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Background Left ventricular (LV) systole and diastole are intimately dependent on myocardial torsion, which involves coupling between myocardial rotation (twisting in systole and untwisting in diastole) and longitudinal motion. Heart failure with normal ejection fraction (HFNEF) is known to involve exercise-induced wall motion abnormalities, but torsion on exercise has not been explored. We hypothesised that torsional dyssynchrony may also be involved and be exaggerated by exercise. Methods and Results 67 patients (age 73±7 years, 45 female) with HFNEF and 38 controls underwent cardiopulmonary exercise testing and echocardiography at rest and on supine exercise. Analysis of three plane motions was performed using speckle tracking and tissue Doppler imaging. Torsional dyssynchrony was quantified as the SD of the time to peak systolic motion (SDSM) (basal and apical rotation, longitudinal and radial displacement); the time difference between peak twist and peak longitudinal displacement (twist-longitudinal motion delay, TLMD) and the ratio of untwist to longitudinal extension (UT:LE). At rest, HFNEF patients had similar SDSM, TLMD and UT:LE compared with controls. Exercise was associated with significantly more dyssynchrony in the HFNEF patients (SDSM 38.8±27.6 ms vs 25.9±15.5 ms, p=0.02; TLMD 28.4±46.2 ms vs 2.9±31.2 ms, p=0.005 and UT:LE 10.4±15.3 vs 3.3±3.8, p=0.022). The SDSM correlated positively with LV wall thickness (r=0.31, p=0.015) and negatively with peak oxygen consumption (r=−0.299, p=0.01) and changes in stroke volume on exercise (r=−0.371, p=0.001). Conclusions HFNEF involves exercise-induced torsional dyssynchrony in systole and diastole, which relates to LV hypertrophy as well as exercise capacity.

Background Myocardial deformation can be key to clinical decision. 2D feature-tracking of cardiovascular magnetic resonance (CMR-FT) imaging is user-friendly but has poor reproducibility, particularly for radial strain. 3D CMR-FT may improve repeatability by reducing through-plane artefact. The aim of this study was to provide normal ranges for 3D CMR-FT and compare its reproducibility to older generation 2D CMR-FT. Method 56 asymptomatic, healthy subjects (43.7±12.9 year, 52% male) undertook CMR (1.5 Tesla scanner Magnetom Avanto, Siemens, Erlangen, Germany). 3D FT-CMT was generated using the SSFP HLA, VLA and short axis cine images (Figure 1). A single observer (BL) analysed the CMR studies using 2D and 3D CMR-FT (Circle cvi 42 ® version 5.3) and after 4 weeks, re-analysed blinded scans for intra-observer variability. Inter-observer variability was generated by separate tracking by a second blinded observer (AS) in a randomly generated subset of 15 subjects. Agreement was tested by calculating mean bias and 95% limits of agreement (confidence intervals) from Bland–Altman analyses, coefficient of variation, and inter-class correlation coefficient (ICC). Results There is modest agreement between all measures of 2D and 3D peak strain analysis (ICC=0.44 to 0.58). Mean global circumferential strain (GCS) on 3D analysis is −16.8±2.5, compared to 2D GCS of −20.2±3.31 and −20.6±3.4 at the base and mid-ventricular level respectively. Mean global longitudinal strain (GLS) is −13.7±2.3 on 3D CMT-FT and −19.3±2.7 on 2D CMR-FT. Global radial strain (GRS) is 45.5±10.9 for 3D, compared to 55.1±14.4 and 48.0±13.4 at the base and mid-ventricular level respectively. Table 1 displays the inter- and intra-observer variability of each technique. Intra-observer variability was significantly improved by 3D CMT-FT for GCS, whilst inter-observer variability was significantly improved for GCS, GRS and strain rates. No reproducibility differences were identified for GLS. Discussion Peak strains using 3D FT-CMR is different to 2D normal range values. 3D CMR-FT has superior intra- and inter-observer reproducibility compared with 2D CMR-FT, particularly for GCS and GRS strain, the latter being the principal systolic strain and should improve detection of sub-clinical ventricular dysfunction.

