Aims
A multitude of cardiac magnetic resonance (CMR) techniques are used for myocardial strain assessment; however, studies comparing them are limited. We sought to compare global longitudinal (GLS), ...circumferential (GCS), segmental longitudinal (SLS), and segmental circumferential (SCS) strain values, as well as reproducibility between CMR feature tracking (FT), tagging (TAG), and fast‐strain‐encoded (fast‐SENC) CMR techniques.
Methods and results
Eighteen subjects (11 healthy volunteers and seven patients with heart failure) underwent two CMR scans (1.5T, Philips) with identical parameters. Global and segmental strain values were measured using FT (Medis), TAG (Medviso), and fast‐SENC (Myocardial Solutions). Friedman's test, linear regression, Pearson's correlation coefficient, and Bland–Altman analyses were used to assess differences and correlation in measured GLS and GCS between the techniques. Two‐way mixed intra‐class correlation coefficient (ICC), coefficient of variance (COV), and Bland–Altman analysis were used for reproducibility assessment.
All techniques correlated closely for GLS (Pearson's r: 0.86–0.92) and GCS (Pearson's r: 0.85–0.94). Intra‐observer and inter‐observer reproducibility was excellent in all techniques for both GLS (ICC 0.92–0.99, CoV 2.6–10.1%) and GCS (ICC 0.89–0.99, CoV 4.3–10.1%). Inter‐study reproducibility was similar for all techniques for GLS (ICC 0.91–0.96, CoV 9.1–10.8%) and GCS (ICC 0.95–0.97, CoV 7.6–10.4%). Combined segmental intra‐observer reproducibility was good in all techniques for SLS (ICC 0.914–0.953, CoV 12.35–24.73%) and SCS (ICC 0.885–0.978, CoV 10.76–19.66%). Combined inter‐study SLS reproducibility was the worst in FT (ICC 0.329, CoV 42.99%), while fast‐SENC performed the best (ICC 0.844, CoV 21.92%). TAG had the best reproducibility for combined inter‐study SCS (ICC 0.902, CoV 19.08%), while FT performed the worst (ICC 0.766, CoV 32.35%). Bland–Altman analysis revealed considerable inter‐technique biases for GLS (FT vs. fast‐SENC 3.71%; FT vs. TAG 8.35%; and TAG vs. fast‐SENC 4.54%) and GCS (FT vs. fast‐SENC 2.15%; FT vs. TAG 6.92%; and TAG vs. fast‐SENC 2.15%). Limits of agreement for GLS ranged from ±3.1 (TAG vs. fast‐SENC) to ±4.85 (FT vs. TAG) for GLS and ±2.98 (TAG vs. fast‐SENC) to ±5.85 (FT vs. TAG) for GCS.
Conclusions
We found significant differences in measured GLS and GCS between FT, TAG, and fast‐SENC. Global strain reproducibility was excellent for all techniques. Acquisition‐based techniques had better reproducibility than FT for segmental strain.
Aims
Exploratory assessment of the potential benefits of the novel soluble guanylate cyclase stimulator vericiguat on health status in patients with heart failure (HF) with preserved ejection ...fraction.
Methods and results
The SOCRATES‐PRESERVED trial randomized patients with chronic HF and ejection fraction ≥ 45% within 4 weeks of decompensation to 12 weeks of treatment with titrated doses of vericiguat (1.25, 2.5, 5, and 10 mg once daily) or placebo. Health status was assessed with the disease‐specific Kansas City Cardiomyopathy Questionnaire (KCCQ) and the generic health‐related quality of life measure EQ‐5D. In total, 477 patients were randomized 12.9 ± 9.0 days after hospitalization or if requiring outpatient treatment with intravenous diuretics for HF. Baseline KCCQ clinical summary score (CSS), a combination of symptom and physical function domains, was 52.3 ± 20.4 in the 10 mg arm and 54.1 ± 23.0 in placebo, and EQ‐5D US index score was 0.74 ± 0.2 and 0.73 ± 0.2, respectively. A larger proportion of patients treated with vericiguat in the 10 mg arm, compared with placebo, achieved clinically meaningful improvements in KCCQ‐CSS (82.0% vs. 59.0%, number needed to treat = 4.35, P = 0.0052). Important domains of the KCCQ as well as EQ‐5D scores demonstrated a dose‐dependent relationship with vericiguat. In the 10 mg arm, the mean physical limitations domain increased by +17.2 ± 19.1 at 12 weeks, compared with +4.5 ± 21.6 in placebo (P = 0.0009). The EQ‐5D US index score increased by +0.064 ± 0.167 in the 10 mg arm, compared with a decrease of −0.009 ± 0.195 in placebo (P = 0.0461). Improvements in KCCQ and EQ‐5D scores paralleled physician‐assessed NYHA class and clinical congestion.
