Changes in systemic sympathetic nervous system activity after mitral valve surgery and their relationship to changes in left ventricular size and systolic performance in patients with mitral regurgitation.

BACKGROUND: We have shown that the systemic sympathetic nervous system (SNS) is activated in patients with chronic mitral regurgitation (MR). However, the fate of systemic SNS activity after surgical correction of MR is currently unknown. METHODS: We examined 14 patients with MR who had normal sinus rhythm with an investigational, preoperative cardiac catheterization, including arterial norepinephrine (NE) sampling and [(3)H]-NE infusions and arterial blood sampling to determine NE kinetic parameters using a 2-compartment modeling analysis. The arterial NE and NE kinetic parameters were determined in all patients after mitral valve surgery (MVS) at a mean of 12 months. A 2-dimensional echocardiographic examination was also performed before and after MVS. RESULTS: The average extravascular NE release rates (NE(2)) before and after MVS were 1.89 +/- 0.66 and 2.26 +/- 0.82 microg/min/m(2) (P =.24), respectively. The average left ventricular (LV) end-diastolic dimension, fractional shortening, and ejection fraction decreased, whereas the mean LV end-systolic dimension did not change between the pre- and post-MVS echocardiographic studies. However, these group averages were comprised of patients with MR in whom the NE(2) and echocardiographic values both increased and decreased. This lack of homogeneity was a reflection of our new observation that the pre- to post-MVS changes in NE(2) were directly proportional to the changes in LV end-systolic dimension (r = 0.91, P <.001) and inversely related to the changes in LV fractional shortening (r = -0.82, P <.001) and ejection fraction (r = -0.78, P <.001). CONCLUSIONS: The response in systemic SNS activity in patients with MR after MVS is not homogeneous, and these changes are concordant with the post-MVS changes in LV size and systolic performance. These data further support our earlier observations and extend them to suggest that systemic SNS activation in patients with chronic MR is related to LV remodeling and impaired systolic performance.

Cardiac-specific norepinephrine mass transport and its relationship to left ventricular size and systolic performance.

Objectives of this study were to develop a technique for quantifying cardiac-specific norepinephrine (NE) mass transport and determine whether cardiac NE kinetic modeling parameters were related to physiological variables of left ventricular (LV) size and systolic performance in nine patients with chronic mitral regurgitation. Biplane contrast cineventriculograms were used to determine LV size and ejection fraction (EF), micromanometer LV pressures and radionuclide LV volumes from a range of loading conditions to calculate LV end-systolic elastance, and [(3)H]NE infusions with LV and coronary sinus sampling for [(3)H]NE and endogenous NE during and after termination of infusions to model NE mass transport. Total NE release rate into cardiac interstitial fluid (M(IF)(R)) averaged 859 +/- 214 and NE released de novo into cardiac interstitial fluid (M(IF)(u,r,en)) averaged 546 +/- 174 pmol/min. Both M(IF)(R) and M(IF)(u,r,en)correlated directly with LV end-systolic volume (r = 0.84, P = 0.005; r = 0.86, P = 0.003); inversely with LV EFs (r = -0.75, P = 0.02; r = -0.81, P = 0.008); and inversely with LV end-systolic elastance values, optimally fit by a nonlinear function (r = 0.89, P = 0.04; r = 0.96, P = 0.01). We conclude that total and newly released NE into interstitial fluid of the heart, determined by regional mass transport kinetic model, are specific measures of regional cardiac-specific sympathetic nervous system activity and are strongly related to measures of LV size and systolic performance. These data support the concept that this new model of organ-specific NE kinetics has physiological relevance.

Evaluation of routine functional testing after percutaneous coronary intervention.

Following percutaneous coronary intervention, 348 patients were randomized to either routine or selective functional testing strategies. For the primary end point of maximal exercise endurance on a treadmill at 9 months, achievement was similar in the routine and selective groups. For the secondary end points measuring functional status and quality of life, scores were also similar. There was little difference in the rates of invasive cardiac procedures for the 2 groups at 9 months.

Compared with control subjects, the systemic sympathetic nervous system is activated in patients with mitral regurgitation.

