Baseline demographics, clinical features and predictors of conversion among 200 individuals in a longitudinal prospective psychosis-risk cohort.

BACKGROUND: DSM-5 proposes an Attenuated Psychosis Syndrome (APS) for further investigation, based upon the Attenuated Positive Symptom Syndrome (APSS) in the Structured Interview for Psychosis-Risk Syndromes (SIPS). SIPS Unusual Thought Content, Disorganized Communication and Total Disorganization scores predicted progression to psychosis in a 2015 NAPLS-2 Consortium report. We sought to independently replicate this in a large single-site high-risk cohort, and identify baseline demographic and clinical predictors beyond current APS/APSS criteria. METHOD: We prospectively studied 200 participants meeting criteria for both the SIPS APSS and DSM-5 APS. SIPS scores, demographics, family history of psychosis, DSM Axis-I diagnoses, schizotypy, and social and role functioning were assessed at baseline, with follow-up every 3 months for 2 years. RESULTS: The conversion rate was 30% (n = 60), or 37.7% excluding participants who were followed under 2 years. This rate was stable across time. Conversion time averaged 7.97 months for 60% who developed schizophrenia and 15.68 for other psychoses. Mean conversion age was 20.3 for males and 23.5 for females. Attenuated odd ideas and thought disorder appear to be the positive symptoms which best predict psychosis in a logistic regression. Total negative symptom score, Asian/Pacific Islander and Black/African-American race were also predictive. As no Axis-I diagnosis or schizotypy predicted conversion, the APS is supported as a distinct syndrome. In addition, cannabis use disorder did not increase risk of conversion to psychosis. CONCLUSIONS: NAPLS SIPS findings were replicated while controlling for clinical and demographic factors, strongly supporting the validity of the SIPS APSS and DSM-5 APS diagnosis.

The relationship of social function to depressive and negative symptoms in individuals at clinical high risk for psychosis.

BACKGROUND: Social dysfunction is a hallmark symptom of schizophrenia which commonly precedes the onset of psychosis. It is unclear if social symptoms in clinical high-risk patients reflect depressive symptoms or are a manifestation of negative symptoms. METHOD: We compared social function scores on the Social Adjustment Scale-Self Report between 56 young people (aged 13-27 years) at clinical high risk for psychosis and 22 healthy controls. The cases were also assessed for depressive and 'prodromal' symptoms (subthreshold positive, negative, disorganized and general symptoms). RESULTS: Poor social function was related to both depressive and negative symptoms, as well as to disorganized and general symptoms. The symptoms were highly intercorrelated but linear regression analysis demonstrated that poor social function was primarily explained by negative symptoms within this cohort, particularly in ethnic minority patients. CONCLUSIONS: Although this study demonstrated a relationship between social dysfunction and depressive symptoms in clinical high-risk cases, this association was primarily explained by the relationship of each of these to negative symptoms. In individuals at heightened risk for psychosis, affective changes may be related to a progressive decrease in social interaction and loss of reinforcement of social behaviors. These findings have relevance for potential treatment strategies for social dysfunction in schizophrenia and its risk states and predict that antidepressant drugs, cognitive behavioral therapy and/or social skills training may be effective.

Membrane-type-1 matrix metalloproteinase transcription and translation in myocardial fibroblasts from patients with normal left ventricular function and from patients with cardiomyopathy.

Past studies have identified that a unique type of matrix metalloproteinase, the membrane-type-1 MMP (MT1-MMP), is increased within the left ventricle (LV) of patients with dilated cardiomyopathy (DCM). However, the cellular and molecular basis for this induction of MT1-MMP with DCM is unknown. LV myocardial biopsies from nonfailing, reference normal patients (defined as LV ejection fraction >50%, elective coronary bypass surgery, no perfusion defect at biopsy site, n = 6) and DCM patients (LV ejection fraction <20%, at transplant, n = 5) were used to establish fibroblast cultures (FIBROS). Confluent LV FIBROS from culture passages 2-5 were measured with respect to MT1-MMP mRNA and protein levels and the distribution of the MT1-MMP mRNA pool in ribosomal fractions. Total MT1-MMP mRNA within DCM FIBROS increased by over 140%, and MT1-MMP protein increased by over 190% from reference normal FIBROS (both P < 0.05). MT1-MMP mRNA in monosome fractions decreased by over twofold in DCM FIBROS compared with reference normal (P < 0.05) and remained lower in polyribosomal fractions (i.e., 15.7 +/- 5.2 vs. 1.4 +/- 0.6% in polysomal fraction 6, P < 0.05). These differences in DCM MT1-MMP FIBROS transcription and translation persisted throughout passages 2-5. The unique findings from this study demonstrated that elevated steady-state MT1-MMP mRNA and protein levels occurred in DCM FIBROS despite a decline in translational deficiency. These phenotypic changes in DCM fibroblasts may provide the basis for developing cell specific pharmacological targets for control of MT1-MMP expression.

