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Aims: To characterize adverse ventricular remodelling after withdrawing therapy in recovered dilated cardiomyopathy (DCM).Methods and Results: TRED-HF was a randomized controlled trial with a follow-on single-arm cross-over phase that examined the safety and feasibility of therapy withdrawal in patients with recovered DCM over 6 months. The primary endpoint was relapse of heart failure defined by (i) a reduction in left ventricular (LV) ejection fraction >10% and to <50%, (ii) >10% increase in LV end-diastolic volume and to above the normal range, (iii) a twofold rise in N-terminal pro-B-type natriuretic peptide and to >400 ng/L, or (iv) evidence of heart failure. LV mass, LV and right ventricular (RV) global longitudinal strain (GLS) and extracellular volume were measured using cardiovascular magnetic resonance at baseline and follow-up (6 months or relapse) for 48 patients. LV cell and extracellular matrix masses were derived. The effect of withdrawing therapy, stratified by relapse and genotype, was investigated in the randomized and follow-on phases. In the randomized comparison, withdrawing therapy led to an increase in mean LV mass [5.4 g/m2 ; 95% confidence interval (CI) 1.3-9.5] and cell mass (4.2 g/m2 ; 95% CI 0.5-8.0) and a reduction in LV (3.5; 95% CI 1.6-5.5) and RV (2.4; 95% CI 0.1-4.7) GLS. In a non-randomized comparison of all patients (n = 47) who had therapy withdrawn in either phase, there was an increase in LV mass (6.2 g/m2 ; 95% CI 3.6-8.9; P = 0.0001), cell mass (4.0 g/m2 ; 95% CI 1.8-6.2; P = 0.0007) and matrix mass (1.7 g/m2 ; 95% CI 0.7-2.6; P = 0.001) and a reduction in LV GLS (2.7; 95% CI 1.5-4.0; P = 0.0001). Amongst those who had therapy withdrawn and did not relapse, similar changes were observed (n = 28; LV mass: 5.1 g/m2 , 95% CI 1.5-8.8, P = 0.007; cell mass: 3.7 g/m2 , 95% CI 0.3-7.0, P = 0.03; matrix mass: 1.7 g/m2 , 95% CI 0.4-3.0, P = 0.02; LV GLS: 1.7, 95% CI 0.1-3.2, P = 0.04). Patients with TTN variants (n = 10) who had therapy withdrawn had a greater increase in LV matrix mass (mean effect of TTN: 2.6 g/m2 ; 95% CI 0.4-4.8; P = 0.02).Conclusion: In TRED-HF, withdrawing therapy caused rapid remodelling, with early tissue and functional changes, even amongst patients who did not relapse. [ABSTRACT FROM AUTHOR]

Aims: There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling.Methods and Results: Prospective study of patients with recent-onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12 months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12 months, P = 0.02). Baseline myocardial strain (P = 0.39 global longitudinal strain), interstitial myocardial fibrosis (P = 0.41), replacement myocardial fibrosis (P = 0.25), and right ventricular contractile reserve (P = 0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r = -0.22, P = 0.23) or baseline LVEF (r = 0.07, P = 0.62). Men were more likely to experience adverse LV remodelling (P = 0.01) but age (P = 0.88) and disease-modifying heart failure medication (beta-blocker, P = 0.28; angiotensin-converting enzyme inhibitor, P = 0.92) did not predict follow-up LVEF.Conclusions: Substantial recovery of LV function occurs within 12 months in most patients with recent-onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover. [ABSTRACT FROM AUTHOR]