Conclusion
Vericiguat, in exploratory hypothesis‐generating analyses, was associated with clinically important improvements in patients' health status, as assessed by the KCCQ and EQ‐5D. Further studies should be conducted to test the hypothesis that vericiguat improves physical functioning and health‐related quality of life in patients with HF with preserved ejection fraction.
The purpose of this study was to analyze the potential usefulness and clinical relevance of adding left atrial (LA) strain to left atrial volume index (LAVI) in the detection of left ventricular ...diastolic dysfunction (LVDD) in patients with preserved left ventricular ejection fraction (LVEF).
Recent studies have suggested that LA strain could be of use in the evaluation of LVDD. However, the potential utility and clinical significance of adding LA strain to LAVI in the detection of LVDD remains uncertain.
Using 2-dimensional speckle-tracking echocardiography, we analyzed a population of 517 patients in sinus rhythm at risk for LVDD such as those with arterial hypertension, diabetes mellitus, or history of coronary artery disease and preserved LVEF.
In patients with LV diastolic alterations and estimated elevated LV filling pressures, the rate of abnormal LA strain was significantly higher than an abnormal LAVI (62.4% vs. 33.6%, p < 0.01). In line with this, in patients with normal LAVI, high rates of LV diastolic alterations and abnormal LA strain were present (rates 80% and 29.4%, respectively). In agreement with these findings, adding LA strain to LAVI in the current evaluation of LVDD increased significantly the rate of detection of LVDD (relative and absolute increase 73.3% and 9.9%; rate of detection of LVDD: from 13.5% to 23.4%; p < 0.01). Regarding the clinical relevance of these findings, an abnormal LA strain (i.e., <23%) was significantly associated with worse New York Heart Association functional class, even when LAVI was normal. Moreover, in a retrospective post hoc analysis an abnormal LA strain had a significant association with the risk of heart failure hospitalization at 2 years (odds ratio: 6.6 95% confidence interval: 2.6 to 16.6) even adjusting this analysis for age and sex and in patients with normal LAVI.
The findings from this study provide important insights regarding the potential usefulness and clinical relevance of adding LA strain to LAVI in the detection of LVDD in patients with preserved LVEF.
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Aims
The clinical outcomes for patients with worsening chronic heart failure (WCHF) remain exceedingly poor despite contemporary evidence‐based therapies, and effective therapies are urgently needed. ...Accumulating evidence supports augmentation of cyclic guanosine monophosphate (cGMP) signalling as a potential therapeutic strategy for HF with reduced or preserved ejection fraction (HFrEF and HFpEF, respectively). Direct soluble guanylate cyclase (sGC) stimulators target reduced cGMP generation due to insufficient sGC stimulation and represent a promising method for cGMP enhancement.
Methods
The phase II SOluble guanylate Cyclase stimulatoR in heArT failurE Study (SOCRATES) programme consists of two randomized, parallel‐group, placebo‐controlled, double‐blind, multicentre studies, SOCRATES‐REDUCED (in patients with LVEF <45%) and SOCRATES‐PRESERVED (in those with LVEF ≥45%), that will explore the pharmacodynamic effects, safety and tolerability, and pharmacokinetics of four dose regimens of the once‐daily oral sGC stimulator vericiguat (BAY 1021189) over 12 weeks compared with placebo. These studies will enrol patients stabilized during hospitalization for HF at the time of discharge or within 4 weeks thereafter. The primary endpoint in SOCRATES‐REDUCED is change in NT‐proBNP at 12 weeks. The primary endpoints in SOCRATES‐PRESERVED are change in NT‐proBNP and left atrial volume at 12 weeks.
Perspectives
SOCRATES will be the first programme to enrol specifically both inpatients and outpatients with WCHF and patients with reduced or preserved ejection fraction. Results will inform the benefits of pursuing subsequent event‐driven clinical outcome trials with sGC stimulators in this patient population.
Trial registration
NCT01951625 (SOCRATES‐REDUCED) and NCT01951638 (SOCRATES‐PRESERVED)
Aims
The purpose of this retrospective analysis was to examine the association of left atrial (LA) strain (i.e. LA reservoir function) with left ventricular diastolic dysfunction (DD) in patients ...with heart failure with reduced and preserved left ventricular ejection fraction (LVEF).