Cardiac transplantation in South Carolina: 300 transplants.

For nearly 20 years, the Medical University's Heart Transplant Program has been providing the citizens of South Carolina with excellent results with a minimum of delay. We present here the results of our first 300 heart transplants, spanning the first 18 years of the Cardiac Transplant Program at the Medical University. Overall survival has been very good, with one, five and ten year survival rates in the adults being 92 +/- 2%, 78 +/- 3%, and 58 +/- 4%. The children's group showed survival rates of 94 +/- 5%, 79 +/- 11%, and 79 +/- 11% over the same lengths of time. Most recently, the federally sponsored Scientific Registry of Transplant Recipients (www.ustransplant.org, July 2005) reports for MUSC a one-year survival of 97.67% and three-year survival of 90.74%; both leading the Southeast. We attribute this success to the dedicated work of health care workers at all levels who believe in attention to detail and that the patient always comes first. It is our hope that we will be able to continue to provide expert, state-of-the-art, cardiac transplant services long into the future, while continuing to expand our heart failure management program as dictated by further developments in this rapidly evolving specialty.

Selective induction of matrix metalloproteinases and tissue inhibitor of metalloproteinases in atrial and ventricular myocardium in patients with atrial fibrillation.

Atrial fibrillation (AF) produces changes in atrial structure and extracellular matrix composition, which is regulated by matrix metalloproteinases (MMPs). Moreover, AF often occurs in the setting of congestive heart failure (CHF), which also affects MMPs. Whether changes in MMPs or the tissue inhibitors of metalloproteinases (TIMPs) within atrial and ventricular myocardium are differentially regulated with AF remains unclear. Myocardium from the walls of the right atrium, right ventricle, left atrium, and left ventricle was obtained from the explanted hearts of 43 patients with end-stage CHF. AF was present in 23 patients (duration 1 to 84 months). The remaining 20 patients served as non-AF controls. The groups were well matched clinically, but left atrial (LA) size was increased in the AF cohort (5.5 +/- 0.8 vs 4.9 +/- 0.7 cm, p <0.05). Myocardial collagen content and levels of MMP-1, -2, -8, -9, -13, and -14, and TIMP-1, -2, -3, and TIMP-4 were determined. With AF, collagen content was greater within the atrial myocardium but less in the ventricular myocardium. There were chamber-specific differences in MMPs and TIMPs with AF. For example, MMP-1 in the right atrium and MMP-9 in the left atrium were greater with AF. TIMP-3 levels were greater in the right ventricle, left atrium, and left ventricle. Although total LA collagen was positively correlated with AF duration (r = 0.49, p <0.03), there was an inverse relation between soluble collagen I and AF duration (n = 6, r = -0.84, p <0.04). In conclusion, AF is associated with chamber-specific alterations in myocardial collagen content and MMP and TIMP levels, indicative of differential remodeling and altered collagen metabolism. Differences in MMP and TIMP profiles may provide diagnostic and mechanistic insights into the pathogenesis of AF with CHF.

CD3 monitoring and thymoglobulin therapy in cardiac transplantation: clinical outcomes and pharmacoeconomic implications.

INTRODUCTION: CD3 monitoring of antithymocyte globulin therapy in renal transplantation has been shown to be more cost-effective than standard regimens. The objective of this study was to evaluate CD3 monitoring with Thymoglobulin in cardiac transplantation. METHODS: Cardiac transplant patients who required antithymocyte globulin therapy were dose-adjusted to maintain absolute CD3 counts <25 cells/microL. Endomyocardial biopsies and hemodynamic parameters were used to assess efficacy. The incidences of hematological side effects, opportunistic infections, and malignancies were recorded; in addition we performed a cost comparison. RESULTS: Eight patients were treated with Thymoglobulin using CD3 monitoring to adjust the dosing. All patients responded with few side effects. Compared to standard dosing, CD3 monitoring allowed a 60% reduction in the average total dose and a 58% reduction in cost per patient. CONCLUSION: CD3 monitoring of Thymoglobulin therapy in cardiac transplant patients results in lower doses and reduced costs with equivalent efficacy and a low incidence of complications.

