Thomas P. Mast

A prospective validation of the HEART score for chest pain patients at the emergency department

BACKGROUND The focus of the diagnostic process in chest pain patients at the emergency department is to identify both low and high risk patients for an acute coronary syndrome (ACS). The HEART score was designed to facilitate this process. This study is a prospective validation of the HEART score. METHODS A total of 2440 unselected patients presented with chest pain at the cardiac emergency department of ten participating hospitals in The Netherlands. The HEART score was assessed as soon as the first lab results and ECG were obtained. Primary endpoint was the occurrence of major adverse cardiac events (MACE) within 6 weeks. Secondary endpoints were (i) the occurrence of AMI and death, (ii) ACS and (iii) the performance of a coronary angiogram. The performance of the HEART score was compared with the TIMI and GRACE scores. RESULTS Low HEART scores (values 0-3) were calculated in 36.4% of the patients. MACE occurred in 1.7%. In patients with HEART scores 4-6, MACE was diagnosed in 16.6%. In patients with high HEART scores (values 7-10), MACE occurred in 50.1%. The c-statistic of the HEART score (0.83) is significantly higher than the c-statistic of TIMI (0.75)and GRACE (0.70) respectively (p<0.0001). CONCLUSION The HEART score provides the clinician with a quick and reliable predictor of outcome, without computer-required calculating. Low HEART scores (0-3), exclude short-term MACE with >98% certainty. In these patients one might consider reserved policies. In patients with high HEART scores (7-10) the high risk of MACE may indicate more aggressive policies.

Evaluation of structural progression in arrhythmogenic right ventricular dysplasia/cardiomyopathy

Importance Considerable research has described the arrhythmic course of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, objective data characterizing structural progression, such as ventricular enlargement and cardiac dysfunction, in ARVD/C are relatively scarce. Objectives To define the extent of structural progression, identify determinants of structural progression, and determine the association between structural progression and electrocardiographic (ECG) changes in patients with ARVD/C. Design, Setting, and Participants In this cohort study, first- and last-available echocardiograms of 85 patients with ARVD/C fulfilling 2010 Task Force diagnostic criteria (TFC) from a transatlantic ARVD/C registry were retrospectively compared to assess structural disease progression. Right ventricular (RV) size and systolic function between baseline and last follow-up were compared. The RV size was determined by RV outflow tract dimension, and RV and left ventricular (LV) systolic function were determined by RV fractional area change (RV-FAC) and LV ejection fraction (LVEF), respectively. Multivariable logistic regression was used to study associations between baseline characteristics and the occurrence of structural progression. Main Outcomes and Measures The main outcome was the change in variables indicating structural progression. Secondary outcomes were the correlation with electrical progression and identification of the association between baseline characteristics and occurence structural progression. Results Among the 85 patients with ARVD/C, mean (SD) age at baseline was 42.8 (14.4) years and 47 (55%) were men. After a mean (SD) follow-up of 6.4 (2.5) years, RV outflow tract dimension increased from 35 mm (interquartile range [IQR], 31 to 39) to 37 mm (IQR, 33 to 41) (P < .001), RV-FAC decreased from 39% (IQR, 33% to 44%) to 34% (IQR, 24% to 42%) (P < .001) (rate −3.3% per 5 years; IQR, −8.9% to 1.2%), indicating large interpatient variability. The LVEF decreased from 55% (IQR, 52% to 60%) to 54% (IQR, 49% to 57%) (P = .001) (rate, −0.2% per 5 years; IQR, −6.5% to 1.7%). Forty examinations were reanalyzed to establish the measurement error. Patients exceeding the measurement error by ±2 SDs were identified with significant progressive disease for RV, with a decrease in RV-FAC greater than 10% (n = 21) and, for LV, a decrease in LVEF greater than 7% (n = 23). Progression of RV disease was associated with depolarization criteria at baseline (odds ratio [OR], 9.0; 95% CI, 1.1-74.2; P = .04), whereas progression of LV disease was associated with phospholamban (PLN) mutation (OR, 8.8; 95% CI, 2.1-37.2; P = .003). There was no association between progressive RV/LV structural disease and newly developed ECG TFC. Conclusions and Relevance Structural dysfunction in ARVD/C is progressive with substantial interpatient variability. Significant structural RV progression was associated with prior depolarization abnormalities, whereas LV progression is modified by genetic background. Structural progression was not associated with development of new ECG TFC. The results of this study pave the way for designing and launching trials aimed at reducing structural progression in patients with ARVD/C.

