Three-year clinical outcome of percutaneous treatment of bifurcation lesions in multivessel coronary artery disease with the sirolimus-eluting stent: insights from the Arterial Revascularisation Therapies Study, part II (ARTS II).

AIMS: The long-term impact of treating bifurcation lesions on the overall outcome of patients with multivessel coronary disease treated percutaneously with drug-eluting stents is unknown. This analysis determined the influence of bifurcation treatment using sirolimus-eluting stents on 3-year clinical outcomes. METHODS AND RESULTS: Of the 607 patients (2,160 lesions) in the ARTS II study, 324 patients underwent revascularisation procedures involving treatment of at least one bifurcation (465 lesions). Three-year outcomes were compared to those without bifurcations. Despite more diffuse and complex disease in the bifurcation group, survival free of adverse events was equivalent in the two groups. At 3-years, there was no difference in rate of overall MACCE (20.2% vs. 18.5%, p=NS) or any of the component events between the bifurcation and the non-bifurcation group. There was a trend for a higher rate of definite stent thrombosis in the bifurcation group (4.6 vs 2.1%, p=0.1), but in multivariate analysis the CK value post-procedure served as the only independent predictor of definite stent thrombosis (p=0.015), with the presence of a bifurcation lesion of borderline significance (p=0.056). CONCLUSIONS: In multivessel disease treated by PCI with DES, the presence of bifurcation disease had no adverse influence on 3-year clinical outcomes.

Morphology discrimination in implantable cardioverter-defibrillators: consistency of template match percentage during atrial tachyarrhythmias at different heart rates.

BACKGROUND: Morphology discrimination (MD) in implantable cardioverter-defibrillators (ICDs) is based on the comparison of the ventricular electrogram during tachycardia with a stored reference template obtained during baseline rhythm. However, the effect of heart rate on the template match percentage during supraventricular tachyarrhythmias (SVT) is not known. The purpose of this study was to evaluate the performance of the template match percentage during SVT at different heart rates. METHODS AND RESULTS: Stored electrograms of 868 tachyarrhythmias from 88 patients with a dual-chamber ICD (St Jude Medical, USA) were analysed by the investigators. The effect of heart rate on template match percentage was estimated by regression analysis. For performance measures, data were corrected for multiple episodes in a patient by using the generalized estimating equation method. The mean template match percentage was 86.6 +/- 22.2% (median 100%) for SVT episodes. No significant differences in template match percentage between fast [ventricular cycle length (CL) 300-350 ms] and slow (ventricular CL >400 ms) SVTs were observed (85.4 +/- 27.0 vs. 87.1 +/- 19.7%). Using nominal settings, MD alone provided sensitivity and specificity of 70.2% and 89.4% overall, respectively. Morphology discrimination in conjunction with rate branch analysis, sudden onset, and stability yielded sensitivity and specificity of 98.5% and 91.2%, respectively. CONCLUSION: Morphology discrimination has a consistently high template match percentage during SVTs, which is independent of ventricular CL. The consistent high match percentage results in high specificity for arrhythmia discrimination.

Relevant and redundant lung function parameters in discriminating asthma from COPD.

A relevant set of lung function parameters, derived from spirometry, flow-volume curves, diffusion capacity and bodyplethysmography, to discriminate asthma from COPD was established via logistic regression analysis. All new patients, referred to the outpatient clinic and later defined as asthma or COPD, underwent extensive lung function testing with reversibility testing. Logistic regression was used to calculate the probability to be a COPD or asthma patient. Selection of relevant parameters was done via 1] forward-, 2] backward-, 3] stepwise selection and 4] the best score method. All four methods were supplemented by bootstrapping to obtain a validated selection and estimation of the logistic regression parameters. The area under the ROC curve (mean+/-sd) for respectively the forward, backward, stepwise and best score selection method is 0.9348+/-0.0115, 0.9346+/-0.0115, 0.9348+/-0.0115 and 0.9296+/-0.0121. The TLCO, VA and the postdilator MEF50, VC and PEF were selected as the most relevant parameters in discriminating asthma from COPD: they appeared most often as relevant discriminators in 500 bootstrapped samples: TLco was present in all bootstrapped samples and VA, postdilator MEF50, VC and PEF in resp. 70.8%, 46.2%, 42.8% and 36.8%. Bodyplethysmography derived parameters turned out to be of limited value. Diffusion capacity testing and spirometry/flow-volume curve after administration of bronchodilators are the methods of choicewhen having to chose between asthma or COPD.

Evaluation of morphology discrimination for ventricular tachycardia diagnosis in implantable cardioverter-defibrillators.