Cardiac fibroma in an infant: single ventricle palliation as a bridge to heart transplantation.

A prenatal echocardiogram revealed a large right ventricular mass. Following birth, there was obstruction to pulmonary blood flow and cyanosis. The tumor's size and location prevented resection. The patient underwent "single ventricle palliation," including placement of a systemic-to-pulmonary shunt as a newborn. This palliation served as a successful bridge to heart transplantation at 7 months of age. Pathologic examination revealed cardiac fibroma.

Reversible left ventricular dysfunction simulating a myocardial infarction after pericardiectomy.

A 39 year old man with postoperative constrictive pericarditis after pericardiectomy developed major left ventricular systolic dysfunction with an anterior wall infarct pattern on ECG but no regional wall motion abnormalities by echocardiography or serum enzymatic evidence of a myocardial infarction. The left ventricular dysfunction resolved over two weeks with supportive treatment. It is postulated that this patient's transient left ventricular dysfunction and ECG changes were caused by myocardial inflammation and oedema induced by operative trauma during pericardiectomy.

Endothelin-1 during and after cardiopulmonary bypass: association to graft sensitivity and postoperative recovery.

OBJECTIVE: Our objectives are 2-fold: (1) to serially measure the release of endothelin and graft-conduit endothelin sensitivity during and after coronary artery bypass grafting and (2) to define potential relationships of changes in endothelin levels to perioperative parameters. METHODS: Endothelin plasma content was measured in patients (n = 105) undergoing bypass grafting from select vascular compartments before operations and at specific intervals up to 24 hours postoperatively. Endothelin sensitivity was determined in isolated internal thoracic artery segments. RESULTS: Systemic arterial and pulmonary arterial endothelin levels were increased by approximately 50% immediately after bypass grafting and increased by another 85% during the first 24 hours postoperatively. Endothelin levels were highest in patients with prolonged ventilatory requirements and extended stays in the intensive care unit (10.2 +/- 0.8 vs 13.2 +/- 1.1 fmol/mL, P =.02, and 9.8 +/- 0.7 vs 13.9 +/- 1.2 fmol/mL, P =.01, respectively. Endothelin sensitivity of the internal thoracic artery was increased in patients requiring prolonged vasodilator support with nitroglycerin. CONCLUSIONS: Systemic and pulmonary arterial endothelin levels remained increased for at least 24 hours postoperatively. Prolonged pharmacologic management and increased intensive care unit stay were associated with increased systemic endothelin release and heightened graft-conduit sensitivity to endothelin.

Coronary artery bypass grafting with and without cardiopulmonary bypass: a comparison analysis.

Coronary artery bypass grafting (CABG) using stabilization devices in place of the heart-lung machine is being performed on a wide range of patients. This study retrospectively compared the performance of off-pump coronary artery grafting bypass (OPCAB) with conventional bypass patients over the same 6-month period at The Medical University of South Carolina. Data were collected and compared from the National Cardiac Database of the Society of Thoracic Surgeons (STS). Parameters studied included age, gender, left ventricular ejection fraction (LVEF), previous myocardial infarction (MI), disease severity, number of grafts, complications, blood usage, ventilation times, operating room (OR) time, and hospital length of stay (LOS). There were no significant difference between the patient groups with regard to age, gender, LVEF, previous MI, predicted mortality, and LOS. Operative mortality was also similar in the two groups: conventional bypass 4/117 (3%) and OPCAB 2/86 (2%). The conventional bypass patients (CPB) had significantly (p < 0.05) more diseased vessels (2.9 vs. 2.6) and distal grafts (4.1 vs. 2.7), as compared to the OPCAB group. OPCAB procedures resulted in significantly (p < 0.05) lower mean OR time (365 min vs. 406 min) and reduced mean postoperative ventilation hours (3.4 vs. 8.3 hours), as compared to conventional bypass. There were significantly (p < 0.05) fewer blood transfusions in the OPCAB group (1.1 units vs. 2.4 units), and the percentage of patients transfused blood was significantly less (34.9% vs. 57.3%). Nine out of 95 (9.5%) of patients who presented for OPCAB were converted to conventional bypass. Although there may be potential benefits to OPCAB, further studies must be directed at determining those patients who would benefit most from CABG using the off-pump technique.

beta-Adrenergic and endothelin receptor interaction in dilated human cardiomyopathic myocardium.

