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.     

Effects of aging on left atrioventricular coupling and left ventricular filling assessed using cardiac magnetic resonance imaging in healthy subjects

Left ventricular (LV) filling results from diastolic suction of the left ventricle and passive left atrial (LA) emptying at early diastole and LA contraction at end-diastole. Effects of aging on LA and LV geometric characteristics and function and its consequences for LV filling are incompletely understood. Insight into these effects may increase the understanding of diastolic function. Cardiac magnetic resonance imaging was used to study effects of aging on left atrioventricular coupling and LV filling. Forty healthy volunteers underwent cardiac magnetic resonance imaging and were subdivided into 2 age groups of 20 to 40 (younger group) and 40 to 65 years (older group). For the older group, LA volumes were larger (p <0.05) and LV volumes, including stroke volumes, were smaller (p <0.05), whereas ejection fraction remained constant. LA/LV volume ratios were larger (0.27 +/- 0.06 vs 0.19 +/- 0.03; p <0.001) and correlated with LV mass-volume ratio (r = 0.42, p <0.01). The older group also had lower LA passive emptying (15 +/- 3.0 vs 19 +/- 4.8 ml/m(2); p <0.05) and higher LA active emptying volumes (13 +/- 3.1 vs 11 +/- 3.9 ml/m(2); p <0.05). For both groups, conduit volume contributed most to LV filling, but was lower in the older group (21 +/- 5.1 vs 27 +/- 9.0 ml; p <0.05). In conclusion, changes in LA volume and function were age dependent and related to changes in LV mass-volume ratio. Conduit volume contributed most to LV filling and decreased with age, suggesting it to be an indicator of diastolic function.     

Influence of regression of left ventricular hypertrophy on left atrial size and function in patients with moderate hypertension

OBJECTIVES: The aim of the study was to evaluate the effect of regression of left ventricular (LV) hypertrophy on left atrial (LA) size and function in patients treated with telmisartan, an angiotensin II receptor blocker. METHODS: Patients population included 80 patients with mild-moderate LV hypertrophy treated with telmisartan. Patients were followed over a period of 12 months from the start of telmisartan treatment. LA size was measured during systole from the parasternal long-axis view from M-mode. Atrial function was assessed by Doppler-echocardiography and the following parameters were measured: transmitral peak A velocity, atrial filling fraction, atrial ejection force (AEF), peak E velocity, deceleration time and isovolumic relaxation time, LA maximal and minimal volume, and LV cardiac mass index (LVMI). RESULTS: All patients had an increased LVMI and decrease during follow-up. LA dimensions were greater at baseline and reduced after 1 year of treatment. LA volume indexes maximal volume, minimal volume and P volume were reduced compared with baseline value (maximal volume from 35+/-5 to 32+/-5, p<0.05; minimal volumes from 14+/-2 to 10+/-4, p<0.05). AEF, a parameter of atrial systolic function, increased from 12+/-3 to 15+/-2.4 (p<0.01). The reduction of LA volumes correlate with reduction of LVMI (LA maximal volume and LVMI r = 0.45; p<0.01; LA minimal volume and LVMI r = 0.34; p<0.05). A positive correlation was also found between LV mass index and P volume (r = 0.41; p<0.01), LV mass index and LA active emptying volume (r = 0.39; p<0.01), and LV mass index and LA total emptying volume (r = 0.38; p<0.05). CONCLUSIONS: The present study suggests that regression of LV hypertrophy due to telmisartan is associated with reduction of LA volumes that expresses variation of LV end-diastolic pressure. The reduction of LV end-diastolic pressure is associated with an increase in diastolic filling and with a significant reduction of active and passive emptying contribution of left atrium to LV stroke volume.     

Usefulness of new diastolic strain and strain rate indexes for the estimation of left ventricular filling pressure

Tissue Doppler indexes of left ventricular (LV) filling pressure are prone to angulation errors and tethering and are less reliable in patients with preserved LV ejection fraction and indeterminate early peak transmitral diastolic flow (E)/mitral early diastolic velocity (Ea) (8 or =8 had higher sensitivity and specificity (95% and 94%, respectively; area under the curve = 0.96, p <0.0001) than E/Ea > or =15 (sensitivity 81%, specificity 75%; area under the curve = 0.85, p <0.0001) for the prediction of LV pre-A pressure > or =15 mm Hg (p = 0.01 for comparison). In patients with LV ejection fraction > or =50% and 8 or =50% or indeterminate E/Ea, both E/Ds and E/10DSr (a ratio based on global DSR) were better predictors of LV filling pressure than E/Ea.     

