Markus Engelen | University of Münster (original) (raw)

Papers by Markus Engelen

Journal of Heart and Lung Transplantation, Apr 1, 2015

Background: Due to the lack of nephrotoxic activity, proliferation signal inhibitors (PSI) such a... more Background: Due to the lack of nephrotoxic activity, proliferation signal inhibitors (PSI) such as everolimus are recommended for immunosuppression after heart transplantation, but the assessment of renal function in patients receiving PSI has led to conflicting results. We examined renal integrity and function using neutrophil gelatinase-associated lipocalin (NGAL) and conventional markers [plasma creatinine, cystatin C, urine albumin, a1-microglobulin (a1M)] in heart transplant patients, who underwent conversion to everolimus due to allograft vasculopathy, graft rejection episodes, or renal function deterioration, and in patients maintained on calcineurin inhibitors (CNI). Methods: This cross-sectional study included 121 consecutive heart transplant recipients: 44 patients received CNI-free immunosuppressive therapy with everolimus and 77 patients received CNI. Renal parameters were determined in plasma and urine samples using standard enzymatic or immunochemical methods. Results: Heart transplant recipients receiving everolimus therapy had significantly lower NGAL concentrations in plasma [median (95% CI): 128 (97–176) ng/mL vs. 252 (224–283) ng/mL, p < 0.001] and urine [median (95% CI): 6.4 (4.5–7.6) ng/g vs. 15.7 (10.2–25.9) ng/g creatinine, p < 0.001]. In contrast, no significant differences were observed between everolimusand CNI-treated groups with regard to creatinine and cystatin C, as well as urine albumin and a1M levels. Significant correlations were noted between plasma NGAL and creatinine (r = 0.42, p < 0.001), cystatin C (r = 0.44, p < 0.001), N-terminal brain natriuretic propeptide (r = 0.31, p < 0.01) and indicators of chronic inflammation [lipoprotein-associated phospholipase A2 (Lp-PLA2), r = 0.31, p < 0.01] and soluble CD40 ligand (sCD40L, r = 0.22, p < 0.05), and between urinary NGAL and a1M (r = 0.21, p < 0.05). Multiple regression analysis indicated that cystatin C and Lp-PLA2 were the best predictors of plasma NGAL. Conclusion: The present study documents reduced plasma and urinary NGAL levels in the absence of differences in conventional renal parameters in patients on CNI-free immunosuppressive therapy with everolimus. These results support favorable effects of everolimus on renal integrity in heart transplant recipients. 2015 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.

Transplant International, Aug 31, 2011

Laboratory Animals, Apr 1, 2009

Doppler-echocardiographic assessment of cardiovascular structure and function in murine models ha... more Doppler-echocardiographic assessment of cardiovascular structure and function in murine models has developed into one of the most commonly used non-invasive techniques during the last decades. Recent technical improvements even expanded the possibilities. In this review, we summarize the current options to assess global left ventricular (LV) function in mice using echocardiographic techniques. In detail, standard techniques as structural and functional assessment of the cardiovascular phenotype using one-dimensional M-mode echocardiography, two-dimensional B-mode echocardiography and spectral Doppler signals from mitral inflow respective aortal outflow are presented. Further pros and contras of recently implemented techniques as three-dimensional echocardiography and strain and strain rate measurements are discussed. Deduced measures of LV function as the myocardial performance index according to Tei, estimation of the mean velocity of circumferential fibre shortening, LV wall stress and different algorithms to estimate the LV mass are described in detail. Last but not least, specific features and limitations of murine echocardiography are presented. Future perspectives in respect to new examination techniques like targeted molecular imaging with advanced ultrasound contrast bubbles or improvement of equipment like new generation matrix transducers for murine echocardiography are discussed.

Heart Rhythm, May 1, 2005

No abstract is available. To read the body of this article, please view the Full Text online. ...... more No abstract is available. To read the body of this article, please view the Full Text online. ... © 2005 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved. ... Visit SciVerse ScienceDirect to see if you have access via your institution. ... Advertisements on this site do not ...

