The presence of cardiotropic viral genomes is not increased in atrial tissue of atrial fibrillation patients.

BACKGROUND: Infections with potentially cardiotropic viruses are associated with the development of atrial fibrillation (AF). However, whether direct viral infection of the atria is involved in the pathogenesis of AF is unclear. We have therefore analysed the presence of cardiotropic viral genomes in AF patients. METHODS: Samples of left atrial tissue were obtained from 50 AF patients (paroxysmal, n = 20; long-standing persistent/permanent, n = 30) during cardiac surgery and from autopsied control patients (n = 14). Herein, the presence of PVB19, EBV, CMV, HHV­6, adenovirus and enterovirus genomes was determined by polymerase chain reaction. The densities of CD45+ and CD3+ cells and fibrosis in the atria were quantified by (immuno)histochemistry. RESULTS: Of the tested viruses only the PVB19 genome was detected in the atria of 10% of patients, paroxysmal AF (2 of 20) and long-standing persistent/permanent AF (3 of 30). Conversely, in 50% of controls (7 of 14) PVB19 genome was found. No significant association was found between PVB19 and CD45+ and CD3+ cells, or between the presence of PVB19 and fibrosis, in either control or AF patients. CONCLUSION: The presence of viral genomes is not increased in the atria of AF patients. These results do not support an important role for viral infection of the atria in the pathogenesis of AF.

Evolution of coronary artery calcium and absolute myocardial perfusion after percutaneous revascularization: A 3-year serial hybrid [15O]H2O PET/CT imaging study.

BACKGROUND AND AIMS: The value of serial coronary artery calcium (CAC) scores to predict changes in absolute myocardial perfusion and epicardial vasomotor function is poorly documented. This study explored the association between progression of CAC score and changes in absolute myocardial perfusion. METHODS: Fifty-three patients (26% female) with de novo single-vessel coronary artery disease underwent [15O]H2O positron emission tomography/computed tomography at 1 month (baseline), 1 year, and 3 years after complete revascularization with percutaneous coronary intervention (PCI) to assess CAC scores, hyperemic myocardial blood flow (hMBF), coronary flow reserve (CFR) and cold pressor test MBF (CPT-MBF), within the context of the VANISH trial. RESULTS: Baseline CAC score was 0 in 9%, 0.1-99.9 in 40%, 100-399.9 in 36% and ≥400 in 15% of patients, respectively. Mixed model-analysis allowed for averaging perfusion indices over all time points: hMBF (3.74 ± 0.83; 3.33 ± 0.79; 3.08 ± 0.78 and 2.44 ± 0.74 mL min-1·g-1) and CFR (3.82 ± 1.12; 3.17 ± 0.80; 3.19 ± 0.81; 2.63 ± 0.92) were lower among higher baseline CAC groups (p < 0.01; p = 0.03). However, no significant interaction was found between baseline CAC groups and time after PCI for all perfusion indices, denoting that evolution of perfusion indices over time was not significantly different between CAC groups. Furthermore, CAC progression was not correlated with evolution of hMBF (r = 0.08, p = 0.57), CFR (r = 0.09, p = 0.53) or CPT-MBF (r = 0.03, p = 0.82) during 3 years of follow-up. CONCLUSIONS: Higher baseline CAC was associated with lower hMBF and CFR. However, both baseline CAC and its progression were not associated with evolution of absolute hMBF, CFR and CPT-MBF over time, suggesting that CAC score and progression of CAC are poor indicators of change in absolute myocardial perfusion.

Sonothrombolysis in the ambulance for ST-elevation myocardial infarction: rationale and protocol.

BACKGROUND: Treatment of ST-elevation myocardial infarction (STEMI) has improved over the years. Current challenges in the management of STEMI are achievement of early reperfusion and the prevention of microvascular injury. Sonothrombolysis has emerged as a potential treatment for acute myocardial infarction, both for epicardial recanalisation as well as improving microvascular perfusion. This study aims to determine safety and feasibility of sonothrombolysis application in STEMI patients in the ambulance. METHODS: Ten patients with STEMI will be included and treated with sonothrombolysis in the ambulance during transfer to the PCI centre. Safety will be assessed by the occurrence of ventricular arrhythmias and shock during sonothrombolysis intervention. Feasibility will be assessed by the extent of protocol completion and myocardial visibility. Efficacy will be determined by angiographic patency rate, ST-elevation resolution, infarct size and left ventricular volumes, and function measured with cardiovascular magnetic resonance imaging, and contrast and strain echocardiography. A comparison will be made with matched controls using an existing STEMI database. DISCUSSION: Sonothrombolysis is a novel technique for the treatment of cardiovascular thromboembolic disease. The first clinical trials on its use for STEMI have demonstrated promising results. This study will be the first to examine the feasibility of in-ambulance sonothrombolysis for STEMI. TRIAL REGISTRATION: EU Clinical Trials Register (identifier: 2019-001883-31), registered 2020-02-25.

