Donna Killip

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.

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.

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.

Changes in left ventricular filling and left atrial function six months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy

OBJECTIVES The purpose of this study was to evaluate changes in left ventricular (LV) filling, left atrial (LA) volumes and function six months after nonsurgical septal reduction therapy (NSRT) for hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND Patients with HOCM frequently have enlarged left atria, which predisposes them to atrial fibrillation. Nonsurgical septal reduction therapy results in significant reduction in left ventricular outflow tract (LVOT) obstruction and symptomatic improvement. However, its effect on LV passive filling volume, LA volumes and function is not yet known. METHODS Thirty patients with HOCM underwent treadmill exercise testing as well as 2-dimensional and Doppler echocardiography before and six months after NSRT. Data included clinical status, exercise duration, LVOT gradient, mitral regurgitant (MR) volume, LV pre-A pressure and LA volumes. Left atrial ejection force and kinetic energy (KE) were computed noninvasively and were compared with 12 age-matched, normal subjects. RESULTS New York Heart Association (NYHA) class was lower and exercise duration was longer (p < 0.05) six months after NSRT. The LVOT gradient, MR volume and LV pre-A pressure were all significantly reduced. HOCM patients had larger atria, which had a higher ejection force and KE, compared with normal subjects (p < 0.01). After NSRT, LV passive filling volume increased (p < 0.01), whereas LA volumes, ejection force and KE decreased (p < 0.01). Reduction in LA maximal volume was positively related to changes in LV pre-A pressure (r = 0.8, p < 0.05) and MR volume (0.4, p < 0.05). Changes in LA ejection force were positively related to changes in LA pre-A volume (r = 0.7, p < 0.01) and KE (r = 0.81, p < 0.01). The increase in exercise duration paralleled the increase in LV passive filling volume (r = 0.85, p < 0.05). CONCLUSIONS Nonsurgical septal reduction therapy results in an increase in LV passive filling volume and a reduction in LA size, ejection force and KE.

Changes in Left Ventricular Diastolic Function 6 Months After Nonsurgical Septal Reduction Therapy for Hypertrophic Obstructive Cardiomyopathy

BACKGROUND Nonsurgical septal reduction therapy (NSRT) decreases left ventricular outflow tract (LVOT) gradient and improves symptoms in patients with hypertrophic obstructive cardiomyopathy (HOCM). NSRT effects on LV/left ventricular diastolic function are currently unknown. METHODS AND RESULTS HOCM patients (n=29) had Doppler echocardiography at baseline and 6 months after NSRT to evaluate changes in LV volume, pre-A-wave pressure, early diastolic mitral annulus velocity (Ea) by tissue Doppler, and tau. At 6 months, a significant reduction in LVOT gradient (from 53.6+/-15 to 6+/-5 mm Hg; P<0.001) was accompanied by improvement in exercise duration (from 284+/-147 to 408+/-178 seconds; P=0.04) and New York Health Association class (from III to I; P<0.001). Pre-A pressure (18+/-6 to 14+/-5 mm Hg; P<0.01) and tau (62+/-8 to 51+/-8 ms; P<0.01) decreased, whereas Ea (5.8+/-1.8 to 8+/-1.8 cml/s; P<0.01) and LV end-diastolic volume (117+/-16 to 130+/-22 mL; P<0.01) increased. CONCLUSIONS NSRT improves LV relaxation and compliance, which contributes to the symptomatic relief seen at 6 months.

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.

Decreased Expression of Tumor Necrosis Factor-α and Regression of Hypertrophy After Nonsurgical Septal Reduction Therapy for Patients With Hypertrophic Obstructive Cardiomyopathy

