Citations

BackgroundAortic valve replacement for aortic stenosis (AS) carries an increased risk in the presence of left ventricular (LV) systolic dysfunction. Few data are available on the outcome of such patients.Methods and ResultsBetween 1985 and 1992, 154 consecutive patients (107 men and 47 women) with LV systolic dysfunction (ejection fraction [EF] ≤35%) underwent aortic valve replacement for AS. The mean preoperative characteristics included EF, 27±6%; aortic valve mean gradient, 44±18 mm Hg; aortic valve area, 0.6±0.2 cm2; and cardiac output, 4.1±1.5 L/min. Simultaneous coronary artery bypass graft surgery was performed in 78 patients (51%). Perioperative (30-day) mortality was 9% (14 of 154 patients). Fifty patients died during follow-up. Coronary artery disease (P=.002) and a reduced preoperative cardiac output (P=.03) were significantly related to reduced overall survival rate by multivariate analysis. Postoperative improvement occurred in most patients; 88% were New York Heart Association class III or IV before surgery versus 7% after surgery. Postoperative EF was assessed in 76% of survivors; 76% of these demonstrated improvement. By multivariate analysis, change in EF was inversely related to coronary disease (P=.002) and preoperative aortic valve area (P=.03).ConclusionsDespite LV dysfunction, the risk of aortic valve replacement for AS was acceptable and related to coronary artery disease and mean aortic gradient, and long-term survival was related to coronary disease and cardiac output. Improvement in symptoms and EF occurred in most patients.

BackgroundSinus venosus atrial septal defect (SVD) is underdiagnosed with transthoracic echocardiography because of its posterior (far field) location. Transesophageal echocardiography (TEE) should be ideally suited to diagnose SVD, given the proximity of the transducer to the defect.Methods and ResultsA retrospective study was undertaken that used the medical history, echocardiographic findings, and surgical data of patients identified from computer records as having the diagnosis of SVD during the period in which TEE has been in use (1987 to 1995). Twenty-five patients (14 females and 11 males; median age, 45 years; range, 10 to 75 years) with SVD had TEE between 1987 and 1995. Prior transthoracic echocardiography clearly defined the SVD in 3 of these patients, and it was suspected in another 11 on the basis of color-flow imaging. Ten patients had unexplained dilatation of the right side of the heart, which prompted TEE examination. SVD was visualized with TEE in all 25 patients and ranged in size from 1 to 3 cm. Thirty-seven right-sided anomalous pulmonary venous connections were identified in 23 patients. No left-sided anomalous pulmonary venous connections were detected. Anatomic confirmation was obtained in all 23 surgical patients. No patient required preoperative cardiac catheterization for diagnosis.ConclusionsTEE is accurate for the diagnosis of SVD and should be undertaken in any patient with unexplained dilatation of the right side of the heart. The associated pulmonary venous abnormalities can be identified with TEE. Cardiac catheterization for diagnostic purposes should not be required before surgical correction.

BACKGROUND Transthoracic Doppler echocardiography examination has become an integral part of the investigations performed in patients with mitral valve prostheses. The limitations of the transthoracic approach are well documented. Transesophageal echocardiography provides a unique window for achieving a clear view of the mitral prosthesis. METHODS AND RESULTS This study shows the usefulness of transesophageal echocardiography in clinical practice for assessment of patients with a mitral valve prosthesis. This technique demonstrated an abnormality in 48% of patients who had normal results on transthoracic examination. The overall sensitivity of transesophageal echocardiography was 96%. CONCLUSIONS Transesophageal echocardiography constitutes an essential part of a comprehensive two-dimensional/Doppler echocardiographic examination in patients with suspected malfunction of mitral prostheses.