Assessment of a standalone photoplethysmography (PPG) algorithm for detection of atrial fibrillation on wristband-derived data.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed world. Using photoplethysmography (PPG) and software algorithms, AF can be detected with high accuracy using smartphone camera-derived data. However, reports of diagnostic accuracy of standalone algorithms using wristband-derived PPG data are sparse, while this provides a means to perform long-term AF screening and monitoring. This study evaluated the diagnostic accuracy of a well-known standalone algorithm using wristband-derived PPG data. MATERIALS AND METHODS: Subjects recruited from a community senior care organization were instructed to wear the Wavelet PPG wristband on one arm and the Alivecor KardiaBand one-lead-ECG wristband on the other. Three consecutive measurements (duration per measurement: 60 s for PPG and 30 s for one-lead ECG) were performed with both devices, simultaneously. The PPG data were analyzed by the Fibricheck standalone algorithm and the ECG data by the Kardia algorithm. The results were compared to a reference standard (interpretation of the one-lead ECG by two independent cardiologists). RESULTS: A total of 180 PPGs and one-lead ECGs were recorded in 60 subjects, with a mean age of 70±17. AF was identified in 6 (10%) of the users, two users (3%) were not classifiable by the PPG algorithm and 1 user (2%) was not classifiable by the one-lead ECG algorithm. The diagnostic performance (sensitivity/specificity/positive predictive value/negative predictive value/accuracy) on user level was 100/96/75/100/97% for the PPG wristband and 100/98/86/100/98% for the one-lead ECG wristband. CONCLUSIONS: In a small real-world cohort of elderly people, the standalone Fibricheck AF algorithm can accurately detect AF using Wavelet wristband-derived PPG data. Results are comparable to the Alivecor Kardia one-lead ECG device, with an acceptable unclassifiable/bad quality rate. This opens the door for long-term AF screening and monitoring.

Coronary computed tomography angiography and [15O]H2O positron emission tomography perfusion imaging for the assessment of coronary artery disease.

Determining the anatomic severity and extent of coronary artery disease (CAD) by means of coronary computed tomography angiography (CCTA) and its effect on perfusion using myocardial perfusion imaging (MPI) form the pillars of the non-invasive imaging assessment of CAD. This review will 1) focus on CCTA and [15O]H2O positron emission tomography MPI as stand-alone imaging modalities and their combined use for detecting CAD, 2) highlight some of the lessons learned from the PACIFIC trial (Comparison of Coronary CT Angiography, SPECT, PET, and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve (FFR) (NCT01521468)), and 3) discuss the use of [15O]H2O PET MPI in the clinical work-up of patients with a chronic coronary total occlusion (CTO).

TrimetaziDine as a Performance-enhancING drug in heart failure with preserved ejection fraction (DoPING-HFpEF): rationale and design of a placebo-controlled cross-over intervention study.

BACKGROUND: Currently, no specific treatment exists for heart failure with preserved ejection fraction (HFpEF). Left ventricular (LV) relaxation during diastole is a highly energy-demanding process, while energy homeostasis is known to be compromised in HFpEF. We hypothesise that trimetazidine - a fatty acid ß­oxidation inhibitor - improves LV diastolic function in HFpEF, by altering myocardial substrate use and improving the myocardial energy status. OBJECTIVES: To assess whether trimetazidine improves LV diastolic function by improving myocardial energy metabolism in HFpEF. METHODS: The DoPING-HFpEF trial is a randomised, double-blind, placebo-controlled cross-over intervention trial comparing the efficacy of trimetazidine and placebo in 25 patients with stable HFpEF. The main inclusion criteria are: New York Heart Association functional class II to IV, LV ejection fraction ≥50%, and evidence of LV diastolic dysfunction. Patients are treated with one 20-mg trimetazidine tablet or placebo thrice daily (twice daily in the case of moderate renal dysfunction) for two periods of 3 months separated by a 2-week washout period. The primary endpoint is the change in pulmonary capillary wedge pressure during different intensities of exercise measured by right heart catheterisation. Our key secondary endpoint is the myocardial phosphocreatine (PCr)/ATP ratio measured by phosphorus-31 magnetic resonance spectroscopy and its relation to the primary endpoint. Exploratory endpoints are 6­min walk distance, N-terminal pro-brain natriuretic peptide levels, and quality of life. CONCLUSION: The DoPING-HFpEF is a phase-II trial that evaluates the effect of trimetazidine, a metabolic modulator, on diastolic function and myocardial energy status in HFpEF. [EU Clinical Trial Register: 2018-002170-52; NTR registration: NL7830].

