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Background: Previous studies indicated the importance of the intrinsic left ventricular (LV) electric delay (QLV) for optimal benefit to cardiac resynchronization therapy. We investigated the use of QLV for achieving optimal acute hemodynamic response to cardiac resynchronization therapy with a quadripolar LV lead. Methods and Results: Forty-eight heart failure patients with a left bundle branch block were prospectively enrolled (31 men; age, 66±10 years; LV ejection fraction, 28±8%; QRS duration, 176±14 ms). Immediately after cardiac resynchronization therapy implantation, invasive LV pressure–volume loops were recorded during biventricular pacing with each separate electrode at 4 atrioventricular delays. Acute cardiac resynchronization therapy response, measured as change in stroke work (Δ%SW) compared with intrinsic conduction, was related to intrinsic interval between Q on the ECG and LV sensing delay (QLV), normalized for QRS duration (QLV/QRSd), and electrode position. QLV/QRSd was 84±9% and variation between the 4 electrodes 9±5%. Δ%SW was 89±64% and varied by 39±36% between the electrodes. In univariate analysis, an anterolateral or lateral electrode position and a high QLV/QRSd had a significant association with a large Δ%SW (all P P Conclusions: The large variation in acute hemodynamic response indicates that the choice of the stimulated electrode on a quadripolar lead is important. Although QLV/QRSd was associated with acute hemodynamic response at group level, it cannot be used to select the optimal electrode in the individual patient.

Background The aims of this study were to determine the optimal tracer kinetic model for [11C]-meta-hydroxyephedrine ([11C]HED) and to evaluate the performance of several simplified methods. Methods Thirty patients underwent dynamic 60-min [11C]HED scans with online arterial blood sampling. Single-tissue and both reversible and irreversible two-tissue models were fitted to the data using the metabolite-corrected arterial input function. For each model, reliable fits were defined as those yielding outcome parameters with a coefficient of variation (CoV)

Summary Autonomic function tests require standardised test conditions. We compared testing under non-standardised and standardised conditions and investigated the agreement between heart and pulse rate variability in 30 subjects with diabetes mellitus. Deep breathing, Valsalva manoeuvre and quick standing tests showed non-standardised reproducibility intraclass correlations (95% CI) of 0.96 (0.82–0.99), 0.96 (0.81–0.99) and 0.75 (−0.98 to 0.94), respectively. Intraclass correlations for sustained handgrip and quick standing were poor. Heart and pulse rate variability showed high-frequency band intraclass correlations (95% CI) of 0.65 (−0.07 to 0.89) and 0.47 (−0.88 to 0.85) for the very low-frequency band, respectively, 0.68 (0.00−0.90) and 0.70 (−0.09 to 0.91) for the low-frequency band, and 0.86 (0.57−0.95) and 0.82 (0.39−0.95) for the high-frequency band. Reproducibility under standardised conditions was comparable. The mean difference (95% limits of agreement) between heart and pulse rate variability was 0.99 (0.80−1.22) for very low frequency, 1.03 (0.88−1.21) for low frequency and 1.35 (0.84−2.16) for high frequency, with a Spearman's correlation coefficient of 1.00, 0.99 and 0.98, respectively. We demonstrated a high agreement between heart and pulse rate variability and acceptable reproducibility with most autonomic function tests, heart and pulse rate variability.

Background Left ventricular segmental wall motion analysis is important for clinical decision making in cardiac diseases. Strain analysis with myocardial tissue tagging is the non-invasive gold standard for quantitative assessment, however, it is time-consuming. Cardiovascular magnetic resonance myocardial feature-tracking (CMR-FT) can rapidly perform strain analysis, because it can be employed with standard CMR cine-imaging. The aim is to validate segmental peak systolic circumferential strain (peak SCS) and time to peak systolic circumferential strain (T2P-SCS) analysed by CMR-FT against tissue tagging, and determine its intra and inter-observer variability. Methods Patients in whom both cine CMR and tissue tagging has been performed were selected. CMR-FT analysis was done using endocardial (CMR-FTendo) and mid-wall contours (CMR-FTmid). The Intra Class Correlation Coefficient (ICC) and Pearson correlation were calculated. Results 10 healthy volunteers, 10 left bundle branch block (LBBB) and 10 hypertrophic cardiomyopathy patients were selected. With CMR-FT all 480 segments were analyzable and with tissue tagging 464 segments. Significant differences in mean peak SCS values of the total study group were present between CMR-FTendo and tissue tagging (-23.8 ± 9.9% vs -13.4 ± 3.3%, p

