Normative reference data, determinants, and clinical implications of right atrial reservoir function in women assessed by 2D speckle-tracking echocardiography.

AIM: We aim to determine normative reference data of phasic right atrial (RA) strain and to investigate determinants, possible clinical implications as well as feasibility and reproducibility of RA strain analysis. METHODS AND RESULTS: Right atrial strain was analyzed in 266 participants of the cross-sectional Berlin Female Risk Evaluation (BEFRI) study using 2D speckle-tracking echocardiography (2D STE). To determine reference values, phasic RA strain was determined in a subgroup of 123 individuals without known cardiovascular diseases or risk factors. Mean RA reservoir strain (RAS), RA conduit, and contraction strain in this reference group were 44.9 ± 11.6%, 27.1 ± 9.5%, and 17.0 ± 5.9%, respectively. Regarding possible clinical implications, RAS was significantly reduced in women with a BMI ≥ 25, compared with women with a BMI < 25 (35.5 ± 11.1% vs 43.4 ± 11.6%, P < 0.0001). RA strain analysis showed a good feasibility (92.7%); intra- and inter-observer variability was low (<5%). BMI, global longitudinal peak systolic LV strain (LVGLS%), RA area, TAPSE, and early diastolic myocardial relaxation velocity of the RV (RV-e') were significantly associated with RA mechanics in a multivariate logistic regression analysis. CONCLUSION: In this cross-sectional trial, we determined reference values, feasibility and reproducibility, clinical and echocardiographic determinants, and possible clinical implications of RA strain analysis. Our data may help to introduce the analysis of RA mechanics into future echocardiographic routine use.

Shear-wave amplitudes measured with cardiac MR elastography for diagnosis of diastolic dysfunction.

PURPOSE: To test whether shear-wave amplitudes (SWAs) in the myocardium measured with cardiac magnetic resonance (MR) elastography enable diagnosis of myocardial relaxation abnormalities in patients with diastolic dysfunction. MATERIALS AND METHODS: Each subject gave written informed consent to participate in this institutional review board-approved prospective study. Electrocardiographically triggered SWA-based cardiac MR elastography with 24.13-Hz external vibration frequency was performed in 50 subjects grouped into asymptomatic young (n = 10, 18-39 years) and asymptomatic old (n = 10, 40-68 years) subjects and patients with echocardiographically proved mild, moderate, or severe diastolic dysfunction (n = 30, 44-73 years). SWA images were analyzed in the left ventricular (LV) region and were normalized against reference SWA of the thoracic wall. Analysis of variance with Bonferroni-corrected pairwise comparison and Pearson correlation were used for statistical evaluation. RESULTS: Young and old control subjects had normalized mean LV SWA of 0.67 ± 0.04 (standard error of the mean) and 0.56 ± 0.04 (P = .18, F test), respectively. Compared with the control groups, patients with mild, moderate, and severe diastolic dysfunction displayed significantly reduced normalized mean LV SWA of 0.37 ± 0.04, 0.34 ± 0.04, and 0.29 ± 0.04 (P < .001, F test), respectively, which was inversely correlated to the severity of diastolic dysfunction (R = -0.61, P < .001). The best cutoff value to differentiate between asymptomatic volunteers and patients was 0.43, yielding an area under the receiver operating characteristic curve of 0.92, with 90% sensitivity and 89.7% specificity. CONCLUSION: LV SWA measured with cardiac MR elastography provides image contrast sensitive to myocardial relaxation abnormalities and shows significantly lower values in patients with diastolic dysfunction.

Effect of ivabradine-induced heart rate reduction on flow-mediated dilation measured with high-sensitivity ultrasound in patients with stable coronary heart disease.

