Author + information
- Received October 23, 1998
- Revision received May 5, 1999
- Accepted June 22, 1999
- Published online October 1, 1999.
- Michael Y Henein, MD, PhD, FACCa,
- Christine A O’Sullivan, BSca,
- Ihab S Ramzy, MB, MSca,
- Ulrich Sigwart, MD, FRCP, FACCa and
- Derek G Gibson, MB, FRCPa,* ()
- ↵*Reprint requests and correspondence: Dr. Derek G. Gibson, Royal Brompton Hospital, Sydney Street, London SW3 6NP, United Kingdom
To investigate the electromechanical consequences of nonsurgical septal reduction in a group of patients with hypertrophic obstructive cardiomyopathy (HOCM).
Patients with HOCM may benefit symptomatically from nonsurgical septal reduction as an alternative to dual chamber pacing and sensing (DDD) pacing and surgical myectomy.
We studied 20 symptomatic patients with HOCM (12 men), mean age 52 ± 17 years, before and after septal reduction using echocardiography and electrocardiogram (ECG).
Septal reduction with a significant rise in cardiac enzymes was successfully achieved in all patients resulting in a 50% reduction in resting left ventricular (LV) outflow tract gradient within 24 h of procedure and an 80% reduction after six months. Left ventricular outflow tract diameter increased at 24 h with a further increase six months later. QRS duration increased by 35 ms at 24 h after procedure associated with right bundle branch block (RBBB) and significant rightward axis rotation in 16 patients. R-wave amplitude in V1 fell by 7 ± 4 mm in 15/20 patients, 13 of whom developed reduction of septal long axis excursion. Left-axis deviation appeared in three patients and septal q-wave was suppressed in 12 long-axis excursion; peak shortening and lengthening rates all fell at the septal site by 20% at 24 h. Only septal excursion returned back to baseline values at six months. Wall motion also became incoordinate so that postejection septal shortening increased by three times control values at 24 h and by four times six months later.
Nonsurgical septal reduction is associated with a drop in LV outflow tract obstruction and the creation of a localized myocardial infarction (MI) increasing LV outflow tract diameter. The technique also results in a consistent alteration of septal activation and secondary incoordination. The latter could play a significant role in gradient reduction and symptomatic improvement in a manner similar to that seen with DDD pacing.
Exercise tolerance is limited for many patients with hypertrophic obstructive cardiomyopathy (HOCM) despite optimal medical treatment. In such patients, pacing of the right ventricle (RV) may be beneficial in reducing left ventricular (LV) outflow tract gradient, presumably by altering septal activation (1). Direct surgical relief of outflow tract obstruction by septal myectomy has also been used although its complications are well known, including shunt creation and permanent conduction disturbances (2). A third approach, nonsurgical septal reduction, has recently been described in cases resistant to medical therapy or pacing, in an attempt to avoid surgery (3–6). Its early results are promising in alleviating symptoms and outflow tract gradient, though its exact mechanism of action is not yet clear (7). We therefore attempted to study in detail LV electromechanical behavior following septal ablation procedure with a special emphasis on long axis function which represents that of the subendocardium where the conduction system is situated.
We studied 20 patients with HOCM, mean age 52 ± 17 years, before, 24 h after and 6 months after nonsurgical septal reduction using alcohol. Twelve patients were men. The patients all experienced limitation of exercise tolerance by shortness of breath or angina that had failed to respond to medical therapy. All claimed significant symptomatic improvement after the procedure. All patients were on beta-adrenergic blocking agents before procedure. This was not altered afterwards. No patient with a dual chamber pacing and sensing (DDD) pacemaker inserted before or after the procedure was included in this study.
Twelve lead electrocardiograms (ECGs) were recorded on a Hewlett-Packard pagewriter XLi electrocardiograph (Palo Alto, California) with a built-in analysis package. Electrocardiogram intervals and amplitudes were measured automatically and registered on the printed chart. The frequency response of the electrocardiograph was 0.05 Hz to 150 Hz with the baseline filter (0.4 Hz) inactivated.