BACKGROUND: Although end-stage dilated cardiomyopathy (DCM) is characterized by defects in beta-adrenergic receptor (beta-AR) activity and increased endothelin-1 (ET-1), possible interactions between these 2 systems remain to be defined. Accordingly, the goal of this study was to determine the effects of ET receptor activation on beta-AR signaling through measurement of cyclic adenosine monophosphate (cAMP) in normal and DCM myocardium. METHODS AND RESULTS: Myocardial sarcolemmal preparations were prepared from normal human (n = 6), dilated cardiomyopathic (n = 10), and ischemic cardiomyopathic (ICM, n = 10) tissue. Basal cAMP production was measured in the presence of ET-1 alone (10(-6) to 0(-9) mol/L) as well as after (-)isoproterenol (10(-6) to 10(-2) mol/L) or forskolin (0.05 to 30.0 micromol/L) stimulation. beta-AR and ET receptor profiles were determined by radiolabeled ligand assays. ET-1 inhibited basal cAMP production in all preparations in a concentration-dependent manner. However, beta-AR-stimulated cAMP production by either isoproterenol or forskolin was not significantly affected by ET-1. beta-AR receptor density was reduced, and a selective reduction of the ET(B) receptor occurred in both forms of DCM. CONCLUSIONS: Under basal conditions, ET receptor stimulation reduced cAMP levels, which may influence contractility, particularly with DCM.

Cardiopulmonary bypass induces the synthesis and release of matrix metalloproteinases.

BACKGROUND: A number of cellular and molecular events can be induced after cardiac procedures requiring cardiopulmonary bypass (CPB). The matrix metalloproteinases (MMPs) are a recently discovered family of enzymes that degrade the extracellular matrix, but expression during and after CPB is unknown. METHODS: Systemic plasma MMP levels were measured in patients (n = 28, 63 +/- 1 years) undergoing elective coronary revascularization requiring CPB at baseline, termination of CPB, and 30 minutes, 6 and 24 hours after CPB. Representative classes of MMP species known to degrade matrix and basement membrane components were selected for study. Specifically, the interstitial collagenases MMP-8 and MMP-13, and the gelatinases MMP-2 and MMP-9 were determined by internally validated enzyme-linked immunosorbent assay. RESULTS: The MMP-8 levels increased by fourfold at separation from CPB, and returned to within normal values within 30 minutes after CPB. The proenzyme forms of MMP-13 and MMP-9 increased by more than twofold at cross-clamp release and returned within normal limits within 6 hours after CPB. The proform of MMP-2 increased from baseline values at 6 and 24 hours postoperatively; likely indicative of de novo synthesis. CONCLUSIONS: A specific portfolio of MMPs are released and synthesized during and after CPB. Because MMPs can degrade extracellular proteins essential for maintaining normal cellular architecture and function, enhanced MMP release and activation may contribute to alterations in tissue homeostasis in the early postoperative period.

A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure.

BACKGROUND: Matrix metalloproteinases (MMPs) contribute to matrix remodeling in disease states such as tumor metastases. Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to increase MMP expression, and membrane-type MMP or MT1-MMP has been implicated to activate MMPs. The present study examined whether and to what degree EMMPRIN and MT1-MMP were expressed in human left ventricular (LV) myocardium as well as the association with MMP activity and expression in dilated cardiomyopathy (DCM). METHODS AND RESULTS: LV myocardial zymographic MMP activity increased by >2-fold with both nonischemic DCM (n=21) and ischemic DCM (n=16) compared with normal (n=13). LV myocardial abundance of MMP-9 was increased with both forms of DCM. MMP-2 and MMP-3 were increased with nonischemic DCM. MMP-1 levels were decreased with both forms of DCM. EMMPRIN increased by >250% and MT1-MMP increased by >1000% with both forms of DCM. CONCLUSIONS: Increased LV myocardial MMP activity and selective upregulation of MMPs with nonischemic and ischemic forms of DCM occurred. Moreover, a local MMP induction/activation system was identified in isolated normal human LV myocytes that was upregulated with DCM. The control of MMP activation and expression in the failing human LV myocardium represents a new and potentially significant therapeutic target for this disease process.