BACKGROUND: Experimental data suggests that exclusive heart rate reduction with ivabradine is associated with the amelioration of the endothelial function. Since it is presently unknown whether this also applies to humans, the aim of this pilot study was to investigate whether heart rate reduction with ivabradine modulates the endothelial function in humans with an established coronary heart disease. METHODS: Using high-sensitivity ultrasound, we analysed the flow-mediated (FMD) and nitro-mediated dilation (NMD) of the brachial artery in 25 patients (62.9 ± 8.4 years) with a stable coronary heart disease and a resting heart rate of ≥70 beats per minute (bpm). To assess acute effects, measurements were performed before and 4 hours after the first intake of ivabradine 7.5 mg. Sustained effects of an ivabradine therapy (5 mg to 7.5 mg twice daily) were investigated after 4 weeks. RESULTS: We found a significant decrease in heart rate, both 4 hours after the intake of 7.5 mg of ivabradine (median -8 [interquartile range (IQR) -14 to -4] bpm) and after 4 weeks of twice daily intake (median -10 [IQR-17 to -5] bpm) (p < 0.05). However, the FMD did not change significantly: neither after first dose of ivabradine nor after sustained therapy (baseline FMD: median 5.0 [IQR 2.4 to 7.9]%; FMD 4 hours after 7.5 mg of ivabradine: median 4.9 [IQR 2.7 to 9.8]%; FMD after 4 weeks of ivabradine therapy: median 6.1 [IQR 4.3 to 8.2]%). No significant changes of the NMD were observed. In regression analysis, the heart rate and FMD did not correlated, irrespective of the ivabradine intake (r2 = 0.086). CONCLUSION: In conclusion, in our study heart rate reduction through ivabradine does not improve the endothelial function in patients with a stable coronary heart disease. Moreover, we found no correlation between the heart rate and the endothelial function.

Single beat 3D echocardiography for the assessment of right ventricular dimension and function after endurance exercise: Intraindividual comparison with magnetic resonance imaging.

BACKGROUND: Our study compares new single beat 3D echocardiography (sb3DE) to cardiovascular magnetic resonance imaging (CMR) for the measurement of right ventricular (RV) dimension and function immediately after a 30 km run. This is to validate sb3DE against the "gold standard" CMR and to bring new insights into acute changes of RV dimension and function after endurance exercise. METHODS: 21 non-elite male marathon runners were examined by sb3DE (Siemens ACUSON SC2000, matrix transducer 4Z1c, volume rates 10-29/s), CMR (Siemens Magnetom Avanto, 1,5 Tesla) and blood tests before and immediately after each athlete ran 30 km. The runners were not allowed to rehydrate after the race. The order of sb3DE and CMR examination was randomized. RESULTS: Sb3DE for the acquisition of RV dimension and function was feasible in all subjects. The decrease in mean body weight and the significant increase in hematocrit indicated dehydration. RV dimensions measured by CMR were consistently larger than measured by sb3DE.Neither sb3DE nor CMR showed a significant difference in the RV ejection fraction before and after exercise. CMR demonstrated a significant decrease in RV dimensions. Measured by sb3DE, this decrease of RV volumes was not significant. CONCLUSION: First, both methods agree well in the acquisition of systolic RV function. The dimensions of the RV measured by CMR are larger than measured by sb3DE. After exercise, the RV volumes decrease significantly when measured by CMR compared to baseline.Second, endurance exercise seems not to induce acute RV dysfunction in athletes without rehydration.

Percutaneous biventricular Impella support in therapy-refractory cardiogenic shock.

INTRODUCTION: Percutaneous mechanical circulatory support systems have increasingly been adopted as a bail out strategy in patients with cardiogenic shock. Since studies showed mostly mixed results, however, the use of support systems remains a case by case decision. CASE: Here, we report on a case of therapy-refractory cardiogenic shock due to acute myocardial infarction treated with percutaneous right and left ventricular assist devices (Impella RP and CP). CONCLUSION: Due to myocardial stunning, even patients with fulminant cardiogenic shock have the potential for full recovery. In the present case, we demonstrate the feasibility of biventricular Impella support in therapy-refractory cardiogenic shock facilitating bridge to recovery.

