Frye, Robert L.

Background In patients with mitral regurgitation, surgical intervention produces immediate improvement in symptoms, but the long-term incidence and significance of postoperative congestive heart failure are unknown. Methods and Results The long-term outcome of 576 operative survivors of surgical correction of pure mitral regurgitation performed between 1980 and 1989 was analyzed. Survival was 77±2% and 56±3% at 5 and 10 years, respectively. Cumulative incidence of congestive heart failure was 23±2%, 33±3%, and 37±3% at 5, 10, and 14 years, respectively. Survival after the first episode of congestive heart failure was dismal, 44±4% at 5 years. Cause of congestive heart failure was left ventricular dysfunction in two thirds of the patients and valvular dysfunction in the other third. With multivariate analysis, the independent predictors of postoperative heart failure were preoperative ejection fraction ( P =.0001), coronary artery disease ( P =.0017), and New York Heart Association functional class ( P =.012), with borderline value for atrial fibrillation ( P =.10). The performance of valve repair was independently predictive of a lower incidence of the combined end point of death and heart failure ( P =.001), compared with valve replacement. Conclusions Congestive heart failure frequently occurs late after surgical correction of mitral regurgitation and portends dismal prognosis. This complication is due most often to left ventricular dysfunction; its main determinant is decreased left ventricular function preoperatively. These data should lead to earlier indication of surgical correction of mitral regurgitation, before left ventricular dysfunction occurs.

BackgroundMitral valve repair has been suggested as providing a better postoperative outcome than valve replacement for mitral regurgitation, but this impression has been obscured by differences in baseline characteristics and has not been confirmed in multivariate analyses.Methods and ResultsThe outcomes in 195 patients with valve repair and 214 with replacement for organic mitral regurgitation were compared using multivariate analysis. All patients had preoperative echocardiographic assessment of left ventricular function. Before surgery, patients with valve repair were less symptomatic than those with replacement (42% in New York Heart Association functional class I or II versus 24%, respectively;P=.001), had less atrial fibrillation (41% versus 53%;P=.017), and had a better ejection fraction (63±9% versus 60±12%,P=.016). After valve repair, compared with valve replacement, overall survival at 10 years was 68±6% versus 52±4% (P=.0004), overall operative mortality was 2.6% versus 10.3% (P=.002), operative mortality in patients under age 75 was 1.3% versus 5.7% (P=.036), and late survival (in operative survivors) at 10 years was 69±6% versus 58±5% (P=.018). Late survival after valve repair was not different from expected survival. After surgery, ejection fraction decreased significantly in both groups but was higher after valve repair (P=.001). Multivariate analysis indicated an independent beneficial effect of valve repair on overall survival (hazard ratio, 0.39;P=.00001), operative mortality (odds ratio, 0.27;P=.026), late survival (hazard ratio, 0.44;P=.001), and postoperative ejection fraction (P=.001).ConclusionsValve repair significantly improves postoperative outcome in patients with mitral regurgitation and should be the preferred mode of surgical correction. The low operative mortality is an incentive for early surgery before ventricular dysfunction occurs.