BACKGROUND We have previously characterized the left ventricular diastolic filling abnormalities in cardiac amyloidosis by Doppler methods. The various filling patterns were shown to be related to the degree of cardiac amyloid infiltration. The purpose of this study was to determine the value of Doppler diastolic filling variables for assessing prognosis in cardiac amyloidosis. METHODS AND RESULTS We performed pulsed-wave Doppler studies of the left ventricular inflow and obtained clinical follow-up data in 63 consecutive patients with biopsy-proven systemic amyloidosis. All patients had typical echocardiographic features of cardiac involvement. The patients were subdivided into two groups according to deceleration time: Group 1 (33 patients) had a deceleration time of 150 msec or less, indicative of restrictive physiology, and group 2 (30 patients) had a deceleration time of more than 150 msec. Of the 63 patients, 32 (51%) died during a mean follow-up period of 18 +/- 12 months. Of these deaths, 25 (78%) were cardiac deaths, and 19 of the 25 patients (76%) were from group 1. The 1-year probability of survival in group 1 was significantly less than that in group 2 (49% versus 92%, p less than 0.001). Bivariate analysis revealed that the combination of the Doppler variables of shortened deceleration time and increased early diastolic filling velocity to atrial filling velocity ratio were stronger predictors of cardiac death than were the two-dimensional echocardiographic variables of mean left ventricular wall thickness and fractional shortening. CONCLUSIONS Doppler-derived left ventricular diastolic filling variables are important predictors of survival in cardiac amyloidosis.

Background —The outcome of aortic valve replacement in patients with severe aortic stenosis, low transvalvular gradient, and severe left ventricular dysfunction is not well known. Methods and Results —Between 1985 and 1995, 52 patients with left ventricular ejection fraction (EF) ≤35% and aortic stenosis with transvalvular mean gradient <30 mm Hg underwent aortic valve replacement. The mean (±SD) preoperative characteristics included EF, 26±8%; aortic valve mean gradient, 23±4 mm Hg; aortic valve area, 0.7±0.2 cm 2 ; and cardiac output, 3.7±1.2 L/min. Simultaneous coronary artery bypass graft surgery was performed in 32 patients (62%). Perioperative (30-day) mortality was 21% (11 of 52 patients). Ten additional patients died during follow-up. Advanced age ( P =0.048) and small aortic prosthesis size ( P =0.03) were significant predictors of hospital mortality by univariate analysis. By multivariate analysis, the only predictor of surgical mortality was smaller prosthesis size. The only predictor of postoperative survival was improvement in postoperative functional class ( P =0.04). Postoperative functional improvement occurred in most patients. Postoperative EF was assessed in 93% of survivors; 74% demonstrated improvement. Positive change in EF was related to smaller preoperative aortic valve area and female sex. Conclusions —Despite severe left ventricular dysfunction, low transvalvular mean gradient, and increased operative mortality, aortic valve replacement was associated with improved functional status. Postoperative survival was related to younger patient age and larger aortic prosthesis size, and medium-term survival was related to improved postoperative functional class.

Background —The clinical spectrum of constrictive pericarditis (CP) has been affected by a change in incidence of etiological factors. We sought to determine the impact of these changes on the outcome of pericardiectomy. Methods and Results —The contemporary spectrum of CP in 135 patients (76% male) evaluated at the Mayo Clinic from 1985 to 1995 was compared with that of a historic cohort. Notable trends were an increasing frequency of CP due to cardiac surgery and mediastinal radiation and presentation in older patients (median age, 61 versus 45 years). Perioperative mortality decreased (6% versus 14%, P =0.011), but late survival was inferior to that of an age- and sex-matched US population (57±8% at 10 years). The long-term outcome was predicted independently by 3 variables in stepwise logistic regression analyses: (1) age, (2) NYHA class, and most powerfully, (3) a postradiation cause. Of 90 late survivors in whom functional class could be determined, functional status had improved markedly (2.6±0.7 at baseline versus 1.5±0.8 at latest follow-up [ P <0.0001]), with 83% being free of clinical symptoms. Conclusions —The evolving profile of CP, with increasingly older patients and those with radiation-induced disease in the past decade, significantly affects postoperative prognosis. Long-term results of pericardiectomy are disappointing for some patient groups, especially those with radiation-induced CP. By contrast, surgery alleviates or improves symptoms in the majority of late survivors.