Methods and results
We analysed the baseline echocardiographic recordings of 300 patients in sinus rhythm from the SOCRATES‐PRESERVED and SOCRATES‐REDUCED studies. LA volume index was normal in 89 (29.7%), of whom 60.6% had an abnormal LA reservoir strain (i.e. ≤23%). In addition, the extent of LA strain impairment was significantly associated with the severity of DD according to the 2016 American Society of Echocardiography recommendations (DD grade I: LA strain 22.2 ± 6.6, rate of abnormal LA strain 62.9%; DD grade II: LA strain 16.6 ± 7.4, rate of abnormal LA strain 88.6%; DD grade III: LA strain 11.1 ± 5.4%, rate of abnormal LA strain 95.7%; all P < 0.01). In line with these findings, LA strain had a good diagnostic performance to determine severe DD area under the curve 0.83 (95% CI 0.77–0.88), cut‐off 14.1%, sensitivity 80%, specificity 77.8%, which was significantly better than for LA volume index, LA total emptying fraction, and the mitral E/e′ ratio.
Conclusions
The findings of this analysis suggest that LA strain could be a useful parameter in the evaluation of DD in patients with heart failure and sinus rhythm, irrespective of LVEF.
Aims
Small studies and observations suggested that exercise training may improve peak oxygen consumption (peakVO2) in patients with advanced heart failure and left ventricular assist device (LVAD). ...We investigated whether in this patient group a supervised exercise training can improve exercise capacity.
Methods and results
In this multicentre, prospective, randomized, controlled trial, patients with stable heart failure and LVAD were randomly assigned (2:1) to 12 weeks of supervised exercise training or usual care, with 12 weeks of follow‐up. The primary endpoint was the change in peakVO2 after 12 weeks (51 patients provided a power of 90% with an expected group difference in peakVO2 of 3 ml/kg/min). Secondary endpoints included changes in submaximal exercise capacity and quality of life. Among 64 patients enrolled (97% male, mean age 56 years), 54 were included in the analysis. Mean difference in the change of peakVO2 after 12 weeks was 0.826 ml/min/kg (95% confidence interval CI −0.37, 2.03; p = 0.183). There was a positive effect of exercise training on 6‐min walk distance with a mean increase in the intervention group by 43.4 m (95% CI 16.9, 69.9; p = 0.0024), and on the Kansas City Cardiomyopathy Questionnaire physical domain score (mean 14.3, 95% CI 3.7, 24.9; p = 0.0124), both after 12 weeks. The overall adherence was high (71%), and there were no differences in adverse events between groups.
Conclusion
In patients with advanced heart failure and LVAD, 12 weeks of exercise training did not improve peakVO2 but demonstrated positive effects on submaximal exercise capacity and physical quality of life.
Exercise training in patients with advanced heart failure and left ventricular assist device (Ex‐VAD) trial. 6MWT, 6‐min walk test; KCCQ, Kansas City Cardiomyopathy Questionnaire physical domain score; peakVO2, peak oxygen consumption; RCT, randomized controlled trial.
Aims
We hypothesized that left atrial (LA) remodelling and function are associated with poor exercise capacity as prognostic marker in chronic heart failure (CHF) across a broad range of left ...ventricular ejection fraction (LVEF).
Methods and results
One hundred seventy‐one patients with CHF were analysed age 65 ± 11 years, 136 males (80%); 86 heart failure with reduced ejection fraction (HFrEF), 27 heart failure with mid‐range ejection fraction (HFmrEF), 58 heart failure with preserved ejection fraction (HFpEF). All patients underwent echocardiography and maximal cardiopulmonary exercise testing and were classified according to a prognostic cut‐off of peak VO2 (pVO2; 14 mL/kg/min). Seventy‐seven (45%) patients reached pVO2 < 14 and 94 (55%) pVO2 ≥ 14 mL/kg/min. Between the two groups, there was a considerable difference in both left atrial volume (LAVi, 53 ± 24 vs. 44 ± 18 mL/m2, P = 0.005) and function (LA reservoir strain 12 ± 5 vs. 20 ± 10%, P < 0.0001). Receiver‐operating characteristic curves identified LA reservoir strain (area under the curve: 0.73 0.65–0.80, P < 0.0001) as strong predictor for impaired pVO2 among all echocardiographic variables; LA reservoir strain < 23% had 37% specificity but a very high sensitivity (96%) in identifying a severely reduced pVO2. In logistic regression analysis, LA reservoir strain < 23% was associated with a highly increased risk of pVO2 < 14 mL/kg/min (odds ratio 16.0 4.7–54.6; P < 0.0001). The multivariate analysis showed that a reduced LA reservoir strain was associated with pVO2 < 14 mL/kg/min after adjustment for age, body mass index (BMI), and clinical variables, that is, New York Heart Association class, atrial fibrillation, haemoglobin, and creatinine (b 0.22 95% confidence interval, CI, 0.12–0.31; P < 0.0001), and after adjustment for echocardiographic variables, that is, LVEF or left ventricular global longitudinal strain (LVGLS) and tricuspid annular plane systolic excursion (TAPSE) (b 0.16 95% CI 0.08–0.24; P < 0.0001). Patients with HFrEF, HFmrEF, and HFpEF were separately analysed. Among LA reservoir strain, LAVi, LVEF, LVGLS, and TAPSE, LA reservoir strain was the only one significantly associated with pVO2 in all subgroups (after adjustment for sex and BMI, P = 0.003, 0.04, and 0.01, respectively).