Journal of Heart and Lung Transplantation, Feb 1, 2010

Purpose: Everolimus is a proliferation signal inhibitor introduced for heart transplantion in 200... more Purpose: Everolimus is a proliferation signal inhibitor introduced for heart transplantion in 2004. This study reports the 2 years' results of CNI-free immunosuppression using everolimus after HTx. There is only sparse data on this issue. Methods and Materials: Patients after HTx being switched to everolimus due to CNI-induced adverse drug effects as deterioration of kidney function and recurrent rejections were continuously enrolled. 60 pats underwent standardized switching protocols, 42 pats completed 24-months follow-up. Blood was sampled for lipid status, renal function, and levels of everolimus. On days 0, 14, 28, and then every 3 months, echocardiography and physical examination were performed. Biopsies were carried out only if rejection was suspected. An angiogram and a myocardial scintigraphy were performed before and 1 year after switching. Results: After switching to everolimus, most pats recovered from the side effects associated with CNIs. Renal function improved significantly after 12 months and after 24 months (creatinine: 2.1Ϯ0.6 vs. 1.8Ϯ1 mg/dL, PϽ0.001; creatinine clearance: 41.8Ϯ22 vs. 48.6Ϯ21.8 mL/min, PϽ0.001 at baseline and 24 months). Tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved. Levels of interleukin 6 where stable when comparing baseline and 24 months. Temporary adverse events occurred in 62 cases (84% of them light adverse events [light: skin disorders (acne) (nϭ23), edema (nϭ11), lipometabolic disorders (nϭ10), other (nϭ2); moderate/severe: influenzal infection (nϭ6), pneumonia (nϭ6), rejection (nϭ1), other (nϭ4).] There were no relevant signs for deterioration of heart function in echocardiograms, angiograms and scintigrams. Conclusions: CNI-free immunosuppression using everolimus is safe, with excellent efficacy and acceptance after HTX. Renal function significantly improved. CNI-induced side effects such as tremor and peripheral edema markedly improved in most patients. Everolimus prevents long term morbidity after HTX and possibly improves quality of live.

European Heart Journal, Sep 1, 2007

International Journal of Cardiology, Oct 1, 2011

The Annals of Thoracic Surgery, Mar 1, 2014

Background. Immunosuppression is necessary after transplantation but it is associated with distin... more Background. Immunosuppression is necessary after transplantation but it is associated with distinct adverse side effects. These negative effects could at least partially be overcome with the mammalian target of Rapamycin (mTOR) inhibitor everolimus. Few studies have examined everolimus therapy with calcineurin inhibitor (CNI) withdrawal in maintenance heart transplant patients (HTx). Methods. In this prospective, single-arm, single-center study, maintenance patients after HTx were converted from CNI to everolimus. They were followed for 48 months. Primary endpoints were kidney-function and arterial hypertension. Results. Forty-eight patients were recruited (mean posttransplant time 5.4 ± 3.5 years). Of these, 36 were followed for the entire 4-year period. Median calculated glomerular filtration rate increased from 40.7 (32.4 to 59.1) mL/minute at baseline to 48.9 (29.7 to 67)) mL/minute at month 48 (p ¼ not significant). Median systolic and diastolic blood pressure, triglycerides, and high-density lipoprotein and low-density lipoprotein cholesterol, did not change significantly in a comparison of the values at baseline and at 48 months. Early resolution of most non-renal CNI-related adverse events was sustained. Due to adverse events, CNI therapy had to be reintroduced in 6 patients (12.5%). No significant changes in cardiac function parameters were observed. Conclusions. Calcineurin inhibitor-free immunosuppression with everolimus is an effective and safe option in selected maintenance HTx patients. Most adverse effects under everolimus occurred early after conversion and in most cases resolved without intervention within a few weeks. Refining selection criteria may help both in identifying patients who will profit most from switching and in alleviating the need to reintroduce CNI therapy.

Basic Research in Cardiology, Jul 4, 2006

Background Cytostatic agents such as anthracyclines may cause changes in the electrophysiologic p... more Background Cytostatic agents such as anthracyclines may cause changes in the electrophysiologic properties of the heart. We hypothesized that anthracyclines facilitate life-threatening proarrhythmic side effects of cardiovascular and non-cardiovascular repolarization prolonging drugs. Methods and results The electrophysiologic effects of chronic administration of doxorubicin (Dox) were studied in ten rabbits, which were treated with Dox twice a week (1.5 mg/kg i. v.). A control group (11 rabbits) was given NaCl solution. Two of ten Dox rabbits died suddenly, the remaining animals showed mild clinical signs of heart failure after a period of six weeks. Echocardiography demonstrated a decrease in ejection fraction (pre treatment: 74 ± 23 % to post treatment: 63 ± 16 % (p < 0.05)). In isolated hearts, action potential duration measured by eight simultaneously recorded monophasic action potentials (MAP) was similar in Dox and control hearts. However, in Dox rabbits, administration of the I Kr-blocker erythromycin (150-300 µM) led to a significant greater prolongation of the mean MAP duration (63 ± 21 ms vs 29 ± 12 ms, p < 0.05) and the QT interval (100 ± 32 ms vs 58 ± 17 ms, p < 0.05) as compared to control. Moreover, I Kr-block led to a more marked increase of dispersion of MAP 90 in the Dox group as compared to control hearts (23 ± 7 ms vs. 9 ± 4 ms). In the presence of hypokalemia more episodes of early afterdepolarizations and torsade de pointes occurred (p < 0.05). Conclusion Even during the early phase of chemotherapeutic treatment, before significant QT-prolongation is present, anthracyclines lead to an increased sensitivity to the proarrhythmic potency of I Kr-blocking drugs. Thus, anthracycline therapy reduces repolarization reserve and thereby represents a novel contributing factor for the development of lifethreatening proarrhythmia.

