Regression of left ventricular hypertrophy after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by left ventricular hypertrophy (LVH) in the absence of increased external load. Recently, nonsurgical septal reduction therapy (NSRT) with intracoronary ethanol has been introduced to treat severely symptomatic patients with outflow tract obstruction. Its long-term effects on LV mass, however, are unknown. METHODS AND RESULTS: The LV size, function, and outflow tract gradient of 26 HOCM patients (53+/-15 years old) who underwent NSRT were assessed by echocardiography at baseline and 1 and 2 years after the procedure. LVH was evaluated by wall thickness of individual myocardial segments, planimetered myocardial area, and mass. The outflow gradient decreased from 36+/-6 mm Hg before NSRT to 0+/-3 mm Hg at 2 years (P<0.001), with patients experiencing symptomatic improvement (P<0.05). LV end-diastolic and end-systolic dimensions increased significantly at both 1 and 2 years (P<0.001). All parameters of LVH showed evidence of regression. LV mass decreased (301+/-78 g at baseline, 223+/-5 g at 1 year, and 190+/-58 g at 2 years; P<0.01), with the 2-year reduction in mass related to infarct size and the acute reduction in outflow tract gradient (r=0.48, P<0.05 and r=0.63, P<0.01, respectively). CONCLUSIONS: NSRT results in LV remodeling that is characterized by an increase in LV size and a decrease in the extent of LVH.

Decreased expression of tumor necrosis factor-alpha and regression of hypertrophy after nonsurgical septal reduction therapy for patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Nonsurgical 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)-alpha, a cytokine capable of producing fibrosis, left ventricular hypertrophy (LVH), and cardiomyopathy. METHODS AND RESULTS: We 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-alpha levels. At baseline, myocardial TNF-alpha levels were increased in all patients. After NSRT, myocyte size, collagen content, and TNF-alpha were significantly decreased. These changes were accompanied by an increase in left ventricular volumes and a reduction in LVH and chamber stiffness. CONCLUSIONS: We suggest that pressure overload in HOCM patients contributes to the development of hypertrophy. These data provide the initial experimental evidence to suggest that TNF-alpha may play a pathogenetic role in the hypertrophy of pressure overload.

Simultaneous multisite mapping of the right and the left atrial septum in the canine intact beating heart.

BACKGROUND: The spread of activation between the right atrium (RA) and left atrium (LA), particularly along the right and left aspects of the interatrial septum, is not clear. METHODS AND RESULTS: Basket-shaped catheters carrying 64 electrodes were deployed into both the RA and LA of 10 dogs. Position and orientation of the baskets were determined by fluoroscopy and echocardiography. Basket unipolar electrograms were simultaneously recorded in each dog during sinus rhythm, right ventricular pacing, and pacing of the right septum through the basket in the superior and inferior regions. Isochrone maps depicting all aspects of the atria, including the septum, were compared. During sinus rhythm and superior right septal pacing, wave fronts propagated predominantly from superior to inferior regions on both the right and left septum. However, activation of the left septum was delayed compared with the right septum. During right ventricular pacing and inferior right septal pacing, activation of the septum was discordant; 1 wave front propagated rapidly on the right septum from inferior to superior regions, whereas 2 opposing wave fronts originated on the left septum in both the superior and inferior regions. The left septum was activated predominantly by the superior wave front. Activation of the left septum was completed in a significantly shorter time during pacing of the right septum in the inferior region compared with the superior region. CONCLUSIONS: In dogs, activation of the right and left aspects of the interatrial septum is discordant. Electrical connections are present between the RA and LA in regions superior as well as inferior to the septum.

Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy.

BACKGROUND: Conventional Doppler parameters are unreliable for estimating left ventricular (LV) filling pressures in hypertrophic cardiomyopathy (HCM). This study was undertaken to evaluate flow propagation velocity by color M-mode and early diastolic annular velocity (Ea) by tissue Doppler 2 new indices of LV relaxation, combined with mitral E velocity for estimation of filling pressures in HCM. METHODS AND RESULTS: Thirty-five HCM patients (52+/-15 years) underwent LV catheterization simultaneously with 2-dimensional and Doppler echocardiography. Pulsed Doppler echocardiography of mitral and pulmonary venous flows was obtained along with flow propagation velocity and Ea. LV preA pressure had weak or no relations with mitral, pulmonary venous velocities and atrial volumes. In contrast, preA pressure related strongly to E velocity/flow propagation velocity (r=0.67; SEE=4) and E/Ea (r=0.76; SEE=3.4). In 17 patients with repeat measurements, preA pressure changes were well detected by measuring E velocity/flow propagation velocity (r=0.68; P=0.01) or E/Ea (r=0.8; P<0.001). PreA pressure estimation with these 2 methods was tested prospectively in 17 additional HCM patients with good results (E velocity/flow propagation velocity, r=0.76; E/Ea, r=0.82). CONCLUSIONS: LV filling pressures can be estimated with reasonable accuracy in HCM patients by measuring E velocity/flow propagation velocity or E/Ea. These ratios also track changes in filling pressures.

