Myocardial collagen turnover after surgical ventricular restoration in heart failure patients.

AIMS: Surgical ventricular restoration (SVR) aims to normalize left ventricular (LV) volume and shape in patients with ischaemic cardiomyopathy and anterior wall scar. The chronic effects on LV function may depend on alterations in myocardial collagen metabolism. The present study evaluated myocardial collagen synthesis and degradation rates at baseline and at 6 months follow-up after SVR. We hypothesize that the chronic effects of SVR on LV function and clinical outcome depend on alterations in myocardial collagen metabolism. METHODS AND RESULTS: Serum levels of aminoterminal propeptides of type I and III collagen (PINP, PIIINP), carboxyterminal telopeptide of type I collagen (ICTP), and tenascin-C (TNC) were measured at baseline and 6 months after SVR in 24 patients. In addition, New York Heart Association (NYHA) functional class, LV volumes and function were evaluated. At follow-up, a significant improvement in NYHA class (from 3.2 ± 0.8 to 1.4 ± 0.6, P< 0.001) and LV ejection fraction (from 28 ± 9 to 35 ± 7%, P< 0.001) was found, whereas E/A ratio tended to increase (from 1.4 ± 1.1 to 1.9 ± 1.1, P= 0.064). Serum levels of PINP, PIIINP, ICTP, and TNC increased significantly (PINP: from 37 ± 15 to 67 ± 26 µg/L, P< 0.001; PIIINP: from 4.9 ± 1.7 to 7.9 ± 4.0 µg/L, P< 0.001; ICTP: from 5.9 ± 3.7 to 10.0 ± 5.3 µg/L, P< 0.001; TNC: from 30 ± 20 to 44 ± 23 µg/L, P= 0.020). At follow-up, an LV ejection fraction <34% and E/A ratio ≥ 2.0 were significantly associated with increased serum levels of PIIINP and ICTP. CONCLUSION: In patients who underwent SVR, myocardial collagen metabolism was significantly enhanced 6 months after surgery. Serum levels of myocardial collagen turnover biomarkers were related to post-surgical LV systolic and diastolic function.

Comprehensive assessment of changes in left atrial volumes and function after ST-segment elevation acute myocardial infarction: role of two-dimensional speckle-tracking strain imaging.

BACKGROUND: Left atrial (LA) size has been associated with adverse outcome in patients after acute myocardial infarction. However, data about the occurrence of late LA enlargement and changes in LA function during follow-up are scarce. The purpose of the current study was to evaluate changes in LA size and function during 1-year follow-up. METHODS: The study population comprised 407 patients with acute myocardial infarction who were treated with primary percutaneous coronary intervention. At baseline and 12 months, two-dimensional echocardiography was performed to assess LA volumes and function using speckle-tracking strain and strain rate. RESULTS: The mean age was 60 ± 11 years, and most patients were men (78%). LA maximal volume increased from 25 ± 8 to 28 ± 8 mL/m(2) (P < .001) from baseline to 1 year. Echocardiographic assessment at 1-year follow-up showed that 92 patients (25%) had developed LA remodeling (defined as an increase of ≥8 mL/m(2) in LA maximal volume). On multivariate analysis, only LA maximal volume at baseline (odds ratio, 0.95; 95% confidence interval, 0.91-0.98; P = .003) and LA strain at baseline (odds ratio, 0.94; 95% confidence interval, 0.92-0.97; P < .001) were independent predictors of LA remodeling during follow-up. Interestingly in patients without LA remodeling, no changes were observed in LA function during follow-up. However, in patients with LA remodeling, LA function significantly worsened during follow-up. In line, LA strain and strain rate were significantly lower at 12 months compared with baseline (24 ± 7% vs 27 ± 6%, P < .001, and 1.8 ± 0.5 vs 2.4 ± 0.7 sec(-1), P < .001, respectively). CONCLUSIONS: LA remodeling occurred in 22% of patients after acute myocardial infarction. In patients without LA remodeling, no changes in LA function were observed, but in patients with LA remodeling, LA function deteriorated significantly.

