Acyl ghrelin improves cardiac function in heart failure and increases fractional shortening in cardiomyocytes without calcium mobilization.

BACKGROUND AND AIMS: Ghrelin is an endogenous appetite-stimulating peptide hormone with potential cardiovascular benefits. Effects of acylated (activated) ghrelin were assessed in patients with heart failure and reduced ejection fraction (HFrEF) and in ex vivo mouse cardiomyocytes. METHODS AND RESULTS: In a randomized placebo-controlled double-blind trial, 31 patients with chronic HFrEF were randomized to synthetic human acyl ghrelin (0.1 µg/kg/min) or placebo intravenously over 120 min. The primary outcome was change in cardiac output (CO). Isolated mouse cardiomyocytes were treated with acyl ghrelin and fractional shortening and calcium transients were assessed. Acyl ghrelin but not placebo increased cardiac output (acyl ghrelin: 4.08 ± 1.15 to 5.23 ± 1.98 L/min; placebo: 4.26 ± 1.23 to 4.11 ± 1.99 L/min, P < 0.001). Acyl ghrelin caused a significant increase in stroke volume and nominal increases in left ventricular ejection fraction and segmental longitudinal strain and tricuspid annular plane systolic excursion. There were no effects on blood pressure, arrhythmias, or ischaemia. Heart rate decreased nominally (acyl ghrelin: 71 ± 11 to 67 ± 11 b.p.m.; placebo 69 ± 8 to 68 ± 10 b.p.m.). In cardiomyocytes, acyl ghrelin increased fractional shortening, did not affect cellular Ca2+ transients, and reduced troponin I phosphorylation. The increase in fractional shortening and reduction in troponin I phosphorylation was blocked by the acyl ghrelin antagonist D-Lys 3. CONCLUSION: In patients with HFrEF, acyl ghrelin increased cardiac output without causing hypotension, tachycardia, arrhythmia, or ischaemia. In isolated cardiomyocytes, acyl ghrelin increased contractility independently of preload and afterload and without Ca2+ mobilization, which may explain the lack of clinical side effects. Ghrelin treatment should be explored in additional randomized trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05277415.

Effects of Spinal Cord Stimulation on Cardiac Sympathetic Nerve Activity in Patients with Heart Failure.

BACKGROUND: Spinal cord stimulation (SCS) reduces sympathetic activity in animal models of heart failure with reduced ejection fraction (HF) but limited data exist of SCS in patients with HF. The aim of the present study was to test the primary hypothesis that SCS reduces cardiac sympathetic nerve activity in HF patients. Secondary hypotheses were that SCS improves left ventricular function and dimension, exercise capacity, and clinical variables relevant to HF. METHODS: HF patients with a SCS device previously participating in the DEFEAT-HF trial were included in this crossover study with 6-week intervention periods (SCS-ON and SCS-OFF). SCS (50 Hz, 210-µs pulse duration, aiming at T2-T4 segments) was delivered for 12 hours daily. Indices of myocardial sympathetic neuronal function (heart-to-mediastinum ratio, HMR) and activity (washout rate, WR) were assessed using 123 I-metaiodobenzylguanidine (MIBG) scintigraphy. Echocardiography, exercise testing, and clinical data collection were also performed. RESULTS: We included 13 patients (65.3 ± 8.0 years, nine males) and MIBG scintigraphy data were available in 10. HMR was not different comparing SCS-ON (1.37 ± 0.16) and SCS-OFF (1.41 ± 0.21, P = 0.46). WR was also unchanged comparing SCS-ON (41.5 ± 5.3) and SCS-OFF (39.1 ± 5.8, P = 0.30). Similarly, average New York Heart Association class (2.4 ± 0.5 vs 2.3 ± 0.6, P = 0.34), quality of life score (24 ± 16 vs 24 ± 16, P = 0.94), and left ventricular dimension and function as well as exercise capacity were all unchanged comparing SCS-ON and SCS-OFF. CONCLUSION: In patients with HF, SCS (12 hours daily, targeting the T2-T4 segments of the spinal cord) does not appear to influence cardiac sympathetic neuronal activity or function as assessed by MIBG scintigraphy.

