MEdical TReatment Optimization in cardiac rehabilitation (METRO study) : a French multicenter study.

BACKGROUND: Cardiac rehabilitation (CR) is the right place to optimize the medical treatment in coronary artery disease (CAD) patients. AIMS: To report the medical management in CAD patients during CR and evaluate the consequences. METHODS: CAD patients who attended a CR program within less than three months of an acute coronary syndrome (ACS), a percutaneous coronary intervention (PCI), or a coronary artery bypass graft (CABG) were included in a prospective multicenter study. Medical treatments were analyzed at the beginning and at discharge of the CR stay. Results of exercise tests were compared between 4 groups. G1: unchanged medication, n=443, G2: beta-blockers or bradycardic agents adaptation n=199, G3: renin-angiotensin system (RAS) inhibitors adaptation, n=194, G4: both medications adaptation, n=164. RESULTS: One thousand consecutive patients were included in 23 French CR centers (85.3% males; mean age 59.9 ± 11 years). The index event was ACS (68.5%), PCI (62.6%) and CABG (36.3%). During CR, we noted an adaptation for beta-blockers in 32.1%, in other bradycardic agents (ivabradine, verapamil, diltiazem, amiodarone) in 9.5%, and in RAS inhibitors in 36.3%. Patients of group 1 had an initial resting heart rate lower than in group 2 and 4, but at the final exercise testing, the range of the decrease was more important in group 2 and 4. The combination of physical training and therapeutic modifications resulted in similar exercise capacities in the four groups, from 5.2, 5.3, 5.4 and 5.2 MET (p=0.68), to 6.3, 6.5, 6.5 and 6.1 MET (p=0.44), respectively. CONCLUSION: The METRO study showed that significant alteration in medical treatment during cardiac rehabilitation programs could take part in improving physical capacity.

Strain predicts left ventricular functional recovery after acute myocardial infarction with systolic dysfunction.

OBJECTIVE: Regional and global longitudinal strain (RLS-GLS) are considered reliable indexes of myocardial viability in chronic ischemic patients and prediction of left ventricular (LV) functional recovery after acute myocardial infarction (MI) with preserved left ventricular ejection fraction (LVEF). We tested in the present study whether RLS and GLS could also identify transmural extent of myocardial scar and predict LV functional recovery and remodeling in patients with reduced LVEF after acute MI. METHODS: Echocardiography and late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) were performed in 71 patients with reduced LVEF (≤45%) after acute MI treated with acute percutaneous coronary intervention. At 8-month follow-up, echocardiography was repeated to determine global LV functional recovery and remodeling. RESULTS: RLS was worse in transmural than in non-transmural infarcted segments (-6.6 ± 6.1% vs -10.3 ± 5.9%, p < 0.0001) and in non-transmural than in normal segments (-10.3 ± 5.9% vs -14.5 ± 6.4%, p < 0.0001). RLS > -12% had sensitivity of 78% and specificity of 69% to identify transmural infarcted segments (AUC = 0.79; 95% CI, 0.77-0.81, p < 0.0001). GLS > -11.3% had sensitivity of 53% and specificity of 100% to predict the absence of LV global functional improvement (AUC = 0.73, CI, 0.55-0.87, p = 0.01) at 8-month follow-up. GLS < -12.5% predicted the absence of adverse LV remodeling with sensitivity of 100% and specificity of 54% (AUC = 0.83; CI, 0.66-0.94, p < 0.0001). GLS > -11.5% was associated with a poor prognosis. CONCLUSIONS: In patients with reduced LVEF after acute MI, RLS and GLS allow: (1) identification of transmural extent of myocardial scar and (2) predict LV global functional recovery and remodeling at 8-month follow-up.

Early exercise training feasibility after aortic valve repair: A multicentre prospective French survey on behalf of the Aortic Valve repair International Registry (AVIATOR).