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.     

Improvement of afterload mismatch of left atrial booster pump function with positive inotropic agent

OBJECTIVES: The objective of this study was to examine the hypothesis that a positive inotropic agent improves left ventricular (LV) filling during left atrial (LA) contraction in the presence of markedly elevated LV filling pressure. BACKGROUND: In patients with old myocardial infarction (MI), an increase in the operational LV chamber stiffness reduces LV filling during the LA contraction, resulting from an "afterload mismatch" of the LA booster pump function. METHODS: We investigated the effect of dobutamine infusion (3 microg/kg/min) on the LA pump function in the presence of elevated LV filling pressure induced by aortic constriction (Aoc) during acute MI in 10 dogs. Transmitral flow velocity was determined by transesophageal echocardiography, LV pressure by a micromanometer and LV volume by a conductance catheter. We measured the early (E) and late (A) diastolic peak transmitral flow velocities (cm/s) and LV chamber stiffness (deltaP/deltaV: mm Hg/ml; where deltaP is developed pressure and deltaV is the absolute filling volume during LA contraction). RESULTS: When the deltaP/deltaV was increased by Aoc during MI (from 1.1 +/- 0.8 to 3.1 +/- 2.6 mm Hg/ml, p < 0.01), A decreased significantly (from 30 +/- 5 to 22 +/- 8 cm/s, p < 0.01), and the ratio of E to A increased (from 1.0 +/- 0.3 to 1.4 +/- 0.8, p < 0.05) compared with MI without Aoc, showing the pseudonormal transmitral flow pattern, the so called "LA afterload mismatch." Dobutamine under this condition significantly reduced the deltaP/deltaV (to 1.7 +/- 1.2 mm Hg/ml, p < 0.05), resulting in an increase in A (to 31 +/- 8 cm/s, p < 0.01) and a decrease in E/A (to 1.0 +/- 0.3, p < 0.05), and the transmitral flow became a prolonged relaxation pattern as in MI without Aoc in all dogs. There was an inverse correlation between the deltaP/deltaV and the time-velocity integral of A (r = -0.70, p < 0.01). CONCLUSIONS: Dobutamine improved the afterload mismatch of the LA booster pump function. This effect may have been due to the reduction in LV operational chamber stiffness, resulting in an increase in the LA forward ejection into the LV.     

Comparison of ethanol septal reduction therapy with surgical myectomy for the treatment of hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was designed to compare the hemodynamic efficacy of nonsurgical septal reduction therapy (NSRT) by intracoronary ethanol with standard therapy (surgical myectomy) for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Nonsurgical septal reduction therapy has gained interest as a new treatment modality for patients with drug-refractory symptoms of HOCM; however, its benefits in comparison to surgery are unknown. METHODS: Forty-one consecutive NSRT patients at Baylor College of Medicine with one-year follow-up were compared with age- and gradient-matched septal myectomy patients at the Mayo Clinic. All patients had left ventricular outflow obstruction with a resting gradient > or =40 mm Hg and none had concomitant procedures. RESULTS: There were no baseline differences in New York Heart Association class, severity of mitral regurgitation, use of cardiac medications or exercise capacity. One death occurred during NSRT because of dissection of the left anterior descending artery. At one year, all improvements in both groups were similar. After surgical myectomy, more patients were on medications (p < 0.05) and there was a higher incidence of mild aortic regurgitation (p < 0.05). After NSRT, the incidence of pacemaker implantation for complete heart block was higher (22% vs. 2% in surgery; p = 0.02). However, seven of the nine pacemakers in the NSRT group were implanted before a modified ethanol injection technique and the use of contrast echocardiography. CONCLUSIONS: Nonsurgical septal reduction therapy resulted in a significantly higher incidence of complete heart block, but the risk was reduced with contrast echocardiography and slow ethanol injection. Surgical myectomy resulted in a significantly higher incidence of mild aortic regurgitation. Nonsurgical septal reduction therapy, guided by contrast echocardiography, is an effective procedure for treating patients with HOCM. The hemodynamic and functional improvements at one year are similar to those of surgical myectomy.     