Heart rate and dyssynchrony in patients with cardiac resynchronization therapy: a pilot study.

OBJECTIVES: The objective of this pilot study was to describe the impact of paced heart rate on left ventricular (LV) mechanical dyssynchrony in synchronous compared to dyssynchronous pacing modes in patients with heart failure. METHODS: Echocardiography was performed in 14 cardiac resynchronization therapy (CRT) patients at paced heart rates of 70 and 90 bpm in synchronous- (CRT), and dyssynchronous (atrial pacing + wide QRS activation) pacing modes. LV dyssynchrony was quantified using the 12-segment standard deviation model (Ts-SD) derived from Tissue Doppler Imaging. In addition, cardiac cycle intervals were assessed using cardiac state diagrams and stroke volume (SV) and filling pressure were estimated. RESULTS: Ts-SD decreased significantly with CRT at 90 bpm (25 ± 12 ms) compared to 70 bpm (35 ± 15 ms, p = .01), but remained unchanged with atrial pacing at different paced heart rates (p = .96). The paced heart rate dependent reduction in Ts-SD was consistent when Ts-SD was indexed to average Ts and systolic time interval. Cardiac state diagram derived analysis of cardiac cycle intervals demonstrated a significant reduction of the pre-ejection interval and an increase in diastole with CRT compared to atrial pacing. SV was maintained at the higher paced heart rate with CRT pacing but decreased with atrial pacing. DISCUSSION: Due to the small sample size in this pilot study general and firm conclusions are difficult to render. However, the data suggest that pacing at higher heart rates acutely reduces remaining LV dyssynchrony during CRT, but not during atrial pacing with dyssynchronous ventricular activation. These results need confirmation in a larger patient cohort.

The impact of arterial load on left ventricular performance: an invasive haemodynamic study in severe mitral stenosis.

KEY POINTS: A hallmark of mitral stenosis (MS) is the markedly altered left ventricular (LV) loading. As most of the methods used to determine LV performance in MS patients are influenced by loading conditions, previous studies have shown conflicting results. The present study calculated LV elastance, which is a robust method to quantify LV function. We demonstrate that LV loading in MS patients is elevated but normalizes after valve repair and might be a result of reflex pathways. Additionally, we show that the LV in MS is less compliant than normal due to a combination of right ventricular loading and the valvular disease itself. Immediately after valve dilatation the increase in blood inflow into the LV results in even greater LV stiffness. Our findings enrich our understanding of heart function in MS patients and provide a simple reproducible way of assessing LV performance in MS. ABSTRACT: Left ventricular (LV) function in rheumatic mitral stenosis (MS) remains an issue of controversy, due to load dependency of previously employed assessment methods. We investigated LV performance in MS employing relatively load-independent indices robust to the altered loading state. We studied 106 subjects (32 ± 8 years, 72% female) with severe MS (0.8 ± 0.2 cm(2) ) and 40 age-matched controls. MS subjects underwent simultaneous bi-ventricular catheterization and transthoracic echocardiography (TTE) before and immediately after percutaneous transvenous mitral commisurotomy (PTMC). Sphygmomanometric brachial artery pressures and TTE recordings were simultaneously acquired in controls. Single-beat LV elastance (Ees ) was employed for LV contractility measurements. Effective arterial elastance (Ea ) and LV diastolic stiffness were measured. MS patients demonstrated significantly elevated afterload (Ea : 3.0 ± 1.3 vs. 1.5 ± 0.3 mmHg ml(-1) ; P < 0.001) and LV contractility (Ees : 4.1 ± 1.6 vs. 2.4 ± 0.5 mmHg ml(-1) ; P < 0.001) as compared to controls, with higher Ea in subjects with smaller mitral valve area (≤ 0.8 cm(2) ) and pronounced subvalvular fusion. Stroke volume (49 ± 16 to 57 ± 17 ml; P < 0.001) and indexed LV end-diastolic volume (LVEDVindex : 57 ± 16 to 64 ± 16 ml m(-2) ; P < 0.001) increased following PTMC while Ees and Ea returned to more normal levels. Elevated LV stiffness was demonstrated at baseline and increased further following PTMC. Our findings provide evidence of elevated LV contractility, increased arterial load and increased diastolic stiffness in severe MS. Following PTMC, both LV contractility and afterload tend to normalize.