Temporal synthesis and release of endothelin within the systemic and myocardial circulation during and after cardiopulmonary bypass: relation to postoperative recovery.

OBJECTIVE: To determine endothelin levels in arterial, pulmonary, and myocardial vascular compartments in patients undergoing coronary artery bypass graft surgery and to examine the influence of endothelin on postoperative recovery. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Fifty patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Endothelin plasma content (fmol/mL) was measured in 50 patients undergoing coronary revascularization from various vascular compartments before surgery and at specific intervals up to 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Myocardial endothelin gradient (coronary sinus - aorta) was calculated before cardiopulmonary bypass (CPB), at release of the aortic cross-clamp, immediately after CPB, and 0.5 hour after CPB. The requirement for inotropic therapy and duration of patient stay in the intensive care unit were determined. Systemic and pulmonary endothelin levels were increased by >80% immediately after CPB when compared with preoperative values and increased again by approximately 60% during the first 24 hours postoperatively (p < 0.05). The myocardial endothelin gradient was reversed after CPB, indicating myocardial production of endothelin (pre-CPB, -0.72+/-0.39 fmol/mL v 0.5 hour post-CPB, 0.60+/-0.49 fmol/mL; p < 0.05). Longer intensive care unit times (>28 hours) were associated with higher systemic endothelin levels when compared with shorter times (<18 hours) (16.30+/-1.33 fmol/mL v 9.81+/-1.67 fmol/mL; p < 0.05). Patients with higher endothelin levels 6 hours postoperatively had greater inotropic requirements during the intensive care unit period. CONCLUSION: Endothelin levels after CPB remained persistently increased for at least 24 hours after surgery and were associated with increased myocardial production of endothelin. These results suggest that the increased endothelin observed in the early postoperative period may contribute to a complex recovery from coronary artery bypass graft surgery.

Early and long-term results of coronary artery bypass grafting in dialysis patients.

BACKGROUND: Dialysis patients frequently present with debilitating coronary artery disease but are regarded as challenging patients for coronary artery bypass grafting. METHODS: The operative, early postoperative, and late results of 44 dialysis patients undergoing coronary artery bypass grafting from 1984 to 1997 were retrospectively reviewed. RESULTS: Compared with patients in The Society of Thoracic Surgeons database who underwent coronary artery bypass grafting, only cerebrovascular accident and postoperative cardiac arrest occurred more frequently in dialysis patients. However, 73% experienced some type of complication. Operative mortality was 11.4%. Decreased left ventricular ejection fraction and severe distal disease were predictive of increased operative mortality. New York Heart Association angina class fell from 2.8 to 1.5, and New York Heart Association congestive heart failure class fell from 2.6 to 1.8. Overall quality-of-life scores did not improve; however, walking distances remained consistently improved. Actuarial survival at 5 years was 32.0%+/-12.0%. Five-year survival was 0% for smokers and 83.6%+/-7.6% for nonsmokers (p = 0.0142). Causes of late death were myocardial infarction (4), sepsis (1), subdural hematoma (1), stroke (1), and unknown (6). CONCLUSIONS: Coronary artery bypass grafting should be avoided in dialysis patients with severe diffuse disease. A smoking history is associated with poor outcome. Coronary artery bypass grafting in dialysis patients is associated with a higher incidence of complications but can be performed with an acceptable operative mortality and is associated with good symptomatic relief of angina and heart failure.

Differential effects of calcium channel antagonists in the amelioration of radial artery vasospasm.

