Because alcohol septal ablation (ASA) for the treatment of symptomatic hypertrophic cardiomyopathy (HC) with left ventricular (LV) outflow tract (LVOT) obstruction results in a myocardial infarct of up to 10% of ventricular mass, LV systolic function could decline over time. We evaluated LV function during longitudinal follow-up in a cohort of patients who underwent ASA. We studied 145 consecutive patients with HC that underwent 167 ASA procedures from 2002 to 2011. Echocardiographic follow-up was available in 139 patients (96%). Echocardiographic indexes included LV ejection fraction (LVEF), mitral regurgitation severity, systolic anterior motion of the anterior mitral leaflet, and resting and provoked LVOT gradients. All patients had a baseline LVEF of >55%. LVEF was preserved in 97.1% of patients over a mean follow-up time of 3.1 ± 2.3 years (maximum 9.7). Mild LV systolic dysfunction was observed (LVEF range 44% to 54%) in only 4 patients. Mitral regurgitation severity improved in 67% (n = 112 of 138 with complete data). Resting LVOT gradient declined from a mean of 75 to 19 mm Hg (p <0.001), and provoked gradient declined from a mean of 101 to 33 mm Hg (p <0.001). New York Heart Association class improved from a mean of 2.9 ± 0.4 to 1.3 ± 0.5 (p <0.001). In conclusion, LV systolic function is only mildly reduced in a minority of patients after ASA for symptomatic HC; other echocardiographic and functional measures were significantly improved.
Hypertrophic cardiomyopathy (HC) is a genetic cardiovascular condition affecting as many as 600,000 people in the United States, many of whom frequently remain unidentified. Up to 2/3 of patients with HC develop left ventricular (LV) outflow tract (LVOT) obstruction related to septal wall thickening, systolic anterior motion (SAM) of the mitral leaflet, and mitral-septal contact. For patients whose symptoms are not adequately relieved by pharmacotherapy, septal reduction therapy by means of either surgical myectomy or alcohol septal ablation (ASA) is considered. Because ASA results in a transmural infarct occupying up to 10% of the ventricular myocardium, LV systolic function could decrease over time. Long-term follow-up of patients who have undergone ASA has been limited and has not always included echocardiographic evaluation of the same measurements that guided the initial intervention. Here we report the echocardiographic and clinical outcomes of 145 consecutive patients who underwent ASA.
Methods
We studied consecutive patients with HC complicated by LVOT obstruction who underwent ASA procedures from 2002 to 2011 at both the University of Colorado Hospital and the Denver Veterans Affairs Medical Center. Indications for ASA included persistent symptoms (New York Heart Association [NYHA] class II to IV) despite medical therapy, significant resting or provoked LVOT gradients, and coronary anatomy amenable for proximal septal ablation. No patients had had previous surgical myectomy.
Before undergoing the ASA procedure all patients had a baseline transthoracic echocardiogram that demonstrated a normal LV ejection fraction (LVEF >55%), as measured by the biplane method of discs. Additional echocardiographic indexes included interventricular septal wall thickness, resting and provokable LVOT gradients, assessment of SAM of the mitral leaflet, and grading of severity of mitral regurgitation. The Colorado Multiple Institutional Review Board approved this analysis.
The septal ablation procedure was performed in a standard fashion in a manner similar to previous descriptions. Coronary angiography was performed to demonstrate suitable anatomy for septal ablation. Aortic and LV pressures were recorded with simultaneous hemodynamic measurements. If indicated, provocative maneuvers such as the induction of a premature ventricular depolarization or the administration of amyl nitrate were performed. An angioplasty balloon was advanced over a guide wire positioned in the proximal portion of the septal perforator artery. After the balloon was inflated, a mixture of angiographic and echocardiographic contrast material was injected through the balloon lumen into the selected artery. If the delineated area of myocardium was a suitable target for septal ablation as assessed by myocardial contrast echocardiography, 1.5 to 5 mL of ethanol was infused slowly over a period of 3 to 5 minutes. The hemodynamic assessment was repeated and if the patient had a <50% decrease in the resting or provoked LVOT gradient, a second septal perforator artery was targeted in a similar manner. Postprocedure hemodynamics were recorded. Patients were monitored in the intensive care unit for a minimum of 48 hours after procedure.
Patients were evaluated after procedure to assess functional status (NYHA class), clinical symptoms, medication regimen, and echocardiographic indexes. Follow-up clinical assessments up to September 2013 occurred at intervals as deemed appropriate by their cardiologist but generally occurred annually. Comprehensive 2-dimensional and Doppler echocardiography included evaluation of septal wall thickness, LVEF, presence or absence of SAM, mitral regurgitation severity, as well as both resting and provoked LVOT gradients. Patients’ functional status as determined by their clinician was also recorded during at least the initial follow-up appointment along with frequent recordings of the same during subsequent clinic visits.
