Kaatje Goetschalckx

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension

AIMS The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort. METHODS AND RESULTS Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence. CONCLUSION Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Prediction model to estimate presence of coronary artery disease: Retrospective pooled analysis of existing cohorts

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (≥50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

Aerobic interval training and continuous training equally improve aerobic exercise capacity in patients with coronary artery disease: the SAINTEX-CAD study.

BACKGROUND Exercise-based cardiac rehabilitation increases peak oxygen uptake (peak VO₂), which is an important predictor of mortality in cardiac patients. However, it remains unclear which exercise characteristics are most effective for improving peak VO₂ in coronary artery disease (CAD) patients. Proof of concept papers comparing Aerobic Interval Training (AIT) and Moderate Continuous Training (MCT) were conducted in small sample sizes and findings were inconsistent and heterogeneous. Therefore, we aimed to compare the effects of AIT and Aerobic Continuous Training (ACT) on peak VO₂, peripheral endothelial function, cardiovascular risk factors, quality of life and safety, in a large multicentre study. METHODS Two-hundred CAD patients (LVEF >40%, 90% men, mean age 58.4 ± 9.1 years) were randomized to a supervised 12-week cardiac rehabilitation programme of three weekly sessions of either AIT (90-95% of peak heart rate (HR)) or ACT (70-75% of peak HR) on a bicycle. Primary outcome was peak VO₂; secondary outcomes were peripheral endothelial function, cardiovascular risk factors, quality of life and safety. RESULTS Peak VO₂ (ml/kg/min) increased significantly in both groups (AIT 22.7 ± 17.6% versus ACT 20.3 ± 15.3%; p-time<0.001). In addition, flow-mediated dilation (AIT+34.1% (range -69.8 to 646%) versus ACT+7.14% (range -66.7 to 503%); p-time<0.001) quality of life and some other cardiovascular risk factors including resting diastolic blood pressure and HDL-C improved significantly after training. Improvements were equal for both training interventions. CONCLUSIONS Contrary to earlier smaller trials, we observed similar improvements in exercise capacity and peripheral endothelial function following AIT and ACT in a large population of CAD patients.

Reproducibility of different methods to measure the endothelial function

This study compares the reliability and reproducibility of flow-mediated dilatation (FMD) and peripheral arterial tonometry (PAT) to assess endothelial function. Eighteen volunteers with coronary heart disease underwent simultaneous testing of FMD by means of brachial artery ultrasound scanning and PAT with the EndoPAT 2000. The subjects underwent both tests twice with an interval of 30 minutes and the same protocol was repeated 2 days later. The within-day variability was lower for the FMD measurements than for the PAT measurements (10% versus 18%; p < 0.05). The between-day variability was similar (11%). A significant correlation was found between PAT and FMD (r = 0.57, p < 0.001). The typical errors of measurements for FMD were lower than those for PAT. In conclusion, in this study, FMD demonstrated the best reliability for the within- and between-day and separate day measurements when compared to PAT.

A review of telerehabilitation for cardiac patients

We conducted a literature review of telerehabilitation interventions on cardiac patients. We searched for studies evaluating some form of telerehabilitation in cardiac patients. A total of 116 publications were screened initially, of which 37 publications were eligible for further review. We assessed study strength, based on the level of evidence and the quality of the intervention. The majority of the articles (70%) represented the highest level of evidence. Most interventions were of good (46%) or fair (51%) quality. Most studies evaluated the efficacy of the telerehabilitation interventions (84%), while 38% reported on feasibility and acceptance. Most studies did not include safety and/or cost-benefit analyses. Most telerehabilitation interventions (90%) employed only one or two core components of cardiac rehabilitation (CR). Of the CR core components, physical activity was most frequently evaluated. Telerehabilitation appears to be a feasible and effective additional and/or alternative form of rehabilitation, compared to conventional in-hospital CR. Evaluations of telerehabilitation programmes taking into account patient safety and health economics are now required.

Exercise-based cardiac rehabilitation improves endothelial function assessed by flow-mediated dilation but not by pulse amplitude tonometry.