Objective: We determined, via a bioassay, if inotropic factors are released in the coronary circulation of the rat heart and if changes in cardiac perfusion change papillary muscle inotropy. Methods: An isolated isometrically contracting rat papillary muscle ( n = 5, acceptor) was superfused with Tyrode or with reoxygenated coronary venous effluent from an isolated isovolumically beating rat heart (donor) at 27°C, which was perfused with Tyrode according to Langendorff. The superfusion solution in the muscle bath was exchanged completely in 90 s. During coronary venous effluent superfusion, the flow of the heart (donor) was changed in steps. Results: The peak force of the papillary muscle (acceptor) was unaffected by a change from Tyrode to coronary venous effluent superfusion, but time to half relaxation (RT1/2) significantly increased by 23.0 ± 9.0% (mean ± s.d.) and positive dF/dtmax significantly decreased by 14.6 ± 4.7%. These twitch characteristics were unaffected by changes in coronary perfusion while in the heart isovolumic developed left ventricular pressure did increase with perfusion (the Gregg phenomenon). Conclusions: Factors that affect papillary muscle contractility are released into the coronary circulation, but their effect is independent of the magnitude of coronary perfusion.

Purpose The perfusable tissue index (PTI) is a marker of myocardial viability. Recent technological advances have made it possible to generate parametric PTI images from a single [15O]H2O PET/CT scan. The purpose of this study was to validate these parametric PTI images. Methods The study population comprised 46 patients with documented or suspected coronary artery disease who were studied with [15O]H2O PET and late gadolinium-enhanced (LGE) cardiac magnetic resonance imaging (CMR). Results Of the 736 myocardial segments included, 364 showed some degree of LGE. PTI and perfusable tissue fraction (PTF) diminished with increasing LGE. The areas under the curve of the PTI and PTF, used to predict (near) transmural LGE on CMR, were 0.86 and 0.87, respectively. Optimal sensitivity and specificity were 91 % and 73 % for PTI and 69 % and 87 % for PTF, respectively. Conclusion PTI and PTF assessed with a single [15O]H2O scan can be utilized as markers of myocardial viability in patients with coronary artery disease.

Background The incremental value of CAC over traditional risk factors to predict coronary vasodilator dysfunction and inherent myocardial blood flow (MBF) impairment is only scarcely documented (MBF). The aim of this study was therefore to evaluate the relationship between CAC content, hyperemic MBF, and coronary flow reserve (CFR) in patients undergoing hybrid 15O-water PET/CT imaging. Methods We evaluated 173 (mean age 56 ± 10, 78 men) patients with a low to intermediate likelihood for coronary artery disease (CAD), without a documented history of CAD, undergoing vasodilator stress 15O-water PET/CT and CAC scoring. Obstructive coronary artery disease was excluded by means of invasive (n = 44) or CT-based coronary angiography (n = 129). Results 91 of 173 patients (52%) had a CAC score of zero. Of those with CAC, the CAC score was 0.1-99.9, 100-399.9, and ≥400 in 31%, 12%, and 5% of patients, respectively. Global CAC score showed significant inverse correlation with hyperemic MBF (r = −0.32, P

Cardiac resynchronization therapy (CRT) decreases the morbidity and mortality in patients with end-stage heart failure. However, patient selection remains challenging, because a considerable 30% to 50% do not respond. Controversy exists on the cutoff values for the QRS duration and the optimal lead location. The present study relates these parameters on an individual basis to acute pump function improvement using invasively obtained pressure-volume loops. Fifty-seven patients with symptomatic end-stage heart failure were included in our temporary biventricular stimulation study and were grouped according to the QRS duration (QRS