Mechanical LV function was studied using transthoracic echo-Doppler technique at rest. A SONOS 1500 echocardiograph (Hewlett-Packard, Andover, Massachusetts) was used with a 2.5 MHz transducer. Two D guided M-mode recordings of LV minor axis were obtained from the standard left parasternal window with the patients in the semilateral position and the cursor at mitral valve leaflets tip level. Left ventricular long axis M-mode was recorded from the apical four-chamber view with the cursor positioned at the left and septal angles of the mitral ring (8,9). Transmitral filling velocities were obtained using the transducer in the pulsed wave mode from the apical four-chamber view with the sample volume at the tips of mitral leaflets. Left ventricular outflow tract velocities were recorded using continuous wave Doppler (Doptek, Colchester, United Kingdom) with the transducer positioned at the apex. All traces were recorded on paper at a speed of 100 mm/s with a superimposed ECG and phonocardiogram. M-mode traces were later digitized (10).
PR interval, QRS duration, QT and QT interval corrected for heart rate (QTc) intervals and overall QRS axis were determined directly by the in-built computer software. Early QRS axis (first 40 ms) was measured manually. The presence or absence of the septal q-wave in V5 and V6 of the chest leads was documented.
ECHO.Recordings were obtained by one operator and measurements were made by one observer (11). Left ventricular minor axis dimensions were measured using leading edge methodology at end-diastole (at the onset of the q-wave of the ECG) and end-systole (at the onset of the first high frequency vibration of the aortic component of the second heart sound of the superimposed phonocardiogram). Septal and posterior wall thicknesses were measured from the same trace at end-diastole, using the American Society of Echocardiography criterion taken at the tips of the mitral valve leaflets without any bias to the injured segment. Outflow tract diameter was measured in mid-systole from the standard M-mode mitral valve echogram as the distance between the coapted mitral leaflets and the LV side of the septum. Isovolumic relaxation tie was taken as the time interval between the onset of A2, second heart sound, and the onset of mitral cusp separation. Total LV long axis excursion was taken as that from maximum shortening to maximum lengthening. Post ejection shortening was measured as the amplitude of movement towards the ventricular apex, occurring after A2 (Fig. 1). From the digitized traces, peak minor and long axis shortening rates (in systole) and peak lengthening rates (in diastole) were measured. The pressure difference across LV outflow tract was determined from peak velocity using the simplified Bernoulli equation. Early and late diastolic LV filling velocities were determined from the transmitral Doppler trace.
Echocardiogram and echo values, before, 24 h after and 6 months after procedure were compared using repeated measures analysis of variance (ANOVA). When this was significant, individual values were compared using a paired ttest. The incidence of ECG disturbances before and after the procedure was compared using a chi-square probability test.
Nonsurgical septal reduction was successfully performed in all patients resulting in a 50% early reduction in resting LV outflow tract gradient from a mean of 60 ± 28 to 26 ± 18 mm Hg, falling to 22 ± 16 mm Hg at six months. There was an associated mean enzyme rise to peak values for creatine phosphokinase (CK) of 2,160, for myocardial isoenzyme (CK-MB) of 190, and for aspartate transferase (AST) of 285 U/L, respectively.
Left ventricular dimensions at end-systole and end-diastole increased by 2 mm six months after procedure. Septal thickness fell by 2 mm, but posterior wall thickness remained unchanged (Table 1). Both peak minor axis shortening and lengthening rates fell significantly. Left ventricular outflow tract diameter had increased slightly at 24 h with a further small rise at six months. Left ventricular diastolic measurements including isovolumic relaxation time and transmitral E- and A-wave velocities did not change. The effects of septal reduction on LV long axis are recorded in Table 2. At 24 h, total excursion, peak shortening and peak lengthening rates at the septal site had all fallen by more than 20% resting values. At six months, total excursion had returned to baseline levels, but the abnormal peak rate of shortening and lengthening remained abnormal. In contrast at the left site, peak lengthening rate was the only measurement to be affected by the procedure, falling by almost the same extent as that of the septum and remaining unchanged for six months. The most striking long axis abnormality to appear was the postejection shortening (Fig. 1). Within 24 h of the procedure, its amplitude had increased to three times the control value at the septal site and to four times this value six months later. By contrast the left site was affected only at 24 h and to a lesser extent than that of the septum; it had returned to normal by six months.