Impact of tachycardia and sympathetic stimulation by cold pressor test on cardiac diastology and arterial function in elderly females.

Abnormal vascular-ventricular coupling has been suggested to contribute to heart failure with preserved ejection fraction in elderly females. Failure to increase stroke volume (SV) during exercise occurs in parallel with dynamic changes in arterial physiology leading to increased afterload. Such adverse vascular reactivity during stress may reflect either sympathoexcitation or be due to tachycardia. We hypothesized that afterload elevation induces SV failure by transiently attenuating left ventricular relaxation, a phenomenon described in animal research. The respective roles of tachycardia and sympathoexcitation were investigated in n = 28 elderly females (70 ± 4 yr) carrying permanent pacemakers. At rest, during atrial tachycardia pacing (ATP; 100 min(-1)) and during cold pressor test (hand immersed in ice water), we performed Doppler echocardiography (maximal untwist rate analyzed by speckle tracking imaging of rotational mechanics) and arterial tonometry (arterial stiffness estimated as augmentation index). Estimation of arterial compliance was based on an exponential relationship between arterial pressure and volume. We found that ATP produced central hypovolemia and a reduction in SV which was larger in patients with stiffer arteries (higher augmentation index). There was an associated adverse response of arterial compliance and vascular resistance during ATP and cold pressor test, causing an overall increase in afterload, but nonetheless enhanced maximal rate of untwist and no evidence of afterload-dependent failure of relaxation. In conclusion, tachycardia and cold provocation in elderly females produces greater vascular reactivity and SV failure in the presence of arterial stiffening, but SV failure does not arise secondary to afterload-dependent attenuation of relaxation.

Transesophageal echocardiography measurements of aortic annulus diameter using biplane mode in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Aortic stenosis (AS) is a relevant common valve disorder. Severe AS and symptoms and/or left ventricular dysfunction (EF <50%) have the indication for aortic valve replacement (AVR). Majority of the patients with AS are elderly often with co-morbidities and generally have high preoperative risk. Transcatheter aortic valve implantation (TAVI) is offered in this group. Four different sizes of Corevalve prosthesis are available. Correct measurement of aortic size prior to TAVI is of great important to choose the right prosthesis size to avoid among others paravalvular leak or prosthesis patient mismatch.Aim of the study is to assess the aortic annulus diameter in patients undergoing TAVI by biplane (BP) mode using transesophageal echocardiography (TEE) and compare it to two-dimensional (2D) transthoracic echocardiography (TTE) and 2DTEE using three-dimensional (3D) TEE as reference method. METHODS: The study population consisted of 50 patients retrospectively (24 men and 26 women, mean age 85±8 years of age) who all had undergone echocardiography examination prior to TAVI. RESULTS: The mean aortic annulus diameter was 20.4±2.2 mm with TTE, 22.3±2.5 mm with 2DTEE, 22.9±1.9 mm with BP-mode and 23.1±1.9 mm with 3DTEE. TTE underestimated the mean aortic annulus diameter in comparison to transesophageal imaging modalities (p<0.001). Using 3DTEE, 2% of patients were unsuitable for TAVI due to a too-small AoA (n=1). This figure was similar with BP (4%, n=2; p=1.00) but considerably larger with 2DTTE (36%, n=18; p < 0.001) and 2DTEE (12%, n=6; p=0.06). There was a strong correlation between BP-mode and 3DTEE for assessment of aortic annulus diameter (r-value 0.88) with small mean difference (-0.2±0.9 mm) whereas the other modalities showed larger 95% confidence interval and modest correlation (2DTTE vs. 3DTEE, -6.3 to 0.9 mm, r=0.64 and 2DTEE vs. 3DTEE, -4.8 to 3.2 mm, r=0.61). CONCLUSION: A multi-dimensional method is preferred to assess aortic annulus diameter in TAVI patients since there is risk of underestimation using single plane. Biplane mode is the method of choice in view of speedy post-processing with no need for expensive dedicated software. Lastly, single plane methods lead to misclassification of patients as unsuitable for TAVI. This may be of major clinical importance.

