Background
In patients with hypertrophic cardiomyopathy (HCM), akinetic apical aneurysms are associated with ventricular tachycardia, heart failure, apical thrombus, and mortality. The cause of apical aneurysms remains unresolved, and there is controversy about prevalence and significance of mid–left ventricular (LV) obstruction, often present in these patients. The aim of this study was to test the hypothesis that low velocities in patients with aneurysms are due to near complete cessation of mid-LV flow, characteristically marked by a Doppler signal void.
Methods
This was a retrospective analysis of 39 patients with HCM with segmental hypertrophy of the mid left ventricle and complete systolic emptying at the mid-LV level. The severity of dynamic obstruction was evaluated by measuring the time during which cross-sectional mid-LV cavity area was <1 cm 2 . Presence or absence of an LV Doppler midsystolic signal void was determined.
Results
Akinetic apical aneurysms were present in 21 patients. The duration of two-dimensional mid-LV short-axis complete emptying was longer in patients with akinetic apical aneurysms (194 ± 45 vs 148 ± 63 msec, P = .013), nearly 50% of systole. Midsystolic signal voids were seen only in patients with akinetic apical aneurysms ( P < .001), present in 86%. In patients with akinetic aneurysms, there was a strong correlation between the duration of the systolic signal void and the proportion of systole with complete emptying <1 cm 2 ( r = 0.704; P = .001). Complete emptying <1 cm 2 for ≥38% of systole was associated with akinetic aneurysm (odds ratio, 9.35; P < .004).
Conclusion
Patients with akinetic apical aneurysm HCM have near complete cessation of flow across severe dynamic mid-LV obstruction for nearly 50% of systole. This explains how the adverse effects of obstruction may occur without high velocities on echocardiography.
Hypertrophic cardiomyopathy (HCM) most commonly presents as septal hypertrophy with accompanying left ventricular (LV) outflow tract (LVOT) obstruction due to systolic anterior motion of the mitral valve. Less common variants occur in patients with wall thickening of just the apex, while some have thickening of the apex and the mid left ventricle. Patients with thickening of the mid left ventricle can develop mid-LV obstruction, an uncommon but often highly symptomatic variant of HCM, especially when it is associated with dilation and systolic dysfunction of the apical segments. In patients with HCM, akinetic apical aneurysms are associated with monomorphic ventricular tachycardia, heart failure, apical thrombus, and premature mortality. The mechanism of apical aneurysm remodeling is uncertain, but severe midventricular obstruction could be the cause by producing afterload mismatch and ischemia. Despite the putative presence of obstruction in apical aneurysms, velocities recorded through the mid-LV narrowing are commonly low or absent. We hypothesized that in akinetic apical aneurysms, low to absent mid-LV velocities are due to near complete or complete cessation of systolic flow across the obstructing mid-LV neck, analogous to (but worse than) the fall in gradient that occurs with end-stage aortic stenosis. Diagnostic recognition of advanced mid-LV obstruction by the echocardiographic findings described herein is essential for application of existing and future treatments.
Methods
Patient Selection
Diagnosis of HCM was made by demonstration of a hypertrophied (≥15 mm) nondilated left ventricle in the absence of a clinical cause that would explain the degree of hypertrophy observed. From our prospectively acquired HCM program database, we identified all patients who had both (1) dominant hypertrophy in the mid left ventricle at the papillary muscle level (all these patients had thickening of the mid left ventricle greater than at the base and more than or equal to that at the apex) and (2) complete systolic emptying in the mid left ventricle. From this cohort, group 1 patients were identified if in addition to mid-LV hypertrophy and complete systolic emptying they also had a thin-walled akinetic apical aneurysm. Group 2 patients had mid-LV hypertrophy and complete systolic emptying but no akinetic apical aneurysms. Doppler high systolic velocities were noted when systolic mid-LV flow velocities were ≥2.7 m/sec. Patients were excluded if they had systolic anterior motion of the mitral valve with mitral-septal contact and LVOT obstruction (either at rest or after provocation with Valsalva maneuver, standing, or treadmill exercise), greater than mild mitral regurgitation, greater than mild aortic regurgitation, any aortic stenosis, ventricular pacing at baseline, prior septal myectomy or alcohol ablation, coronary narrowing >70%, or persistent atrial fibrillation at the time of echocardiography. All patients gave written consent for the use of their clinical data for research purposes.
