was fusion of the right and left coronary cusps. Nine patients had mild or moderate aortic valve dysfunction (aortic regurgitation and/or stenosis), and eight had associated aortopathy. LVNC was located at the apex in all patients except one. Mean systolic global longitudinal strain was −16.9 ± 2.7%.
Conclusions
In this series of patients, concomitant BAV and LVNC were observed in 11% of a BAV population. Further studies are needed to understand the genetic and pathophysiologic basis of this association.
Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, occurring in 1% to 2% of the general population. All other forms of congenital cardiac disease combined have a prevalence of 0.8%. Congenital heart defects are associated with BAV, the most common of which are patent ductus arteriosus, ventricular septal defect, and aortic arch obstruction. BAV can be associated with coarctation of the aorta as well as aortic dilation, aneurysm, and dissection. The latter is described as BAV-associated aortopathy.
In the past 25 years, our understanding of left ventricular (LV) noncompaction (LVNC) has evolved through improved imaging modalities in conjunction with evolving genetic links. The original definition of LVNC mandated the absence of any other structural heart disease, so it was referred to as isolated LVNC. Subsequently, the association of LVNC with metabolic diseases, genetic syndromes, and other cardiac abnormalities has been reported. LVNC is well defined in patients with congenital anomalies. LVNC is associated with Ebstein’s anomaly in 15% of cases. A rare condition, Ebstein’s anomaly accounts for <1% of all cases of congenital heart disease. Recently, the association of LVNC with less complex congenital heart disease, such as LV outflow tract abnormalities, was recognized. Isolated cases of BAV along with LVNC have been described in the literature.
At our adult congenital heart disease center, we have identified a number of patients with BAV who had associated features of LVNC on echocardiography. Therefore, we sought to (1) determine the incidence of this combination in our echocardiographic laboratory database and (2) describe the clinical and imaging characteristics of such patients.
Methods
Patients
Our echocardiography database was retrospectively interrogated for the diagnosis of BAV and LVNC from July 1, 2011, to March 31, 2013. We identified 109 patients with BAV within our database. We also interrogated our echocardiographic database for calendar year 2012 to retrospectively analyze the annual prevalence of LVNC among patients who were referred to our echocardiographic laboratory. Approval was obtained from our institutional review board.
Diagnostic Criteria for LVNC
Several echocardiographic and cardiac magnetic resonance (CMR) imaging criteria for the diagnosis of LVNC morphology have been proposed. These definitions are varied and not unanimously accepted. We used previously published echocardiographic criteria, with primary focus on a combination of (1) an evaluation of trabeculations (noncompacted [NC] myocardium) in relation to compacted (C) myocardial wall thicknesses in multiple imaging windows and at different ventricular levels throughout the cardiac cycle; (2) identification of a bilayered myocardium (C and NC), particularly in short-axis views at the mid and apical levels; and (3) intertrabecular spaces perfused from the ventricular cavity, visualized on color Doppler imaging. In all patients (except one) who met the above criteria, we calculated the C/(NC+C) ratio at end-diastole per Chin et al. ‘s criteria, the NC/C ratio at end-systole per Jenni et al. ‘s criteria, and the NC/C ratio at end-diastole per Paterick et al. ‘s criteria. In one patient, the C layer was not well visualized during end-systole, so Jenni et al. ‘s criterion could not be used. A C/(NC+C) ratio ≤ 0.5 and an NC/C ratio > 2 were considered diagnostic. Among patients who underwent CMR imaging, Petersen et al. ‘s criteria was used to confirm the diagnosis. All patients included in the study met at least three criteria for the diagnosis of LVNC. Furthermore, we also measured the maximal systolic compacta thickness in 11 of 12 patients whose C layers could be delineated.
To identify LVNC, the left ventricle was divided into nine segments: one apical segment, four midventricular segments, and four basal segments (septal, anterior, lateral, and inferior). Agreement between two independent reviewers was required to confirm a diagnosis of LVNC or normal myocardium. When two independent reviewers did not agree, a third reviewer made the final decision.
Diagnostic Criteria for BAV
Anatomic evaluation of the aortic valve was based on a combination of short-axis and long-axis images to identify the number of leaflets and to describe leaflet mobility, thickness, and calcification. Diagnosis was most reliably made when the two cusps were seen in systole with only two commissures framing an elliptical systolic orifice. An experienced echocardiographer reviewed the echocardiographic images of all patients with confirmed or suspected BAV in our echocardiographic database. If there was discrepancy, a second echocardiographer made the final diagnosis. In patients who underwent aortic valve surgery, the presence of BAV was confirmed on their pathologic specimens. Only patients with confirmed BAV were included, which accounts for the 109 patients in this study.