Plasma levels of brain natriuretic peptide in various forms of obstruction to the left ventricular outflow tract

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship between plasma concentrations of brain natriuretic peptide (BNP) and the type or degree of stenosis in the left ventricular outflow tract (LVOT). METHODS: The relationship between BNP plasma level and pressure gradient (PG) in the LVOT and LV wall thickness (LVWth) was analyzed in 25 patients with a PG > or = 30 mmHg in the LVOT from the mid-left ventricle to the aortic valve. Among patients, 14 had aortic valve stenosis (AS), five had subaortic type hypertrophic obstructive cardiomyopathy (HOCM), three had mid-ventricular type HOCM, and three had angled ventricular septum. Three patients with AS showed LV systolic dysfunction (ejection fraction (EF) < 50%). All patients were in sinus rhythm. LV peak-systolic pressure (LVPSP) was derived by adding maximum PG to cuff systolic arterial pressure. RESULTS: In AS patients without LV systolic dysfunction and HOCM patients, there was a significant positive correlation between BNP and LVPSP (r = 0.78, p = 0.001; r = 0.76, p = 0.007, respectively). In AS patients without LV systolic dysfunction, BNP was positively correlated with LVWth (r = 0.79, p = 0.001), but no correlation was found between BNP and LVWth in patients with HOCM. In AS patients including systolic LV dysfunction, BNP was negatively correlated with LVEF (r = -0.87, p < 0.0001), but no correlation was found between BNP and LVEF in patients with HOCM. CONCLUSION: These results suggest that BNP level is closely associated with severity of stenosis in patients with HOCM, but mainly with severity of stenosis and also degree of LV systolic dysfunction in patients with AS. The BNP-LVWth relationship appeared to differ between AS (a fixed stenosis with uniform myocardial hypertrophy) and HOCM (a dynamic stenosis with uneven myocardial hypertrophy).     

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.     

Mechanism of augmented rate of left ventricular filling during exercise.

At rest, most of left ventricular (LV) filling occurs early in diastole. This LV filling occurs in response to the pressure gradient produced as LV pressure falls below left atrial (LA) pressure. Because mitral valve flow occurs in response to an LA to LV pressure gradient, augmented diastolic mitral valve flow during exercise may be due to an increased mitral valve pressure gradient resulting from a rise in LA pressure and/or a fall in LV early diastolic pressure. Accordingly, we studied 13 conscious dogs, instrumented to measure micromanometer LV and LA pressures, and determined LV volume from three ultrasonic dimensions during exercise. The animals ran on a treadmill for 8-15 minutes at 5-8 miles/hr. With reflexes intact, during exercise, the heart rate increased from 116 +/- 20 to 189 +/- 24 beats per minute (mean +/- SD, p less than 0.01), the maximum rate of change of LV volume (dV/dtmax) increased from 185 +/- 44 to 282 +/- 76 ml/sec (p less than 0.01), the ejection fraction and cardiac output increased, and the duration of diastole decreased from 296 +/- 83 to 162 +/- 71 msec (p less than 0.01). Mitral valve opening pressure, mean LA pressure (10.9 +/- 4.4 versus 10.2 +/- 3.9 mm Hg, p = NS), and LV end-diastolic pressure (12.8 +/- 4.8 versus 13.1 +/- 3.3 mm Hg, p = NS) were all relatively unchanged. The time constant of the fall of isovolumic LV pressure decreased from 28 +/- 3.3 to 21 +/- 4.4 msec (p less than 0.05). The early diastolic portion of the LV pressure-volume loop was shifted downward during exercise, with the minimum LV pressure decreasing from 3.3 +/- 2.8 to -2.8 +/- 3.4 mm Hg (p less than 0.05) and the maximum mitral valve pressure gradient increasing from 5.5 +/- 1.7 to 11.8 +/- 3.5 mm Hg (p less than 0.01). A similar downward shift of the early diastolic portion of the LV pressure-volume loop was produced by infusion of dobutamine (6 micrograms/kg/min i.v.) at rest, as well as by exercise when the heart rate was held constant by right ventricular pacing at 190-210 beats per minute. The downward shift during exercise was prevented by beta-blockade (metoprolol, 0.5 mg/kg i.v.). We conclude that during exercise, sympathetic stimulation and tachycardia produce a downward shift of the early diastolic portion of the LV pressure-volume loop.(ABSTRACT TRUNCATED AT 400 WORDS)     