The cardinal symptom of heart failure with a normal ejection fraction (HFNEF) is exertional dyspnoea. The authors hypothesised that failure of left atrial (LA) compensatory mechanism particularly on exercise contributes to the genesis of symptoms in HFNEF patients.Fifty HFNEF patients, 15 asymptomatic hypertensive subjects and 30 healthy controls underwent rest and submaximal exercise echocardiography. Rest and exercise systolic, early diastolic and late diastolic (Am) mitral annular velocities were assessed using colour tissue Doppler echocardiography. Left atrial functional reserve index was calculated. Am at rest was comparable between all three groups, but exercise Am was significantly lower in HFNEF compared with hypertensive subjects and healthy controls resulting in a lower LA functional reserve index (0.84 (1.34) vs 2.39 (1.27) and 1.81 (1.39), p0.001). LA volume index was significantly higher in HFNEF patients (30.4 (9.2) vs 27.9 (6.3) and 23.2 (7.1) ml/m(2), p=0.002). There was a significant correlation between Am on exercise with peak VO(2) max (r=0.514, p0.001) and E/Em on exercise (r=-0.547, p0.001). Area under the receiver operating characteristic for Am on exercise was 0.768 (95% CI=0.660 to 0.877).HFNEF patients have reduced LA function on exercise in addition to left ventricular systolic and diastolic dysfunctions. Reduced LA function probably contributes significantly to exercise intolerance and breathlessness in HFNEF patients.

Objective: To develop and validate a prognostic risk index of cardiovascular mortality after cardiac resynchronisation therapy (CRT). Design: Prospective cohort study. Setting: District general hospital. Patients: 148 patients with heart failure (mean age 66.7 (SD 10.4) years), New York Heart Association class III or IV, LVEF

Objectives: Healthcare expenditure per-capita in the USA is higher than in England. We hypothesised that clinical outcomes after cardiac revascularisation are better in the USA. We compared costs and outcomes of patients undergoing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in England and New York State (NYS). Methods: Costs and total mortality were assessed using the Hospital Episode Statistics for England and the Statewide Planning and Research Cooperative System for NYS. Outcomes after a first CABG or PCI were assessed in patients undergoing a first CABG (n=142 969) or PCI (n=431 416). Results: After CABG, crude total mortality in England was 0.72% lower at 30 days and 3.68% lower at 1 year (both P

OBJECTIVE: To determine whether lower limb blood flow is related to serum uric acid concentrations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic treatment and insulin resistance. DESIGN: Lower limb blood flow was measured at rest and after maximum exercise followed by a five minute period of ischaemia (maximum blood flow) using strain gauge venous occlusion plethysmography. All patients underwent a metabolic assessment, which included an intravenous glucose tolerance test (IVGTT)-to obtain an index of insulin sensitivity- and measurement of serum uric acid. SETTING: University and hospital departments specialising in cardiology and metabolic medicine. SUBJECTS: 22 patients with chronic heart failure. RESULTS: Mean (SEM) resting and maximum blood flow values were 2.87 (0.23) and 24.00 (1.83) ml/100 ml/min, respectively. Patients in the upper tertile of serum uric acid had lower maximum blood flow than those in the lowest tertile (15.6 (2.2) v 31.0 (2.1) ml/100 ml/min, P = 0.003). Serum uric acid correlated with maximum blood flow (r = -0.86, P < 0.001), but not with resting blood flow. In stepwise regression analysis, uric acid emerged as the only predictor of maximum blood flow (standardised coefficient = -0.83 (P < 0.001), R2 = 0.68 (P < 0.001)), independently of diuretic dose, age, body mass index, plasma creatinine, fasting and IVGTT glucose and insulin, insulin sensitivity, maximum oxygen uptake and exercise time during the treadmill exercise test, and alcohol intake. CONCLUSIONS: There is a strong inverse relation between serum uric acid concentrations and maximum leg blood flow in patients with chronic heart failure. Further studies are needed to determine whether serum uric acid can be used as an index of vascular function in cardiovascular diseases.