BACKGROUND Left ventricular dysfunction is a frequent cause of death after successful surgical repair of mitral regurgitation. The role of preoperative echocardiographic left ventricular variables in the prediction of postoperative survival and thus their clinical implications remain uncertain. METHODS AND RESULTS The survival of 409 patients operated on between 1980 and 1989 for pure, isolated, organic mitral regurgitation and with a preoperative echocardiogram (within 6 months of operation) was analyzed. The overall survival was 75% at 5 years (90% of expected), 58% at 10 years (88% of expected), and 44% at 12 years (73% of expected). Operative mortality was 6.6% and markedly improved from 1980 to 1984 (10.7%) to 1985 to 1989 (3.7%). Multivariate analysis showed that age (P = .0003), date of operation (P = .003), and functional class (P = .016) but not left ventricular function were predictors of operative mortality. In the most recent period (1985 to 1989), operative mortality was 12.3% in patients age 75 years or older and 1.1% in patients younger than 75 years. Late survival was analyzed in the operative survivors. Multivariate analysis showed that the most powerful predictor was echocardiographic ejection fraction (EF) (P = .0004), followed by age (P = .0031), creatinine level (P = .0062), systolic blood pressure (P = .0164), and presence of coronary artery disease (P = .0237). The late survival at 10 years was 32 +/- 12% for patients with EF < 50%, 53 +/- 9% for EF 50% to 60%, and 72 +/- 4% for EF > or = 60%. The hazard ratio compared with EF > or = 60% was 2.79 (95% confidence interval, 1.65 to 4.72) for EF < 50% and 1.81 (95% confidence interval, 1.11 to 2.95) for EF 50% to 60%. Echocardiographic EF remained the best predictor of late survival, even when combined with left ventricular angiographic variables. The survival of patients with EF > or = 60% was 100% of expected at 10 years but was better in patients in class I or II than in those in class III or IV (82 +/- 6% versus 59 +/- 6%, respectively, at 10 years; P = .0021). The preoperative predictors of operative and late mortality remained significant independent of the type of surgical correction performed in combined multivariate analyses. CONCLUSIONS In organic mitral regurgitation, (1) operative mortality has markedly decreased recently, being at a low 1.1% in patients younger than 75 years, and is predicted by age and symptoms and not by left ventricular function, and (2) left ventricular EF measured by echocardiography is the most powerful predictor of late survival. These results suggest that surgical treatment should be considered early, even in the absence of severe symptoms, in patients with severe mitral regurgitation, before left ventricular dysfunction occurs.

Background —Activation of circulating monocytes in patients with acute coronary syndromes may reflect exposure to bacterial products or stimulation by cytokines such as IFN-γ. IFN-γ induces phosphorylation and nuclear translocation of transcription factor STAT-1, which initiates a specific program of gene induction. To explore whether monocyte activation is IFN-γ driven, patients with unstable (UA) or stable angina (SA) were compared for nuclear translocation of STAT-1 complexes and upregulation of IFN-γ–inducible genes CD64 and IP-10. Methods and Results —Peripheral blood mononuclear cells were stained for expression of CD64 on CD14 + monocytes and analyzed by PCR for transcription of IP-10. Expression of CD64 was significantly increased in patients with UA. Monocytes from UA patients remained responsive to IFN-γ in vitro, with accelerated transcriptional competency of CD64. IP-10–specific sequences were spontaneously detectable in 82% of the UA patients and 15% of SA patients ( P <0.001). Most importantly, STAT-1 complexes were found in nuclear extracts prepared from freshly isolated monocytes of patients with UA, which provides compelling evidence for IFN-γ signaling in vivo. Conclusions —Monocytes from UA patients exhibit a molecular fingerprint of recent IFN-γ triggering, such as nuclear translocation of STAT-1 complexes and upregulation of IFN-γ–inducible genes CD64 and IP-10, which suggests that monocytes are activated, at least in part, by IFN-γ. IFN-γ may derive from stimulated T lymphocytes, which implicates specific immune responses in the pathogenesis of acute coronary syndromes.

The use of roentgen videometry as a means of studying regional left ventricular wall dynamics and performance was evaluated in 32 patients undergoing coronary arteriography. Nine patients had normal coronary arteriograms and hemodynamic findings (group 1), 8 patients had generalized decrease in left ventricular contraction and abnormal hemodynamic findings (group 2), and 15 patients with coronary artery disease had regional wall dynamics abnormalities (group 3). Sixty-per-second determinations of wall thickness were performed in selected sites of the left ventricle. Measurements performed included end-diastolic wall thickness (EDTw), mean and peak rates of systolic wall thickening (m and p dTw/dt), and fractional systolic increase in wall thickness (ΔTw/EDTw). In patients with uniformly performing ventricles (groups 1 and 2), these parameters correlated well with other parameters of ventricular function. Best distinction between the "normal" group (group 1) and the "abnormal" group (group 2) was achieved when the rates of thickening (m and p dTw/dt) were utilized ( P < 0.001). In patients of group 3, three types of abnormal regional wall dynamics could be determined and quantified objectively: hypokinesia (decreased p dTw/dt), akinesia (p dTw/dt = 0), and dyskinesia (p dTw/dt < 0). The severity of the abnormality of the wall dynamics correlated well with the presence or absence of a previous infarction on the electrocardiogram, and the anatomic location was strongly correlated with the distribution and severity of coronary artery lesions within a given ventricle.