Right heart failure in pulmonary arterial hypertension (PH) is associated with mechanical ventricular dyssynchrony, which leads to impaired right ventricular (RV) function and, by adverse diastolic interaction, to impaired left ventricular (LV) function as well. However, therapies aiming to restore synchrony by pacing are currently not available. In this proof-of-principle study, we determined the acute effects of RV pacing on ventricular dyssynchrony in PH. Chronic PH with right heart failure was induced in rats by injection of monocrotaline (80 mg/kg). To validate for PH-related ventricular dyssynchrony, rats (6 PH, 6 controls) were examined by cardiac magnetic resonance imaging (9.4 T), 23 days after monocrotaline or sham injection. In a second group (10 PH, 4 controls), the effects of RV pacing were studied in detail, using Langendorff-perfused heart preparations. In PH, septum bulging was observed, coinciding with a reversal of the transseptal pressure gradient, as observed in clinical PH. RV pacing improved RV systolic function, compared with unpaced condition (maximal first derivative of RV pressure: +8.5 ± 1.3%, P < 0.001). In addition, RV pacing markedly decreased the pressure-time integral of the transseptal pressure gradient when RV pressure exceeds LV pressure, an index of adverse diastolic interaction (−24 ± 9%, P < 0.01), and RV pacing was able to resynchronize time of RV and LV peak pressure (unpaced: 9.8 ± 1.2 ms vs. paced: 1.7 ± 2.0 ms, P < 0.001). Finally, RV pacing had no detrimental effects on LV function or coronary perfusion, and no LV preexcitation occurred. Taken together, we demonstrate that, in experimental PH, RV pacing improves RV function and diminishes adverse diastolic interaction. These findings provide a strong rationale for further in vivo explorations.

Background Normal left ventricular (LV) torsion is caused by opposite basal and apical rotation. Opposite rotation can be lost in heart failure, but might be restored by pacing; therefore, the predictive value of the loss of opposite base-apex rotation in heart failure patients for the response to cardiac resynchronization therapy (CRT) was studied. Methods and Results In 34 CRT candidates and 12 controls, basal and apical LV rotations were calculated using magnetic resonance image tagging. Loss of opposite rotation was quantified by the correlation between both rotation curves: a negative correlation indicates normal, opposite rotation and a positive correlation indicates that base and apex rotate in the same direction. In patients, LV pressure was measured invasively during biventricular stimulation. Acute response to CRT was defined by >10% increase in dP/dt max relative to baseline. LV volume was determined at baseline and 8 months follow-up using echocardiography. The base-apex rotation correlation (BARC) was significantly higher in acute responders (n=22) than in nonresponders (n=12) and controls (0.64±0.51, –0.23±0.67, and –0.68±0.22, respectively; P =.001). The sensitivity and specificity for prediction of acute response were 82% and 83%, respectively, at a cutoff value of 0.5. At follow-up, volumes could be analyzed in 18 patients. In the group with BARC >0.5, end-diastolic volume decreased by 7% (NS), end-systolic volume by 16%, and ejection fraction increased by 28% (both P =.02), whereas in the group with BARC Conclusions The loss of opposite base-apex rotation in patients eligible for CRT is an excellent predictor of acute response and is associated with LV reverse remodeling.

Coronary artery spasm has been known to induce ischaemia and ventricular arrhythmias. We present a case of recurrent ventricular fibrillation caused by spasm-associated transmural myocardial ischaemia. During an intra-coronary acetylcholine provocation test, severe coronary spasm could be induced. The patient was treated with a hybrid approach of medication and an implantable defibrillator.

The heart is an aerobic organ that relies almost exclusively on the aerobic oxidation of substrates for generation of energy. Consequently, there is close coupling between myocardial oxygen consumption (MVo2) and the main determinants of systolic function: heart rate, contractile state, and wall stress.1 As in any mechanical pump, only part of the energy invested is converted to external power. In the case of the heart, the ratio of useful energy produced (ie, stroke work [SW]) to oxygen consumed is defined as mechanical efficiency, as originally proposed by Bing et al.2 Under normal conditions this ratio is ≈25%, and the residual energy mainly dissipates as heat.3 In pathophysiological disease states, such as heart failure, mechanical efficiency is reduced, and it has been hypothesized that the increased energy expenditure relative to work contributes to progression of the disease.4,5 Moreover, therapeutic interventions that enhance mechanical efficiency have proven to be beneficial with respect to outcome.6 It is therefore desirable to quantify efficiency of the heart to study disease processes and monitor interventions. Both cardiac oxidative metabolism and mechanical work, and thus efficiency, can be quantified through invasive measurements. Although these measurements are accurate and currently considered the gold standard, in clinical practice they are limited because of the need for dual-sided heart catheterization and selective catheterization of the coronary sinus. Recent advances in imaging techniques, however, offer the possibility to noninvasively estimate MVo2 and mechanical work by positron emission tomography and echocardiography or by magnetic resonance imaging, respectively. This review discusses the principles of mechanical efficiency, together with its invasive and noninvasive assessment, as well as their strengths and pitfalls. Finally, results from clinical pathophysiological studies are discussed. To calculate the efficiency of the heart, input and output energy must be obtained. The …