Twenty-four h after procedure, heart rate and PR interval did not significantly change and remained the same at six months (Table 3). However, in 16 patients an increase in QRS duration of over 30 ms at 24 h was associated with development of right bundle branch block (RBBB) and a significant axis rotation towards the right (p < 0.001, Fig. 2). In 15/16 patients with RBBB the long axis amplitude fell (p < 0.03) and all 16 became incoordinate in early diastole (p < 0.01). No patient had complete RBBB before the procedure. Mean QRS duration in these patients rose from 99 to 135 ms. In one patient incomplete RBBB (i.e., QRS < 120 ms) was present in the control state and persisted unchanged. In the remaining three patients, either complete or incomplete left bundle branch block (LBBB) was present, either before or afterwards. Both QT and QTc intervals were unchanged at 24 h and six months with respect to preprocedure values despite the changes in activation. A normal septal q-wave was present in 17/20 patients before the procedure. It was lost in 12 of these patients immediately after procedure and was still absent at six months’ follow up. There was a consistent fall in R-wave amplitude in lead V1, by a mean of 7 ± 4 mm in 15/20 patients, 12 of whom also developed reduction in total septal long axis excursion (p < 0.02). Classical left axis deviation was present under control conditions in one patient and was unaffected by septal reduction, and it appeared afterwards in three patients. Either loss of septal q-wave or left axis deviation developed with the procedure in 13 patients; the remaining 2, in whom no left sided conduction disturbance developed, were the only ones in whom R-wave voltage in V1 did not fall (p < 0.02).
In the past, disturbances of ventricular activation were analyzed largely by observing the effects of localized injury on the surface electrocardiogram (12). Experiments were performed on animals because the opportunities for making such observations in humans were limited. Therapeutic septal reduction as performed in patients with symptomatic HOCM provides an unusual opportunity to correlate the effects of local injury on ventricular activation (13). The size and location of the affected region of septum will have varied with the distribution of the first septal branch of the left anterior descending coronary artery, but in general a small portion of the basal septum is likely to have been involved (14).
Consistent elevation of cardiac enzymes strongly suggests that MI did occur with septal reduction. Though pathologic Q-waves did not develop in any patient, there was consistent loss of R-wave on V1 in all but three patients, compatible with septal localization. At the same time, QRS duration increased significantly in 16 patients and was associated with the development of RBBB. This change is likely to have reflected interference with the blood supply to the right bundle which arises from the first septal artery as it traverses from the left to the right side (15). However, the resulting increase in QRS duration by 35 ms to a mean value in excess of 135 ms is longer than that associated with uncomplicated RBBB (16), suggesting that the disturbance to ventricular activation may have been more complex. In three patients, classical left axis deviation did indeed develop, giving rise to the well-established picture of bifasicular block (16). In an additional 12 patients, the septal q-wave, present under control conditions, was suppressed following the procedure. The septal q-wave was identified with septal activation as reported by Lewis (17), so that its disappearance suggests that the early stages of LV activation are frequently modified by the procedure. The two patients who failed to show evidence of left-sided conduction abnormality were those in whom R-wave voltage in V1 did not fall. We conclude, therefore, that ECG changes after septal reduction are compatible with limited septal infarction causing conduction disturbances which involve both main branches of the bundle of His.