Basic Research in Cardiology, Apr 8, 2006

Journal of Cardiovascular Magnetic Resonance, Sep 25, 2014

Background: Cardiac involvement is a frequent finding in patients with Duchenne (DMD) and Becker ... more Background: Cardiac involvement is a frequent finding in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies. With this study, we aimed at elucidating the relationship between the phenotypic expression of cardiac involvement and the occurrence of adverse cardiac events in DMD/BMD patients. Methods: Eighty-eight male DMD/BMD patients (age 29 ± 14 yrs) were prospectively enrolled. All patients underwent cardiovascular magnetic resonance (CMR) comprising cine-and late-gadolinium-enhancement (LGE)-CMR at study entry and were subsequently followed-up for adverse cardiac events. The primary endpoint was defined as all-cause/cardiac death or cardiac transplantation. Secondary endpoints were (1) hospitalization for heart failure and/or (2) occurrence of non-/sustained ventricular tachycardia (VT). Results: During a mean follow-up time of 47 ± 18 months, the primary endpoint was observed in three (3%) and the secondary endpoint in 21 (24%) patients. On multivariable analysis, LV-EF (HR, 95% CI: 0.94, 0.89-0.97, p = 0.001) and the presence of "transmural" LGE (HR, 95% CI: 2.89, 1.09-7.68, p = 0.033) were the only independent predictors for secondary endpoints. A cutoff for LV-EF of 45% was associated with the highest hazard ratio (HR, 95% CI: 11.50, 4.49-29.43, p < 0.0001) in a Cox regression survival analysis. In the group of patients with a LV-EF (>45%), those patients already showing "transmural" LGE had a significantly lower event-free-survival (HR, 95% CI: 13.48, 1.89-96.12, p = 0.009) compared to those without. Conclusions: An impaired LV systolic function (LV-EF ≤45%) and a "transmural" pattern of myocardial fibrosis independently predict the occurrence of adverse cardiac events in DMD/BMD patients. Even in DMD/BMD patients with relatively preserved LV-EF (>45%), the simple and visually assessable parameter "transmural LGE" is of additive prognostic value.

Basic Research in Cardiology, Feb 9, 2005

Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. T... more Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post-repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium. In 12 patients with persistent AF (11 male, 58 +/- 5 yrs, 27 +/- 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined. Both drugs prolonged APD90 during AF (flecainide from 109 +/- 7 ms to 137 +/- 10 ms, sotalol from 108 +/- 6 ms to 131 +/- 8 ms, both p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 +/- 8 ms to 139 +/- 8 ms, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 +/- 9 ms to 197 +/- 28 ms, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 vs. baseline and vs. sotalol). Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.

Journal of The American Society of Echocardiography, Jun 1, 2005

Primary cardiac lymphoma is an extremely rare extranodal non-Hodgkin&amp;amp;amp;amp;amp;... more Primary cardiac lymphoma is an extremely rare extranodal non-Hodgkin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s lymphoma, exclusively located in the heart and/or the pericardium with no evidence of extracardiac dissemination. In this report, we describe a cardiac B-cell lymphoma arising in a 70-year-old woman who presented to the hospital with heart failure symptoms and a high-degree atrioventricular block of unknown origin. Echocardiography revealed a massive infiltrative thickening of the atrial septum, the aortic root, and the pericardium. Pulsed wave and Doppler tissue findings were highly suggestive for pericarditis constrictiva. Positron emission tomography showed unusually strong metabolic activity in the atrial septum, both atria, and the entire pericardium. Suggested malignoma was confirmed by the pericardial biopsy specimens, which revealed a high-grade diffuse CD20+ B-cell lymphoma.