Left atrial strain is related to adverse events in patients after acute myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Left atrial (LA) maximal volume is of prognostic value in patients after acute myocardial infarction (AMI). Recently, LA mechanical function and LA strain have been introduced as alternative methods to assess LA performance more accurately. OBJECTIVE: To evaluate the relation between LA volume, mechanical function and strain, and adverse events in patients after AMI. METHODS: Patients with AMI underwent two-dimensional echocardiography within 48 h of admission. LA volume and LA performance (mechanical function and systolic strain) were quantified. The endpoint was a composite of all-cause mortality, reinfarction and hospitalisation for heart failure. RESULTS: 320 patients (mean age 60±12 years, 78% men) were followed up for 27±14 months. During follow-up, 48 patients (15%) reached the composite endpoint. After adjustment for clinical and echocardiographic parameters, LA maximal volume (HR 1.05, CI 1.00 to 1.10, p=0.04) and LA strain (HR 0.94, CI 0.89 to 0.99, p=0.02) were independently associated with adverse outcome. In addition, LA strain provided incremental value to LA maximal volume (p=0.03) for the prediction of adverse outcome. CONCLUSIONS: After AMI treated with primary percutaneous coronary intervention, LA strain provides additional prognostic value beyond LA maximal volume.

Surgical ventricular restoration for patients with ischemic heart failure: determinants of two-year survival.

BACKGROUND: Surgical ventricular restoration (SVR) improves left ventricular (LV) systolic function by partially restoring the normal geometry of the left ventricle. However, the beneficial effects of this surgical procedure on long-term clinical outcome remain controversial. The present study aimed to evaluate the independent determinants of 2-year morbidity and mortality rates after SVR. METHODS: Seventy-nine patients with ischemic heart disease and LV ejection fraction of 0.35 or less were included. All patients underwent SVR and additionally coronary artery bypass grafting or mitral valve surgery if clinically indicated. Clinical and echocardiographic examination was performed before SVR and at 6 months' follow-up. The primary end point was a composite of all-cause mortality and hospitalizations for heart failure. RESULTS: At 6 months' follow-up a significant improvement in heart failure symptoms was noted. In addition, LV ejection fraction increased from 0.27 ± 0.07 to 0.36 ± 0.10 (p < 0.001). During a median follow-up of 2.7 years, the primary end point was recorded in 22% of the patients. Baseline New York Heart Association functional class IV and a 6-month follow-up LV end-systolic volume index of at least 60 mL/m(2) were independently associated with worse outcome (hazard ratio, 5.4; 95% confidence interval, 1.9 to 15.2; p < 0.001; hazard ratio, 2.7; 95% confidence interval, 1.3 to 5.6; p < 0.001, respectively). CONCLUSIONS: Advanced heart failure status at baseline and large residual postsurgery LV end-systolic volume index were independently associated with increased mortality and heart failure hospitalization rates at 2 years' follow-up after SVR.

Clinical and functional effects of restrictive mitral annuloplasty at midterm follow-up in heart failure patients.