Introduction Feature-tracking (FT) analysis offers a novel, fast and practicable method to calculate strain from routinely acquired steady state free precession (SSFP) images without the need to perform additional tagged sequences. There is no validation of this technique, however, against a reference standard myocardial tagging analysis for any strain parameter other than mid-left ventricular whole slice circumferential strain. In an adult study of patients with dilated cardiomyopathy (DCM) and healthy controls, we sought to validate the FT method (TomTec Imaging systems, Munich) against spatial modulation of magnetisation (SPAMM) tissue tagging analysis (Cardiac Image Modelling Package (CIMTag2D), University of Auckland) for the computation of long axis function. Methods We compared measures of global longitudinal strain from the horizontal long axis view using the two techniques in 45 patients (mean age 44±14 years, male 63%). Normal healthy adults (n=35) were identified from an ongoing prospective, observational research study examining the effects of living kidney donation on cardiovascular structure and function (NCT01028703). Consecutive DCM patients (n=10) were identified after undergoing myocardial tagging for clinically indicated scans. Retrospective off-line analysis was performed on matched tagged and SSFP slices by two independent blinded observers (WEM and RJT). After manually drawing endocardial borders in the end-diastolic frame for each image, the FT software automatically propagated the contour and followed its features (brightness gradient at the tissue-cavity interface, dishomogeneties of the tissue, spatial coherence) throughout the remainder of the cardiac cycle to compute longitudinal strain parameters. Results Longitudinal strain (Ell) . Peak systolic FT-Ell (−18.1±5.0%) correlated most strongly with CIMTag-Ell values derived from the subendocardium (−16.7±4.8%) with a Pearson9s correlation coefficient of 0.70 (p Longitudinal strain rate (SR) There was good agreement between the two techniques for peak systolic global longitudinal SR values but with a small tendency towards higher FT values as compared with tagging (mean difference 0.09±0.26 1/s, p=0.04; r=0.64, p Reproducibility testing Intraobserver and interobserver variability for FT-Ell analysis was small (−0.49±1.83% and 0.22±1.13%, respectively). Timed analysis The average time taken for post-processing strain analysis using FT software was significantly less than that required for CIMTag (5.9±0.8 min vs 23.2±3.5 min, p Conclusions FT based assessment of longitudinal strain correlated highly with values derived from tagged images in a population with a wide range of left ventricular function. Furthermore, FT can be performed without the need for additional imaging and lengthy post-processing times.

The authors' reply : We thank Drs Artis and Gale for their careful review1 of our study on the dyssynchrony, scar and creatinine (DSC) index as a predictor of outcome after cardiac resynchronisation therapy (CRT).2 We shall deal with each point in turn. We agree that atrial fibrillation often makes imaging more challenging, particularly when the ventricular response is uncontrolled. This applies to both cardiovascular magnetic resonance and echocardiography. In our experience, however, prospective gating permits adequate visualisation of the left ventricular endocardium as well as derivation of …

Background Myocardial strain imaging has the potential for clinical application in the detection of pre-clinical disease, stress induced myocardial dysfunction and dyssynchrony. Feature-tracking cardiovascular magnetic resonance (FT-CMR) uses routine CMR imaging (steady-state free-precession imaging) to calculate myocardial strain. Methods Healthy volunteers (n=20, age: 42±13 years, 11 (55%) male) underwent a standard protocol CMR. Endocardial and epicardial borders were manually drawn and automatically tracked through the cardiac cycle. Results As shown in the Table, circumferential strain (E cc ) was the most reproducible, followed by longitudinal strain (E LL ) and radial strain (E rr ). FT-CMR analysis time was 3±1 mins. Conclusions FT-CMR is highly reproducible within operators, particularly with respect to E cc . This, together with a short time required for analysis, enhances the potential of this imaging modality in clinical practice.

Background Increasing evidence from clinical outcomes studies suggest that cardiac resynchronisation therapy with defibrillation (CRT-D) is superior to implantable cardioverter defibrillator (ICD) therapy alone in patients with left ventricular dysfunction. Methods We undertook a retrospective analysis of all ICD and CRT-D implants from April 2006 to July 2012. Cost data was obtained on an individual patient basis, derived from financial records of transactions between payers and the provider. Results A total of 921 patients (aged 63±14 years (mean±SD), 49 (91%) male) underwent device implantation: 486 (53%) de novo CRT-D; 381 (41%) single/dual chamber ICD; and, 54 (6%) upgrade from ICD to CRT-D. In the upgrades from ICD to CRT-D, the median time from ICD to CRT-D implantation was 3.2 years. From the time prior to ICD implantation to prior to CRT-D, the LVEF decreased from 30±9.4% to 22±8.7% (p Conclusions This study indicates that upgrading from ICD to CRT-D is costly. Our findings suggest that implantation of CRT-D in patients with known left ventricular dysfunction may be more cost-effective.