We aimed to investigate the effect of exercise on endothelium-dependent vasodilator function assessed simultaneously in the brachial artery and in the distal arterial bed by flow-mediated dilation and the pulse amplitude tonometry method, respectively, in coronary artery disease patients. The study included 146 patients with stable coronary artery disease (123 men, mean age 62 ± 9 years) who participated in the Cardiac Rehabilitation and Genetics of Exercise performance study. All patients completed a 12-week supervised cardiac rehabilitation programme (three sessions per week at an intensity of 80% of the heart rate reserve). At baseline and upon completion of the training, we measured brachial artery diameters by means of ultrasound scanning (linear array transducer of 12 MHz) and simultaneously assessed pulse amplitudes in the fingertip using a pulse amplitude tonometry device both at rest and after reactive hyperaemia induced by a 5-min forearm cuff occlusion. Peak oxygen uptake significantly increased (+22%; p < 0.0001) and flow-mediated dilation improved from 10.0% to 13.1% (+37%; p < 0.0001), whereas the reactive hyperaemia index of the pulse amplitude tonometry method remained unchanged (p = 0.47) following exercise-based cardiac rehabilitation. However, the basal digital pulse amplitude (+58%; p < 0.001) increased as a result of training, as did the digital pulse amplitude after reactive hyperaemia (+22%; p < 0.05). Exercise-based cardiac rehabilitation is associated with an improvement in endothelial function, as can be measured by flow-mediated dilation but not by the reactive hyperaemia index of the pulse amplitude tonometry method.

Heart failure with mid-range ejection fraction: a distinct clinical entity? Insights from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF)

While the conditions of heart failure (HF) with reduced (HFrEF, LVEF < 40%) and preserved (HFpEF, LVEF ≥ 50%) left ventricular ejection fraction (LVEF) are well characterized, it is unknown whether patients with HF and mid‐range LVEF (HFmrEF, LVEF 40–49%) have to be regarded as a separate clinical entity. The aim of this study was to characterize these three populations and to compare outcome and response to therapy.

Right ventricular function by MRI.

Purpose of review For years, the right ventricle (RV) has been deemed ‘unnecessary’, as shown by procedures such as Fontan surgery. More recently, right ventricular dysfunction has been recognized as a prognostic factor in many cardiovascular diseases. Supported by advances in echocardiography and MRI, assessment of right ventricular function and morphology has gained interest. The goal of this review is to offer a current clinical perspective on right ventricular function as assessed by MRI. Recent findings MRI has progressed towards a fast and reliable technique for assessing right ventricular morphology, volumes and function. Strain-encoded techniques and single breath-hold four-dimensional acquisition techniques are promising, but need to be confirmed in patient studies. Continuous improvement in postprocessing software has further reduced analysis time and effort. Summary Our understanding of right ventricular behavior even in complex heart disease has taken substantial benefit from modern cardiac MRI techniques. MRI imaging of the RV is patient-tailored, integrating right ventricular volumetric and functional analysis in a comprehensive approach, including assessment of cardiac morphology, myocardial tissue characteristics, flow patterns and great vessel anatomy. This approach provides the clinician a complete view, not only of the RV as such, but also of the RV being an essential part of the cardiopulmonary system.

Effect of Infarct Severity on Regional and Global Left Ventricular Remodeling in Patients with Successfully Reperfused ST Segment Elevation Myocardial Infarction