Data Acquisition
Detailed clinical and imaging characteristics of patients with BAV who also met the echocardiographic criteria for LVNC were evaluated. Medical records were reviewed to document baseline demographics, associated dysmorphic features, presence of associated cardiac anomalies, and personal and family histories. Information related to patients’ clinical courses, including management and follow-up, was collected. Holter monitors and 12-lead electrocardiograms were examined for evidence of arrhythmia. CMR imaging with delayed gadolinium enhancement was performed in a subset of patients to confirm the diagnosis of LVNC and detect the presence of myocardial fibrosis.
Genetic counseling was offered to 10 patients, but only four agreed to undergo genetic testing. Genetic testing for LVNC was bundled with dilated cardiomyopathy panels. Testing panels were available to test for 38 genes, including mutations in genes encoding sarcomeric proteins (cardiac actin, β-myosin heavy chain, α-tropomyosin, and troponins T and I), nuclear envelope protein, mitochondrial proteins (MTTH, MTTK, MTTI, etc.), Z-band alternatively spliced PDZ motif-containing protein, and tafazzin protein.
Echocardiography
All patients underwent complete two-dimensional and Doppler echocardiographic examinations according to American Society of Echocardiography recommendations. LV dimensions were measured in the parasternal long-axis view per the American Society of Echocardiography, and aortic stenosis or regurgitation was graded as mild, moderate, or severe on the basis of American Society of Echocardiography recommendations. Measurements of the ascending aorta were performed in the two-dimensional parasternal long-axis view at 3 cm above the aortic valve. LV diastolic function was assessed by measuring the LV inflow pattern at the tip of the mitral valve leaflets, pulmonary venous flow pattern, and tissue Doppler of the medial and lateral annulus. Diastolic function was defined as normal or, when abnormal, was graded as I, II, or III using published criteria. Biplane LV ejection fraction was calculated, with normal LV ejection fraction defined as 55% to 70%. Normal annular systolic function was defined as medial annular systolic velocity > 8 cm/sec. Any additional echocardiographic findings such as other congenital cardiac anomalies or presence of aortopathy, were documented.
Speckle-tracking echocardiography was performed to assess global longitudinal strain during systole. For global strain analysis, images were acquired in apical four-chamber, apical long-axis, and apical two-chamber views. Two-dimensional recordings were collected with frame rates ranging from 50 to 80 frames/sec during a brief breath hold. Three consecutive cardiac cycles were recorded as two-dimensional cine loops and were acquired as raw data format. Optimal image quality was obtained to ensure adequate speckle analysis. Close attention to the endocardium and epicardial borders was key to provide information to aid in tracking of the myocardium during the full cardiac cycle. Using dedicated software (EchoPAC BT11; GE Vingmed Ultrasound AS, Horten, Norway), two-dimensional strain was assessed according to published guidelines.
Results
Study Population
In 2012, a total of 17,016 patients were referred to our echocardiographic laboratory for evaluation of multiple and varied cardiac disorders. Among these, 59 patients were diagnosed with LVNC, so the annual prevalence of LVNC at our institution was estimated at approximately 0.3% (three in 1,000) among patients referred for echocardiography. Of the 109 patients with BAV identified within our echocardiographic database from July 2011 to March 2013, 12 (11.0%) fulfilled the criteria for LVNC. Eleven patients fulfilled all three echocardiographic criteria for LVNC. Because of the poor delineation of the C layer in systole in one patient, Jenni et al. ‘s criteria could not be used, but the patient fulfilled the other two sets of echocardiographic criteria. Six patients, including the patient who fulfilled two rather than three echocardiographic criteria, fulfilled CMR imaging criteria (Petersen et al. ) for LVNC. Thus, all the patients fulfilled at least three sets of published diagnostic criteria for diagnosis of LVNC. The primary reason for referral to the echocardiography laboratory was BAV in seven patients (58.3%), LVNC in three patients (25.0%), and hypertrophic cardiomyopathy in two patients (16.7%).
Clinical Characteristics
Baseline clinical characteristics of the 12 patients (nine men [75%]; 11 whites, one Asian) with concomitant BAV and LVNC are shown in Table 1 . The overall mean age at the time of diagnosis was 33 ± 16.9 years (range, 14–56 years). Eight patients (66.7%) had symptoms during their initial presentation. The most common symptom was shortness of breath (five patients), followed by noncardiac chest pain (two patients), and palpitations (one patient). None of the patients had New York Heart Association class III or IV symptoms. On Holter monitoring, arrhythmias were present in five patients (41.7%), specifically supraventricular tachycardia in two, atrial fibrillation in two, and occasional premature ventricular beats in one. Radiofrequency ablation was performed in one patient with symptomatic supraventricular tachycardia and in one patient with recurrent atrial fibrillation.