BACKGROUND: To reduce inappropriate therapy from implantable cardioverter-defibrillators (ICDs), electrogram morphology discrimination has been developed to improve arrhythmia discrimination without compromising device safety. OBJECTIVES: The purpose of this study was to determine the accuracy of the morphology discrimination algorithm for detecting ventricular tachycardia (VT). METHODS: Stored electrograms of 795 tachyarrhythmias from 106 patients with a St. Jude Medical ICD (51 single-chamber and 55 dual-chamber) were analyzed by the investigators. The data were analyzed for morphology discrimination alone, sudden onset and stability, and morphology discrimination in combination with sudden onset and stability. Data were corrected for multiple episodes within a patient with the generalized estimating equation method. RESULTS: Using the nominal template match of 60%, morphology discrimination alone provided sensitivity and specificity of 78% and 95% for single-chamber ICDs and 63% and 92% for dual-chamber ICDs, respectively. Based on the receiver operator characteristic curve, the optimal-match percent threshold was 80% to 85% but at the expense of specificity. Morphology discrimination combined with sudden onset and stability increased sensitivity to 98% with specificity of 86% in single-chamber devices. In dual-chamber devices, the loss in sensitivity is compensated by rate branch analysis, yielding a sensitivity of 98%. CONCLUSION: Arrhythmia discrimination based on electrogram morphology has the potential to reject atrial tachyarrhythmias. However, there is a risk for underdetection of ventricular tachyarrhythmias if arrhythmia discrimination is primarily based on morphology. To guarantee patient safety in single-chamber devices, the morphology discrimination algorithm must be programmed in combination with established detection algorithms. In dual-chamber devices, loss of sensitivity is compensated by the V > A rate branch.

Treatment benefit by perindopril in patients with stable coronary artery disease at different levels of risk.

AIMS: Patients with stable coronary artery disease (CAD) are at increased risk. Estimation of individual risk is difficult. We developed a cardiovascular risk model based on the EUROPA study population and investigated whether benefit of long-term administration of the angiotensin-converting enzyme (ACE)-inhibitor perindopril was modified by risk level. METHODS AND RESULTS: A total of 12 218 patients with stable CAD were treated with 8 mg perindopril or placebo. Baseline patient characteristics were assessed for association with 1091 cardiovascular deaths or non-fatal myocardial infarction (MI). Risk factors were age over 65 years, male gender [hazard ratio (HR) 1.2], previous MI (HR 1.5), previous stroke and/or peripheral vascular disease (HR 1.7), diabetes, smoking, angina (all HR 1.5), and high serum cholesterol and systolic blood pressure. Treatment benefit by perindopril was consistent among high, intermediate, and low risk patients (HRs 0.88, 0.68, and 0.83, respectively). Risk reduction was thus not modified by absolute risk level. CONCLUSION: Risk factors such as age, male gender, smoking, total cholesterol, and blood pressure continue to play an important role once clinical sequellae of coronary heart disease have developed. Patients at moderate-to-high risk because of uncontrolled risk factors and those with other indications for ACE-inhibitors have the most to gain from ACE-inhibition.

Myocardial repair by percutaneous cell transplantation of autologous skeletal myoblast as a stand alone procedure in post myocardial infarction chronic heart failure patients.

AIMS: In this first multicentre study we assessed the safety and efficacy of percutaneous transendocardial skeletal myoblast injection as a stand alone procedure in congestive heart failure patients. METHODS AND RESULTS: 15 patients (14 male), age 63+/-7 (Mean+/-SD), NYHA class 2-4 were injected with 216+/-119 cells (81+/-19% Desmin+) using a NOGA or fluoroscopy guided injection catheter. The cells were injected in the scarred regions 6+/-4 years after myocardial infarction as a stand alone procedure. After treating the first 6 patients, the protocol was amended to require that remaining patients be fitted with an ICD prior to the cellular cardiomyoplasty procedure. Holter monitoring, ECG and ICD readings were obtained at multiple intervals. Stress echocardiography and LV angiography was performed at baseline, 3, 6 and 12 months post procedure.After 1 year follow-up 13 patients were still alive. Patient # 6 died suddenly 9 days post procedure. Patient #15 (ICD patient) survived an electrical storm 12 days post procedure, but died 2 days later due to cardiogenic shock. Two non-ICD patients received an ICD because of observed ventricular arrhythmias. It remains unknown whether these events are directly related to the cell injections.LV ejection fraction (%) changed from 34.4+/-10.3 to 36.6+/-10.4 (baseline versus 12 months FU, p=0.26). Wall motion score index improved both at rest (3.0+/-0.5 to 2.7+/-0.7, p=0.049) and under low-dose dobutamine stress (2.8+/-0.4 to 2.5+/-0.6, p=0.07, baseline versus 12 months FU). CONCLUSION: Percutaneous autologous skeletal myoblast injection is feasible, resulting in wall motion and functional class improvement, but is potentially associated with an increased risk for ventricular arrhythmias. Randomised studies are needed, however, to further assess overall safety, efficacy and the potential for initial increased risk for arrhythmia following cell injection in these high-risk patients.

Discriminating asthma and COPD based on bronchodilator data: an improvement of the methods.