Current and future role of echocardiography in arrhythmogenic right ventricular dysplasia/cardiomyopathy

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited progressive cardiomyopathy, clinically characterized by ventricular arrhythmias and increased risk of sudden cardiac death. Echocardiography has a role in the diagnosis and prognosis of ARVD/C. However, in the current era of magnetic resonance imaging (MRI), the role of echocardiography in ARVD/C patients and family member screening is subject to debate. Relatively novel echocardiographic techniques, such as three-dimensional right ventricular (3D-RV) imaging and tissue deformation imaging, may improve the diagnostic and prognostic performance of echocardiography in these patients. 3D-RV imaging provides more insights on RV anatomy and global function compared to conventional echocardiography. Subtle RV regional wall motion abnormalities, and mechanical dyssynchrony, are accurately measured by tissue deformation imaging. Several studies suggest an incremental value of novel echocardiographic parameters in addition to conventional measurements. Moreover, new parameters indicating subtle RV dysfunction, and mechanical dyssynchrony, are of predictive value and could help in risk stratification of ARVD/C patients. New robust parameters, derived from 3D-RV echocardiography and RV tissue deformation imaging, in combination with established conventional parameters, suggest that there is a current and future role for echocardiography in ARVD/C supplementing MRI.

Volumetric response beyond six months of cardiac resynchronization therapy and clinical outcome

Aims Response to cardiac resynchronization therapy (CRT) is often assessed six months after implantation. Our objective was to assess the number of patients changing from responder to non-responder between six and 14 months, so-called late non-responders, and compare them to patients who were responder both at six and 14 months, so-called stable responders. Furthermore, we assessed predictive values of six and 14-month response concerning clinical outcome. Methods 105 patients eligible for CRT were enrolled. Clinical, laboratory, ECG, and echocardiographic parameters and patient-reported health status (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were assessed before, and six and 14 months after implantation. Response was defined as ≥15% LVESV decrease as compared to baseline. Major adverse cardiac events (MACE) were registered until 24 months after implantation. Predictive values of six and 14-month response for MACE were examined. Results In total, 75 (71%) patients were six-month responders of which 12 (16%) patients became late non-responder. At baseline, late non-responders more often had ischemic cardiomyopathy and atrial fibrillation, higher BNP and less dyssynchrony compared to stable responders. At six months, late non-responders showed significantly less LVESV decrease, and higher creatinine levels. Mean KCCQ scores of late non-responders were lower than those of stable responders at every time point, with the difference being significant at 14 months. The 14 months response was a better predictor of MACE than six months response. Conclusions The assessment of treatment outcomes after six months of CRT could be premature and response rates beyond might better correlate to long-term clinical outcome.

Measurements of electrical and mechanical dyssynchrony are both essential to improve prediction of CRT response.

INTRODUCTION Predicting reverse remodeling after cardiac resynchronization therapy (CRT) remains challenging and different etiologies of heart failure might hamper identification of predictors. OBJECTIVE Assess the incremental value of mechanical dyssynchrony besides electrical dyssynchrony for predicting CRT response. METHODS 227 patients (51% ischemic) received CRT. Response was defined as ≥15% left ventricular end systolic volume decrease after six months. Prediction models were developed comprising clinical parameters and electrical dyssynchrony (Model A), subsequently complemented with mechanical dyssynchrony (Model B). Models were compared by area under the receiver-operating curve (AUC), net reclassification index (NRI) and integrated discrimination improvement (IDI) for the complete cohort, ischemic (ICM) and non-ischemic (NICM) subpopulations. RESULTS Model B performed significantly better than Model A supported by AUC, NRI and IDI. Furthermore, model B significantly better predicted response for NICM than ICM. CONCLUSION Electrical dyssynchrony and mechanical dyssynchrony are essential to predict CRT response. Nevertheless, response prediction for ICM remains challenging.