BACKGROUND: Standardization of aortic valve repair by the external ring annuloplasty approach is an alternative to valve replacement to avoid prosthetic valve-related events. Although the benefit of exercise training to improve postoperative exercise tolerance has been demonstrated in many conditions after cardiac surgery, it has never been described after aortic valve repair. OBJECTIVES: To evaluate the feasibility of an early exercise training programme after aortic valve repair. METHODS: Consecutive patients were prospectively included in 13 postoperative centres. Patients underwent an exercise training programme for approximately 3-5 weeks. Transthoracic echocardiography and a cardiopulmonary exercise test were performed before and after the exercise training programme. RESULTS: Fifty patients (mean±standard deviation [SD] age: 50±13 years) were included a mean of 13.6±12.0 days after aortic valve repair. The preoperative degree of aortic insufficiency was moderate to severe in 35 patients (70%) and the aortic valve was bicuspid in 24 patients (48%). Valve-sparing root replacement and isolated aortic valve repair (including 10% supracoronary aorta replacement) were performed in 64% and 36% of patients, respectively. We found no aortic insufficiency occurrence or worsening and no adverse clinical events after the exercise training programme. Mean left ventricular ejection fraction increased significantly (from 54%±8% to 57%±9%; P=0.0007). Mean peak oxygen consumption and first ventilatory threshold increased from 17.0±5.3 to 22.5±7.8mL/kg/min (32% increase) and from 12.0±3.9 to 14.3±5.2mL/kg/min (19% increase), respectively (both P<0.05). CONCLUSION: Exercise training early after aortic valve repair is safe and seems to significantly improve exercise capacity.

Mitral Annular Calcium and Mitral Stenosis Determined by Multidetector Computed Tomography in Patients Referred for Aortic Stenosis.

Mitral annular calcium (MAC) is a common finding in older patients referred for transcatheter aortic valve implantation (TAVI). Multidetector computed tomography (MDCT) allows fine quantification of the calcific deposits. Our objective was to estimate the prevalence of MAC and associated mitral stenosis (MS) in patients referred for TAVI using MDCT. A cohort of 346 consecutive patients referred for TAVI evaluation was screened by MDCT for MAC: 174 had MAC (50%). Of these patients, 165 patients (95%) had mitral valve area (MVA) assessable by MDCT planimetry (age 83.8 ± 5.9 years). Median mitral calcium volume and MVA were 545 mm3 (193 to 1,253 mm3) and 234 mm2 (187 to 297 mm2), respectively. The MS was very severe, severe, and moderate in 2%, 22%, and 10% patients, respectively. By multivariate analysis, MVA was independently correlated to mitral calcium volume, aortic annular area, and some specific patterns of mitral leaflet calcium. Based on these findings, a formula was elaborated to predict the presence of a significant MS. In conclusion, MDCT allows detailed assessment of MAC in TAVI populations, demonstrating a high prevalence. Mitral analysis should become routine during MDCT screening before TAVI as it may alter therapeutic strategy.

Incidence, diagnostic methods, and evolution of left ventricular thrombus in patients with anterior myocardial infarction and low left ventricular ejection fraction: a prospective multicenter study.

BACKGROUND AND OBJECTIVES: We aimed to assess the incidence and evolution of left ventricular (LV) thrombi in a high-risk population of patients with LV systolic dysfunction after anterior myocardial infarction (ant-MI). We also compared the accuracy of transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging with contrast-delayed enhancement (CMR-DE) in detecting LV thrombi. METHODS: We prospectively included 100 consecutive patients with LV ejection fraction (LVEF) <45% at the first TTE performed <7 days after ant-MI. A second evaluation with TTE and CMR-DE (by blinded examiners) was performed at 30 days. A third TTE and assessment of clinical status were performed between 6 and 12 months after ant-MI. RESULTS: Patients (males 71%; mean age 59.1 ± 12.1 years; mean LVEF 33.5% ± 6.0%) were included at a median of 5.5 days (interquartile range 25th-75th percentile 4.25-6.0 days) after ant-MI. Thrombi were detected among 26 (26%) patients at a median of 12.0 days after ant-MI (7 patients at 1-7 days after MI; 15 at 8-30 days; and 4 after day 30). Sensitivity and specificity for LV thrombi detection were 94.7% and 98.5%, respectively, for TTE as compared with CMR-DE. Most thrombi (n = 24; 92.3%) disappeared after triple antithrombotic therapy (vitamin K antagonist in addition to dual antiplatelet therapy). CONCLUSION: Left ventricular thrombus is a frequent complication after ant-MI with systolic dysfunction. When a search for thrombus is prespecified, the accuracy of TTE is high as compared with CMR-DE. The best antithrombotic strategy is not known.

Greater prognostic value of peak VO2 after exercise training program completion in heart failure patients.