BackgroundNonsurgical septal reduction therapy (NSRT) is a novel therapeutic strategy for patients with hypertrophic obstructive cardiomyopathy (HOCM). Although the clinical benefits of this technique appear to be clear, the structural and functional changes that lead to improvements in cardiac function are not completely defined. In these studies, we sought to define the effect of NSRT on myocardial function as well as various markers of hypertrophy including the expression of tumor necrosis factor (TNF)-&agr;, a cytokine capable of producing fibrosis, left ventricular hypertrophy (LVH), and cardiomyopathy. Methods and ResultsWe performed endomyocardial biopsies of the RV side of the septum and echocardiograms on 15 HOCM patients at baseline and after successful NSRT. Comparative analysis on paired myocardial samples were performed to determine the effects of NSRT on LVH, end-diastolic volume and chamber stiffness, myocyte size, collagen content, and TNF-&agr; levels. At baseline, myocardial TNF-&agr; levels were increased in all patients. After NSRT, myocyte size, collagen content, and TNF-&agr; were significantly decreased. These changes were accompanied by an increase in left ventricular volumes and a reduction in LVH and chamber stiffness. ConclusionsWe suggest that pressure overload in HOCM patients contributes to the development of hypertrophy. These data provide the initial experimental evidence to suggest that TNF-&agr; may play a pathogenetic role in the hypertrophy of pressure overload.

The Effect of a Marathon Run on Plasma and Urine Mineral and Metal Concentrations

BACKGROUND Little data exist on the requirements of trace metals and minerals for endurance athletes. Changes in body status of these elements must be examined before specific nutritional recommendations can be made. This study was designed to determine whether a marathon run was associated with changes in serum and urine metal and mineral concentrations. METHODS Forty subjects who planned to complete the 1996 Houston-Tennaco marathon were recruited. Subjects had blood and urine samples collected 2 weeks prior to the race and immediately following the race. Blood and urine specimens were analyzed for copper, iron, magnesium and zinc concentrations. Blood was also analyzed for calcium concentration and ceruloplasmin activity. RESULTS Twenty-six subjects (24 male, 2 female) completed the marathon. Finish times varied between 2 hours 43 minutes and 5 hours 28 minutes. There was no significant change in serum calcium, copper or zinc concentrations or ceruloplasmin activity. Serum and urine magnesium concentration decreased significantly (19.55+/-1.73 to 16.55+/-1.53 ppm, p=0.00001; 34.02+/-8.64 to 21.80+/-12.24 ppm, p=0.003, respectively). Serum iron concentration increased significantly (1.06+/-0.48 to 1.35+/-0.42 ppm, p=0.006), while urine copper and iron concentrations were below the limits of detection, zinc concentration did not change. CONCLUSIONS Serum and urinary magnesium concentrations decrease during endurance running, consistent with the possibility of magnesium deficiency. This may be related to increased demand in skeletal muscle. Serum iron concentration increases, possibly related to tissue injury. The exact etiology for these observations, as well as their clinical significance, requires further investigation.

Efficacy of Nonsurgical Septal Reduction Therapy in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy and Provocable Gradients

The hemodynamic burden caused by left ventricular obstruction along with impaired systolic and diastolic function explains the disabling symptoms of heart failure that are common in patients with obstructive hypertrophic cardiomyopathy (HC). 1 Relief of the outflow obstruction is the cornerstone of the successful treatment of this disease. 2 Medical therapy with negative inotropic medications like b blockers, calcium antagonists, and disopyramide are the first line of treatment. 3,4 Many patients, however, continue to experience symptoms despite optimal medical therapy. These patients are left with 3 options: myotomymyomectomy, 5‐7 dual-chamber pacing, 8 ‐12 or nonsurgical septal reduction. 13‐20 In this report, we share our experience with nonsurgical septal reduction in symptomatic patients with low resting gradients (,30 mm Hg), and significant (.60 mm Hg) provocable gradients after the infusion of low-dose dobutamine. ••• All patients were evaluated before the procedure by 1 of the primary investigators to verify their symptoms and diagnosis. Only patients with severe, drugresistant symptoms of dyspnea (New York Heart Association [NYHA] class III or IV), angina (Canadian Cardiovascular Society class III or IV), or syncope were accepted for therapy. All patients underwent echocardiographic evaluation with Doppler studies. All enrolled patients had a septal to posterior wall thickness wall ratio of

Plasma choline in normal newborns, infants, toddlers, and in very-low–birth-weight neonates requiring total parenteral nutrition☆

1.3. Patients with symptoms and a low resting gradient were provoked with a mean dose of 10.0 mg/kg/min of dobutamine; the same dose was used at follow-up. Patients were considered candidates for this treatment if their dobutamine-provoked gradient was .60 mm Hg. Informed consent, as approved by the Institutional