Manual correction of semi-automatic three-dimensional echocardiography is needed for right ventricular assessment in adults; validation with cardiac magnetic resonance.

BACKGROUND: Three-dimensional echocardiography (3DE) and semi-automatic right ventricular delineation has been proposed as an appropriate method for right ventricle (RV) evaluation. We aimed to examine how manual correction of semi-automatic delineation influences the accuracy of 3DE for RV volumes and function in a clinical adult setting using cardiac magnetic resonance (CMR) as the reference method. We also examined the feasibility of RV visualization with 3DE. METHODS: 62 non-selected patients were examined with 3DE (Sonos 7500 and iE33) and with CMR (1.5T). Endocardial RV contours of 3DE-images were semi-automatically assessed and manually corrected in all patients. End-diastolic (EDV), end-systolic (ESV) volumes, stroke volume (SV) and ejection fraction (EF) were computed. RESULTS: 53 patients (85%) had 3DE-images feasible for examination. Correlation coefficients and Bland Altman biases between 3DE with manual correction and CMR were r = 0.78, -22 ± 27 mL for EDV, r = 0.83, -7 ± 16 mL for ESV, r = 0.60, -12 ± 18 mL for SV and r = 0.60, -2 ± 8% for EF (p < 0.001 for all r-values). Without manual correction r-values were 0.77, 0.77, 0.70 and 0.49 for EDV, ESV, SV and EF, respectively (p < 0.001 for all r-values) and biases were larger for EDV, SV and EF (-32 ± 26 mL, -21 ± 15 mL and - 6 ± 9%, p ≤ 0.01 for all) compared to manual correction. CONCLUSION: Manual correction of the 3DE semi-automatic RV delineation decreases the bias and is needed for acceptable clinical accuracy. 3DE is highly feasible for visualizing the RV in an adult clinical setting.

Altered ventriculo-arterial coupling during exercise in athletes releasing biomarkers after endurance running.

Exercise can lead to release of biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), a poorly understood phenomenon proposed to especially occur with high-intensity exercise in less trained subjects. We hypothesised that haemodynamic perturbations during exercise are larger in athletes with cTnT release, and studied athletes with detectable cTnT levels after an endurance event (HIGH; n = 16; 46 ± 9 years) against matched controls whose levels were undetectable (LOW; n = 11; 44 ± 7 years). Echocardiography was performed at rest and at peak supine bicycle exercise stress. Left ventricular (LV) end-systolic elastance (E (LV) a load-independent measure of LV contractility), effective arterial elastance (E (A) a lumped index of arterial load) and end-systolic meridional wall stress were calculated from cardiac dimensions and brachial blood pressure. Efficiency of cardiac work was judged from the ventriculo-arterial coupling ratio (E (A)/E (LV): optimal range 0.5-1.0). While subgroups had similar values at rest, we found ventriculo-arterial mismatch during exercise in HIGH subjects [0.47 (0.39-0.58) vs. LOW: 0.73 (0.62-0.83); p < 0.01] due to unopposed increase in E (LV) (p < 0.05). In LOW subjects, a greater increase occurred in E (A) during exercise (+81 ± 67 % vs. HIGH: +39 ± 32 %; p = 0.02) which contributed to a maintained coupling ratio. Subjects with higher baseline NT-proBNP had greater systolic wall stress during exercise (R (2) = 0.39; p < 0.01) despite no correlation at rest (p = ns). In conclusion, athletes with exercise-induced biomarker release exhibit ventriculo-arterial mismatch during exercise, suggesting non-optimal cardiac work may contribute to this phenomenon.

Two-dimensional color Doppler echocardiography for left ventricular stroke volume assessment: a comparison study with three-dimensional echocardiography.