Atrial inflammation in different atrial fibrillation subtypes and its relation with clinical risk factors.

OBJECTIVE: Inflammation of the atria is an important factor in the pathogenesis of atrial fibrillation (AF). Whether the extent of atrial inflammation relates with clinical risk factors of AF, however, is largely unknown. This we have studied comparing patients with paroxysmal and long-standing persistent/permanent AF. METHODS: Left atrial tissue was obtained from 50 AF patients (paroxysmal = 20, long-standing persistent/permanent = 30) that underwent a left atrial ablation procedure either or not in combination with coronary artery bypass grafting and/or valve surgery. Herein, the numbers of CD45+ and CD3+ inflammatory cells were quantified and correlated with the AF risk factors age, gender, diabetes, and blood CRP levels. RESULTS: The numbers of CD45+ and CD3+ cells were significantly higher in the adipose tissue of the atria compared with the myocardium in all AF patients but did not differ between AF subtypes. The numbers of CD45+ and CD3+ cells did not relate significantly to gender or diabetes in any of the AF subtypes. However, the inflammatory infiltrates as well as CK-MB and CRP blood levels increased significantly with increasing age in long-standing persistent/permanent AF and a moderate positive correlation was found between the extent of atrial inflammation and the CRP blood levels in both AF subtypes. CONCLUSION: The extent of left atrial inflammation in AF patients was not related to the AF risk factors, diabetes and gender, but was associated with increasing age in patients with long-standing persistent/permanent AF. This may be indicative for a role of inflammation in the progression to long-standing persistent/permanent AF with increasing age.

Impact of scan quality on the diagnostic performance of CCTA, SPECT, and PET for diagnosing myocardial ischemia defined by fractional flow reserve.

BACKGROUND: Scan quality can have a significant effect on the diagnostic performance of non-invasive imaging techniques. However, the extent of its influence has scarcely been investigated in a head-to-head manner. METHODS: Two-hundred and eight patients underwent CCTA, SPECT, and PET prior to invasive fractional flow reserve measurements. Scan quality was classified as either good, moderate, or poor. RESULTS: Distribution of good, moderate, and poor quality scans was; CCTA; 66%, 22%, 13%; SPECT; 52%, 38%, 9%; PET; 86%, 13%, 1%. Good quality CCTA scans possessed a higher specificity (75% vs. 31%, p = 0.001), positive predictive value (PPV, 71% vs. 51%, p = 0.050), and accuracy (80% vs. 60%, p = 0.009) compared to moderate quality scans, while sensitivity (94%) and negative predictive value (NPV, 88%) were similar to moderate and poor quality scans. Sensitivity (76%), NPV (84%), and accuracy (85%) of good quality SPECT scans was superior to those of moderate (41% p = 0.001, 56% p = 0.010, 70% p = 0.010) and poor quality (30% p = 0.003, 65% p = 0.069, 63% p = 0.038). Specificity (92%) and PPV (87%) of good quality SPECT scans did not differ from scans of diminished quality. Good quality PET scans exhibited high sensitivity (84%), specificity (86%), NPV (88%), PPV (81%) and accuracy (85%), which was comparable to scans of lesser quality. Good quality CCTA, SPECT, and PET scans demonstrated a similar diagnostic accuracy (p = 0.247). CONCLUSION: Diagnostic performance of CCTA, and SPECT is hampered by scan quality, while the diagnostic value of PET is not affected. Good quality CCTA, SPECT, and PET scans possess a high diagnostic accuracy.

Hemodynamic Effects of Pulmonary Arterial Hypertension-Specific Therapy in Patients With Heart Failure With Preserved Ejection Fraction and With Combined Post- and Precapillay Pulmonary Hypertension.