Clinical Characteristics and Outcomes
Follow-up data were obtained via direct contact and chart review. All-cause mortality was checked using the Social Security Death Index.
Echocardiography
It has been our laboratory policy since 2000 to use intravenous left-sided contrast agents for patients with apical or mid-LV hypertrophy and suspicion of akinetic apical aneurysm and since 2005 for all patients with apical HCM. The present study included the echocardiograms of all patients with HCM from May 2006 to February 2013. Echocardiograms were obtained in separate studies, not during catheterization procedures, if done.
Two-Dimensional Measurements
All two-dimensional (2D) and Doppler measurements were tabulated as means of three measured values. On standard 2D parasternal long-axis and short-axis (SAX) views, we measured diastolic and systolic LV diameters at the mitral valve tips, septal and posterior wall thickness, and maximal basilar wall thickness. At the mid left ventricle, we measured cross-sectional SAX cavity areas and cross-sectional papillary muscle areas.
Depth was decreased to increase frame rates. On parasternal SAX cine loops at the mid left ventricle, the 2D severity of obstruction was determined graphically and temporally by measuring the duration of systole with a narrowed SAX cavity area < 1 cm 2 (2D SAX complete systolic emptying < 1 cm 2 ) (see Figure 1 ). Sequential SAX areas were traced excluding the papillary muscles for each systolic frame in standard fashion. The number of systolic frames in which the cavity area was <1 cm 2 was noted; duration was the number of frames multiplied by 1,000 and divided by the frame rate.
On 2D apical views, the maximal apical and mid-LV wall thicknesses, length of systolic wall apposition in the apical long axis, and biplane left atrial and LV volumes were measured using the modified Simpson method. Maximal mid-LV wall thickness was obtained from either the parasternal or apical views. The akinetic apical aneurysm maximal width and biplane volume were measured during systole after complete systolic emptying in the mid left ventricle.
Doppler Measurements
From apical four-chamber views, pulsed-wave (PW) recordings of systolic ejection velocities were acquired at the apical, midventricular, and outflow tract levels. We measured maximal continuous-wave (CW) Doppler velocities through the mid left ventricle in early, mid, and late systole to early diastole. When a Doppler systolic signal void was detected, repeated attempts to detect flow were made with both CW and PW Doppler (see Figures 2–4 , showing patients with akinetic apical aneurysms and signal voids). In patients with akinetic apical aneurysms, though the midsystolic signal voids were qualitatively the same with both CW and PW Doppler, quantification of void duration was more precise on PW frames, and these were chosen for analysis. Void duration was measured from when Doppler velocities approached zero in early systole to the resumption of flow out of the apex in late systole. The presence of diastolic paradoxical jet flow was tabulated. In contrast, Figure 5 shows a patient with midventricular obstruction but preserved systolic apical function and high mid-LV velocities. The stroke volume and cardiac output were calculated using the LVOT velocity-time integral and diameter. The RR interval was measured from the electrocardiogram acquired during the 2D LV parasternal SAX acquisition. The duration of systole was the duration of M-mode aortic valve opening on the same study. Diastolic mitral inflow and annular tissue velocities were acquired. Cardiac catheterization was performed in patients with symptoms refractory to pharmacotherapy who were deemed potential surgical candidates.
Statistical Analysis
Data are expressed as mean ± SD for continuous variables and as proportions for categorical variables. Differences between groups were analyzed using unpaired t tests, Fisher exact tests, or χ 2 tests as appropriate. Pearson correlation coefficients were determined between continuous variables. P values < .05 were considered to indicate statistical significance. Statistical analyses were performed using SPSS for Windows version 16.0 (SPSS, Chicago, IL).
