Jeanne K. Drinko

Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery.

OBJECTIVES This study was conducted to evaluate follow-up results in patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent either percutaneous transluminal septal myocardial ablation (PTSMA) or septal myectomy. BACKGROUND Controversy exists with regard to these two forms of treatment for patients with HOCM. METHODS Of 51 patients with HOCM treated, 25 were treated by PTSMA and 26 patients via myectomy. Two-dimensional echocardiograms were performed before both procedures, immediately afterwards and at a three-month follow-up. The New York Heart Association (NYHA) functional class was obtained before the procedures and at follow-up. RESULTS Interventricular septal thickness was significantly reduced at follow-up in both groups (2.3 +/- 0.4 cm vs. 1.9 +/- 0.4 cm for septal ablation and 2.4 +/- 0.6 cm vs. 1.7 +/- 0.2 cm for myectomy, both p < 0.001). Estimated by continuous-wave Doppler, the resting pressure gradient (PG) across the left ventricular outflow tract (LVOT) significantly decreased immediately after the procedures in both groups (64 +/- 39 mm Hg vs. 28 +/- 29 mm Hg for PTSMA, 62 +/- 43 mm Hg vs. 7 +/- 7 mm Hg for myectomy, both p < 0.0001). At three-month follow-up, the resting PG remained lower in the PTSMA and myectomy groups (24 +/- 19 mm Hg and 11 +/- 6 mm Hg, respectively, vs. those before procedures, both p < 0.0001). The NYHA functional class was also significantly improved in both groups (3.5 +/- 0.5 vs. 1.9 +/- 0.7 for PTSMA, 3.3 +/- 0.5 vs. 1.5 +/- 0.7 for myectomy, both p < 0.0001). CONCLUSIONS Both myectomy and PTSMA reduce LVOT obstruction and significantly improve NYHA functional class in patients with HOCM. However, there are benefits and drawbacks for each therapeutic method that must be counterbalanced when deciding on treatment for LVOT obstruction.

Myeloperoxidase and Plasminogen Activator Inhibitor 1 Play a Central Role in Ventricular Remodeling after Myocardial Infarction

Left ventricular (LV) remodeling after myocardial infarction (MI) results in LV dilation, a major cause of congestive heart failure and sudden cardiac death. Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function. We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO−/−). MPO−/− demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function. The mechanism appears to be due to decreased oxidative inactivation of plasminogen activator inhibitor 1 (PAI-1) in the MPO−/−, leading to decreased tissue plasmin activity. MPO and PAI-1 are shown to have a critical role in the LV response immediately after MI, as demonstrated by markedly delayed myocardial rupture in the MPO−/− and accelerated rupture in the PAI-1−/−. These data offer a mechanistic link between inflammation and LV remodeling by demonstrating a heretofore unrecognized role for MPO and PAI-1 in orchestrating the myocardial response to AMI.

Contrast and harmonic imaging improves accuracy and efficiency of novice readers for dobutamine stress echocardiography.

Background: Newer contrast agents as well as tissue harmonic imaging enhance left ventricular (LV) endocardial border delineation, and therefore, improve LV wall‐motion analysis. Interpretation of dobutamine stress echocardiography is observer‐dependent and requires experience. This study was performed to evaluate whether these new imaging modalities would improve endocardial visualization and enhance accuracy and efficiency of the inexperienced reader interpreting dobutamine stress echocardiography. Methods and Results: Twenty‐nine consecutive patients with known or suspected coronary artery disease underwent dobutamine stress echocardiography. Both fundamental (2.5 MHZ) and harmonic (1.7 and 3.5 MHZ) mode images were obtained in four standard views at rest and at peak stress during a standard dobutamine infusion stress protocol. Following the noncontrast images, Optison was administered intravenously in bolus (0.5–3.0 ml), and fundamental and harmonic images were obtained. The dobutamine echocardiography studies were reviewed by one experienced and one inexperienced echocardiographer. LV segments were graded for image quality and function. Time for interpretation also was recorded. Contrast with harmonic imaging improved the diagnostic concordance of the novice reader to the expert reader by 7.1%, 7.5%, and 12.6% (P < 0.001) as compared with harmonic imaging, fundamental imaging, and fundamental imaging with contrast, respectively. For the novice reader, reading time was reduced by 47%, 55%, and 58% (P < 0.005) as compared with the time needed for fundamental, fundamental contrast, and harmonic modes, respectively. With harmonic imaging, the image quality score was 4.6% higher (P < 0.001) than for fundamental imaging. Image quality scores were not significantly different for noncontrast and contrast images. Conclusion: Harmonic imaging with contrast significantly improves the accuracy and efficiency of the novice dobutamine stress echocardiography reader. The use of harmonic imaging reduces the frequency of nondiagnostic wall segments.