BACKGROUND: Restrictive mitral annuloplasty (RMA) is increasingly applied to treat functional mitral regurgitation in heart failure patients. Previous studies indicated beneficial clinical effects with low recurrence rates. However, the underlying pathophysiology is complex and outcome in terms of left ventricular function is not well known. We investigated chronic effects of RMA on ventricular function in relation to clinical outcome. METHODS: Heart failure patients (n = 11) with severe mitral regurgitation scheduled for RMA were analyzed at baseline (presurgery) and midterm follow-up by invasive pressure-volume loops, using conductance catheters. Clinical performance was evaluated by New York Heart Association class, quality-of-life-score, and 6-minute hall-walk-test. RESULTS: All patients were alive without recurrence of mitral regurgitation at follow-up (9.4 ± 4.1 months). Clinical parameters improved significantly (all p < 0.05). Global cardiac function, assessed by cardiac output, stroke volume, and stroke work did not change after RMA. Reverse remodeling was demonstrated by decreased end-systolic and end-diastolic volumes (16% and 11%, both p < 0.001). Systolic function improved, evidenced by increased ejection fraction (0.32 ± 0.05 to 0.36 ± 0.07, p = 0.001) and leftward shift of the end-systolic pressure-volume relation (ESV(100): 116 ± 43 to 74 ± 26 mL, p < 0.001). Diastolic function, however, demonstrated impairment by increased tau (69 ± 13 to 80 ± 14 ms, p < 0.001) and stiffness constant (0.022 ± 0.022 to 0.031 ± 0.028 mL(-1), p = 0.001). CONCLUSIONS: Restrictive mitral annuloplasty significantly improved clinical status without recurrence of mitral regurgitation at midterm follow-up in patients with heart failure. Hemodynamic analyses demonstrated significant reverse remodeling with unchanged global function and improved systolic function, but some signs of diastolic impairment. Overall, RMA appears an appropriate therapy for patients with dilated cardiomyopathy and functional mitral regurgitation.

Predictive value of total atrial conduction time estimated with tissue Doppler imaging for the development of new-onset atrial fibrillation after acute myocardial infarction.

Patients who develop new-onset atrial fibrillation (AF) after acute myocardial infarction (AMI) show an increased risk for adverse events and mortality during follow-up. Recently, a novel noninvasive echocardiographic method has been validated for the estimation of total atrial activation time using tissue Doppler imaging of the atria (PA-TDI duration). PA-TDI duration has shown to be independently predictive of new-onset AF. However, whether PA-TDI duration provides predictive value for new-onset AF in patients after AMI has not been evaluated. Consecutive patients admitted with AMIs and treated with primary percutaneous coronary intervention underwent echocardiography <48 hours after admission. All patients were followed at the outpatient clinic for > or =1 year. During follow-up, 12-lead electrocardiography and Holter monitoring were performed regularly, and the development of new-onset AF was noted. Baseline echocardiography was performed to assess left ventricular and left atrial (LA) function. LA performance was quantified with LA volumes, function, and PA-TDI duration. A total of 613 patients were evaluated. LA maximal volume (hazard ratio 1.07, 95% confidence interval 1.04 to 1.11), the total LA ejection fraction (hazard ratio 0.96, 95% confidence interval 0.93 to 0.99) and PA-TDI duration (hazard ratio 1.05, 95% confidence interval 1.04 to 1.06) were univariate predictors of new-onset AF. After multivariate analysis, LA maximal volume and PA-TDI duration independently predicted new-onset AF. Furthermore, PA-TDI duration provided incremental prognostic value to traditional clinical and echocardiographic parameters for the prediction of new-onset AF. In conclusion, PA-TDI duration is a simple measurement that provides important value for the prediction of new-onset AF in patients after AMI.

Long-term effects of surgical ventricular restoration with additional restrictive mitral annuloplasty and/or coronary artery bypass grafting on left ventricular function: six-month follow-up by pressure-volume loops.