Conclusions
In patients with CHF, an impaired LA reservoir function is independently associated with a severely reduced pVO2. LA dysfunction represents a marker of poor prognosis across LVEF borders in the CHF population.
Aims
Exercise intolerance is the leading manifestation of heart failure with preserved or mid‐range ejection fraction (HFpEF or HFmrEF), and left atrial (LA) function might contribute to modulating ...left ventricular filling and pulmonary venous pressures. We aim to assess the association between LA function and maximal exercise capacity in patients with HFpEF or HFmrEF.
Methods and results
Sixty‐five patients, prospectively enrolled in the German HFpEF Registry, were analysed. Inclusion criteria were New York Heart Association functional class ≥ II, left ventricular ejection fraction > 40%, structural heart disease or diastolic dysfunction, and elevated levels of N terminal pro brain natriuretic peptide (NT‐proBNP). LA function was evaluated through speckle‐tracking echocardiography by central reading in the Charité Academic Echocardiography core lab. All patients underwent maximal cardiopulmonary exercise test and were classified according to a peak VO2 cut‐off of prognostic value (14 mL/kg/min). NT‐pro‐BNP was measured. Twenty‐nine patients (45%) reached a peak VO2 < 14 mL/kg/min (mean value 12.4 ± 1.5) and 36 patients (55%) peak VO2 ≥ 14 mL/kg/min (mean value 19.4 ± 3.9). There was no significant difference in left ventricular ejection fraction (60 ± 9 vs. 59 ± 8%), left ventricular mass (109 ± 23 vs. 112 ± 32 g/m2), LA volume index (45 ± 17 vs. 47 ± 22 mL/m2), or E/e´ (13.1 ± 4.7 vs. 13.0 ± 6.0) between these groups. In contrast, all LA strain measures were impaired in patients with lower peak VO2 (reservoir strain 14 ± 5 vs. 21 ± 9%, P = 0.002; conduit strain 9 ± 2 vs. 13 ± 4%, P = 0.001; contractile strain 7 ± 4 vs. 11 ± 6%, P = 0.02; reported lower limits of normality for LA reservoir, conduit and contractile strains: 26.1%, 12.0%, and 7.7%). In linear regression analysis, lower values of LA reservoir strain were associated with impaired peak VO2 after adjustment for age, sex, body mass index, heart rhythm (sinus/AFib), and log‐NTproBNP β 0.29, 95% confidence interval (CI) 0.02–0.30, P = 0.02, with an odds ratio 1.22 (95% CI 1.05–1.42, P = 0.01) for peak VO2 < 14 mL/kg/min for LA reservoir strain decrease after adjustment for these five covariates. Adding left ventricular ejection fraction, it did not influence the results. On the other hand, the addition of LA strain to the adjustment parameters alone described above provided a significant increase of the predictive value for lower peak VO2 values (R2 0.50 vs. 0.45, P = 0.02). With receiver operating characteristic curve analysis, we identified LA reservoir strain < 22% to have 93% sensitivity and 49% specificity in predicting peak VO2 < 14 mL/kg/min. Using this cut‐off, LA reservoir strain < 22% was associated with peak VO2 < 14 mL/kg/min in logistic regression analysis after comprehensive adjustment for age, sex, body mass index, heart rhythm, and log‐NTproBNP odds ratio 95% CI 10.4 (1.4–74), P = 0.02.
Conclusions
In this HFpEF and HFmrEF cohort, a reduction in LA reservoir strain was a sensible marker of decreased peak exercise capacity. Therefore, LA reservoir strain might be of clinical value in predicting exercise capacity in patients with HFpEF or HFmrEF.
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