Left atrial anatomy and function after conversion from atrial fibrillation in hypertrophic hearts

The aim of the study was to evaluate the influence of left ventricular (LV) hypertrophy on left atrial (LA) electrical and mechanical function after cardioversion atrial fibrillation (A-Fib) of brief duration. Study group A included 100 patients with a first diagnosis of hypertension who had a moderate LV hypertrophy. The patient population included 64 men and 36 women with a mean age of 55 +/-7 years who were hospitalized because of A-Fib and were cardioverted with external DC shock. Control group B included 100 patients without cardiac hypertrophy cardioverted because of lone A-Fib. Atrial function and size were assessed by Doppler echocardiography and the following parameters were measured: transmitral peak A velocity, atrial filling fraction, atrial ejection force, peak E velocity, deceleration time, and isovolumic relaxation time, LA maximal and minimal volume, and LV cardiac mass index. Baseline echocardiography showed that LA diameters and volumes were enlarged in all patients during A-Fib. After the restoration of sinus rhythm LA diameters and volumes decreased and the reduction was more evident in group B compared to group A. LA function as a continuous variable was negatively related to LV mass index (r = -0.77), LA diameter (r = -0.66 and r = -0.69 for the superoinferior diameter), LA maximal volume (r = -0.61) and LA minimal volume (r = -0.55) (all p<0.01). Atrial ejection force as a continuous variable was positively related to age (r =0.78), peak A wave velocity (r =0.71), systolic blood pressure (r =0.51), and IVRT (r =0.41) (all p<0.01). Hypertrophy influenced the recovery of atrial function after cardioversion of A-Fib. Atrial function was reduced in patients with LV hypertrophy even after A-Fib of brief duration.     

Improvements in left ventricular diastolic function after cardiac resynchronization therapy are coupled to response in systolic performance.

OBJECTIVES: To determine the short-term effects of cardiac resynchronization therapy (CRT) on measurements of left ventricular (LV) diastolic function in patients with severe heart failure. BACKGROUND: Cardiac resynchronization therapy improves systolic performance; however, the effects on diastolic function by load-dependent pulsed-wave Doppler transmitral indices has been variable. METHODS: Fifty patients with severe heart failure were evaluated by two-dimensional Doppler echocardiography immediately prior to and 4 +/- 1 month after CRT. Measurements included LV volumes and ejection fraction (EF), pulsed-wave Doppler (PWD)-derived transmitral filling indices (E- and A-wave velocities, E/A ratio, deceleration time [DT], diastolic filling time [DFT], and isovolumic relaxation time). Tissue Doppler imaging was used for measurements of systolic and diastolic (Em) velocities at four mitral annular sites; mitral E-wave/Em ratio was calculated to estimate LV filling pressure. Color M-mode flow propagation velocities were also obtained. RESULTS: After CRT, LV volumes decreased significantly (p < 0.001) and LVEF increased >5% in 28 of 50 patients (56%) and were accompanied by reduction in PWD mitral E-wave velocity and E/A ratio (both p < 0.01), increased DT and DFT (both p < 0.01), and lower filling pressures (i.e., E-wave/Em septal; p < 0.01). Patients with LVEF response < or =5% after CRT had no significant changes in measurements of diastolic function; LV relaxation (i.e., Em velocities) worsened in this group. CONCLUSIONS: In heart failure patients receiving CRT, improvement in LV diastolic function is coupled to the improvement in LV systolic function.     