BACKGROUND: Exercise capacity, best reflected by peak exercise oxygen consumption (peak VO(2)), is a powerful prognostic factor in patients with chronic heart failure (CHF). However, the optimal time to assess exercise capacity for prognosis remains unclear and whether an exercise training program (ETP) to improve exercise capacity alters the prognostic value of cardiopulmonary exercise (CPX) testing variables in CHF is unknown. METHODS AND RESULTS: CHF patients who underwent an ETP in two cardiac rehabilitation centers between 2004 and 2009 were prospectively included, and CPX testing was performed before and after ETP completion. We included 285 consecutive patients who underwent an ETP (19.4 ± 8.7 training sessions in 4 to 10 weeks), including segmental gymnastics and cycling sessions. During follow-up (12 months), 14 patients died, 6 underwent cardiac transplantation and 15 were hospitalized for acute heart failure. Univariate analysis and receiver operating characteristic (ROC) curve analysis showed that CPX variables, especially peak oxygen consumption and circulatory power (product of peak VO(2) × peak systolic blood pressure) before and after ETP completion predicted prognosis. However, CPX data obtained after ETP completion had the best prognostic value (area under the ROC curve = 0.79 ± 0.03 for peak VO(2) after ETP completion vs 0.64 ± 0.04 before ETP completion, p < 0.0001). The results did not change even when considering only deaths. CONCLUSION: In patients with stable CHF who can exercise, the prognostic value of CPX data seems greater after versus before completion of a hospital-based ETP. Therefore, CPX capacity for prognostic purposes should at best be assessed after cardiac rehabilitation.

Distribution of left ventricular ejection fraction and heart rate values in a cohort of stable coronary patients: the INDYCE registry.

BACKGROUND: The distribution of left ventricular ejection fraction (LVEF) - a key factor in coronary artery disease (CAD) patient management and prognostication - is poorly documented. OBJECTIVE: To determine LVEF and heart rate (HR) values, and describe the management of stable CAD patients in France. METHODS: The INDYCE survey was a prospective, multicentre registry of consecutive stable CAD outpatients attending a cardiology consultation. The survey focused on LVEF values measured using the echocardiographic Simpson biplane method. Drug therapy, resting HR, blood pressure and symptoms were also recorded. RESULTS: Overall, 3119 patients (68.4 +/- 11.0 years; 80% men) were enrolled. LVEF was 56.1+/-11.8% on average, and was poor (<40%) and moderately impaired (40-50%) in 9.6% (n=298) and 19.8% (n=619) of cases, respectively. Symptomatic angina pectoris was present in 19.2% of cases and only 40.6% of patients were asymptomatic (no angina and NYHA class < or = I) despite relatively aggressive management (79.0% of patients had undergone coronary angioplasty and/or bypass graft). Interestingly, 14.1% of patients with LVEF less than 40% were asymptomatic. In multivariable analysis, LVEF less than 40% was associated most strongly with symptomatic status (odds ratio 3.82; 95% CI 2.59-5.63; P<0.0001), together with female sex, age greater than 75 years, diabetes, HR greater or equal to 70 bpm, sedentariness, obesity and disease duration. CONCLUSION: Only 9.6% of stable CAD patients had severe left ventricular dysfunction; among them, 14.1% were strictly asymptomatic. This could justify regular LVEF measurement in CAD patients. Three potentially reversible factors (HR>or=70 bpm, being overweight and sedentariness) were linked independently to the presence of symptoms.

Nonsteroidal anti-inflammatory drug treatment for postoperative pericardial effusion: a multicenter randomized, double-blind trial.

BACKGROUND: The incidence of asymptomatic pericardial effusion is high after cardiac surgery. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in this setting, but no study has assessed their efficacy. OBJECTIVE: To assess whether the NSAID diclofenac is effective in reducing postoperative pericardial effusion volume. DESIGN: Multicenter randomized, double-blind, placebo-controlled study. (Clinical trials.gov registration number: NCT00247052) SETTING: 5 postoperative cardiac rehabilitation centers. PATIENTS: 196 patients at high risk for tamponade because of moderate to large persistent pericardial effusion (grade 2, 3, or 4 on a scale of 0 to 4, as measured by echocardiography) more than 7 days after cardiac surgery. INTERVENTION: Random assignment at each site in blocks of 4 to diclofenac, 50 mg, or placebo twice daily for 14 days. MEASUREMENTS: The main end point was change in effusion grade after 14 days of treatment. Secondary end points included frequency of late cardiac tamponade. RESULTS: The initial mean pericardial effusion grade was 2.58 (SD, 0.73) for the placebo group and 2.75 (SD, 0.81) for the diclofenac group. The 2 groups showed similar mean decreases from baseline after treatment (-1.08 grades [SD, 1.20] for the placebo group vs. -1.36 (SD, 1.25) for the diclofenac group). The mean difference between groups was -0.28 grade (95% CI, -0.63 to 0.06 grade; P = 0.105). Eleven cases of late cardiac tamponade occurred in the placebo group and 9 in the diclofenac group (P = 0.64). These differences persisted after adjustment for grade of pericardial effusion at baseline, treatment site, and type of surgery. LIMITATION: The sample was not large enough to find small beneficial effects of diclofenac or assess the cardiovascular tolerance of diclofenac. CONCLUSION: In patients with pericardial effusion after cardiac surgery, diclofenac neither reduced the size of the effusions nor prevented late cardiac tamponade. PRIMARY FUNDING SOURCE: French Society of Cardiology.