For a small subset of patients who underwent additional procedures, our analysis and reporting is based on the first procedure. Continuous variables are presented as mean ± SD. Longitudinal changes of continuous variables were assessed using a 2-tailed Student t test. Mann-Whitney U testing was used to assess both categorical and longitudinal changes of rank-order variables. With either assessment, a p value of ≤0.05 was deemed statistically significant. All-cause mortality was evaluated by censoring patients at the date of death or last known follow-up. Survival estimates were determined with traditional Kaplan-Meier estimation. Statistical analysis was performed using R: A Language and Environment for Statistical Computing, version 3.0.1 (R Foundation for Statistical Computing; Vienna, Austria).
Results
One hundred forty-five consecutive patients underwent 167 ASA procedures. Characteristics of the study population are outlined in Table 1 . The mean age was 57.5 ± 15.5 years. There were 72 female patients (49%). Sixty-one patients (43%) had at least nonobstructive coronary artery disease; hypertension was present in 71 (49%) and atrial fibrillation in 21 patients (15%). The mean follow-up time of repeat echocardiography was 3.1 ± 2.3 years and was available for 139 patients (96%).
| Variable | Value |
|---|---|
| Age (yrs) | 57.5 ± 15.5 |
| Women | 72 (50) |
| Syncope | 41 (28) |
| Atrial fibrillation | 21 (15) |
| Previous stroke | 8 (6) |
| Hypertension | 71 (49) |
| Diabetes mellitus | 10 (7) |
| Coronary artery disease | 61 (43) |
| Chronic kidney disease | 8 (6) |
| Family history of sudden cardiac death | 18 (13) |
| Medications | |
| β Blocker | 108 (77) |
| Calcium channel blocker | 63 (45) |
| Angiotensin-converting enzyme inhibitor | 22 (16) |
| Disopyramide | 13 (9) |
| Amiodarone | 3 (2) |
During the procedure, a mean of 1.1 ± 0.4 septal perforating arteries were injected with a mean of 4.1 ± 1.7 ml of ethanol ( Table 2 ). Immediately after the procedure, resting and provoked LVOT gradients decreased to ≤30 mm Hg in 124 patients (91%; of 136 patients with complete data). Complete heart block during anytime during the study period occurred in 39 patients (26.9%). Twenty-two (15%) patients underwent a second ASA procedure with 1 patient undergoing a third septal ablation. No ventricular septal defects, myocardial perforations, or pericardial effusions were observed as a complication of the ASA procedure. Dissection of the common femoral artery necessitating open surgical repair occurred in 1 patient. Asystole and ventricular fibrillation arrest occurred in 2 patients, which, after successful resuscitation, necessitated implantation of a pacemaker and an implantable cardioverter-defibrillator, respectively.
| Variable | Value |
|---|---|
| Troponin peak (ng/ml) | 68.0 ± 89.8 |
| Creatinine kinase-MB peak (ng/ml) | 188.0 ± 121 |
| Creatine kinase peak (ng/ml) | 1,172 ± 524 |
| Number of septal arteries ablated | 1.1 ± 0.4 |
| Volume of alcohol injected (ml) | 4.1 ± 1.7 |
| Number of subsequent ASA procedures | 22 (15) |
| Complete heart block | 39 (27) |
| Deaths | 16 (11) |
Of the patients with echocardiographic follow-up, 135 (97%) had preserved (>55%) LVEF ( Table 3 ). The 4 patients (3%) with decreased systolic function had only mildly decreased LVEF (range 44% to 54%). All but 1 of these 4 patients received <4.0-ml ethanol. Before the procedure, all patients had symptoms attributable to LVOT obstruction with a mean NYHA class of 2.9 ± 0.4, which on follow-up improved significantly to 1.3 ± 0.5 (change = −1.6, p <0.001). Of the 4 patients with mildly reduced LVEF, each experienced short-term improvement in their functional class that waned over time in context of co-morbid illness.
| Parameter | Baseline | After Procedure | Change | p Value |
|---|---|---|---|---|
| Septal thickness (cm) | 2.0 ± 0.4 | 1.4 ± 0.5 | −0.6 | <2.2 × 10 −16 |
| Resting LVOT gradient (mm Hg) | 75.4 ± 44.9 | 18.6 ± 23.3 | −56.8 | <2.2 × 10 −16 |
| LVOT gradient with Valsalva (mm Hg) | 101.5 ± 43.7 | 33.5 ± 36.4 | −68.0 | <2.2 × 10 −16 |
| LVOT gradient with amyl nitrate (mm Hg) | 98.1 ± 28.2 | 33.6 ± 26.4 | −64.4 | 1.6 × 10 −15 |
| Mitral regurgitation severity (0–4) | 2.4 ± 0.7 | 1.5 ± 0.7 | −0.9 | <2.2 × 10 −16 |
| SAM of mitral valve | 129 (96) | 58 (42) | −53 | <2.2 × 10 −16 |
| Normal LVEF (>55%) | 145 (100) | 135 (97) | −3 | 0.040 |
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