PURPOSE To evaluate the relationship between myocardial infarction ( MI myocardial infarction ) severity at magnetic resonance (MR) imaging and regional and global postinfarction left ventricular ( LV left ventricular ) remodeling. MATERIALS AND METHODS This HIPAA-compliant study was institutional review board approved. In 186 patients, reperfused ST segment elevation MI myocardial infarction (mean age ± standard deviation, 59 years ± 11) was prospectively studied the first week and 4 months after infarction. Microvascular obstruction ( MVO microvascular obstruction ) and intramyocardial hemorrhage ( IMH intramyocardial hemorrhage ) helped define three infarct severity groups: S0, no MVO microvascular obstruction or IMH intramyocardial hemorrhage (n = 68); S1, MVO microvascular obstruction , no IMH intramyocardial hemorrhage (n = 84); and S2, MVO microvascular obstruction and IMH intramyocardial hemorrhage (n = 34). RESULTS were compared in 40 control patients (mean age, 58 years ± 10). One-way analysis of variance or Kruskal-Wallis test with post hoc Bonferroni correction was used. Follow-up analysis was performed with paired Student t test or Mann-Whitney U test. Results Infarct severity was positively related (P < .001) to peak of troponin I, inflammatory biomarkers, area at risk, and infarct volume and inversely related to myocardial salvage ratio, systolic wall thickening ( SWT systolic wall thickening ) in the infarct, and adjacent myocardium and LV left ventricular ejection fraction ( EF ejection fraction ). At follow-up, LV left ventricular EF ejection fraction significantly improved in S0 and S1 (S0: 53% ± 8 to 56% ± 8, P < .001; S1: 48% ± 8 to 52% ± 10, P = .006), while S2 adversely remodeled with increase in LV left ventricular end-diastolic (175 mL ± 35 to 201 mL ± 40) and end-systolic (100 mL ± 24 to 115 mL ± 29) volumes (P < .001). SWT systolic wall thickening recovery in the infarct (S0: 32% ± 21 to 42% ± 24, P < .001; S1: 19% ± 13 to 29% ± 19, P < .001; S2: 11% ± 9 to 15% ± 15, P = .22) and adjacent (S0: 41% ± 19 to 52% ± 21, P < .001; S1: 32% ± 11 to 38% ± 16, P = .002; S2: 24% ± 13 to 29% ± 14, P = .092) and remote (S0: 54% ± 18 to 62% ± 20, P = .002; S1: 53% ± 18 to 57% ± 20, P = .092; S2: 50% ± 35 to 53% ± 22, P = .75) myocardium was related to infarct severity. LV left ventricular wall thinning with LV left ventricular mass decrease occurred at follow-up (S0: 110 g ± 27 to 100 g ± 27, P < .001; S1: 115 g ± 24 to 109 g ± 26, P = .019; S2: 134 g ± 35 to 117 g ± 27, P = .043). CONCLUSION MVO microvascular obstruction and IMH intramyocardial hemorrhage significantly affect postinfarct myocardial and LV left ventricular remodeling; hemorrhagic infarcts behave worse than nonhemorrhagic infarcts, with lack of functional recovery and adverse LV left ventricular remodeling extending to remote myocardium.

Rationale and design of a randomized trial on the effectiveness of aerobic interval training in patients with coronary artery disease: The SAINTEX-CAD study

BACKGROUND Exercise-based cardiac rehabilitation is considered an important adjunct treatment and secondary prevention measure in patients with coronary artery disease (CAD). However, the issues of training modality and exercise intensity for CAD patients remain controversial. OBJECTIVE Main aim of the present study is to test the hypothesis that aerobic interval training (AIT) yields a larger gain in peak aerobic capacity (peakVO2) compared to a similar training programme of moderate continuous training (MCT) in CAD patients. STUDY DESIGN In this multicentre study stable CAD patients with left ventricular ejection fraction>40% will be randomized after recent myocardial infarction or revascularization (PCI or CABG) to a supervised 12-week programme of three weekly sessions of either AIT (85-90% of peak oxygen uptake [peakVO2], 90-95% of peak heart rate) or MCT (60-70% of peakVO2, 65-75% of peak heart rate). The primary endpoint of the study is the change of peakVO2 after 12 weeks training. Secondary endpoints include safety, changes in peripheral endothelial vascular function, the evolution of traditional cardiovascular risk factors, quality of life and the number and function of circulating endothelial progenitor cells as well as endothelial microparticles. Possible differences in terms of long-term adherence to prescribed exercise regimens will be assessed by regular physical activity questionnaires, accelerometry and reassessment of peakVO2 12 months after randomization. A total number of 200 patients will be randomized in a 1:1 manner (significance level of 0.05 and statistical power of 0.90). Enrolment started December 2010; last enrolment is expected for February 2013.