Ventilatory efficiency and the selection of patients for heart transplantation.

BACKGROUND: Ventilatory efficiency, assessed by the slope of minute ventilation (VE) versus carbon dioxide production (VCO(2)), is a powerful prognostic marker in patients with chronic heart failure. We hypothesized that VE/VCO(2) slope would be more accurate than the current listing criteria for heart transplantation (HTx) in identifying patients likely to derive a survival benefit from this intervention. METHODS AND RESULTS: A total of 663 patients with chronic heart failure who underwent cardiopulmonary exercise testing were tracked for cardiac mortality and HTx. Ve/Vco(2) slope was the strongest independent predictor of mortality. Using a VE/VCO(2) slope threshold instead of the current exercise criteria would classify 39 more subjects as being high risk (196 versus 157), correctly identifying 19 more patients who died during follow-up (57 versus 38) and 16 others who underwent transplantation (52 versus 36). Unlike the current listing criteria for HTx, VE/VCO(2) slope provided significant discrimination between the 3-year survival of high- and low-risk patients and posttransplant patients selected from the International Society for Heart and Lung Transplantation registry. Reanalysis of survival data using death or HTx as the end point showed similar results. CONCLUSIONS: VE/VCO(2) slope is more accurate than the current listing criteria for HTx in identifying patients likely to derive a survival benefit from HTx.

Benefits of exercise training in chronic heart failure.

Exercise training performed in cardiac rehabilitation centres is an adjuvant therapy in chronic heart failure patients with left ventricular dysfunction; it decreases the deleterious consequences of chronic heart failure. Exercise training attenuates neurohormonal stimulation, the production of proinflammatory cytokines and natriuretic peptide overexpression. Trained patients showed a significant decrease in the peripheral organ injuries encountered in chronic heart failure, with a reduction in vascular resistance and improvements in endothelial dysfunction and the oxidative capacity of peripheral muscles, without a deleterious effect on left ventricular remodelling. Ultimately, exercise training leads to a notable improvement in ventilatory capacity. These beneficial effects are accompanied by improvements in symptoms at rest, exercise capacity and quality of life. Several training programmes are in current use: exercise training sessions always include endurance exercise performed either at a constant load intensity or with interval training, combining periods of exercise performed at high intensity with periods performed at low intensity. Most of the time, training programmes also include resistance training sessions, which improves large muscle strength. Exercise training programmes seem to have a favourable effect on prognosis, even if the results of Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) remain controversial, emphasizing the difficulty in monitoring observance and the importance of compliance with a long-term exercise training programme. Patients who do not improve their exercise capacity significantly after an exercise training programme have a poorer prognosis.

Noninvasively determined radial dP/dt is a predictor of mortality in patients with heart failure.

BACKGROUND: The left ventricular (LV) developed pressure is a marker of contractility, associated with a poor prognosis during systolic heart failure. The maximal first derivative or slope of the radial pulse wave (Rad dP/dt) has been proposed as a marker of LV systolic function. This study sought to assess the prognostic value of the baseline dP/dt of the radial pulse in patients with heart failure. METHODS: The Rad dP/dt was noninvasively measured by applanation tonometry, and its effect on mortality was analyzed by using multivariate Cox regression models. We studied 310 consecutive patients. Mean follow-up was 327 +/- 187 days, and 64 patients died or were transplanted during this period. RESULTS: Death or transplantation was associated with New York Heart Association class III or IV, low systolic or mean blood pressure, low LV ejection fraction, and low Rad dP/dt (634.6 +/- 373.3 vs 730.2 +/- 367.4 mm Hg/s for patients who survived without transplantation, P < .02). A Rad dP/dt <440 mm Hg/s was associated with death or transplantation before and after adjustment for confounding variables (OR [95% CI] 2.19 [1.33-3.58] and 2.88 [1.29-6.38], respectively, P < .01 for both). This relationship was independent of pulse pressure and no significant interaction was found between the Rad dP/dt and the pulse pressure. CONCLUSION: This study demonstrates, for the first time, that the Rad dP/dt, proposed as a noninvasive peripheral marker of LV systolic function, is an independent predictor of death or transplantation in patients with HF regardless of LV ejection fraction.