AIM: Whether measurement of left ventricular outflow tract diameter (LVOTd) using color Doppler (CD) in order to more accurately define LVOTd is more accurate for determination of stroke volume (SV) than gray scale and compare it with direct measurement of LVOT area (a) using three-dimensional echocardiography (3DE) for SV determination. METHODS AND RESULTS: Twenty-one volunteers were examined. LVOTa was calculated by two-dimensional echocardiography (2DE) using the following formula: π× (d/2)(2) , d = LVOT diameter by gray scale and CD, respectively. Planimetry of LVOTa was performed in parasternal long axis using 3DE. Eccentricity Index was calculated using the lateral and anterior-posterior LVOTd. SV was obtained by four different methods: (1) 2D gray scale, (2) 2D color, (3) LVOTa × LVOT velocity time integral, and (4) SV by Simpson's biplane method. Gray scale LVOTd was significantly smaller compared to LVOTd obtained with CD (P < 0.05). Significant differences occurred between LVOTa gray scale and CD (3.29 ± 0.74 cm(2) vs 3.67 ± 0.70 cm(2) , P < 0.05) and between LVOTa calculated by gray scale in comparison to 3DE planimetry; (3.29 ± 0.74 cm(2) vs 3.61 ± 0.89 cm(2) , P = 0.011). Half of the subjects had at least 17% difference between the lateral and anterior-posterior LVOTd. There were significant differences between SV by 2D gray scale and 2D CD (82.8 ± 17.1 mL vs 92.4 ± 16.8 mL, P < 0.05) and between 2D gray scale and 3DE planimetry (82.8 ± 17.1 mL vs 90.7 ± 19.8 mL, P = 0.025). CONCLUSION: Our study demonstrates LVOT being frequently elliptical. SV and LVOTa were found to be similar when comparing 2DE CD and 3DE planimetry and showed higher values in comparison to 2DE gray scale, which suggests 2DE CD to be an alternative approach for SV assessment.

Evaluation of patients with high burden of premature ventricular contractions by comprehensive transthoracic echocardiography.

Background: The prevalence and prognosis of premature ventricular contractions (PVCs) among individuals without structural heart disease are uncertain. Standard transthoracic echocardiography is a common method in evaluation of underlying cardiovascular disease and is recommended as a diagnostic method in PVC patients. However, it is unclear whether comprehensive echocardiographic examination can identify pathological findings in PVC patients with a normal standard echocardiogram. Method: We included forty consecutive patients with a high PVC burden (>10,000 PVCs/day) and normal findings at a standard echocardiogram and exercise test. All subjects were investigated by a comprehensive echocardiographic examination using parameters usually not included in a routine work-up. We compared the results with 22 age and sex-matched controls. Results: In six additional parameters-global longitudinal strain, right ventricular strain, septal-lateral delay, ventricular-arterial coupling, integrated backscatter and left atrial activation time-a statistically significant difference was shown between PVC patients and controls. Among these parameters, global longitudinal strain had a high reliability between operators. Conclusions: Despite normal findings at standard echocardiography, the PVC group showed signs of impaired heart function when more comprehensive echocardiography parameters were used.

Arterial vasodilatory and ventricular diastolic reserves determine the stroke volume response to exercise in elderly female hypertensive patients.

Elderly female hypertensives with arterial stiffening constitute a majority of patients with heart failure with preserved ejection fraction (HFpEF), a condition characterized by inability to increase cardiac stroke volume (SV) with physical exercise. As SV is determined by the interaction between the left ventricle (LV) and its load, we wished to study the role of arterial hemodynamics for exertional SV reserve in patients at high risk of HFpEF. Twenty-one elderly (67 ± 9 yr) female hypertensive patients were studied at rest and during supine bicycle stress using echocardiography including pulsed-wave Doppler to record flow in the LV outflow tract and arterial tonometry for central arterial pressure waveforms. Arterial compliance was estimated based on an exponential relationship between pressure and volume. The ratio of aortic pressure-to-flow in early systole was used to derive characteristic impedance, which was subsequently subtracted from total resistance (mean arterial pressure/cardiac output) to yield systemic vascular resistance (SVR). It was found that patients with depressed SV reserve (NoRes; reserve <15%; n = 10) showed decreased arterial compliance during exercise, while patients with SV reserve ≥15% (Res; n = 11) showed increased compliance. Exercise produced parallel increases in LV end-diastolic volume and arterial volume in Res patients while NoRes patients exhibited a lesser decrease in SVR and a drop in effective arterial volume. Poor SV reserve in elderly female hypertensives is due to simultaneous failure of LV preload and arterial vasodilatory reserves. Abnormal arterial function contributes to a high risk of HFpEF in these patients.