The mechanical function of the LV also changed. End-diastolic and end-systolic diameters increased slightly and were associated with a reduction in shortening and, in particular, of early diastolic lengthening velocity. At the same time, outflow tract diameter increased by approximately 2 mm at 24 h, and by an additional 4 mm at six months after procedure. Changes in long axis function also appeared at 24 h in both septal and LV free-wall sites. Those on the free wall of the LV were no longer present at six months, but the septal ones persisted, where they included reduced peak shortening and lengthening rates and appearance of asynchrony, with postejection shortening. Overall, septal long axis excursion was reduced at 24 h but was normal at six months.
At least two factors may have contributed to these mechanical changes. Outflow tract dimension increased, and the pressure difference fell from a control value of 60 mm Hg to 22 mm Hg at six months. A second potential cause of a change in ventricular mechanical activity is altered activation, which is reflected in the timing of septal ventricular long axis motion. Isolated RBBB delays the onset of RV long axis shortening but is without effect on the septum or LV. Loss of the septal q-wave has previously been shown to be associated with septal asynchrony whose most obvious characteristic is postejection shortening in patients without hypertrophic cardiomyopathy (18). The results of our study are compatible with these findings. The appearance of postejection shortening involving the free LV wall as well as the septum had not previously been seen in patients with spontaneous absence of the septal q-wave and suggests that the early activation disturbance induced by septal reduction in our patients may have been more extensive. A reduced amplitude of long axis shortening present at 24 h, but absent at six months, however, is more likely to have been the effect of the infarct itself rather than any change in activation. Whether the reduced rates of septal long axis shortening and lengthening were the effects of the infarction itself or the associated activation change, we are unable to say, though their persistence and even progression when overall amplitude returns to normal would be in favor of the latter.
We used standard criteria in interpreting the ECGs, including a QRS duration <120 ms as excluding complete RBBB. We have also assumed that the first 40 ms of ventricular activation is unaffected by RBBB. We are aware that the extent of any prolongation of ventricular activation may be underestimated on standard 12 lead ECG. Neither the exact mechanism underlying LV outflow tract obstruction in hypertrophic cardiomyopathy nor its relation to exertional symptoms has been well-established. We therefore consider that a fall in pressure gradient in the outflow tract is better viewed as an indirect marker of change rather than a direct mechanism of symptomatic improvement.
Our results demonstrate that septal reduction via the first septal coronary artery alters ventricular activation as well as causing a localized MI. These mechanisms may contribute to the beneficial effects of the procedure. There is a consistent increase in outflow tract dimension, which persists at six months and is associated with the fall in pressure gradient. Activation changes include RBBB in most patients as well as a change in the initial forces of LV activation. The mechanical changes persisting at six months were very similar to those previously associated with loss of the septal q-wave (18)although the additional early involvement of the free wall of the LV suggests that they might have been more extensive. Further understanding of these interrelations will come from anatomic studies of the relations between arteries and conducting systems in the upper septum. It may be significant that altered septal activation by DDD pacing from the RV has also been shown to reduce the outflow tract pressure gradient (1)and that successful surgical myotomy in hypertrophic cardiomyopathy is characteristically followed by LBBB (2). All these procedures are similar in that they all alter LV activation, which may thus provide a unitary mechanism underlying their action. If the benefits of septal ablation do indeed depend on electrical effects as well as on the extent of MI, it may then be feasible to modify the procedure in order to achieve an appropriate change in activation pattern with minimal myocardial loss.
☆ This study was supported by the Royal Brompton Special Cardiac Fund.
- analysis of variance
- aspartate transferase
- creatine phosphokinase
- myocardial isoenzyme
- dual chamber pacing and sensing
- hypertrophic obstructive cardiomyopathy
- left bundle branch block
- left ventricle or ventricular
- QT interval corrected for heart rate
- right bundle branch block
- right ventricle
- Received October 23, 1998.
- Revision received May 5, 1999.
- Accepted June 22, 1999.
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