BACKGROUND: Whether the systemic sympathetic nervous system is activated as a compensatory mechanism in response to mitral regurgitation (MR) in humans is unknown. We tested the hypotheses that the systemic sympathetic nervous system would be activated in patients with MR in comparison with control subjects and that this activation would occur early in the disease process as a compensatory mechanism for chronic left ventricular (LV) volume overload. METHODS: We studied 37 patients with MR who underwent right heart catheterization and biplane cineventriculography to obtain LV end-diastolic and end-systolic volumes, ejection fractions, and regurgitant volumes. In these 37 patients with MR and in 23 control subjects, an [(3)H]-norepinephrine ([(3)H]-NE) infusion and multiple arterial blood samples provided data for a 2-compartment modeling analysis to calculate extravascular NE release rates (NE(2)). RESULTS: The mean NE(2) (2.05 +/- 0.76 microg/min/m(2)) in the patients with MR was greater than that in the control subjects (1.48 +/- 0.75 microg/min/m(2), P =.007). Furthermore, the mean NE(2) values were also greater in the patients with MR who were in clinical class I (P =.05), with a pulmonary capillary wedge pressure <12 mm Hg (P =.05) or a LV ejection fraction >or=0.60 (P =.06) compared with the control subjects. The mean NE(2) values were increased further in patients with MR who had a LV ejection fraction <0.60 (P =.02). CONCLUSIONS: The systemic sympathetic nervous system is activated in patients with MR in comparison with control subjects, and this activation appears to occur early in the disease process as a compensatory mechanism for LV volume overload.

Myocardial proinflammatory cytokine expression and left ventricular remodeling in patients with chronic mitral regurgitation.

BACKGROUND: In an animal model, stretch was shown to induce myocardial tumor necrosis factor-alpha (TNF-alpha) expression. The purposes of this study were to determine whether the left ventricular (LV) volume overload that occurs in patients with chronic mitral regurgitation (MR) can induce myocardial and systemic TNF-alpha expression and whether there is a relationship between TNF-alpha expression and LV remodeling. METHODS AND RESULTS: Plasma TNF-alpha and its receptors were measured before mitral valve (MV) repair surgery in 26 MR patients and 23+/-12 months after MV repair surgery in 9 MR patients. Myocardial mRNA copies of TNF-alpha were determined in 11 MR and 10 donor hearts using quantitative RT-PCR. Compared with 15 control subjects, pre-MV repair plasma TNF-alpha (3.59+/-1.81 versus 2.03+/-1.02 pg/mL, P<0.005) and its receptor levels were elevated in MR patients. Myocardial TNF-alpha mRNA copies (corrected for beta-actin mRNA expression) in MR patients and donor hearts were 38.96+/-42.74x10(6) and 0.88+/-0.75x10(6), respectively (P=0.01). After MV surgery, there was a decrease in the plasma levels of TNF-alpha (2.79+/-1.14 versus 3.51+/-1.34 pg/mL, P=0.02) and its receptors. There was a correlation between myocardial TNF-alpha expression and preoperative LV end-diastolic and end-systolic volumes. Moreover, there was an inverse correlation between myocardial TNF-alpha expression and regression in LV end-diastolic (r=-0.76, P=0.007) and end-systolic (r=-0.73, P=0.01) volumes after MV surgery. CONCLUSIONS: TNF-alpha is expressed in the myocardium and plasma of MR patients. Correction of the LV volume overload with MV surgery results in reversal of TNF-alpha expression. There is a relationship between TNF-alpha expression and parameters of LV remodeling, suggesting that TNF-alpha may play a role in the pathogenesis of the LV remodeling that occurs in MR.

A randomized controlled trial of information-giving to patients referred for coronary angiography: effects on outcomes of care.

OBJECTIVE: To assess the impact of providing an educational videotape, 'Treatment Choices for Ischaemic Heart Disease: a Shared Decision-Making Program Videotape,' to patients referred for coronary angiography compared with standard patient-physician decision making (usual care). STUDY DESIGN: Randomized controlled clinical trial. SETTING: University Hospital and Veterans Affairs Hospital. PATIENTS: A consecutive sample of 217 patients referred for coronary angiography were randomized to receive 'usual care' or to receive the videotape in addition to standard patient physician decision making (videotape): 109 completed the study (50% completion rate). MAIN OUTCOME MEASURES: Knowledge of coronary artery disease, satisfaction, self-reported physical and mental health functioning, and the proportion of patients who were referred for coronary revascularization. RESULTS: Compared with patients who received 'usual care,' those who received the videotape were more knowledgeable (mean score 83 vs. 58%; P < 0.0001) but less satisfied with their treatment (79 vs. 88%; P = 0.038). There were no significant differences between the videotape and 'usual care' groups with respect to satisfaction with the decision making process (mean score 73 vs. 77%; P = 0.37), satisfaction with the decision made (mean score 73 vs. 78%; P = 0.28), physical functioning (38 vs. 38%; P = 0.76), mental health functioning (49 vs. 49%; P = 0.94), or in referral for coronary revascularization (OR 0.60; 95% CI 0.22-1.65; P = 0.33). CONCLUSION: Although the educational videotape increased patients' knowledge level, it was associated with a decrease in their level of satisfaction with treatment. Before there is wide-spread dissemination of this technology, advocates should demonstrate its effectiveness in everyday practice.