Journal of Cardiovascular Electrophysiology, Aug 1, 2005

A 70-year-old woman with signs of acute heart failure was referred to our emergency department. S... more A 70-year-old woman with signs of acute heart failure was referred to our emergency department. She had no cardiac history. The ECG on admission (Fig. 1, left panel) demonstrated interatrial conduction delay with a broad biphasic Pwave (200 ms) and a third degree AV block. Transesophageal echocardiography revealed massive thickening of the interatrial septum (maximum 21 mm). Additional cardiac magnetic resonance imaging revealed an extensive tumorous mass in-

The FASEB Journal, Apr 24, 2006

To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.05-5517fje ... more To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.05-5517fje SPECIFIC AIM Cathepsin L (CTSL) belongs to the papain-like family of lysosomal cysteine proteases. Unlike other cathepsin-deficient animals, CTSL knockout mice show a marked dilated cardiomyopathy (DCM) at 1 yr of age. The present study was initiated to investigate the pathogenic sequence that occurs in the heart of ctsl Ϫ/Ϫ mice. Specifically, we aimed to establish the time course of disease progression and to identify the cell biological processes that are altered by CTSL deficiency in the myocardium.

Journal of Cardiovascular Electrophysiology, Jun 1, 2007

Predictors of Proarrhythmia in Quinolones. Background: Numerous noncardiovascular drugs prolong r... more Predictors of Proarrhythmia in Quinolones. Background: Numerous noncardiovascular drugs prolong repolarization and thereby increase the risk for patients to develop life-threatening tachyarrhythmias of the torsade de pointes (TdP) type. The development of TdP is an individual, patient-specific response to a repolarization-prolonging drug, depending on the repolarization reserve. The aim of the present study was to analyze the underlying mechanisms that discriminate hearts that will develop TdP from hearts that will not develop TdP. We therefore investigated the group of quinolone antibiotics that reduce repolarization reserve via I Kr blockade in an intact heart model of proarrhythmia. Methods and Results: In 47 Langendorff-perfused, AV-blocked rabbit hearts, ciprofloxacin (n = 10), ofloxacin (n = 14), levofloxacin (n = 10), and moxifloxacin (n = 13) in concentrations from 100 µM to 1,000 µM were infused. Eight monophasic action potentials (MAPs) and an ECG were recorded simultaneously. After incremental pacing at cycle lengths from 900 ms to 300 ms to compare the action potential duration, potassium concentration was lowered to provoke TdP. All antibiotics led to a significant increase in QT interval and MAP duration, and exhibited reverse-use dependence. Eight simultaneously recorded MAPs demonstrated an increase in dispersion of repolarization in the presence of all antibiotics. MAP triangulation (ratio: MAP 90/50) and fluctuation of consecutive action potentials were increased for all tested drugs at high concentrations. In the presence of low potassium concentration, all quinolones led to TdP: ciprofloxacin, 4 out of 10 (40%); ofloxacin, 3 out of 14 (21%); moxifloxacin, 9 out of 13 (69%); and levofloxacin, 2 out of 10 (20%). Hearts that developed TdP demonstrated a significant greater influence on dispersion of repolarization and on triangulation as compared with hearts without TdP. Conclusion: Quinolone antibiotics may be proarrhythmic due to a significant effect on myocardial repolarization. The individual response of a heart to develop TdP in this experimental model is characterized by a greater effect on dispersion of repolarization and on triangulation of action potential as compared with hearts that do not develop TdP.

European Journal of Echocardiography, Jun 25, 2015

Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked recessive disorders associated ... more Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked recessive disorders associated with both skeletal myopathy and progressive cardiomyopathy in males. Female DMD/BMD carriers (DMDc/BMDc) are mostly free of skeletal muscle symptoms, but they are also prone to cardiomyopathy. The aim of the current study was to characterize the frequency, pattern, and extent of cardiomyopathy in female DMD/BMD carriers (DMDc/BMDc) in comparison to their first-degree male MD relatives. Methods and results Thirty-six (age 44 + 14 years) female MD carriers (20 DMDc and 16 BMDc) constituted the 'MD carrier group' and were prospectively enrolled. All MD carriers underwent a complete CMR study comprising cine-and late gadolinium enhancement (LGE) imaging. In 22 of these women ('female MD carrier comparison group', 7 DMD and 15 BMD), at least one first-degree male relative with a previously established diagnosis of MD underwent the same CMR protocol and was assigned to the 'male MD comparison group' (n ¼ 24, 6 DMD and 18 BMD). In the total MD carrier group, 17 (47%) MD carriers had at least one pathological CMR finding [5 (14%) with a reduced left ventricular ejection fraction (LV-EF) and 16 (44%) with the presence of LGE]. All LGE-positive patients (n ¼ 16) showed non-ischaemic LGE with subepicardial involvement of the LV lateral free wall being the most frequent pattern (13/16, 81%). Compared with BMDc, DMDc demonstrated more frequently a pathological CMR result (65 vs. 19%; P ¼ 0.008)-in spite of being significantly younger (40 + 11 vs. 50 + 16 years, P ¼ 0.038). In the male MD comparison group, the same LGE pattern as in female carriers was seen, but with a significantly higher prevalence of cardiac abnormalities compared with their female carrier relatives constituting the female MD comparison group (75 vs. 27%; P ¼ 0.003). Conclusion Cardiac involvement is a frequent finding in female carriers of DMD, but less frequently observed in carriers of BMD. Those DMDc and BMDc with cardiac involvement demonstrate the same myocardial fibrosis pattern as their male counterparts with overt disease.