The effect of oral aspirin in doses known to influence in vitro platelet aggregation was evaluated in patients undergoing brachial artery catheterization. Neither arterial thrombus formation nor pulse reduction was affected in patients given aspirin when compared to controls. Aspirin in small doses does not decrease the incidence of vascular occlusion after brachial artery catheterization.

Left ventricular hemodynamics at rest and during supine exercise were studied before and 1 year after internal mammary artery implantation in 24 patients with severe coronary artery disease and angina pectoris and in five similar patients before and after 1 year of medical treatment. In the surgical group, 14 had evidence of one or more implants providing collaterals to coronary arteries, and 10 had no evidence of collaterals from the implant. Only two patients, both with functioning implants, showed a return to normal of left ventricular end-diastolic pressure at rest and during exercise. There was no correlation between clinical improvement and hemodynamics at the time of the postoperative study. It is concluded that left ventricular hemodynamics may return to normal after internal mammary artery implantation but this was uncommon in the present study.

The status of 58 patients, 3 to 57 years of age, with ventricular septal defect and a marked increase in pulmonary vascular resistance (pulmonary obstructive disease) was determined 5 years or longer after diagnostic catheterization. Forty-six (80%) were alive 5 years after that study. The probability of living 5 years was 95% for patients aged 10 through 19 years and 56% for those 20 years of age or older. The dissimilarity of actuarial curves between these two groups is consistent with the hypothesis that pulmonary vascular obstructive disease develops under age 20. Calculated pulmonary resistance increased with age of patient on admission to the study, suggesting its progressive nature. Hemoptysis was rare under age 20, and its presence over this age indicated a poor prognosis. The most common causes of death were "sudden" or "unknown." Most surviving patients were gainfully employed or attending school without severe symptoms.

Left ventricular (LV) performance was studied during mild exercise (100 kg-m/min for 3 minutes) in 19 cases of coronary artery disease (CAD). Each patient suffered from a severe anginal syndrome. None had ventricular aneurysm, cardiomegaly, or clinical heart failure. Mean resting values follow: LV end-diastolic pressure (LVEDP), 19 ± 7 mm Hg; LV systolic pressure (LVSP), 150 ± 16 mm Hg; stroke volume index (SVI), 48 ± 10 ml/beat/m 2 ; and LV stroke work index (LVSWI), 81 ± 19 g-m/m 2 . During exercise LVEDP rose to 30 ± 8 mm Hg ( P ≤0.001) and LVS to 160 ± 20 (not significant [NS]); SVI diminished to 46 ± 11 (NS) and LVSWI, to 76 ± 24 (NS). Patients with decreased or asynchronous areas of LV myocardium identified on cine left ventriculograms had higher mean LVEDPs during exercise than did those with normal ventriculograms (34 ± 10 versus 26 ± 4 mm Hg; P ≤0.05). The difference between responses to exercise of patients who experienced angina during the study and of those who did not was NS. Administration of nitroglycerin reduced the increase in LVEDP during exercise. An abnormality in LV performance-a significant rise in LVEDP without a significant increase in SVI or LVSWI-was observed in 13 of 19 cases of CAD.

A patient with an atrial septal defect, paroxysmal tachycardia, and the Wolff-Parkinson-White syndrome (type B) had epicardial exploration to determine the nature of the excitation anomaly. Right bundle-branch block in association with the WPW syndrome (type B) was evidenced by the late activation (0.12 sec) of the epicardium over the outflow tract of the right ventricle. Early activation of the base of the right ventricle (near the atrioventricular groove at the right border of the heart) was interpreted as indicating an actively conducting atrioventricular muscle bridge (bundle of Kent) in this region. During paroxysms of tachycardia, the ventricular area excited much later than when sinus mechanism was present, and the adjacent right atrium was excited in sequence. This sequence supported the concept of a circus movement, that is, movement from atrium to ventricle via atrioventricular bundle (His) and ventricle to atrium via a muscle bridge (Kent). Injection of procaine into the base of the right ventricle abolished the pre-excitation of the ventricle.