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.

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.

Long-term assessment of unipolar and bipolar stimulation and sensing thresholds using a lead configuration programmable pacemaker.

Acute and long-term pacing thresholds were measured prospectively in 74 patients with a unipolar/bipolar multiprogrammable pacemaker. At implantation, mean current threshold was 0.48 +/- 0.16 mA with unipolar mode and 0.55 +/- 0.16 mA bipolar mode (p less than 0.01). R wave amplitude at implantation was 7.78 +/- 2.4 mV with unipolar and 7.67 +/- 2.1 mV in bipolar mode (p = NS). During long-term follow-up (mean 9.3 months; range 3 to 24), no clinically significant differences in pacing or sensing thresholds were observed between bipolar and unipolar configurations. Lead configuration was changed 23 times in 11 patients. Symptomatic myopotential inhibition was corrected in two patients by reprogramming to the bipolar pacing mode. High thresholds and loss of capture were corrected in two patients by reprogramming to the unipolar pacing mode. The remaining configurational changes were made for improved sensing or pacing thresholds. This study documents, in a large group of patients, the equivalence of long-term unipolar and bipolar pacing and sensing thresholds and, in addition, demonstrates that lead configuration programmability offered some advantage in a subgroup of patients and may have prevented reoperation in five patients.

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.

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.

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.

Epithelialization of the anterior chamber after transcorneal (McCannel) suture.

A 35-year-old woman developed epithelialization of the anterior chamber with secondary glaucoma, following the use of a transcorneal (McCannel-type) suture to repair a traumatic iridodialysis. Clinical photographs and histologic documentation illustrate the potential for this serious complication from this surgical technique.

Conjunctival nodules associated with onchocerciasis.

A 14-year-old native of Ethiopia with previously treated onchocerciasis moved to California where he was examined for evidence of persisting nematode infestation. Skin and conjunctival biopsy specimens initially disclosed no abnormalities. Subsequently, conjunctival nodules developed, and a biopsy specimen of one of these revealed microfilariae of Onchocerca volvulus lying adjacent to a necrotic eosinophilic granulomatous inflammatory nodule. To our knowledge, nodules of this type have not heretofore been reported to be a notable feature of ocular onchocerciasis. This type of inflammation has a relationship to degenerating microfilaria in onchocerciasis and in other nematode infestation.

Fluorescein angiographic patterns of iris melanocytic tumors.

Iris fluorescein angiography was performed on 23 patients with primary iris melanocytic tumors. Four angiographic patterns were identified, the first three of which were considered to be usually indicative of a benign lesion, based on clinical duration and follow-up, biopsy specimens, and stable patterns on repeated angiography. (1) Eleven moderately to heavily pigmented placoid lesions were angiographically silent, in that they failed to display either a tumor-associated vasculature or diffuse leakage. (2) Seven generally nonpigmented lesions demonstrated a quasi-geometric filigree vascular network, approximating the caliber of the normal radial vasculature. These tumor-associated vessels fluoresced early and in synchrony with the appearance of dye in the radial vasculature from which they probably were derived, but they diffusely and confluently leaked fluorescein in the late phases of the angiogram. (3) Three brown or variably pigmented lesions manifested a mixed angiographic pattern, combining features of groups 1 and 2. (4) The final angiographic pattern was comprised of two pathologically proved mixed spindle-epithelioid cell melanomas, each of which in part or in toto showed diffuse and eventually confluent fluorescence emanating from ill-defined vascular foci. One of these two lesions additionally exhibited a large area that was perfused late by irregular leashes of vessels. The ability to distinguish benign from malignant melanocytic lesions of the iris can be greatly enhanced by iris fluorescein angiography.

Sympathetic uveitis after trauma and vitrectomy.

