Electromechanical left ventricular behavior after nonsurgical septal reduction in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: To investigate the electromechanical consequences of nonsurgical septal reduction in a group of patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Patients with HOCM may benefit symptomatically from nonsurgical septal reduction as an alternative to dual chamber pacing and sensing (DDD) pacing and surgical myectomy. METHODS: We studied 20 symptomatic patients with HOCM (12 men), mean age 52 +/- 17 years, before and after septal reduction using echocardiography and electrocardiogram (ECG). RESULTS: 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. CONCLUSIONS: 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.     

Sustained improvement in left ventricular diastolic function after alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

AIMS: Impaired diastolic function is responsible for many of the clinical features of hypertrophic cardiomyopathy. In patients with hypertrophic obstructive cardiomyopathy (HOCM) whose symptoms are refractory to medical therapy, alcohol septal ablation (ASA) reduces left ventricular (LV) outflow tract gradient, with short-term improvement in LV diastolic function. Little is known about the longer term impact of ASA on diastolic function. METHODS AND RESULTS: We evaluated LV diastolic function at baseline and 1- and 2-year follow-up after successful ASA. In 30 patients (58+/-15 years, 22 men) who underwent successful ASA, New York Heart Association class was lower at 1-year follow-up compared with baseline (3.0+/-0.5 to 1.5+/-0.7; P<0.0001). LV outflow tract gradient (76+/-37 to 19+/-12; P<0.0001), interventricular septal thickness (19+/-2 to 14+/-2; P<0.0001), and left atrial volume (26+/-5 to 20+/-4; P<0.0001) were decreased. Significant improvement in E-wave deceleration time, isovolumic relaxation time, early diastolic mitral lateral annular velocity (E'), mitral inflow propagation velocity (V(p)), ratio of transmitral early LV filling velocity (E) to early diastolic Doppler tissue imaging of the mitral annulus (E/E'), and E/V(p) were observed at 1 year following successful ASA. These changes persisted in the subset cohort (n=21) for whom 2-year data were available. CONCLUSION: Successful ASA for HOCM leads to significant and sustained improvement in echocardiographic measures of diastolic function, which may contribute to improved functional status after successful ASA.     

Role of myocardial contrast echocardiography during nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy

Objectives. This study was undertaken to evaluate the ability of myocardial contrast echocardiography (MCE) to guide the targeted delivery of ethanol during nonsurgical septal reduction therapy (NSRT) and to assess the relation between the MCE risk area and infarct size determined by enzymatic and radionuclide methods.Background. NSRT with intracoronary ethanol is a new promising treatment for patients with hypertrophic obstructive cardiomyopathy (HOCM). Proper localization and quantification of the septal infarct before ethanol injection are highly desirable. MCE can provide accurate delineation of the vascular territory of the coronary arteries.Methods. Twenty-nine patients with HOCM and maximal medical therapy underwent NSRT. The left ventricular outflow tract (LVOT) gradient by Doppler echocardiography at baseline was 53 ± 16 mm Hg (mean ± SD). Before NSRT, MCE was performed in all patients with intracoronary sonicated albumin (Albunex). Diluted sonicated albumin (Albunex) was selectively injected into the septal perforator arteries during simultaneous transthoracic imaging. Immediately after MCE, ethanol was injected into the same vessel. Plasma total creatine kinase (CK), total CK-MB fraction and CK-MB fraction subforms were measured at baseline and serially for 36 h.Results. LVOT gradient decreased to 12 ± 6 mm Hg (p < 0.001) after NSRT. Accurate mapping of the vascular beds of the septal perforators was successfully attained in all patients by MCE. Furthermore, the MCE risk area correlated well with peak CK (r = 0.79, p < 0.001). Six weeks after NSRT, 23 patients underwent myocardial perfusion studies performed with single-photon emission computed tomography (SPECT). Mean SPECT septal perfusion defect size involved 9.5 ± 6% of the left ventricle and correlated well with MCE area (r = 0.7), with no statistically significant difference between the risk area estimated by MCE and that by SPECT.Conclusions. Estimation of the size of the septal vascular territory with MCE is accurate, safe and feasible in essentially all patients during NSRT. MCE can delineate the perfusion bed of the septal perforators and can predict the infarct size that follows ethanol injection.     