Time-Resolved Analysis of Left Ventricular Shear Wave Amplitudes in Cardiac Elastography for the Diagnosis of Diastolic Dysfunction.

OBJECTIVES: The aim of this study was to investigate the diagnostic potential of changes in left ventricular (LV) shear wave amplitudes (SWAs) over the cardiac cycle measured by cardiac magnetic resonance elastography. MATERIALS AND METHODS: Electrocardiography-triggered SWA-based cardiac magnetic resonance elastography with 24.13-Hz external vibration frequency was performed in asymptomatic young (n = 10) and old (n = 10) subjects and patients (n = 30) with echocardiographically proven mild, moderate, or severe diastolic dysfunction. The temporal delay between change in SWA and morphological change in the LV wall, that is, time of isovolumetric elasticity relaxation normalized against heart rate, was calculated for diastole (τR0). Diastolic levels of LV SWA were calculated and normalized against SWA in the chest wall (U0[dia]). Nonparametric testing was used for statistical evaluation. Accuracy of the parameters was investigated using receiver operating characteristic analysis against echocardiography. Interobserver and intraobserver variability for the temporal delay between change in SWA and morphological changes was tested according to Bland and Altman. RESULTS: Young and old control subjects showed median (standard error of mean, interquartile range) τR0 of 99 (5, 93-103) and 82 (7, 66-95). In patients with diastolic dysfunction, τR0 was 131 (20, 107-171), 158 (14, 108-172), and 138 (14, 107-174) with statistically significant differences between old subjects and patients with diastolic dysfunction (P = 0.01). U0(dia) was 0.94 (0.05, 0.86-1.04) and 0.71 (0.06, 0.61-0.92) in young and old controls, respectively (P = 0.063). Compared with young subjects, patients with mild, moderate, and severe diastolic dysfunction displayed significantly reduced U0(dia) of 0.69 (0.06, 0.53-0.82), 0.56 (0.04, 0.46-0.64), and 0.48 (0.04, 0.43-0.61) (P < 0.001). τR0/U0(dia) cutoff values for prediction of diastolic dysfunction were 107/0.66, corresponding to the area under the receiver operating characteristic values of 0.84/0.87 with 74%/74% sensitivity and 85%/85% specificity. Interobserver and intraobserver variability ranged from -0.05 to 0.05 with 95% agreement. CONCLUSIONS: In diastolic dysfunction, low-frequency SWAs show distinct changes in the normalized time of isovolumetric elasticity relaxation for the LV (τR0) and the diastolic level of SWA (U0[dia]). Both parameters have good diagnostic performance for diagnosis of diastolic dysfunction.

Left Atrial Function in Preclinical Diastolic Dysfunction: Two-Dimensional Speckle-Tracking Echocardiography-Derived Results from the BEFRI Trial.

BACKGROUND: Patients with preclinical left ventricular (LV) diastolic dysfunction (DD) are prone to develop heart failure with preserved ejection fraction. Although left atrial (LA) enlargement and deterioration of LA function in apparent DD and heart failure with preserved ejection fraction have been previously described, data regarding phasic LA strain (LAS) in preclinical DD are scarce. METHODS: In a cross-sectional trial, echocardiographic parameters of DD, LA volume index, and global LA reservoir, conduit, and pump function were prospectively analyzed in 473 women from the general population in Berlin, Germany (BErlin Female RIsk evaluation (BEFRI) study), using standard and two-dimensional speckle-tracking echocardiography. RESULTS: One hundred thirty-one women (29.7%) showed early-stage DD (impaired relaxation [DD1]) and 22 (5.0%) showed an echocardiographically more advanced stage of DD (pseudonormal filling [DD2]). Compared with women with normal diastolic function (DD0), those with DD1 displayed lower LA reservoir and conduit function (DD0, 43.2 ± 8.5% and 27.2 ± 8.0%; DD1, 33.3 ± 8.0% and 16.1 ± 7.1%; P < .001) but significantly higher LA pump function (DD0, 17.6 ± 5.4%; DD1, 18.9 ± 5.5%; P < .05). In patients with DD2, all three phases of LAS were markedly impaired compared with those with DD0 (reservoir, conduit, and pump function, 29.0 ± 6.3%, 15.1 ± 5.4% [P < .001], and 14.9 ± 4.1% [P < .05], respectively). LA reservoir and conduit function was significantly associated with DD; in receiver operating characteristic curve analysis, these parameters showed higher diagnostic accuracy in detecting early DD compared with LA volume index. In multivariate analysis, LA reservoir strain remained significantly associated with DD. CONCLUSIONS: All three components of LAS showed specific alterations in different stages of DD. LA reservoir and conduit function was markedly reduced before symptoms, LA enlargement, and elevations of noninvasively estimated LV filling pressures occurred. Analysis of LA function featured higher discriminative strength in diagnosing early-stage DD compared with the well-established parameter LA volume index. Assessment of LAS allows diagnosis of impaired LA function and DD in a subclinical stage and might enable timely preventive and therapeutic interventions.