A case is describes in which the earliest clinical manifestations of sympathetic uveitis that occurred after trauma and pars plana vitrectomy were confined primarily to the retina, retinal pigment epithelium, and choroid posteriorly, and resembled focal lesions of acute posterior multifocal placoid pigment epitheliopathy. Similar focal lesions were noted on gross examination of the enucleated inciting eye. Histopathological examination revealed that these lesions were caused by focal choroidal granulomas and overlying Dalen-Fuchs nodules. Sympathetic ophthalmia was also noted in four other patients in whom the condition developed after trauma and vitrectomy.

Eyelid tumors anmd renal transplantation.

The high incidence of malignant neoplasms in renal transplant recipients and other immunosuppressed patients is well recognized. A large proportion of these neoplasms are skin cancers. The frequent occurrence of other ocular complications, such as cataract, elevated intraocular pressure, hypertensive retinopathy, cytomegalovirus retinitis, and herpetic keratitis in patients after kidney transplant, has also been described. This report presents the clinical and histopathologic features of eyelid involvement by keratoacanthoma and squamous cell carcinoma in two patients after renal transplantation and alerts ophthalmologists to the potential for this association.

Orbital leiomyosarcoma after radiation therapy for bilateral retinoblastoma.

Leiomyosarcoma rarely occurs in the orbit and is seldom encountered as a postirradiation sarcoma in any anatomic location. Three patients with bilateral retinoblastoma who had received radiation therapy are known to have orbital leiomyosarcoma develop in their third decade of life. The clinical and pathological data pertaining to two of these patients are given and discussed herein.

Intravascular papillary endothelial hyperplasia of the eyelid.

Intravascular papillary endothelial hyperplasia (IPEH), a benign lesion histopathologically characterized by intravascular fibrous papillary fronds covered by pleomorphic endothelium, is usually found in the subcutaneous tissues of the head and extremities. We describe the clinical and histologic findings of IPEH in the upper eyelid of a 20-year-old woman. Intravascular papillary endothelial hyperplasia has been confused with angiosarcoma. The differential diagnosis and key distinguishing features are discussed and the literature is reviewed.

Fibrous histiocytoma metastatic to the orbit.

The term fibrous histiocytoma encompasses a heterogenous group of tumors believed to have a common origin in the histiocyte. These tumors demonstrate a wide histopathologic spectrum ranging from a predominantly cellular to a predominantly fibrous pattern. No clinical or histological criteria have been identified that can predict malignant behavior. Although generally characterized by local recurrence, a metastatic potential does exist. Fibrous histiocytoma of the thigh metastasized to the orbit.

Monitoring ophthalmology graduate education. The Residency Review Committee.

Formal monitoring of quality control in American graduate medical education is the task of the residency review committees (RRCs). The RRC for ophthalmology consists of nine members appointed by the American Board of Ophthalmology, the American Academy of Ophthalmology, and the American Medical Association. The RRC meets twice each year to determine the accreditation status of residency training programs. As of 1978, the residents ae board eligible only if they have graduated from accredited programs. The review process is based on data collected in standard hospital information forms and a site survey. An RRC member evaluates this information and makes a recommendation that is discussed and voted on by the nine-member RRC body. In response to pressures for greater quality control and regulatory visibility, the review process has been bolstered by improvements in the data-gathering forms and in the surveyors and by a revision of the minimum requirements for accreditation that provides clearer and more stringent guidelines.

Drusen of the optic disk and aberrant axoplasmic transport. The XXXIV Edward Jackson memorial lecture.

We believe axoplasmic transport alteration is the anatomic substrate for formation of drusen of the optic disk. In familial cases the cause of axoplasmic transport alteration may be related to the presence of a genetically determined, small, crowded optic nerve head. We believe these congenitally elevated nerve heads evolve over a period of many years through stages of atrophy and drusen formation. Vascular malformations in the familial cases are primarily developmental; however, secondary vascular alterations may occur as the drusen enlarge. In retinitis pigmentosa the drusen may be caused by diminished production of axoplasmic material by the ganglion cell. Chronic alterations in axonal transport from any cause produce aggregates of swollen nerve fibers. These give a yellow-white appearance to the disk tissue and account for the yellow, filled-in appearance of the disk in patients with drusen, chronic atrophic papilledema, melanocytomas, and, in part, for the waxy yellow appearance of the disk in retinitis pigmentosa.