BACKGROUND: Drugs approved for pulmonary arterial hypertension have been considered for patients with heart failure with preserved ejection fraction and combined post- and precapillary pulmonary hypertension (Cpc-PH). We aimed to study changes in cardiac volumes, cardiac load and left ventricular (LV) filling pressures in patients with heart failure with preserved ejection fraction and Cpc-PH in response to pulmonary arterial hypertension-specific treatment. METHODS AND RESULTS: In this prospective study, 23 patients with heart failure with preserved ejection fraction and Cpc-PH underwent right-heart catheterization, including acute provocation testing (fluid loading and inhaled nitric oxide) and cardiac MRI at baseline. Right-heart catheterization and cardiac MRI were repeated after 4 months of treatment. At baseline, acutely increasing preload by fluid loading resulted in a significant increase in pulmonary arterial wedge pressure (PAWP), whereas reducing right ventricular (RV) afterload and increasing LV distensability by acute administration of inhaled nitric oxide had no effect on PAWP. After 4 months of treatment, we observed a significant reduction in RV and LV afterload and increased RV and LV stroke volume, but PAWP significantly increased. CONCLUSIONS: In patients with heart failure with preserved ejection fraction and Cpc-PH, 4 months of pulmonary arterial hypertension-specific treatment increased RV and LV stroke volume at the expense of increased PAWP. This increase in PAWP was similarly observed acutely after fluid loading.

Data on the impact of scan quality on the diagnostic performance of CCTA, SPECT, and PET for diagnosing myocardial ischemia defined by fractional flow reserve on a per vessel level.

Scan quality directly impacts the diagnostic performance of non-invasive imaging modalities as reported in a substudy of the PACIFC-trial: "Impact of Scan Quality on the Diagnostic Performance of CCTA, SPECT, and PET for Diagnosing Myocardial Ischemia Defined by Fractional Flow Reserve" [1]. This Data-in-Brief paper supplements the hereinabove mentioned article by presenting the diagnostic performance of CCTA, SPECT, and PET on a per vessel level for the detection of hemodynamic significant coronary artery disease (CAD) when stratified according to scan quality and vascular territory.

The association of coronary lumen volume to left ventricle mass ratio with myocardial blood flow and fractional flow reserve.

BACKGROUND: A diminished coronary lumen volume to left ventricle mass ratio (V/M) derived from coronary computed tomography angiography (CCTA) has been proposed as factor contributing to impaired myocardial blood flow (MBF) even in the absence of obstructive disease on invasive coronary angiography (ICA). METHODS: Patients underwent CCTA, and positron emission tomography (PET) prior to ICA. Matched global V/M, global, and vessel specific hyperaemic MBF (hMBF), coronary flow reserve (CFR), and, FFR were available for 431 vessels in 152 patients. The median V/M (20.71 mm3/g) was used to divide the population into patients with either a low V/M or a high V/M. RESULTS: Overall, a higher percentage of vessels with an abnormal hMBF and FFR (34% vs. 19%, p = 0.009 and 20% vs. 9%, p = 0.004), as well as a lower FFR (0.93 [interquartile range: 0.85-0.97] vs. 0.95 [0.89-0.98], p = 0.016) values were observed in the low V/M group. V/M was weakly associated with vessel specific hMBF (R = 0.148, p = 0.027), and FFR (R = 0.156, p < 0.001). Among vessels with non-obstructive CAD on ICA (361 vessels), no association between V/M and vessel specific hMBF nor CFR was noted. However, in the absence of obstructive CAD, V/M was associated with (R = 0.081, p = 0.027), and independently predictive for FFR (p = 0.047). CONCLUSION: Overall, an abnormal vessel specific hMBF and FFR were more prevalent in patients with a low V/M compared to those with a high V/M. Furthermore, V/M was weakly associated with vessel specific hMBF and FFR. In the absence of obstructive CAD on ICA, V/M was weakly associated with notwithstanding independently predictive for FFR.

Correction to: Extra energy for hearts with a genetic defect: ENERGY trial.

Correction to: Neth Heart J 2019 https://doi.org/10.1007/s12471-019-1239-0 In the version of the article originally published online, there was an error in Fig. 1a. In the 3â€¯× 3 panel, the images indicated as 'CMR cine of four-chamber view', 'Parametric image of k2' and 'Polar map of k2' were ….

Extra energy for hearts with a genetic defect: ENERGY trial.