Mechanism of left a trial enlargement related to ventricular diastolic impairment in hypertension

Background and hypothesis: Systemic hypertension is the leading cause of left ventricular (LV) hypertrophy. The present study aimed to investigate the mechanism of left atrial (LA) enlargement in patients with hypertensive heart disease during cardiac catheterization. Methods: Data were obtained from eight control subjects and seven patients with hypertensive heart disease. Left atrial and LV pressures from catheter-tip micromanometer, and LA and LV volumes from biplane cineangiograms were analyzed during the same cardiac cycle. Results: Left atrial maximal volume were 93 ± 26 ml in patients with hypertensive heart disease and 63 ± 12 ml in control subjects (p<0.05). In patients with hypertensive heart disease, time constant of LV relaxation was significantly greater than that in controls (54 ± 18 vs. 31 ± 16 ms, respectively p<0.01). Left atrial maximal volume correlated with time constant of LV relaxation (r = 0.86, p<0.01). The ratio of LV filling volume before LA contraction to LV stroke volume in patients with hypertensive heart disease was significantly lower than that in control subjects (65 ± 13 vs. 76 ± 7%, respectively p<0.05). On the other hand, the ratio of LV filling volume during LA contraction to stroke volume in patients with hypertensive heart disease was significantly higher than that in controls (35 ± 13 vs. 24± 7%, respectively p<0.05). Left atrial volume before LA contraction in patients with hypertensive heart disease was significantly larger than that in controls (74 ± 22 vs. 47 ± 10 ml, respectively, p<0.01). During LA contraction, LA work was significantly increased in patients with hypertensive heart disease compared with that in controls (274 ± 101 vs. 94 ± 42 mmHg. ml, respectively p<0.001). Left atrial work showed significant correlation with LA volume before LA contraction (r = 0.75, p <0.01). Conclusion: Left ventricular diastolic filling was impaired in patients with hypertensive heart disease. Enlargement of left atrium might be attributed to the impairment of blood flow from left atrium to left ventricle due to the increased LV stiffness.     

The effect of pulmonary hypertension on left atrial mechanical functions in chronic obstructive lung disease

BACKGROUND: Left atrial (LA) function is an important determinant of left ventricular (LV) filling. However, the effect of pulmonary hypertension (PH) on LA mechanical function in chronic obstructive lung disease (COLD) has not been studied, yet. METHODS: 49 patients with COLD and 25 controls were included in this study. Patients were divided into two subgroups: patients without PH (group 1, n=21) and with PH (group 2, n=28). LA volumes were determined at mitral valve opening (Vmax), at onset of atrial systole (Vp) and at mitral valve closure (Vmin) according to biplane area-length method. The following LA parameters were calculated: passive emptying volume (PEV=Vmax-Vp), conduit volume [CV=LV stroke volume-(Vmax-Vmin)], passive emptying fraction (PEF=PEV/Vmax), active emptying volume (AEV=Vp-Vmin), active emptying fraction (AEF=AEV/Vp), total emptying volume (TEV=Vmax-Vmin), percent contribution of PEV, CV and AEV to LV stroke volume. RESULTS: Vmax (p<0.01), PEV (p<0.001) and TEV (p<0.05) were lower in group 2 than in the controls, and the differences between group 1 and control group were insignificant (p>0.05). Vp, Vmin, CV and AEV did not differ among three groups. Percent contribution to LV filling of the PEV was decreased in group 2 when compared to group 1 (p<0.05) and the controls (p<0.01). Percent contribution to LV filling of the AEV was increased in group 2 when compared to the controls (p<0.05). There were inverse correlations between pulmonary artery pressure and the following parameters: LV stroke volume (r=-0.43, p<0.01), mitral E/A (r=-54, p<0.001), Vmax (r=-0.35, p<0.05), PEV (r=-40, p<0.01) and PEF (r=-0.43, p<0.01). CONCLUSION: This study shows that the alterations of LA mechanical functions in patients with COLD are closely correlated to PH levels. Furthermore, these results underline the importance of maintaining a sinus rhythm in these patients.     

Significance of left atrial volume in patients < 20 years of age with hypertrophic cardiomyopathy