Background Respiratory variation of ≥25% in mitral E velocity is a characteristic Doppler echocardiographic feature in constrictive pericarditis. However, a subset of patients with constriction do not exhibit the typical respiratory change, most likely because of marked increase in the left atrial pressure, and preload reduction may unmask the respiratory variation. Methods and Results In 12 patients with surgically confirmed constrictive pericarditis who had <25% respiratory variation in mitral E velocity during an initial preoperative examination, the Doppler study was repeated after an attempt to decrease left ventricular filling pressure. At baseline, mean mitral E velocity was similar after inspiration and expiration (0.81±0.24 and 0.84±0.21 m/s, respectively). On repeat Doppler examination, with the patient in a head-up tilt or sitting position, the decrease in mitral E velocity with inspiration (0.61±0.13 m/s) was significant ( P <.004), whereas it did not change significantly with expiration. The mean percent respiratory change in E velocity was 5±7% at baseline and 32±28% with preload reduction. Eight (75%) of the 12 patients developed respiratory variation of ≥25%. Conclusions When the respiratory variation in Doppler mitral E velocity is blunted or absent during the evaluation of suspected constrictive pericarditis, repeat Doppler recording of mitral flow velocities after maneuvers to decrease preload is recommended to unmask the characteristic respiratory variation in mitral E velocity.

BACKGROUND The implications of hypotension occurring during dobutamine stress echocardiography have not been elucidated. We observed in some patients that hyperdynamic left ventricular function developed during dobutamine stress echocardiography and hypothesized that intracavitary obstruction was occurring and might account for hypotension in some patients. METHODS AND RESULTS Fifty-seven consecutive patients undergoing dobutamine stress echocardiography underwent pulsed-wave and continuous-wave Doppler examination of the left ventricular cavity at rest and at peak dobutamine infusion. The development of an intraventricular gradient with dobutamine stress was defined as a late-peaking left ventricular Doppler velocity profile that exceeded basal velocity by at least 1 m/sec. During dobutamine stress testing, left ventricular outflow velocity or intracavitary velocity increased in all patients. Obstruction occurred in 12 patients (21%, group 1). Group 2 was the remaining 45 patients. Peak velocities in group 1 ranged from 2.0 to 5.0 m/sec (mean, 3.5 m/sec), and the mean increase from velocity at rest was 2.3 m/sec. The mean change in systolic blood pressure was significantly lower in patients in group 1 (-15 versus 4 mm Hg, p = 0.02). When the 18 patients with an ischemic response to stress testing (evidenced by new or worsening wall motion abnormalities) were excluded from analysis, systolic blood pressure response was still significantly different for the two groups (-19 versus 2 mm Hg, p = 0.03). CONCLUSIONS Dynamic left ventricular obstruction is a new observation; it may develop frequently in patients undergoing dobutamine stress echocardiography. Obstruction rather than ischemia may explain a decrease in blood pressure during dobutamine stress echocardiography.

Abstract Purpose: miRNA plays an important role in human disease and cancer. We seek to investigate the expression status, clinical relevance, and functional role of miRNA in non–small cell lung cancer. Experimental Design: We conducted miRNA expression profiling in matched lung adenocarcinoma and uninvolved lung using 56 pairs of fresh-frozen (FF) and 47 pairs of formalin-fixed, paraffin-embedded (FFPE) samples from never smokers. The most differentially expressed miRNA genes were evaluated by Cox analysis and log-rank test. Among the best candidate, miR-708 was further examined for differential expression in two independent cohorts. Functional significance of miR-708 expression in lung cancer was examined by identifying its candidate mRNA target and through manipulating its expression levels in cultured cells. Results: Among the 20 miRNAs most differentially expressed between tested tumor and normal samples, high expression level of miR-708 in the tumors was most strongly associated with an increased risk of death after adjustments for all clinically significant factors including age, sex, and tumor stage (FF cohort: HR, 1.90; 95% CI, 1.08–3.35; P = 0.025 and FFPE cohort: HR, 1.93; 95% CI, 1.02–3.63; P = 0.042). The transcript for TMEM88 gene has a miR-708 binding site in its 3′ UTR and was significantly reduced in tumors high of miR-708. Forced miR-708 expression reduced TMEM88 transcript levels and increased the rate of cell proliferation, invasion, and migration in culture. Conclusions: miRNA-708 acts as an oncogene contributing to tumor growth and disease progression by directly downregulating TMEM88, a negative regulator of the Wnt signaling pathway in lung cancer. Clin Cancer Res; 18(13); 3658–67. ©2012 AACR.