Determination of exercise training level in coronary artery disease patients on beta blockers.

OBJECTIVES: To compare the intensity of three exercise training regimens. BACKGROUND: During a cardiac rehabilitation program coronary artery disease (CAD) patients should be trained at an intensity as close as possible to the ventilatory threshold (VT) level. The precise way to obtain this intensity of training during the sessions, however, remains unclear. METHODS: In stable beta-blocked CAD patients, heart rate (HR) and workload (WL) at the VT were determined from a cardiopulmonary exercise test. The 3 following days, each patient performed (in a randomized order) one bicycle training session per day at an intensity determined by (i) HR at VT, (ii) WL at VT, (iii) patient's feelings (14 on the Borg scale). HR, WL, systolic blood pressure, oxygen consumption (VO2) and the respiratory exchange ratio were monitored during each session, to compare the intensity of each regimen. RESULTS: Twenty patients, 57+/-10 years old were included. VO2, WL, HR and systolic blood pressure were significantly higher in the sessions driven by feelings and WL, than in the HR-driven sessions. As respiratory exchange ratio remained less than 1, we can assume that there was no important and deleterious participation of anaerobic metabolism. CONCLUSION: Classical training HR prescription could lead to undertrain CAD patients, although a training session prescription driven by the feelings or by the WL observed at VT allows the patients to train at a higher--but still aerobic--intensity.

Transient worsening of renal function during hospitalization for acute heart failure alters outcome.

OBJECTIVE: We studied prevalence, causes and consequences of worsening renal function (WRF) during hospitalization for acute heart failure (AHF). METHODS: Patients admitted for AHF were enrolled. Patients with severe chronic renal failure, cardiogenic shock and contrast medium-induced nephropathy were excluded. WRF was defined as an increase of 25 mumol/l or more in serum creatinine relative to the admission level. Survivors were monitored for 6 months, focusing on deaths and first unscheduled readmissions for heart failure. RESULTS: Among the included 416 patients, WRF occurred in 152 cases (37%), 5+/-3 days after admission, and two-thirds of patients recovered their baseline renal function before discharge. Old age, diabetes, hypertension and acute coronary syndromes increased the risk of WRF. In-hospital furosemide doses as well as discharge treatment were similar in WRF and no-WRF patients. Serum creatinine elevation was the strongest independent determinant of a longer hospital stay (r=0.37, p=0.001). Adverse events occurred in 158 patients (38%) during follow-up, with 23 deaths and 135 readmissions. Cox analysis showed that WRF, transient or not, was an independent predictor of the risk of death or readmission (hazard ratio=1.74 [1.14-2.68], p=0.01). CONCLUSION: WRF is frequent after admission for AHF and, although transient, is associated with longer hospitalization and with a higher risk of death and readmission, irrespectively of baseline renal function.

Thromboembolic events early after mitral valve repair: incidence and predictive factors.

BACKGROUND AND OBJECTIVES: The incidence of thromboembolic events (TE) in the early period following mitral valve repair (MV repair) is poorly documented. The aim of this prospective study was to evaluate it, and to determine predictive factors. METHODS AND RESULTS: In this prospective multicenter non-randomized study, 350 consecutive patients were included after MV repair and monitored until post-operative day 44+/-6. 65.7% received Vitamin K antagonists (VKA), 18.8% aspirin (ASA), 5.4% ASA+VKA and 10% received no antithrombotic therapy (AT). All patients with AF received VKA or VKA+ASA. Twelve patients had a cerebral TE during follow-up:14.3% among untreated patients, 3.0% in the VKA group, and 0% in the ASA and in the ASA+VKA groups (p=0.03 for comparison no AT group versus the three other combined groups; p=NS for VKA versus ASA). In univariate analysis, only the absence of post-operative AT was related to the risk of TE (HR=6.7, CI 95%[2.1-21], p=0.0002). In a prespecified subgroup (n=185) of patients with sinus rhythm and without concomitant cardiac surgery (in which the choice of AT is not influenced by these associate conditions), only the absence of post-operative AT remained related to the risk of TE (HR=10.0, CI 95%[2.45-40], p=0.001). CONCLUSION: In the first six weeks following MV repair, the incidence of thromboembolic events is far from negligible (3.5%), even in patients with sinus rhythm. The main predictive factor for thromboembolic event determined in this study is the absence of an antithrombotic therapy.