Results
Clinical Characteristics
From our prospective HCM database, we identified 49 patients, who were studied from 2006 to 2013, had predominant mid-LV hypertrophy at the papillary muscle level, and had complete systolic emptying. Of the 878 patients with HCM enrolled in our database by February 2013, 566 had been seen during the corresponding time period (2006–2013). The study group thus represents 8.7% of all patients with HCM referred to our center during this period. Several patients were excluded because of concomitant systolic anterior motion of the mitral valve ( n = 3), inadequate echocardiograms for quantification ( n = 4), atrial fibrillation or pacing ( n = 2), and incomplete follow-up ( n = 1). After applying exclusion criteria, 39 patients were included in the analysis. There were 21 patients with mid-LV complete systolic emptying and akinetic apical aneurysms (group 1) and 18 patients with mid-LV complete systolic emptying without akinetic apical aneurysms (group 2). Table 1 shows the clinical and demographic characteristics of the two groups. Men were more frequent in group 1 than group 2 (67% vs 28%, P = .015). There were no other significant differences in coexisting medical conditions, symptoms, and pharmacologic treatment. Implantable cardioverter-defibrillator placement was eventually more common in the akinetic apical aneurysm group.
| Variable | Akinetic apical aneurysm ( n = 21) | Complete systolic emptying, no akinetic aneurysm ( n = 18) | P |
|---|---|---|---|
| Age at time of echocardiography (y) | 57.1 ± 14 | 53.3 ± 14 | .40 |
| Duration of follow-up (mo) | 37.1 ± 21 | 43.3 ± 22 | .37 |
| Men | 14 (67%) | 5 (28%) | .015 ∗ |
| Race | .62 | ||
| African American | 7 (33%) | 4 (22%) | — |
| Asian | 2 (10%) | 1 (6%) | — |
| White | 12 (57%) | 13 (72%) | — |
| Hypertension | 8 (38%) | 9 (50%) | .46 |
| Family history of HCM | 6 (29%) | 7 (39%) | .50 |
| NYHA class | 2.3 ± 0.6 | 1.9 ± 0.8 | .07 |
| Syncope | 5 (24%) | 8 (44%) | .31 |
| Angina | 8 (38%) | 10 (56%) | .28 |
| Dyspnea | 10 (48%) | 11 (61%) | .40 |
| Paroxysmal atrial fibrillation | 5 (24%) | 2 (11%) | .30 |
| Potentially lethal ventricular arrhythmia | 4 (19%) | 0 (0%) | .11 |
| β-blockade | 18 (86%) | 16 (89%) | .77 |
| Calcium channel blockade | 2 (10%) | 5 (28%) | .14 |
| Disopyramide | 2 (10%) | 2 (11%) | .87 |
| ICD implantation at follow-up | 12 (57%) | 3 (17%) | .010 ∗ |
Echocardiography
All patients had predominant mid-LV hypertrophy and also had complete systolic emptying. Two-dimensional echocardiographic and Doppler findings representative of the two groups are shown in Figures 2 to 5 , and comparison of 2D characteristics of the two groups is shown in Table 2 .