Exercise-induced changes of left ventricular diastolic function in postmenopausal amateur marathon runners: assessment by echocardiography and cardiac biomarkers.

PURPOSE: Diastolic dysfunction is common among elderly women. Recently, concerns regarding marathon-induced myocardial damage were raised among young male runners. The goal of our study was to assess the impact of marathon running on systolic and diastolic ventricular function before and immediately after completing a marathon among postmenopausal well-trained amateur women. METHODS: A total of 89 female runners of the Berlin Marathon were included (35 postmenopausal and 54 premenopausal female controls) and examined before, immediately, and 2 weeks after the race by echocardiography (including tissue Doppler- and 2D strain speckle tracking) and underwent blood tests. RESULTS: After the marathon, there was a significant increase in E/E' (postmenopausal 8.5 ± 2.3 vs. 10.9 ± 3.2 post race; control: 8.1 ± 1.8 vs. 9.9 ± 2.9 post race, p < 0.001) and a decrease in E/A in both groups (postmenopausal 1.3 ± 0.36 vs. 0.9 ± 0.21 post race; control 1.7 ± 0.6 vs. 1.1 ± 0.3; p < 0.001). In contrast, regardless of the hormonal status the atrial contraction increased significantly. Left and right ventricular systolic contractility, as assessed by speckle tracking and pulsed-wave tissue Doppler velocities, showed a significant increase in both groups. Of all runners, 55 (61.8%) experienced increases in troponin T and/or N-terminal-B-type natriuretic peptide after the race. All echocardiographic and laboratory parameters returned to normal within 2 weeks. CONCLUSIONS: 2D strain analysis of the left and right ventricles showed an acute improvement of the systolic function after marathon running in pre- and postmenopausal well-trained women. There were no long lasting detrimental effects on the diastolic function.

Galectin-3 increase in endurance athletes.

BACKGROUND: Galectin-3 is a new and promising biomarker for heart failure and myocardial fibrosis. Although endurance exercise is a crucial element in cardiovascular disease prevention, the relationship between exercise and plasma levels of galectin-3 is still unknown. To date, the relationship between regular exercise and myocardial fibrosis is not fully understood. This study investigates the relationship between endurance exercise and plasma levels of galectin-3. METHODS: Twenty-one male, healthy non-elite marathon runners were examined before and within 1 hour after a strenuous run of 30 km after 4-day training abstinence. Examination included blood samples for galectin-3, echocardiography, and cardiac magnetic resonance imaging (CMR). In addition, to distinguish between cardiac or skeletal muscular origin of galectin-3, 27 C57Bl/6 J mice performing voluntary wheel running and 25 sedentary mice were analysed. RESULTS: Plasma galectin-3 in endurance athletes increased from baseline to post exercise (12.8 ± 3.4 ng/ml to 19.9 ± 3.9 ng/ml, p < 0.001) while the systolic left and right ventricular function remained unchanged. Interestingly, baseline plasma levels of galectin-3 were in normal range but higher than in healthy sedentary controls. However, in CMR there was no correlation between baseline galectin-3 levels and the detection of myocardial fibrosis. In animal studies, the relative level of mRNA for galectin-3 in active mice was significantly higher compared to sedentary mice. This increase was most pronounced in skeletal muscle (98.0% higher, p < 0.001) and not in the myocardium of the left ventricle (19.9% higher, p = 0.043). CONCLUSIONS: Plasma galectin-3 is substantially elevated in endurance athletes after running but does not correlate with cardiac function, other biomarkers, or myocardial fibrosis. In mice, we demonstrate that galectin-3 increase during endurance exercise originates primarily from skeletal muscle.