BACKGROUND: Radial artery (RA) is being used for coronary artery bypass grafting (CABG) with greater frequency. However, RA is prone to post-CABG vasospasm, which may be neurohormonally mediated. Use of the calcium channel antagonist diltiazem has been advocated as a strategy to reduce post-CABG RA vasospasm. However, whether and to what degree different calcium channel antagonists influence neurohormonally induced RA vasoconstriction remains unknown. METHODS: RA segments were collected from patients undergoing elective CABG (n = 13), and isometric tension was examined in the presence of endothelin (10 nM) or norepinephrine (1 microM). In matched RA, endothelin- or norepinephrine-induced contractions were measured in the presence of diltiazem (277 nM), amlodipine (73 nM), or nifedipine (145 nM). These concentrations of calcium channel antagonists were based upon clinical plasma profiles. RESULTS: Endothelin and norepinephrine caused a significant increase in RA-developed tension (0.54+/-0.1 and 0.68+/-0.1 g/mg, respectively; p<0.05). Amlodipine or nifedipine significantly reduced RA vasoconstriction in the presence of endothelin (30+/-6% and 41+/-9%, respectively; p<0.05) or norepinephrine (27+/-8% and 53+/-9%, respectively; p<0.05), whereas diltiazem did not significantly reduce RA vasoconstriction. CONCLUSIONS: These results demonstrate that neurohormonal factors released post-CABG can cause RA vasoconstriction, and that calcium channel antagonists are not equally effective in abrogating that response. Both amlodipine and nifedipine, which have a higher degree of vascular selectivity, appear to be the most effective in reducing RA vasoconstriction.

Long-term experience with the St. Jude Medical valve prosthesis.

BACKGROUND: All patients undergoing St. Jude Medical valve replacement at the Medical University of South Carolina since January 1979 have been followed prospectively at 12-month intervals. METHODS: This report describes long-term experience in 710 adult patients undergoing isolated aortic (AVR) (418) or mitral valve replacements (MVR) (292) with this prosthesis from January 1979 to December 1996. RESULTS: Ages ranged from 19 to 84 years (54.8 +/- 15.1 AVR, 51.8 +/- 12.9 MVR; mean +/- SD). Male gender predominated in the AVR group (70%) and female gender in the MVR group (62%). One hundred and fifty-seven patients (22%) had associated coronary artery bypass grafting (AVR 27%, MVR 15%). Thirty-day operative mortality was 5.3% (22/418) in the AVR group and 5.1% (15/292) in the MVR group. Follow-up is 96.9% complete and ranges from 1 month to 16.9 years (AVR, 2,376 patient-years, mean 5.7 +/- 4.5 years; MVR, 1,868 patient-years, mean 6.4 +/- 4.8 years). In the AVR group, 120 late deaths have occurred and actuarial survival was 78.0 +/- 2.3%, 58.0 +/- 3.2%, and 36.8 +/- 4.8%; at 5, 10, and 15 years, respectively. Forty-six patients have sustained 55 thromboembolic (TE) events (2.3%/patient-year). Fifty-one patients had anticoagulant-related bleeding complications (2.7%/patient-year). The mean improvement in New York Heart Association (NYHA) functional class from preoperative to postoperative was 3.0 +/- 0.8 to 1.7 +/- 0.1 (p < 0.05). In the MVR group, there have been 84 late deaths, and the actuarial survival was 79.3 +/- 2.5%, 60.1 +/- 3.5%, and 49.3 +/- 4.1% at 5, 10, and 15 years, respectively. Fifty-two patients have had 64 TE events (3.5%/patient-year). Twenty-three patients had anticoagulant-related bleeding complications (1.6%/patient-year). The mean improvement in NYHA functional class was from 3.3 +/- 0.6 to 1.8 +/- 0.1. There were no mechanical failures in either group. CONCLUSIONS: With a follow-up now extending to 17 years, the St. Jude Medical valve continues to be a reliable mechanical prosthesis with low and stable rates of valve-related complications.

Current concepts in heart valve surgery.

After a period of relatively regimented approaches for mitral and aortic valve surgery, recent years have seen numerous innovations including improved prostheses, improved techniques for repair, better understanding of the physiology of ventricular function and myocardial protection, advances in anticoagulation control, and most recently the application of minimally invasive techniques. Each of these has contributed to the improved short and long term results obtained from valve surgery, and further evolution of these techniques will undoubtedly improve the results even more. As operative risks are decreased and long term results are improved, it is hoped that patients with valvular heart disease will be referred at progressively earlier stages of their disease for consideration for surgery. Earlier referral increases the likelihood that valve repair will be possible in the case of the mitral valve and also increases the odds that the outcome from valve surgery will be successful for both aortic and mitral valves.