Echocardiographic insights into the mechanisms of relief of left ventricular outflow tract obstruction after nonsurgical septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy

OBJECTIVES: We sought to evaluate the mechanisms by which nonsurgical septal reduction therapy (NSRT) reduces left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic obstructive cardiomyopathy (HOCM) both acutely and on a long-term basis. BACKGROUND: NSRT reduces LVOT obstruction in patients with HOCM and leads to symptomatic improvement. The mechanisms involved, however, are not well studied. METHODS: An initial group of 30 HOCM patients (age 46 +/- 17, 16 women) who underwent NSRT had echocardiographic studies performed at baseline and six months after the procedure. Measurements included LVOT diameter, end-diastolic distance between the anterior mitral leaflet and interventricular septum, septal base function and the angle between LV systolic flow and the protruding mitral leaflets. In addition, pulse Doppler recordings at a point 2.5 cm apical to the mitral valve were acquired and analyzed for peak and mean ejection velocity, peak acceleration rate and the ratio of acceleration time to ejection time (AT/ET). RESULTS: Significant changes were observed after the procedure, with widening in the LVOT, thinning and akinesis of the septal base, decrease in the angle between LV systolic flow and the protruding mitral leaflets, a decrease in peak acceleration rate and an increase in AT/ET. All of these variables had significant relations with the decrease in LVOT obstruction (r = 0.5 to 0.79, p < 0.01). These correlations were then evaluated in a test group of 15 patients who underwent echocardiographic examinations at baseline, acutely in the catheterization laboratory with ethanol injection and at six weeks post NSRT. Acute changes in peak acceleration rate (r = 0.65) and AT/ET (r = 0.73) related significantly (p < 0.01) to the decrease in LVOT obstruction with ethanol. At six weeks, changes similar to those noted in the initial group were observed in LVOT geometry, the angle between LV systolic flow and the protruding mitral leaflets, peak acceleration rate and AT/ET. In both populations combined, these parameters accounted for 72% to 77% of the variance in gradient reduction. CONCLUSIONS: Changes in LV ejection dynamics and septal base function account in part for the acute relief of LVOT gradient after NSRT. The long-term relief of obstruction is dependent on remodeling of LVOT as well as the changes in LV ejection.     

Balloon positioning difficulties during nonsurgical septal reduction therapy in a patient with hypertrophic obstructive cardiomyopathy.

Dual chamber (DDD) pacing and catheter-based nonsurgical septal reduction therapy (NSRT) with ethanol are evaluated for treatment of patients with hypertrophic cardiomyopathy. This report describes a patient with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction who had failed to respond to DDD pacing but showed benefit from subsequent NSRT. Procedural difficulties during NSRT due to massive septal hypertrophy are presented.     

Effects of alcohol septal ablation on left ventricular diastolic filling patterns in obstructive hypertrophic cardiomyopathy

Alcohol septal ablation (ASA) has been shown to improve left ventricular (LV) diastolic function in patients with obstructive hypertrophic cardiomyopathy (HCM). However, its beneficial effect on diastolic function assessed by cardiac magnetic resonance (CMR) has not been reported. We investigated the mid-term changes of diastolic function by CMR combined with echocardiography in HCM patients after ASA at a median of 14-month follow-up. CMR parameters of diastolic function including peak filling rate (PFR), and time to peak filling rate (TPFR) were evaluated in 43 patients (aged 48 ± 9 years). LV diastolic function improved significantly measured by echocardiography with the decrease in ratio of transmitral early LV filling velocity (E) to early diastolic mitral lateral annular velocity (E′) (14.20 ± 1.17 to 11.58 ± 1.16, p < 0.001) and E-wave deceleration time (194.04 ± 19.30 to 168.45 ± 12.58 ms, p < 0.001). PFR increased significantly with associated decrease in TPFR after ASA (both p < 0.001) at follow-up. Furthermore, patients with larger decrease in LVOT gradients had a greater improvement of LV diastolic function, as measured by the reduction of E/E′ (p < 0.001) and increase of PFR (p < 0.001). In conclusion, this study demonstrated that successful ASA results in both echocardiographic and CMR indices of diastolic function improvement after ASA at 14-month follow-up. ASA therapy can significantly reduce LVOT gradient and mitral regurgitation, both of which may contribute to the improvement of diastolic function.     