AIMS: Previous studies have shown that hypertrophic cardiomyopathy mutation carriers have a decreased myocardial energy efficiency, which is thought to play a key role in the pathomechanism of hypertrophic cardiomyopathy (HCM). The ENERGY trial aims to determine whether metabolic drugs correct decreased myocardial energy efficiency in HCM mutation carriers at an early disease stage. METHODS: 40 genotype-positive, phenotype-negative MYH7 mutation carriers will be treated for two months with trimetazidine or placebo in a double-blind randomised study design. Directly before and after treatment, study subjects will undergo an [11C]-acetate positron emission tomography/computed tomography (PET/CT) and cardiac magnetic resonance (CMR) scan to measure myocardial energy efficiency. Myocardial efficiency will be calculated as the amount of oxygen the heart consumes to perform work. CONCLUSION: The ENERGY trial will be the first proof of concept study to determine whether metabolic drugs are a potential preventive therapy for HCM. Given that trimetazidine is already being used in clinical practice, there is large potential to swiftly implement this drug in HCM therapy.

Correction to: A mobile one-lead ECG device incorporated in a symptom-driven remote arrhythmia monitoring program. The first 5,982 Hartwacht ECGs.

Correction to: Neth Heart J 2018 https://doi.org/10.1007/s12471-018-1203-4 Unfortunately the original version of this article did not reflect that J.L. Selder and L. Breukel contributed equally to the ….

A mobile one-lead ECG device incorporated in a symptom-driven remote arrhythmia monitoring program. The first 5,982 Hartwacht ECGs.

BACKGROUND: In recent years many mobile devices able to record health-related data in ambulatory patients have emerged. However, well-organised programs to incorporate these devices are sparse. Hartwacht Arrhythmia (HA) is such a program, focusing on remote arrhythmia detection using the AliveCor Kardia Mobile (KM) and its algorithm. OBJECTIVES: The aim of this study was to assess the benefit of the KM device and its algorithm in detecting cardiac arrhythmias in a real-world cohort of ambulatory patients. METHODS: All KM ECGs recorded in the HA program between January 2017 and March 2018 were included. Classification by the KM algorithm was compared with that of the Hartwacht team led by a cardiologist. Statistical analyses were performed with respect to detection of sinus rhythm (SR), atrial fibrillation (AF) and other arrhythmias. RESULTS: 5,982 KM ECGs were received from 233 patients (mean age 58 years, 52% male). The KM algorithm categorised 59% as SR, 22% as possible AF, 17% as unclassified and 2% as unreadable. According to the Hartwacht team, 498 (8%) ECGs were uninterpretable. Negative predictive value for detection of AF was 98%. However, positive predictive value as well as detection of other arrhythmias was poor. In 81% of the unclassified ECGs, the Hartwacht team was able to provide a diagnosis. CONCLUSIONS: This study reports on the first symptom-driven remote arrhythmia monitoring program in the Netherlands. Less than 10% of the ECGs were uninterpretable. However, the current performance of the KM algorithm makes the device inadequate as a stand-alone application, supporting the need for manual ECG analysis in HA and similar programs.

Variable cardiac myosin binding protein-C expression in the myofilaments due to MYBPC3 mutations in hypertrophic cardiomyopathy.

BACKGROUND: Mutations in MYBPC3 are the most common cause of hypertrophic cardiomyopathy (HCM). These mutations produce dysfunctional protein that is quickly degraded and not incorporated in the myofilaments. Most patients are heterozygous and allelic expression differs between cells. We hypothesized that this would lead to cell-to-cell variation in cardiac myosin binding protein-C (cMyBP-C, encoded by MYBPC3 gene) protein levels. METHODS: Twelve HCM patients were included (six had no sarcomere mutations (HCMsmn) and served as the control group and six harbored mutations in the MYBPC3 gene (MYBPC3mut). Western blot and RNA sequencing analysis of cardiac tissue lysates were performed to detect overall cMyBP-C protein and mRNA levels. Cellular expression of cMyBP-C and α-actin was obtained by immunofluorescence staining. Quantification of cell-to-cell variation of cMyBP-C expression between cardiomyocytes was measured by determining the ratio of cMyBP-C:α-actin stained area of each cell. RESULTS: Protein and mRNA analysis revealed significantly reduced cMyBP-C levels in MYBPC3mut patients compared with HCMsmn patients (0.73 ±â€¯0.09 vs. 1.0 ±â€¯0.15, p < .05; 162.3 ±â€¯16.4 vs. 326.2 ±â€¯41.9 RPKM, p = .002), without any sign of truncated proteins. Immunofluorescence staining of individual cardiomyocytes in HCMsmn patients demonstrated homogenous and equal cMyBP-C:α-actin staining ratio. In contrast, MYBPC3mut patients demonstrated inhomogeneous staining patterns with a large intercellular variability per patient. Coefficient of variance for cMyBP-C/α-actin staining for each patient showed a significant difference between both groups (17.30 ±â€¯4.08 vs. 5.18 ±â€¯0.65% in MYBPC3mut vs. HCMsmn, p = .02). CONCLUSION: This is the first study to demonstrate intercellular variation of myofilament cMyBP-C protein expression within the myocardium from HCM patients with heterozygous MYBPC3 mutations.