Background The pathophysiology of heart failure with normal ejection fraction (HFNEF) is complex and not fully understood. We hypothesised that left ventricular hypertrophy (LVH) which is found in most patients with HFNEF might lead to intramural dyssynchrony and uncoupling of the complex 3-dimensional motion of the left ventricle (LV) particularly on exercise. Method 33 patients with the clinical diagnosis of HFNEF (age 69±11 years, 19 female, EF 60±7%) and LVH (according to American Society of Cardiology, female >95 g/m 2 , male 115 g/m 2 ) underwent detailed 2D-echocardiography at rest and on supine exercise. They were compared to 41 clinically diagnosed HFNEF patients without LVH (age 73±8 years, 26 females, EF 61±7%) and 35 age-matched control subjects (age 71±7 years, 27 females, EF 63±7). All subjects underwent cardiopulmonary exercise test to assess peak oxygen consumption (peak VO2). Echocardiographic images were analysed off-line. Apical and basal rotation and radial displacement were measured by speckle tracking. Longitudinal displacement was assessed by colour tissue Doppler imaging. Raw data and timing of events were analysed using a custom-written interpolation algorithm. SDSM (SD of four LV peak systolic motions: basal and apical rotation, longitudinal and radial displacement) was calculated. Results SDSM was comparable at rest for all three groups but controls showed the highest reduction in SDSM compared to both groups of patients on exercise. Patients with LVH had the smallest reduction in SDSM implying greater dyssynchrony in LV motions on exercise. SDSM on exercise correlated with left ventricular mass index (r=0.362, p=0.002) and VO 2 max (r=−0.319, p=0.011). Conclusion LVH in patients with HFNEF is associated with intramural dyssynchrony and uncoupling of the complex 3-dimensional LV motions on exercise. This might contribute to their exertional symptoms.

Background The pathophysiology of heart failure with normal ejection fraction (HFNEF) is complex and not fully understood. Recent publications showed a loss of apical rotation and longitudinal function particularly on exercise in these patients. Whether a deterioration of basal rotation and a dyssynchrony of different three plane motions on exercise might contribute to symptoms in these patients is not known. Method 72 Patients (age 73±7 years, 48 female) with breathlessness on exertion and normal EF (60±7%) underwent cardiopulmonary exercise test to rule out alternative clinical reasons (VO 2 max 18.4±4.9 ml/min/kg). Data were compared to 38 age-matched control subjects (age 71±7 years, 29 female, EF 63±7%) with a normal exercise tolerance (VO 2 max 28.6±5.1 ml/min/kg). All underwent full Doppler 2D-echocardiography at rest and on supine exercise. Echo images were analysed off-line. Apical and basal rotation, longitudinal and radial displacement were measured by speckle tracking. Speckle tracking pictures and colour TDI curves were loaded into custom made software. The software interpolated all curves and calculated twist as the difference of rotation at apex and at base. The software offered timing information to calculate SD and time delays for different motions. Results As previously described apical rotation was reduced at rest and on exercise Basal rotation was comparable at rest but significantly reduced on exercise in patients. The SD for four different systolic peak motions (basal and apical rotation, longitudinal and radial displacement) was comparable at rest but on exercise controls showed a significantly reduced SD compared to patients showing a greater ability to synchronise motions. Furthermore a ratio of untwist during IVRT and longitudinal extension (Ratio Untwist /Extension in IVRT) showed a significant deeper slope on exercise for patients indicating a loss of synchrony in diastole, too. All results are presented in Abstract 81 table 1. Conclusion Patients with HFNEF show a deterioration of basal rotation and a systolic and diastolic three plane dyssynchrony particularly on exercise. This might further contribute to the deterioration of early diastolic suction and therefore decrease stroke volume on exercise. This might be a major contribution to their symptoms.

Editor—We agree with Verma and Strauss that it is naive to consider that angiotensin receptor blockers are like angiotensin converting enzyme (ACE) inhibitors, but without the cough.1 Although the evidence is conflicting, the hypothesis that angiotensin receptor blockers may predispose to myocardial infarction when used in preference to ACE inhibitors warrants further attention. Long term clinical benefits of treatment with ACE inhibitors, including reduction in fatal and non-fatal myocardial infarction, are well established in chronic heart failure, hypertension, and after myocardial infarction.2 These benefits persist, although serum concentrations of angiotensin II return to pre-treatment values after long term treatment with ACE inhibitors.3 This implies that the mechanism(s) of benefit from ACE inhibitors extend beyond simple antagonism of angiotensin II. The effects of ACE inhibitors are related to the upstream blockade of the renin-angiotensin axis, which not only attenuates the conversion of angiotensin I to angiotensin II but also inhibits the degradation of kinins to inactive metabolites. ACE inhibitors, and not angiotensin receptor blockers (which block the renin-angiotensin axis at its most distal, type I receptor site), therefore result in raised concentrations of bioactive kinins such as bradykinin.4 This fundamental difference is important since bradykinin has several beneficial actions—antiarrhythmic effects and reduction of infarct size mediated through ischaemic preconditioning and vascular protection mediated by nitric oxide or prostacyclin.4 In addition, the hypothesis has some rationale that angiotensin II type II receptors, as well as the type I receptors, may have potentially deleterious effects in cardiovascular disease.5 The cautions voiced by Verma and Strauss are biologically credible, and we therefore advise that until these issues are resolved, angiotensin receptor blockers should be used with caution in subjects who are perceived to be at a high coronary risk.