Comprehensive Left Atrial Appendage Optimization of Thrombus Using Surface Echocardiography: The CLOTS Multicenter Pilot Trial

BACKGROUND The aim of this study was to determine the ability to identify thrombus within the left atrial appendage (LAA) in the setting of atrial fibrillation (AF) using transthoracic echocardiography (TTE). In AF, the structure and function of the LAA has historically been evaluated using transesophageal echocardiography (TEE). The role of TTE remains undefined. METHODS The Comprehensive Left Atrial Appendage Optimization of Thrombus (CLOTS) multicenter study enrolled 118 patients (85 men; mean age, 67 +/- 13 years) with AF of >2 days in duration undergoing clinically indicated TEE. On TEE, the LAA was evaluated for mild spontaneous echo contrast (SEC), severe SEC, sludge, or thrombus. Doppler Tissue imaging (DTI) peak S-wave and E-wave velocities of the LAA walls (anterior, posterior, and apical) were acquired on TTE. Transthoracic echocardiographic harmonic imaging (with and without intravenous contrast) was examined to determine its ability to identify LAA SEC, sludge, or thrombus. RESULTS Among the 118 patients, TEE identified 6 (5%) with LAA sludge and 2 (2%) with LAA thrombi. Both LAA thrombi were identified on TTE using harmonic imaging with contrast. Anterior, posterior, and apical LAA wall DTI velocities on TTE varied significantly among the 3 groups examined (no SEC, mild SEC, severe SEC, sludge or thrombus). An apical E velocity < or = 9.7 cm/s on TTE best identified the group of patients with severe SEC, sludge, or thrombus. An anterior S velocity < or = 5.2 cm/s on TTE best identified the group of patients with sludge or thrombus. CONCLUSIONS The CLOTS multicenter pilot trial determined that TTE is useful in the detection of thrombus using harmonic imaging combined with intravenous contrast (Optison; GE Healthcare, Milwaukee, WI). Additionally, LAA wall DTI velocities on TTE are useful in determining the severity of LAA SEC and detecting sludge or thrombus.

LQTS mutation N1325S in cardiac sodium channel gene SCN5A causes cardiomyocyte apoptosis, cardiac fibrosis and contractile dysfunction in mice

OBJECTIVE Mutations in the cardiac sodium channel gene SCN5A cause long QT syndrome (LQTS). We previously generated an LQTS mouse model (TG-NS) that overexpresses the LQTS mutation N1325S in SCN5A. The TG-NS mice manifested the clinical features of LQTS including spontaneous VT, syncope and sudden death. However, the long-term prognosis of LQTS on the structure of the heart has not been investigated in this or any other LQTS models and human patients. METHODS AND RESULTS Impaired systolic function and reduced left ventricular fractional shortening were detected by echocardiography, morphological and histological examination in two lines of adult mutant transgenic mice. Histological and TUNEL analyses of heart sections revealed fibrosis lesions and increased apoptosis in an age-dependent manner. Cardiomyocyte apoptosis was associated with the increased activation of caspases 3 and 9 in TG-NS hearts. Western blot analysis showed a significantly increased expression of the key Ca(2+) handling proteins L-type Ca(2+) channel, RYR2 and NCX in TG-NS hearts. Increased apoptosis and an altered expression of Ca(2+) handling proteins could be detected as early as 3months of age when echocardiography showed little or no alterations in TG-NS mice. CONCLUSIONS Our findings revealed for the first time that the LQTS mutation N1325S in SCN5A causes cardiac fibrosis and contractile dysfunction in mice, possibly through cellular mechanisms involving aberrant cardiomyocyte apoptosis. Therefore, we provide the experimental evidence supporting the notion that some LQTS patients have an increased risk of structural and functional cardiac damage in a prolonged disease course.