Automated SPECT analysis compared with expert visual scoring for the detection of FFR-defined coronary artery disease.

PURPOSE: Traditionally, interpretation of myocardial perfusion imaging (MPI) is based on visual assessment. Computer-based automated analysis might be a simple alternative obviating the need for extensive reading experience. Therefore, the aim of the present study was to compare the diagnostic performance of automated analysis with that of expert visual reading for the detection of obstructive coronary artery disease (CAD). METHODS: 206 Patients (64% men, age 58.2 ± 8.7 years) with suspected CAD were included prospectively. All patients underwent 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) and invasive coronary angiography with fractional flow reserve (FFR) measurements. Non-corrected (NC) and attenuation-corrected (AC) SPECT images were analyzed both visually as well as automatically by commercially available SPECT software. Automated analysis comprised a segmental summed stress score (SSS), summed difference score (SDS), stress total perfusion deficit (S-TPD), and ischemic total perfusion deficit (I-TPD), representing the extent and severity of hypoperfused myocardium. Subsequently, software was optimized with an institutional normal database and thresholds. Diagnostic performances of automated and visual analysis were compared taking FFR as a reference. RESULTS: Sensitivity did not differ significantly between visual reading and most automated scoring parameters, except for SDS, which was significantly higher than visual assessment (p < 0.001). Specificity, however, was significantly higher for visual reading than for any of the automated scores (p < 0.001 for all). Diagnostic accuracy was significantly higher for visual scoring (77.2%) than for all NC images scores (p < 0.05), but not compared with SSS AC and S-TPD AC (69.8% and 71.2%, p = 0.063 and p = 0.134). After optimization of the automated software, diagnostic accuracies were similar for visual (73.8%) and automated analysis. Among the automated parameters, S-TPD AC showed the highest accuracy (73.5%). CONCLUSION: Automated analysis of myocardial perfusion SPECT can be as accurate as visual interpretation by an expert reader in detecting significant CAD defined by FFR.

Improved patient selection for cardiac resynchronization therapy by normalization of QRS duration to left ventricular dimension.

AIMS: This study evaluates the relative importance of two components of QRS prolongation, myocardial conduction velocity and travel distance of the electrical wave front (i.e. path length), for the prediction of acute response to cardiac resynchronization therapy (CRT) in left bundle branch block (LBBB) patients. METHODS AND RESULTS: Thirty-two CRT candidates (ejection fraction <35%, LBBB) underwent cardiac magnetic resonance (CMR) imaging to provide detailed information on left ventricular (LV) dimensions. Left ventricular end-diastolic volume (LVEDV) was used as a primary measure for path length, subsequently QRSd was normalized to LV dimension (i.e. QRSd divided by LVEDV) to adjust for conduction path length. Invasive pressure-volume loop analysis at baseline and during CRT was used to assess acute pump function improvement, expressed as LV stroke work (SW) change. During CRT, SW improved by +38 ± 46% (P < 0.001). The baseline LVEDV was positively related to QRSd (R = 0.36, P = 0.044). Despite this association, a paradoxical inverse relation was found between LVEDV and SW improvement during CRT (R = -0.40; P = 0.025). Baseline unadjusted QRSd was found to be unrelated to SW changes during CRT (R = 0.16; P = 0.383), whereas normalized QRSd (QRSd/LVEDV) yielded a strong correlation with CRT response (R = 0.49; P = 0.005). Other measures of LV dimension, including LV length, LV diameter, and LV end-systolic volume, showed similar relations with normalized QRSd and SW improvement. CONCLUSION: Since normalized QRSd reflects myocardial conduction properties, these findings suggest that myocardial conduction velocity rather than increased path length mainly determines response to CRT. Normalizing QRSd to LV dimension might provide a relatively simple method to improve patient selection for CRT.