Pressure-guided nonsurgical myocardial reduction induced by small septal infarctions in hypertrophic obstructive cardiomyopathy

OBJECTIVES: We sought to assess the safety and efficacy of pressure-guided nonsurgical myocardial reduction (NSMR) with the induction of small septal infarctions in patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Nonsurgical myocardial reduction has been shown to decrease left ventricular outflow tract (LVOT) obstruction and to improve symptoms in patients with HOCM. Infarct sizes differ considerably among studies published so far. METHODS: In 50 patients, the LVOT gradient was invasively determined at the time of the intervention, four to six months (n = 49) and 12 to 18 months (n = 25) after NSMR. New York Heart Association functional class and quality of life were assessed by using a standard questionnaire. Exercise capacity was tested by spiro-ergometry. Left ventricular (LV) mass was determined by electron beam computed tomography. RESULTS: Small septal infarctions (mean creatine kinase value 413 +/- 193 U/l) resulted in a sustained decrease in LVOT gradients, from 80 +/- 33 to 18 +/- 17 mm Hg after four to six months (p < 0.001, n = 49) and to 17 +/- 15 mm Hg (p < 0.001, n = 25) after 12 to 18 months. Nonsurgical myocardial reduction was followed by a decrease in LV hypertrophy, which was associated with a sustained increase in exercise capacity, as well as improvement in quality of life. CONCLUSIONS: Pressure-guided NSMR inducing small septal infarctions was sufficient to result in a sustained decrease in LVOT obstruction and to improve symptoms. The incidence of complications, such as complete heart block with necessary permanent pacemaker implantation (<10%), seems to be diminished by minimizing the infarct size.     

Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up

OBJECTIVE: The objective of this study is to evaluate the one-year outcome of the first 50 patients who underwent nonsurgical septal reduction for symptomatic hypertrophic obstructive cardiomyopathy at our institution. BACKGROUND: Left ventricular outflow tract obstruction is an important determinant of clinical symptoms in patients with hypertrophic obstructive cardiomyopathy. Nonsurgical septal reduction is a new therapy that has been shown to result in left ventricular outflow tract gradient reduction and resolution of symptoms immediately after the procedure and on midterm follow-up. METHODS: Fifty patients with hypertrophic obstructive cardiomyopathy who underwent nonsurgical septal reduction at our institution and completed 1-year follow-up are described. Complete history, physical examination, two-dimensional echocardiography with Doppler and exercise treadmill testing have been analyzed. RESULTS: The mean age of the study group was 53 +/- 17 years. All patients had refractory symptoms before enrollment. Ninety-four percent had class III or IV New York Heart Association class symptoms at baseline compared to none at 1 year (p < 0.001). The exercise duration increased by 136 s at 1 year (p < 0.021). Only 20% of patients were either receiving beta-blockers or calcium-channel blockers on follow-up. The resting left ventricular outflow tract gradient decreased from 74 +/- 23 mm Hg to 6 +/- 18 mm Hg (p < 0.01) and from 84 +/- 28 mm Hg to 30 +/- 33 mm Hg (p < 0.01) in patients with dobutamine-provoked gradient at one year. These changes are associated with decreased septal thickness and preserved systolic function. CONCLUSION: Nonsurgical septal reduction therapy is an effective therapy for symptomatic patients with hypertrophic obstructive cardiomyopathy with persistence of the favorable outcome up to one year after the procedure.     

Permanent pacing for complete atrioventricular block after nonsurgical (alcohol) septal reduction in patients with obstructive hypertrophic cardiomyopathy

Nonsurgical septal reduction is a newly developed, catheter-based therapeutic option for patients with drug-refractory obstructive hypertrophic cardiomyopathy. A circumscribed septal infarction is generated to reduce the left ventricular outflow tract gradient. The spontaneous regression of complete atrioventricular block after the procedure and the main complication of the intervention are examined, and treatment with permanent pacing is evaluated.     