| Variable | Akinetic apical aneurysm ( n = 21) | Complete systolic emptying, no akinetic aneurysm ( n = 18) | P |
|---|---|---|---|
| Mid-LV complete systolic emptying | 21 (100%) | 18 (100%) | — |
| Maximal apical thickness (cm) | 0.7 ± 0.4 | 1.8 ± 0.6 | <.001 ∗ |
| Basal anteroseptal thickness (cm) | 1.5 ± 0.4 | 1.7 ± 0.5 | .21 |
| Basal posterior wall thickness (cm) | 1.2 ± 0.3 | 1.3 ± 0.4 | .54 |
| Basal LV end-diastolic diameter (cm) | 4.5 ± 0.9 | 3.9 ± 0.8 | .07 |
| Basal LV end-systolic diameter (cm) | 2.1 ± 1.5 | 2.3 ± 0.75 | .54 |
| Maximal mid-LV wall thickness (cm) | 1.7 ± 0.3 | 1.5 ± 0.4 | .15 |
| Mid-LV end-diastolic diameter (cm) | 2.0 ± 0.95 | 2.65 ± 0.7 | .019 ∗ |
| Mid-LV anterolateral papillary muscle area (cm 2 ) | 2.4 ± 0.8 | 2.9 ± 1.0 | .09 |
| Mid-LV posteromedial papillary muscle area (cm 2 ) | 2.5 ± 1.2 | 2.5 ± 1.0 | .90 |
| Mid-LV diastolic SAX area (cm 2 ) | 12.8 ± 3.5 | 11.8 ± 4.0 | .406 |
| Papillary muscle area/diastolic SAX area (%) | 39.0 ± 16 | 48.6 ± 19 | .10 |
| Length of systolic apposition, apical four-chamber view (cm) | 3.1 ± 0.6 | 2.6 ± 0.8 | .028 ∗ |
| Biplane LVEDV (mL) | 48.2 ± 17 | 53.2 ± 18 | .39 |
| Biplane LVEDV index (mL/m 2 ) | 25.2 ± 8 | 26.5 ± 8 | .63 |
| Biplane LVESV (mL) | 13.5 ± 7 | 13.7 ± 6 | .93 |
| Biplane LVESV index (mL/m 2 ) | 7.4 ± 4.5 | 7.1 ± 3 | .81 |
| Biplane LVEF (%) | 72.9 ± 10 | 74.7 ± 7 | .56 |
| Biplane left atrial volume (mL) | 73.5 ± 46 | 62.2 ± 23 | .37 |
| Biplane left atrial volume index (mL/m 2 ) | 37.7 ± 24 | 33.0 ± 13 | .52 |
| Heart rate (beats/min) | 66.0 ± 15 | 66.1 ± 13 | .98 |
| Duration of complete systolic emptying (msec) | 195 ± 46 | 148 ± 63 | .013 ∗ |
| Duration of systole with complete systolic emptying/√R-R interval | 201 ± 47 | 154 ± 65 | .015 ∗ |
| Proportion of cycle with complete systolic emptying (%) | 20.8 ± 6 | 16.2 ± 6 | .022 ∗ |
| Proportion of systole with complete systolic emptying (%) | 49.5 ± 13 | 35.3 ± 14 | .004 ∗ |
| Systolic volume of akinetic apical aneurysms (mL) | 6.90 ± 6.7 | — | — |
| Greatest width of akinetic apical aneurysms (cm) | 2.10 ± 0.7 | — | — |
Two-Dimensional Measurements
Patients with akinetic apical aneurysms had thinner apical walls (0.7 ± 0.4 vs 1.8 ± 0.6 cm, P < .001), smaller mid-LV end-diastolic diameters (2.0 ± 0.95 vs 2.7 ± 0.7 cm, P = .019), and longer lengths of systolic wall apposition in the apical four-chamber view (3.1 ± 0.6 vs 2.6 ± 0.8 cm, P = .028). Figures 2 to 4 show three typical patients with mid-LV hypertrophy at the papillary muscle level, akinetic apical aneurysms, and mid-LV Doppler signal voids. Patients from Figures 3 and 4 had high catheterization gradients between the apical aneurysm and the basilar left ventricle, despite absent Doppler velocities across the obstructing neck. Complete systolic emptying often encircled the hypertrophied papillary muscles, whose bulk contributed to obstruction.
Patients with akinetic apical aneurysms had greater absolute durations of 2D SAX complete systolic emptying <1.0 cm 2 (195 ± 46 vs 148 ± 63 msec, P = .013). This difference remained significant after correcting for heart rate (201 ± 47 vs 154 ± 65 msec, P = .015). The percentage of the R-R interval with complete systolic emptying was greater in the akinetic apical aneurysm group (20.8 ± 6% vs 16.2 ± 6%, P = .022), and the proportion of systole with complete systolic emptying was greater (49.5 ± 13% vs 35.3 ± 14%, P = .004). There was a strong correlation between the proportion of systole with complete systolic emptying and the duration of Doppler systolic flow void ( r = 0.704, P = .001), as illustrated in Figure 6 .
