ronit.zadikany@cshs.org
Corresponding author
Dr Charles Pollick
Smidt Heart Institute, Cedars Sinai Medical Center, 127 S San Vicente Blvd, Los Angeles, CA, 90048
Phone: 310 985 2220
charles.pollick@cshs.org
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Abstract
Controversy surrounds the cause of the pressure gradient in patients with hypertrophic obstructive cardiomyopathy (HOCM). Left ventricular cavity obliteration (LVCO) was first described as the cause of the gradient but subsequently systolic anterior motion (SAM) of the mitral valve has been established as the cause.
Nevertheless, the two gradients, though different in origin and significance, share similar characteristics. They both have a similar “dagger” profile, are obtained from the cardiac apex, are associated with a hyperdynamic left ventricle, and the gradients are worsened by Valsalva. The distinction has clinical relevance, because treating the intra cavitary gradient (ICG) of LVCO as if it were a SAM associated gradient associated with HOCM would be inappropriate and possibly harmful.
To clarify the cause and characteristics of the ICG in patients with LVCO in patients without HOCM we assessed the extent and duration of cavity obliteration and for differentiation we compared the spectral profiles with patients with HOCM and severe aortic stenosis (AS).
Higher ICG is associated with greater extent and more prolonged apposition of LV walls, and smaller left ventricular cavity size. The spectral profile of patients with AS, HOCM and LVCO are differentiated by the peak/mean gradient ratios of 2 or less, 2-3, and 3 or greater, respectively in > 90% of patients.
Most patients with LVCO without HOCM or severe LVH have an ICG < 36 mmHg. The magnitude of ICG is quantitatively associated with extent and duration of LVCO. Spectral profiles of severe AS, HOCM, and LVCO can be differentiated by the peak/mean gradient ratio.
Introduction
Left ventricular cavity obliteration (LVCO), defined as obliteration of the apex in systole on angiography, was first described1 in 1965 and proposed as the cause of the intraventricular pressure gradient accompanying hypertrophic cardiomyopathy. It was subsequently documented 2 that cavity obliteration can be seen in states other than hypertrophic cardiomyopathy. Another school of thought 3 opined that the pressure gradient in hypertrophic cardiomyopathy was due to left ventricular outflow tract (LVOT) obstruction. Following decades of study, it is now generally agreed that the characteristic gradient in hypertrophic obstructive cardiomyopathy (HOCM) is a dynamic subaortic pressure gradient due to LVOT obstruction from systolic anterior motion of the mitral valve (SAM) 4,5. These LVOT gradients, when high, are accompanied by exercise intolerance which can be mitigated by pharmacologic or interventional methods to ameliorate the gradient 6. At first, the intracavitary gradients (ICG) accompanying LVCO were dismissed as either not obstructive1 and therefore not important, or possibly an artifact of “catheter entrapment” 3, and therefore also not clinically relevant. Intracavitary gradients with cavity obliteration have been demonstrated during dobutamine stress echocardiography and have, paradoxically, been associated with favorable, rather than adverse, outcomes 7,8. More recently, however, apical cavity obliteration has been associated with adverse outcomes, and has been implicated in the pathogenetic mechanisms of apical aneurysm in hypertrophic cardiomyopathy 9. Despite such studies focusing on cavity obliteration, there is a lack of data studying the temporal and quantitative relationship between the 2D echocardiographic occurrence of obliteration and the magnitude of the ICG.
In addition to the controversy between the mechanism and significance of the gradient associated with LVCO and that of HOCM, the two gradients may be confused for a variety of reasons. They share a similar “dagger” profile, the gradients are both obtained from the cardiac apex, both are associated with a hyperdynamic left ventricle, and the gradients are both worsened by Valsalva. In patients with challenging echocardiographic windows it may not always be possible to distinguish the origin of the gradient. Furthermore, they can coexist in patients with HOCM. The distinction has clinical relevance, because treating the ICG gradient as if it were an LVOT gradient associated with HOCM would be inappropriate and possibly harmful.
Methods
Patients
We studied the most recent 100 patients in our echocardiography laboratory database search with the phrase “cavity obliteration” (LVCO) entered on a transthoracic echocardiogram report. Out of those there were 87 patients without severe valve disease, severe pulmonary hypertension (PA systolic pressure > 65 mmHg), hypertrophic cardiomyopathy (HCM) (non-obstructive or obstructive), significant LV hypertrophy (defined as 15 mm or greater wall thickness) or SAM (moderate or greater) with clearly defined spectral profiles of intra cavitary gradients. Of these 87 patients, there were 65 patients (female 48; mean age 74: range 40-101) who also had a well-defined, non-foreshortened and quantifiable LV cavity demonstrated on apical 4 chamber views. In all patients, cavity obliteration was defined as obliteration of the LV apical cap with variable extension into the mid LV cavity. Of these 65 patients; 49 were inpatients, 17 were on intravenous inotropes, 5 patients had sepsis; there were a variety of other diagnoses including chest pain, pneumonia, sclerosing cholangitis, GI bleed etc.
For comparison, the spectral profiles of 25 patients with HOCM and severe systolic anterior motion of the mitral valve (SAM), and 25 patients with severe AS were assessed and compared with the spectral profile associated with the ICG seen with LVCO in a subset of 25 of the 65 patients with intracavitary gradients of 36 mmHg or greater.
Transthoracic Echocardiography
Standard transthoracic echocardiographic (TTE) studies were performed, using standard American Society of Echocardiography guidelines10, in all patients using a commercially available ultrasound system with phased array transducers (Phillips Medical Systems)
Echocardiographic measurements
In the standard apical 4 (Ap4) chamber view (Figure 1), the following measurements were made from one clear representative cardiac cycle: 1. The end-diastolic length (Ap4d) of the left ventricle from apex endocardium to the mitral annulus (mm). 2. The length of the obliterated cavity (Ap4s) from the most basal point of obliteration to the annulus (mm). 3. The number of frames during which the LV cavity was obliterated was converted into msec. Frame duration was calculated from the frame rate in Hz. For example, if the frame rate was 50 Hz, this means that each frame is 20 msec. If the LV cavity was obliterated for 4 frames at 50 Hz, then that translates to 80 msec of obliteration. Measurements were made by 2 observers blinded to the ICG mmHg measurements.
Doppler measurements
For the LVCO patients, the intracavitary spectral continuous wave Doppler profiles were identified. Peak and mean gradients were measured from one clear representative cycle. For the HOCM and AS patients, one clear representative spectral aortic and LVOT spectral profile was identified, and the mean and peak gradients were measured. Measurements were made by 4 observers blinded to the 2D measurements.
Statistical methods
Standard t-tests for unpaired variables were performed. Standard Pearson’s correlation coefficients were determined.
Permission to access the echocardiographic images and patient data was approved by our institutional review board.
Results