Isovolumetric elasticity alteration in the human heart detected by in vivo time-harmonic elastography.

Time harmonic elastography (THE) has recently been introduced for measurement of the periodic alteration in myocardial shear modulus based on externally induced low-frequency acoustic vibrations produced by a loudspeaker. In this study, we propose further developments of cardiac THE toward a clinical modality including integration of the vibration source into the patient bed and automated parameter extraction from harmonic shear wave amplitudes, wall motion profiles and synchronized electrocardiographic records. This method has enabled us to evaluate the delay between wall motion and wave amplitude alteration for the measurement of isovolumetric times of elasticity alteration during contraction (τ(C)) and relaxation (τ(R)) in a group of 32 healthy volunteers. On average, the wave amplitudes changed between systole and diastole by a factor of 1.7 ± 0.3, with a τ(C) of 137 ± 61 ms and a τ(R) of 68 ± 73 ms, which agrees with results obtained with the more time-consuming and expensive cardiac magnetic resonance elastography. Furthermore, because of the high sampling rate, elasto-morphometric parameters such as transition times and the area of wave amplitude-cardiac motion cycles can be processed in an automated way for the future clinical detection of myocardial relaxation abnormalities.

Short-term effects of transcatheter aortic valve implantation on left atrial mechanics and left ventricular diastolic function.

BACKGROUND: Aortic stenosis (AS) leads to remodeling of the left heart. Strain measurements enable the assessment of left atrial (LA) mechanics. The goal of this study was to evaluate the short-term effects of transcatheter aortic valve implantation (TAVI) on LA myocardial deformation as well as left ventricular (LV) diastolic function. METHODS: Thirty-two patients with severe AS were prospectively enrolled and examined before and 8.2 ± 3.3 days after TAVI. Speckle-tracking echocardiography of the basal septal and lateral segments of the left atrium was performed to determine peak positive strain (R(LA)), strain during early diastole (E(LA)), and, if feasible, strain during atrial contraction (A(LA)). Assessment of LV diastolic function included standard indices, the atrial fraction, and LA volumes. RESULTS: Compared with baseline, the mean atrial reservoir (R(LA)) (24.0 ± 11.2% vs 32.2 ± 14.0%, P < .001) and conduit function (R(LA) - E(LA)) (13.9 ± 5.5% vs 20.8 ± 8.1%, P < .001) improved significantly after TAVI. There was a significant reduction in deceleration time (242 ± 56 vs 195 ± 65 msec, P < .001) and an improvement of pulsed-wave tissue Doppler-derived E' (5.5 ± 1.8 vs 7.3 ± 2.3 cm/sec, P = .01). Regarding LA volumes, only the minimal LA volume index changed significantly. In contrast, there was no improvement in atrial contraction, that is, contractile function (E(LA) - A(LA)) and atrial fraction. Moreover, the E/E' ratio remained unchanged. CONCLUSIONS: 8.2 ± 3.3 days after TAVI, only the reservoir and conduit function of the left atrium improved, whereas LA contraction and LA volumes, except for the systolic volume index, remained unchanged. This was accompanied by improvement of early LV diastolic function, indicating acute recovery of LV relaxation and LA function.