The degree of bronchodilation is usually expressed as a percentage of the predicted or baseline value. It has been shown that the relation between pre- and post-dilation lung function values is not adequately described by this approach: the sensitivity/specificity in separating asthmatics from cases of chronic obstructive pulmonary disease (COPD) could be improved. The alternative method we investigate is based on a logistic regression approach incorporating pre- and post-dilation lung function, age, sex and height. The discriminatory power of forced expiratory volume in one second (FEV1) increase as a percentage of the predicted or baseline FEV1 is compared to our approach using two databases containing bronchodilator data and diagnoses (asthma, chronic bronchitis or emphysema, the latter two grouped as (OPD). The increase as a percentage of the predicted or baseline approach and our alternative method show areas under the receiver operator curve (ROC) (males/females) of 0.552/0.629, 0.523/0.550 and 0.867/0.879 in one database. In the other database the same trend is present although less obvious: 0.628/0.730, 0.592/0.737 and 0.709/0.749. This increase in discriminatory power is obtained in the optimal use of all available information, especially age, which is not used in the increase of the predicted/baseline FEV1 rule.

Prevention of inappropriate therapy in implantable cardioverter-defibrillators: results of a prospective, randomized study of tachyarrhythmia detection algorithms.

OBJECTIVES: The purpose of this randomized study was to investigate the performance of single- and dual-chamber tachyarrhythmia detection algorithms. BACKGROUND: A proposed benefit of dual-chamber implantable cardioverter-defibrillators (ICDs) is improved specificity of tachyarrhythmia detection. METHODS: All ICD candidates received a dual-chamber ICD and were randomized to programmed single- or dual-chamber detection. Of 60 patients (47 male, age 58 +/- 14 years, left ventricular ejection fraction 30%), 29 had single-chamber and 31 had dual-chamber settings. The detection results were corrected for multiple episodes within a patient with the generalized estimating equations method. RESULTS: A total of 653 spontaneous arrhythmia episodes (39 patients) were classified by the investigators; 391 episodes were ventricular tachyarrhythmia (32 patients). All episodes of ventricular tachyarrhythmias were appropriately detected in both settings. In 25 patients, 262 episodes of atrial tachyarrhythmias were recorded. Detection was inappropriate for 109 atrial tachyarrhythmia episodes (42%, 18 patients). Rejection of atrial tachyarrhythmias was not significantly different between both groups (p = 0.55). Episodes of atrial flutter/tachycardia were significantly more misclassified (p = 0.001). Overall, no significant difference in tachyarrhythmia detection (atrial and ventricular) between both settings was demonstrated (p = 0.77). CONCLUSIONS: The applied detection criteria in dual-chamber devices do not offer benefits in the rejection of atrial tachyarrhythmias. Discrimination of atrial tachyarrhythmias with a stable atrioventricular relationship remains a challenge.

Analyzing bronchodilation with emphasis on disease type, age and sex.

In the literature, different statistical methods to evaluate bronchodilator studies are used. These approaches are all based on the absence of residual heterogeneity and on baseline independency of the parameter under analysis. A database containing the lung function values of newly referred patients was used to assess these assumptions as function of the underlying diagnosis (asthma, bronchitis and emphysema) and to chart the characteristics of analysis of covariance, which (partly) deals with these drawbacks. Bronchodilator data of 709 asthmatics, 522 bronchitic and 126 emphysema patients were used. It was shown that, in asthma, for almost all lung function parameters, bronchodilation was indeed dependent on baseline values, which was less strong in bronchitis and even weaker in emphysema. A negative effect of age on bronchodilation was found, which is strong in asthma and almost absent in emphysema, rendering the use of bronchodilation as a diagnostic tool less useful. The conclusion is that analysis of covariance is a good way to evaluate bronchodilation studies in obstructive lung disease, particularly in asthma. For bronchitic or emphysema patients, difference-based approaches may suffice. The assumptions underlying the other methods were not met.

Selecting the best method to evaluate bronchodilation when analysing bronchodilator studies.

Changes in lung function (that is, FEV(1)) are commonly expressed as a percentage of the predicted value. The question is whether this parameter is best suited for statistical analysis. A total of 2199 bronchodilation tests were selected and pre- and post-dilator FEV(1), age, height and sex extracted. Predicted FEV(1) values, the difference between pre- and post-dilator FEV(1) and the change as percentage of predicted or baseline FEV(1) were calculated. The latter parameters were subjected to analysis of variance and pre- and post-dilator FEV(1) to analysis of covariance. The statistical power of these four approaches and the residual structure were used to select the best approach. Analysis of variance of the change as percentage of predicted and covariance analysis of pre- and post-dilator FEV(1) offers the best performance. The residuals of the analysis of variance showed a funnel shaped structure. The latter causes residual heterogeneity, resulting in a loss of power and deviations between the actual and nominal alpha-level. This is not taken into account when calculating sample sizes using the standard equations, which implicitly assume lack of these problems. Analysis of covariance does not suffer from these problems. The best way to evaluate bronchodilation in trials is to use analysis of covariance.