OBJECTIVES: Previous studies demonstrated beneficial short-term effects of surgical ventricular restoration on mechanical dyssynchrony and left ventricular function and improved midterm and long-term clinical parameters. However, long-term effects on systolic and diastolic left ventricular function are still largely unknown. METHODS: We studied 9 patients with ischemic dilated cardiomyopathy who underwent surgical ventricular restoration with additional restrictive mitral annuloplasty and/or coronary artery bypass grafting. Invasive hemodynamic measurements by conductance catheter (pressure-volume loops) were obtained before and 6 months after surgery. In addition, New York Heart Association classification, quality-of-life score, and 6-minute hall-walk test were assessed. RESULTS: At 6 months' follow-up, all patients were alive and clinically in improved condition: New York Heart Association class from 3.3 ± 0.5 to 1.4 ± 0.7, quality-of-life score from 46 ± 22 to 15 ± 15, and 6-minute hall-walk test from 302 ± 123 to 444 ± 78 m (all P < .01). Hemodynamic data showed improved cardiac output (4.8 ± 1.4 to 5.6 ± 1.1 L/min), stroke work (6.5 ± 1.9 to 7.1 ± 1.4 mm Hg · L; P = .05), and left ventricular ejection fraction (36% ± 10% to 46% ± 10%; P < .001). Left ventricular surgical remodeling was sustained at 6 months: end-diastolic volume decreased from 246 ± 70 to 180 ± 48 mL and end-systolic volume from 173 ± 77 to 103 ± 40 mL (both P < .001). Left ventricular dyssynchrony decreased from 29% ± 6% to 26% ± 3% (P < .001) and ineffective internal flow fraction decreased from 58% ± 30% to 42% ± 18% (P < .005). Early relaxation (Tau, minimal rate of pressure change) was unchanged, but diastolic stiffness constant increased from 0.012 ± 0.003 to 0.023 ± 0.007 mL(-1) (P < .001). CONCLUSIONS: Surgical ventricular restoration with additional restrictive mitral annuloplasty and/or coronary artery bypass grafting leads to sustained left ventricular volume reduction at 6 months' follow-up. We observed improved systolic function and unchanged early diastolic function but impaired passive diastolic properties. Clinical improvement, supported by decreased New York Heart Association class, improved quality-of-life score, and improved 6-minute hall-walk test may be related to improved systolic function, reduced mechanical dyssynchrony, and reduced wall stress.

Noninvasive estimation of left ventricular filling pressures in patients with heart failure after surgical ventricular restoration and restrictive mitral annuloplasty.

OBJECTIVE: Doppler echocardiography, including tissue Doppler imaging, is widely applied to assess diastolic left ventricular function using early transmitral flow velocity combined with mitral annular velocity as a noninvasive estimate of left ventricular filling pressures. However, the accuracy of early transmitral flow velocity/mitral annular velocity in patients with heart failure, particularly after extensive cardiac surgery, is debated. Global diastolic strain rate during isovolumic relaxation obtained with 2-dimensional speckle-tracking analysis was recently proposed as an alternative approach to estimate left ventricular filling pressures. METHODS: We analyzed diastolic function in patients with heart failure after surgical ventricular restoration and/or restrictive mitral annuloplasty. Echocardiography, including tissue Doppler imaging and speckle-tracking analysis, was performed to determine early transmitral flow velocity/atrial transmitral flow velocity, isovolumetric relaxation time, deceleration time, early transmitral flow velocity/mean mitral annular velocity, strain rate during isovolumic relaxation, and early transmitral flow velocity/strain rate during isovolumic relaxation. These noninvasive indices were correlated with relaxation time constant Tau, peak rate of pressure decline, and left ventricular end-diastolic pressure obtained in the catheterization room using high-fidelity pressure catheters. RESULTS: Twenty-three patients were analyzed 6 months after restrictive mitral annuloplasty (n = 8), surgical ventricular restoration (n = 4), or a combined procedure (n = 11). The strongest correlation with invasive indices, in particular left ventricular end-diastolic pressure, was found for strain rate during isovolumic relaxation (r = -0.76, P < .001). Early transmitral flow velocity/mean mitral annular velocity did not correlate significantly with any of the invasive indices. Strain rate during isovolumic relaxation (cutoff value < 0.38 s(-1)) accurately predicted left ventricular end-diastolic pressure of 16 mm Hg or more with 100% sensitivity and 93% specificity. CONCLUSIONS: In a group of patients with heart failure who were investigated 6 months after cardiac surgery, early transmitral flow velocity/mean mitral annular velocity correlated poorly with invasively obtained diastolic indexes. Global strain rate during isovolumic relaxation, however, correlated well with left ventricular end-diastolic pressure and peak rate of pressure decline. Our data suggest that global strain rate during isovolumic relaxation is a promising noninvasive index to assess left ventricular filling pressures in patients with heart failure after extensive cardiac surgery, including restrictive mitral annuloplasty and surgical ventricular restoration.