Background: Wave intensity analysis (WIA) of the coronary arteries allows description of the predominant mechanisms influencing coronary flow over the cardiac cycle. The data are traditionally derived from pressure and velocity changes measured invasively in the coronary artery. Cardiovascular magnetic resonance (CMR) allows measurement of coronary velocities using phase velocity mapping and derivation of central aortic pressure from aortic distension. We assessed the feasibility of WIA of the coronary arteries using CMR and compared this to invasive data. Methods: CMR scans were undertaken in a serial cohort of patients who had undergone invasive WIA. Velocity maps were acquired in the proximal left anterior descending and proximal right coronary artery using a retrospectively-gated breath-hold spiral phase velocity mapping sequence with high temporal resolution (19 ms). A breath-hold segmented gradient echo sequence was used to acquire through-plane cross sectional area changes in the proximal ascending aorta which were used as a surrogate of an aortic pressure waveform after calibration with brachial blood pressure measured with a sphygmomanometer. CMR-derived aortic pressures and CMR-measured velocities were used to derive wave intensity. The CMR-derived wave intensities were compared to invasive data in 12 coronary arteries (8 left, 4 right). Waves were presented as absolute values and as a % of total wave intensity. Intra-study reproducibility of invasive and non-invasive WIA was assessed using Bland-Altman analysis and the intraclass correlation coefficient (ICC). Results: The combination of the CMR-derived pressure and velocity data produced the expected pattern of forward and backward compression and expansion waves. The intra-study reproducibility of the CMR derived wave intensities as a % of the total wave intensity (mean ± standard deviation of differences) was 0.0 ± 6.8%, ICC = 0.91. Intra-study reproducibility for the corresponding invasive data was 0.0 ± 4.4%, ICC = 0.96. The invasive and CMR studies showed reasonable correlation (r = 0.73) with a mean difference of 0.0 ± 11.5%. Conclusion: This proof of concept study demonstrated that CMR may be used to perform coronary WIA non-invasively with reasonable reproducibility compared to invasive WIA. The technique potentially allows WIA to be performed in a wider range of patients and pathologies than those who can be studied invasively. [ABSTRACT FROM AUTHOR]

Aim: Heart failure with preserved ejection fraction (HFpEF) is associated with increased sympathetic nervous system (SNS) tone. Attenuating the SNS with renal denervation (RDT) might be helpful and there are no data currently in humans with HFpEF.Methods and Results: In this single-centre, randomized, open-controlled study we included 25 patients with HFpEF [preserved left ventricular (LV) ejection fraction, left atrial (LA) dilatation or LV hypertrophy and raised B-type natriuretic peptide (BNP) or echocardiographic assessment of filling pressures]. Patients were randomized (2:1) to RDT with the Symplicity™ catheter or continuing medical therapy. The primary success criterion was not met in that there were no differences between groups at 12 months for Minnesota Living with Heart Failure Questionnaire score, peak oxygen uptake (VO2 ) on exercise, BNP, E/e', LA volume index or LV mass index. A greater proportion of patients improved at 3 months in the RDT group with respect to VO2 peak (56% vs. 13%, P = 0.025) and E/e' (31% vs. 13%, P = 0.04). Change in estimated glomerular filtration rate was comparable between groups. Two patients required plain balloon angioplasty during the RDT procedure to treat renal artery wall oedema.Conclusion: This study was terminated early because of difficulties in recruitment and was underpowered to detect whether RD improved the endpoints of quality of life, exercise function, biomarkers, and left heart remodelling. The procedure was safe in patients with HFpEF, although two patients did require intraprocedure renal artery dilatation. [ABSTRACT FROM AUTHOR]

Background: Temporal patterns of coronary blood flow velocity can provide important information on disease state and are currently assessed invasively using a Doppler guidewire. A non-invasive alternative would be beneficial as it would allow study of a wider patient population and serial scanning. Methods: A retrospectively-gated breath-hold spiral phase velocity mapping sequence (TR 19 ms) was developed at 3 Tesla. Velocity maps were acquired in 8 proximal right and 15 proximal left coronary arteries of 18 subjects who had previously had a Doppler guidewire study at the time of coronary angiography. Cardiovascular magnetic resonance (CMR) velocity-time curves were processed semi-automatically and compared with corresponding invasive Doppler data. Results: When corrected for differences in heart rate between the two studies, CMR mean velocity through the cardiac cycle, peak systolic velocity (PSV) and peak diastolic velocity (PDV) were approximately 40 % of the peak Doppler values with a moderate - good linear relationship between the two techniques (R² : 0.57, 0.64 and 0.79 respectively). CMR values of PDV/PSV showed a strong linear relationship with Doppler values with a slope close to unity (0.89 and 0.90 for right and left arteries respectively). In individual vessels, plots of CMR velocities at all cardiac phases against corresponding Doppler velocities showed a consistent linear relationship between the two with high R² values (mean +/-SD: 0.79 +/-.13). Conclusions: High temporal resolution breath-hold spiral phase velocity mapping underestimates absolute values of coronary flow velocity but allows accurate assessment of the temporal patterns of blood flow. [ABSTRACT FROM AUTHOR]