| Characteristic | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | Patient 12 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (y) | 51 | 18 | 56 | 19 | 48 | 39 | 20 | 41 | 53 | 23 | 17 | 14 |
| Gender | Female | Male | Male | Male | Female | Male | Male | Female | Male | Male | Male | Male |
| Race | White | White | White | Asian | White | White | White | White | White | White | White | White |
| Family history | Daughter with BAV | None | None | None | Daughter with BAV | None | None | None | None | Cousin with dwarfism syndrome | Father with HCM | None |
| Reason for referral | LVNC | HCM | BAV | BAV | LVNC | LVNC | BAV | BAV | HCM | BAV | BAV | BAV |
| Presenting symptoms | SOB | Chest pain | Palpitation | SOB | SOB | Chest pain | SOB | None | SOB | None | None | None |
| Arrhythmia | PVC | None | SVT s/p RFA | SVT | AF s/p RFA | AF | None | None | None | None | None | None |
Echocardiographic Data
Echocardiographic findings of the patients are summarized in Table 2 and illustrated in Figures 1–3 and Videos 1 to 8 (available at www.onlinejase.com ). The most common morphology of the BAV was fusion of the right and left coronary cusps. One patient had fusion of the noncoronary cusp and the left cusp, and another had fusion of the noncoronary cusp and the right cusp. Three patients had normal functioning aortic valves with no stenosis or regurgitation. Two patients had mild aortic stenosis, and seven had mild aortic regurgitation. Thus, 10 of 12 patients had none or only mildly abnormal aortic valve function. Two patients had moderate aortic regurgitation, one of whom also had severe aortic stenosis. No patient had severe aortic regurgitation. The peak velocity across the aortic valve was 2.06 ± 0.79 m/sec. Aortopathy in the form of ascending aortic dilation > 37 mm was seen in eight patients, six of whom did not have significant aortic valve stenosis or regurgitation.
| Characteristic | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | Patient 12 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bicuspid morphology | R+L | R+L | R+L | R+L | R+L | R+L | L+N | R+L | R+L | R+L | R+L | R+N |
| Aortic valve peak velocity (m/sec) | 1.5 | 2.0 | 2.6 | 1.7 | 2.3 | 2.0 | 2.0 | 2.6 | 4.0 | 1.0 | 1.2 | 1.8 |
| Aortic stenosis | None | None | Mild | None | Mild | None | None | None | Severe | None | None | None |
| Aortic insufficiency | None | Mild | Mild | Mild | Mild | None | Mild | Moderate | Moderate | Mild | None | Mild |
| Aortic size (mm) | 39 | 40 | 45 | 39 | 27 | 25 | 38 | 46 | 40 | 39 | 26 | 25 |
| Location of LVNC | Apical | Apical | Apical | Apical | Midventricular | Apical | Apical | Apical | Apical | Apical | Apical | Apical |
| LVNC diagnosis | ||||||||||||
| C/(NC+C) ratio at end-diastole | 0.18 | 0.20 | 0.24 | 0.2 | 0.23 | 0.16 | 0.13 | 0.17 | 0.22 | 0.24 | 0.20 | 0.23 |
| NC/C ratio at end-systole | 3.5 | 3 | 2.6 | 3 | 3.3 | Not done ∗ | 5.2 | 4.3 | 2.6 | 2.7 | 3 | 2.6 |
| NC/C ratio at end-diastole | 4.6 | 4 | 3.2 | 3.6 | 3.3 | 5.3 | 6.5 | 5 | 3.6 | 3.2 | 4 | 3.4 |
| LVEDD (cm) | 5.2 | 5.1 | 5.8 | 5.0 | 4.9 | 5.3 | 4.0 | 5.1 | 6.1 | 5.5 | 4.0 | 4.3 |
| Septum (mm) | 0.8 | 1.1 | 1.2 | 1.1 | 0.9 | 1.0 | 0.8 | 0.9 | 1.4 | 0.9 | 0.9 | 0.8 |
| LVEF | 47% | 59% | 58% | 58% | 45% | 68% | 48% | 65% | 35% | 50% | 58% | 56% |
| Septal E′ | 9.2 | 8.5 | 5.1 | 12.6 | 6.6 | 9.8 | 6.8 | 7.4 | 11.1 | 13.1 | 12.0 | 12.3 |
| Diastolic function | III | I | II | Normal | III | Normal | I | II | I | Normal | Normal | Normal |
| GLS | −20% | −17% | −17% | −20% | −14% | −16% | −18% | NA | −10.5% | −18% | −18% | −18% |
∗ Measurement could not be performed because the C layer was not well delineated in systole.