Single-beat estimation of the left ventricular end-diastolic pressure-volume relationship in patients with heart failure.

AIMS: To test a method to predict the end-diastolic pressure-volume relationship (EDPVR) from a single beat in patients with heart failure. METHODS AND RESULTS: Patients (New York Heart Association class III-IV) scheduled for mitral annuloplasty (n=9) or ventricular restoration (n=10) and patients with normal left ventricular function undergoing coronary artery bypass grafting (n=12) were instrumented with pressure-conductance catheters to measure pressure-volume loops before and after surgery. Data obtained during vena cava occlusion provided directly measured EDPVRs. Baseline end-diastolic pressure (P(m)) and volume (V(m)) were used for single-beat prediction of EDPVRs. Root-mean-squared error (RMSE) between measured and predicted EDPVRs, was 2.79+/-0.21 mm Hg. Measured versus predicted end-diastolic volumes at pressure levels 5, 10, 15 and 20 mm Hg showed tight correlations (R(2)=0.69-0.97). Bland-Altman analyses indicated overestimation at 5 mm Hg (bias: pre-surgery 44 ml (95% CI 29 to 58 ml); post-surgery 35 ml (23 to 47 ml)) and underestimation at 20 mm Hg (bias: pre-surgery -57 ml (-80 to -34 ml); post-surgery -13 ml (-20 to -7.0 ml)). End-diastolic volumes were significantly different between groups and between conditions, but these differences were not dependent on the method (ie, measured versus predicted). RMSEs were not different between groups or conditions, nor dependent on V(m) or P(m), indicating that EDPVR prediction was equally accurate over a wide volume range. CONCLUSIONS: Single-beat EDPVRs obtained from hearts spanning a wide range of sizes and conditions accurately predicted directly measured EDPVRs with low RMSE. Single-beat EDPVR indices correlated well with directly measured values, but systematic biases were present at low and high pressures. The single-beat method facilitates less invasive EDPVR estimation, particularly when coupled with emerging non-invasive techniques to measure pressures and volumes.

Haemodynamics and left ventricular function in heart failure patients: comparison of awake versus intra-operative conditions.

BACKGROUND: Heart failure patients are increasingly subjected to surgery. Left ventricular (LV) function is generally assessed in awake patients, but intra-operative LV function is not well studied. AIM: To investigate the relation between LV function indices obtained in the catheterization laboratory and those obtained intra-operatively. METHODS: We enrolled 11 patients with heart failure (NYHA III-IV) scheduled for surgical interventions. LV function was assessed by pressure-volume loops (conductance catheter) during diagnostic catheterizations and intra-operatively under anaesthetized conditions. RESULTS: Compared to awake conditions, cardiac output was unchanged intra-operatively but ejection fraction was significantly reduced (-16%) due to increased end-diastolic volume (+13%). Systolic and diastolic LV pressure and afterload (E(A)) dropped significantly (-32%, -22%, -35%, respectively). LV systolic function assessed by dP/dt(MAX) and the end-systolic pressure-volume relation (E(ES)) was significantly reduced (-34%, -35%). LV diastolic stiffness was reduced (-44%). Ventricular-arterial coupling (E(A)/E(ES)) was maintained. CONCLUSION: Intra-operative cardiac output was unchanged compared to awake conditions due to a balance between reduced systolic and improved diastolic function. Ventricular-arterial coupling was maintained by a reduced afterload. Presumably, systolic function and afterload were reduced by anaesthesia, whereas diastolic function improved after pericardectomy. These findings provide insight into the combined effects of anaesthesia, thoracotomy and pericardectomy, and help to interpret LV function measurements in intra-operative conditions.