Left atrial (LA) enlargement is an indicator of chronic elevation in left ventricular (LV) end-diastolic pressure as well as diastolic dysfunction. There is a lack of data on the significance of LA volume in the pediatric population. The objective of this study was to elucidate the relation between LA volume and diastolic dysfunction, clinical symptoms, and exercise capacity in young patients with hypertrophic cardiomyopathy. All patients aged <20 years with obstructive hypertrophic cardiomyopathy who underwent evaluation at the Mayo Clinic from 2002 to 2006 were retrospectively identified. Reviews of the LA volume index and other traditional diastolic Doppler echocardiographic parameters, as well as clinical data, were performed. A total of 88 patients (66 male) were studied. The median age at evaluation was 14 years. The mean LA volume index was 39 +/- 19 ml/m(2). Additional echocardiographic parameters included a mean LV outflow gradient of 55 +/- 51 mm Hg, a mean E/E' ratio of 14.0 +/- 7.6, and a mean maximal septal wall thickness of 23 +/- 9 mm. On univariate linear regression analysis, LA volume index had an excellent correlation with diastolic dysfunction grade (p <0.001, r(2) = 0.6), LV outflow tract gradient, mitral E/E', and the degree of mitral regurgitation. LA volume index was also positively associated with symptom score (p = 0.005) and maximal oxygen consumption on exercise test (n = 22; p = 0.01). On multivariate analysis, LA volume index was related to diastolic dysfunction grade (p <0.001) and mean mitral regurgitation grade (p = 0.05). In conclusion, this study demonstrates the potential clinical importance of LA volume index in pediatric hypertrophic cardiomyopathy as a marker of the severity of underlying diastolic dysfunction, symptom score, and decreased exercise capacity. LA volume index has significant diagnostic and prognostic value in these patients.     

Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: short-term results in 50 consecutive procedures

BACKGROUND: Nonsurgical septal reduction therapy (NSRT) has been shown to improve left ventricular outflow tract (LVOT) gradients, decrease septal thickness, and improve symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM). The major complication of this procedure has been the development of complete heart block (CHB) requiring permanent pacemaker implantation, which has been reported in up to 33% of patients in early studies. Since this procedure was first reported, there have been refinements in the technique such as the use of echocardiographic contrast material to localize the site of infarction, slower injection of alcohol, as well as improvement in balloon technology. HYPOTHESIS: We sought to determine the results of NSRT using echocardiographic contrast localization, slow injection of alcohol, and short balloon length. We theorized that the incidence CHB would be lower than earlier reported results using these refined techniques. METHODS: We performed 50 NSRT procedures on 46 patients using echocardiographic contrast localization, slow alcohol injection, and currently available balloons. Patients had an echocardiogram before, immediately after NSRT, and at 3 months, and a treadmill test before and at 3 months after NSRT. In the hospital, patients were observed for the development of CHB or other complications, and infarct size was determined by serial creatine kinase (CK) measurements. RESULTS: There was a decrease in the LVOT gradient from 84.2 (+/- 30.8) mmHg at baseline, to 18.5 (+/- 14.8) mmHg immediately after NSRT (p < 0.001). At 3 months, the gradient was not statistically different at 22.7 (+/- 22.2) mmHg 0.27). The septal thickness decreased from 2.21 (+/- 0.66) cm at baseline, to 1.67 (+/- 0.51) cm at 3 months (p < 0.001). New York Heart Association symptom class improved from 3.2 (+/- 0.4) at baseline, to 1.1 (+/- 0.6) at 3 months (p < 0.001). Mean treadmill time in 30 patients was 235 (+/- 142) s at baseline, to 367 (+/- 159) s at 3 months (p < 0.001). Of the 50 procedures, 45 were performed in patients without a previously placed permanent pacemaker or intracardiac cardioverter defibrillator, only 3 (6.7%) of the 45 developed complete heart blocks required permanent pacing. While only three patients in the series had a preexisting left bundle-branch block (LBBB), two of the three patients who required a permanent pacemaker had an LBBB before the prcoedure. CONCLUSION: Using contrast echocardiographic localization, slow injection of alcohol, and shorter balloon catheters, there continues to be excellent improvement in LVOT gradients, septal thickness, and symptoms, with a reduced incidence of CHB requiring permanent pacemaker implantation. Left bundle-branch block appears to be a strong predictor for the development of CHB after NSRT.     

Mechanisms for an abnormal radionuclide left ventricular ejection fraction response to exercise in patients with chronic, severe aortic regurgitation.