Comparison of dual-chamber pacing with nonsurgical septal reduction effect in patients with hypertrophic obstructive cardiomyopathy

OBJECTIVES: The aim of the study was to compare the influence of dual-chamber pacing vs. nonsurgical septal reduction on hemodynamic and morphological parameters in patients with obstructive form of hypertrophic cardiomyopathy. METHODS: Nineteen patients with dual-chamber pacing (group I) and 9 patients who underwent nonsurgical septal reduction (group II) were studied at baseline and after a 6-month follow-up. The changes of left ventricular outflow tract gradient and posterior wall thickness (as an index of left ventricular hypertrophy regression) were compared. RESULTS: The baseline left ventricular outflow tract gradient was comparable between group I and group II (77+/-25 vs. 82+/-25 mm Hg, p>0.05). At 6-month follow-up, the left ventricular outflow tract gradient was reduced to a similar level in both groups (28+/-19 vs. 25+/-12 mm Hg, p>0.05). At baseline, posterior wall hypertrophy was comparable between groups (12.9+/-1.7 vs. 13.6+/-2.2 mm, p>0.05). During follow-up, the posterior wall thickness was unchanged in the pacing group (12.9+/-1.7 vs. 12.6+/-1.6 mm, p>0.05), whereas nonsurgical septal reduction induced regression of left ventricular hypertrophy in myocardial region remote from the infarcted septal segment (13.6+/-2.2 vs. 10.5+/-2.3 mm, p<0.003). CONCLUSION: Despite comparable reduction of instantaneous left ventricular outflow tract gradient, the nonsurgical septal reduction decreased posterior wall thickness, whereas pacing did not reduce left ventricular hypertrophy. Thus, regression of left ventricular hypertrophy that appeared solely after nonsurgical septal reduction may reflect the more permanent reduction of left ventricular pressure overload. Thus, not only hemodynamic but also morphological benefit from nonsurgical septal reduction seems to indicate the superiority of this method over dual-chamber pacing.     

Complete heart block: determinants and clinical impact in patients with hypertrophic obstructive cardiomyopathy undergoing nonsurgical septal reduction therapy

OBJECTIVES: The purpose of this paper is to examine the incidence and determinants of permanent complete heart block (CHB) after nonsurgical septal reduction therapy (NSRT), and to evaluate the clinical impact of permanent pacemaker (PPM) placement. BACKGROUND: Nonsurgical septal reduction therapy with ethanol improves the clinical and hemodynamic parameters in patients with symptomatic hypertrophic obstructive cardiomyopathy. Complete heart block is a common complication after NSRT. METHODS: The database of 261 consecutive patients who underwent NSRT at Baylor College of Medicine was reviewed. Clinical variables that were considered as possible determinants for CHB after NSRT were: age, gender, New York Heart Association (NYHA) functional class, left ventricular outflow tract (LVOT) gradient at rest or with provocation, septal thickness, and baseline exercise duration. For electrocardiographic (ECG) variables, the presence of first-degree atrioventricular (AV) block, bifascicular block, left bundle branch block, atrial fibrillation, and left ventricular hypertrophy were analyzed. In addition, the volume of ethanol injected, the method of administration of ethanol (i.e., bolus vs. slow injection [over 30 to 60 s]), number of septal arteries occluded, use of myocardial echocardiography, and infarct size as determined by peak creatine kinase level. RESULTS: Of 261 consecutive patients, 37 had PPM or automatic implantable cardiac defibrillator placed before NSRT. Of the remaining 224 patients, 31 (14%) developed CHB after the procedure. Multivariate logistic regression analysis showed that female gender (odds ratio [OR] 4.3; P = 0.02), bolus injection of ethanol (OR 51; P = 0.004), injecting more than one septal artery (OR 4.6; P = 0.016), the presence of left bundle branch block (OR 39; P = 0.002), and first-degree AV block (OR 14; P = 0.001) on the baseline ECG are independent predictors of CHB after NSRT. Patients requiring PPM placement had a similar improvement in their NYHA functional class, septal thickness reduction, LVOT gradient reduction, and improvement of exercise capacity when compared with patients who did not require pacing. CONCLUSIONS: Multiple demographic, electrocardiographic, and technical factors seem to increase the risk of CHB after NSRT. Patients with CHB after NSRT derive similar clinical and hemodynamic benefit to patients who did not require permanent pacing.