The concept of triple wavefront fusion during biventricular pacing : Using the EGM to produce the best acute hemodynamic improvement in CRT

Previous reports suggest that biventricular pacing (BiVp) fused with intrinsic conduction (BiVp‐fusion, triple wavefront fusion) is associated with improved resynchronization compared to pure‐BiVp in cardiac resynchronization therapy (CRT). This study aimed to assess the association between acute hemodynamic benefit of CRT and signs of BiVp‐fusion by using a novel electrogram (EGM)‐based method.

Echo response and clinical outcome in CRT patients

BackgroundChange in left ventricular end-systolic volume (∆LVESV) is the most frequently used surrogate marker in measuring response to cardiac resynchronisation therapy (CRT). We investigated whether ∆LVESV is the best measure to discriminate between a favourable and unfavourable outcome and whether this is equally applicable to non-ischaemic and ischaemic cardiomyopathy.Methods205 CRT patients (age 65 ± 12 years, 69 % men) were included. At baseline and 6 months echocardiographic studies, exercise testing and laboratory measurements were performed. CRT response was assessed by: ∆LVESV, ∆LV ejection fraction (LVEF), ∆ interventricular mechanical delay, ∆VO2 peak, ∆VE/VCO2, ∆BNP, ∆creatinine, ∆NYHA, and ∆QRS. These were correlated to the occurrence of major adverse cardiac events (MACE) between 6 and 24 months.ResultsMACE occurred in 19 % of the patients (non-ischaemic: 13 %, ischaemic: 24 %). ∆LVESV remained the only surrogate marker for CRT response for the total population and patients with non-ischaemic cardiomyopathy, showing areas under the curve (AUC) of 0.69 and 0.850, respectively. For ischaemic cardiomyopathy, ∆BNP was the best surrogate marker showing an AUC of 0.66.Conclusion∆LVESV is an excellent surrogate marker measuring CRT response concerning long-term outcome for non-ischaemic cardiomyopathy. ∆LVESV is not suitable for ischaemic cardiomyopathy in which measuring CRT response remains difficult.

Comparison of the HEART, TIMI and GRACE risk scores for chest pain patients at the emergency room

Background: Chest pain is a common reason for presentation at the emergency room. Absolute criteria for Acute Coronary Syndrome (ACS) without ST elevation are lacking. Recently, we introduced the HEART score, which was specifically designed to stratify patients with chest pain in the emergency room, consisting of patient History, typical ECG changes, higher Age, classical Risk factors and elevated Troponin levels (table 1). Retrospective validations have been published. The purpose of this prospective observational study was to assess the predictive value for a cardiovascular event of HEART, TIMI and GRACE risk scores for chest pain patients. Methods: A total of 2440 patients presented with chest pain during October 2008 and November 2009 at the cardiac emergency rooms of ten hospitals. HEART, TIMI and GRACE scores are calculated based on patient history, risk factors, medication, physical examination, ECG and laboratory values. The primary end point was major adverse cardiac events (MACE), a composite of Acute Myocardial Infarction (MI), Percutaneous Coronary Intervention (PCI), Coronary Artery Bypass Grafting (CABG), Significant stenosis with conservative treatment and death, within 6 weeks after presentation.

Echocardiographic Applications in the Diagnosis and Management of Patients with ARVC

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a genetically determined myocardial disease predominantly affecting the right ventricle (RV). There is no single gold standard for the diagnosis of ARVC/D. New echocardiographic tools such as tissue deformation imaging allow quantitative regional wall motion analyses. This is especially important for early ARVC/D diagnosis where global RV dysfunction may be lacking. Several studies have shown incremental diagnostic value for tissue deformation imaging derived parameters in comparison to conventional echocardiography. 3D RV echocardiography is a new method to evaluate the RV and provides volumetric measurements in a broad spectrum of ARVC/D patients. Due to the frequent implantation of implantable cardioverter devices, echocardiography could play an important role in the follow-up of ARVC/D patients. Emerging new echocardiographic tools are currently changing the role of echocardiography in ARVC/D. In the future, MRI and echocardiography should be considered complementary to evaluate ARVC/D.