International Journal of Cardiology, Feb 1, 2007

In the past years, Doppler echocardiography has evolved into a commonly used technique. More rece... more In the past years, Doppler echocardiography has evolved into a commonly used technique. More recent sophisticated advances in imaging quality have substantially improved spatial and temporal resolution allowing the adaptation of this technique to small animal models, particularly in rabbits but even in mice. Recently, parameters obtained by Tissue Doppler Imaging (TDI) have been shown to be more independent of pre- and afterload than classic hemodynamic Doppler measurements. Exploration of animal models may require anaesthesia but there is only very little information on the effect of anaesthesia on echocardiographic parameters in rabbits. We therefore performed Doppler-echocardiographic examinations of 20 wild-type New Zealand White rabbits in awake state and under light ketamine-xylazine anaesthesia. Special focus was put on the evaluation of global and regional left ventricular systolic and diastolic function using TDI and the myocardial performance index (Tei-index). Doppler-echocardiographic measurements including TDI in rabbits were feasible to assess cardiac morphology and function within a short examination time. There were some distinct changes of functional parameters during anaesthesia. Exemplary for systolic function, fractional shortening, cardiac output and systolic TDI velocity of the lateral wall decreased distinctly. Global left ventricular function measured by the Tei-index deteriorated. Doppler echocardiography and TDI can be performed easily, quickly and safely in the rabbit. Anaesthesia with the cardiodepressive ketamine-xylazine shows some distinct Doppler-echocardiographically measurable negative effects on cardiac function. Thus, echocardiography with less cardiodepressive anaesthetic regimes or even without anaesthesia after training of the animals should be considered as alternatives whenever possible.

Europace, Jun 1, 2016

Purpose of the study: Vectorcardiography (VCG) has been recently reported as a promising tool to ... more Purpose of the study: Vectorcardiography (VCG) has been recently reported as a promising tool to predict acute hemodynamic response in CRT patients. We evaluated the ability of 9 VCG parameters in addition to QRS duration of the biventricular (BV) paced QRS complex to predict acute hemodynamic CRT response. Methods: VCG parameters from 753 BV paced electrocardiograms (25 patients, in each patient 5 BV, 1 multispot, 1 multivein setting and each setting at 5 different atrioventricular delays) were calculated according to Frank orthogonal lead system using custom made software. Maximum vector amplitude (VA) and maximum QRS area (AREA) in the frontal (X), horizontal (Y) and left sagittal plane (Z) and in 3D projection (3D) were measured. Additionally global QRS duration (QRSD) and time from maximum peak amplitude to the end of the QRS complex were assessed (TMax). For every VCG parameter the difference (D) between the BV paced and atrial paced QRS-complex was calculated. VCG-parameters were compared to changes in left ventricular pressure, expressed as dP/dt max. An increase of 10% in dP/dt max was considered as acute hemodynamic response (AHR). Results: All patients had an indication for CRT according to current ESC/AHA guidelines (84% male, 100% LBBB, mean QRSD 180 + 25ms, 40%/60% NYHA II/III). Hemodynamic response was observed in 655 (84%) of the BV paced electrocardiograms. From all vectorcardiographic parameters VA3D, DVA3D, AREAZ, DAREAZ, DAREA3D, TMax and DQRSD differentiated AHR response from non-response (Table 1). The diagnostic accuracy to predict response was the highest for DAREAZ (AUC ¼ 0.799), and DAREA3D (AUC ¼ 0.723) (Table 1). Conclusion: Reduction in QRS area, measured in the left sagittal plane or in 3D projection, during BV pacing seems a useful VCG parameter to predict acute hemodynamic response in CRT patients. This method may be an easy, non-invasive tool for CRT optimization.