To the Editor: With great interest we read the recent work by Steendijk et al1 that investigated the effects of long-term cardiac resynchronization therapy (CRT) on hemodynamics as evaluated by pressure-volume loops. That study elegantly demonstrates that the previously observed favorable short-term hemodynamic effects of CRT are maintained over time. Among other findings, the authors report a significant increase in end-systolic elastance (Ees …

Cardiac resynchronization therapy (CRT) is based on restoring left ventricular dyssynchrony. It is known that CRT induced changes in QRS duration poorly predict hemodynamic effect. This study assessed invasively obtained endocardial and epicardial left ventricular activation with and without CRT and

The main eligibility criterion (left ventricular ejection fraction (LVEF) ≤35%) for primary prevention implantable cardioverter-defibrillator (ICD) therapy is based on large clinical trials using Two-Dimensional Echocardiography (2DE). Presently, cardiac magnetic resonance imaging (CMR) is

Three-dimensional reconstruction of cardiac structures is becoming increasingly important. Complete spatial visualization of cardiac structures and their relation to each other enable better understanding of both morphologic and functional lesions.

Background: Cardiac resynchronization therapy (CRT) is an established therapy for end-stage heart failure. It is currently recommended to position the left ventricular (LV) lead at the postero-lateral (PL) wall. However, the position of the right ventricular (RV) lead remains controversial, since it may be associated with adverse hemodynamic effects. This may partly explain non-response to CRT. We hypothesized that RV pacing during biventricular pacing signiicantly modulates response. We studied the acute invasive hemodynamic response of RV, LV and biventricular pacing.

The effect of perfusion on diastolic muscle properties was investigated in six isolated right ventricular papillary muscles from rat hearts perfused with a crystalloid solution via the septal artery. Stress-strain relations were obtained at different perfusion pressures. Increased perfusion pressure caused an increase of stress at large strains but a decrease of stress at low strains. Thus stress-free strain increased with increasing perfusion pressure. Stress-strain relations of a given muscle at different perfusion pressures (range 12–122 cmH2O) intersected at a single “crossover” strain. Muscle stiffness, defined as the slope of the stress-strain relation, increased at all strains. Muscle diameter measurements indicated that the observed changes of the stress-strain relation occurred in association with vascular filling rather than with formation of edema. To explain the findings, the papillary muscle was modeled by two parallel compartments: muscle cells (together with the extracellular matrix) and vasculature. Perfusion was assumed to have an effect on the axial vascular properties but not on muscle cells. Combination of the stress-strain data of the muscle compartment and the vascular compartment (taken from literature) predicted stress-strain relations similar to those obtained in our perfused papillary muscles. We conclude that increased muscle stiffness at increased perfusion pressure is mainly caused by pressure-dependent changes in mechanical behavior of the vascular compartment.

Background The incremental value of CAC over traditional risk factors to predict coronary vasodilator dysfunction and inherent myocardial blood flow (MBF) impairment is only scarcely documented (MBF). The aim of this study was therefore to evaluate the relationship between CAC content, hyperemic MBF, and coronary flow reserve (CFR) in patients undergoing hybrid 15O-water PET/CT imaging.

Myocardial strain imaging could potentially improve patient selection for cardiac resynchronization therapy (CRT). Available techniques are CMR tagging (CMR-TAG), feature tracking (CMR-FT) and speckle tracking echocardiography (STE). Despite promising results per modality, a direct comparison is