To clarify the mechanisms for an abnormal radionuclide left ventricular (LV) ejection fraction response to exercise in patients with chronic, severe aortic regurgitation (AR), we studied seven control patients and 21 patients with AR. We used exercise radionuclide angiography and catheterization of the right and left sides of the heart to obtain a calculation of LV chamber elastance. The control and AR groups had similar heart rates, systolic blood pressure responses to exercise, and exercise durations. In both patient groups, LV end-diastolic volume did not change with exercise. In contrast to the decrease in LV end-systolic volume (p less than 0.05) and increase in LV ejection fraction (p less than 0.01) in the control group, LV end-systolic volume in the patients with AR increased, resulting in little change in their LV ejection fraction. By stepwise multiple regression analysis, the radionuclide LV ejection fraction at peak exercise in patients with AR was determined by the LV chamber elastance, LV end-systolic volume, and stroke volume at peak exercise (cumulative r = 0.79, p less than 0.02); the change in radionuclide LV ejection fraction from rest to peak exercise was determined by the corresponding change in systemic vascular resistance, regurgitant index, and LV end-diastolic and end-systolic volumes (cumulative r = 0.88, p less than 0.02). These data demonstrate that in patients with AR, the radionuclide LV ejection fraction at peak exercise is principally determined by the cumulative effects of chronic, severe AR on LV systolic chamber performance, and the change in radionuclide LV ejection fraction from rest to peak exercise is principally established by peripheral vascular responses.     

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.     

Effects of quinapril on left atrial structural remodeling and arterial stiffness

Left atrial (LA) enlargement, left ventricular (LV) diastolic dysfunction, and increased arterial stiffness are all associated with adverse cardiovascular outcomes. The rate, magnitude, and concordance of modifiability of these risk markers have not been well characterized. Twenty-one patients (mean age 69 +/- 8 years; 52% women) with isolated diastolic dysfunction and indexed LA volumes > or =32 ml/m(2) were randomly assigned to receive either quinapril at a target dose of 60 mg/day or matching placebo for 12 months. Echocardiographic maximum LA volume and LV diastolic function and arterial stiffness by the augmentation index were measured at baseline and 6 and 12 months. Analysis was based on intention to treat. Baseline characteristics were comparable between the treatment (n = 9) and placebo (n = 12) groups. The mean reduction in LA volume of 4.2 +/- 7.8 ml/m(2) in the quinapril group was significant (p = 0.01) compared with the increase in LA volume in the placebo group (5.5 +/- 8.1 ml/m(2)). This represents a relative improvement of 9.7 ml/m(2). Change in LV filling pressure in terms of E/e' and diastolic function grade did not reach significance. A reduction in the augmentation index was associated with a decrease in indexed LA volume (odds ratio 11, p = 0.046), independent of changes in systolic blood pressure. In conclusion, LA structural remodeling appeared reversible with quinapril, which occurred in parallel with an improvement in arterial stiffness but independent of blood pressure changes.     

Effects of percutaneous transluminal septal myocardial ablation for obstructive hypertrophic cardiomyopathy on systolic and diastolic left ventricular function assessed by pressure-volume loops

The aim of the present study was to determine the long-term effects of percutaneous transluminal septal myocardial ablation (PTSMA) on systolic and diastolic left ventricular (LV) functions in patients with obstructive hypertrophic cardiomyopathy (HC). Ten consecutive patients with symptomatic HC despite optimal medical treatment were referred for PTSMA at our center. LV systolic and diastolic functions were assessed by online LV pressure-volume loops obtained by conductance catheter at baseline and at 6 months after the procedure. At follow-up, the mean gradients at rest and after extrasystole were significantly decreased compared with baseline (88 +/- 29 to 21 +/- 11 mm Hg and 130 +/- 50 to 35 +/- 22 mm Hg, respectively, p <0.01 for the 2 comparisons). End-systolic and end-diastolic pressures significantly decreased (p <0.01), whereas end-systolic and end-diastolic LV volumes significantly increased (p <0.01 for the 2 comparisons). Cardiac output and stroke volume were unchanged, as were ejection fraction (p = 0.25) and maximum dP/dt (p = 0.13). The slope of the end-systolic pressure-volume relation was not decreased, indicating a preserved contractility. The relaxation constant time, end-diastolic stiffness, projected volume of the end-diastolic pressure-volume relation at 30 mm Hg, and diastolic stiffness constant showed a significant improvement of active and passive myocardial diastolic properties. In conclusion, PTSMA is an effective method in the treatment of symptomatic patients with HC. At 6-month follow-up, the LV-aortic gradient was decreased and active and passive LV diastolic properties were increased. Myocardial contractility was not decreased and general hemodynamics was maintained.