Brain natriuretic peptide is related to diastolic dysfunction whereas urinary albumin excretion rate is related to left ventricular mass in asymptomatic type 2 diabetes patients.

BACKGROUND: The aims of this study were to estimate the prevalence of left ventricular systolic (LVSD) and diastolic (LVDD) dysfunction, and to test if BNP and urinary albumin excretion rate (AER) are related to LVSD, LVD and left ventricular mass (LVM) in asymptomatic type 2 diabetes patients. METHODS: Presence of LVSD, LVDD and LVM, determined with echocardiography, was related to levels of BNP and AER in 153 consecutive asymptomatic patients with type 2 diabetes. RESULTS: LVSD was present in 6.1% of patients whereas 49% (29% mild, 19% moderate and 0.7% severe) had LVDD and 9.4% had left ventricular hypertrophy. Increasing age (P < 0.0001) was the only independent variable related to mild LVDD whereas increasing BNP (P = 0.01), systolic blood pressure (P = 0.01), age (P = 0.003) and female gender (P = 0.04) were independent determinants of moderate to severe LVDD. AER (P = 0.003), age (P = 0.01) and male gender (P = 0.006) were directly and independently related to LVM. CONCLUSION: About half of asymptomatic type 2 diabetes patients have LVDD. Of those, more than one third display moderate LVDD pattern paralleled by increases in BNP, suggesting markedly increased risk of heart failure, especially in females, whereas AER and male sex are related to LVM.

Ultrasonographic strain imaging is superior to conventional non-invasive measures of vascular stiffness in the detection of age-dependent differences in the mechanical properties of the common carotid artery.

AIMS: Elastic properties of large arteries have been shown to deteriorate with age and in the presence of atherosclerotic vascular disease. In this study, the performance of ultrasonographic strain measurements was compared with conventional measures of vascular stiffness in the detection of age-dependent differences in the elastic properties of the common carotid artery (CCA). METHODS AND RESULTS: In 10 younger (25-28 years, four women) and 10 older (50-59 years, four women) healthy individuals, global and regional circumferential, and radial strain variables were measured in the short-axis view of the right CCA using ultrasonographic two-dimensional (2D) strain imaging with recently introduced speckle tracking technique. Conventional elasticity variables, elastic modulus (E(p)), and beta stiffness index, were calculated using M-mode sonography and non-invasive blood pressure measurements. Global and regional circumferential systolic strain and strain rate values were significantly higher (P < 0.01 for regional late systolic strain rate, P < 0.001 otherwise) in the younger individuals, whereas the values of conventional stiffness variables in the same group were lower (P < 0.05). Among all strain and conventional stiffness variables, principal component analysis and its regression extension identified only circumferential systolic strain variables as contributing significantly to the observed discrimination between the younger and older age groups. CONCLUSION: Ultrasonographic 2D-strain imaging is a sensitive method for the assessment of elastic properties in the CCA, being in this respect superior to the conventional measures of vascular stiffness. The method has potential to become a valuable non-invasive tool in the detection of early atherosclerotic vascular changes.

Three-dimensional echocardiography using single-heartbeat modality decreases variability in measuring left ventricular volumes and function in comparison to four-beat technique in atrial fibrillation.

BACKGROUND: Three dimensional echocardiography (3DE) approaches the accuracy of cardiac magnetic resonance in measuring left ventricular (LV) volumes and ejection fraction (EF). The multibeat modality in comparison to single-beat (SB) requires breath-hold technique and regular heart rhythm which could limit the use of this technique in patients with atrial fibrillation (AF) due to stitching artifact. The study aimed to investigate whether SB full volume 3DE acquisition reduces inter- and intraobserver variability in assessment of LV volumes and EF in comparison to four-beat (4B) ECG-gated full volume 3DE recording in patients with AF. METHODS: A total of 78 patients were included in this study. Fifty-five with sinus rhythm (group A) and 23 having AF (group B). 4B and SB 3DE was performed in all patients. LV volumes and EF was determined by these two modalities and inter- and intraobserver variability was analyzed. RESULTS: SB modality showed significantly lower inter- and intraobserver variability in group B in comparison to 4B when measuring LV volumes and EF, except for end-systolic volume (ESV) in intraobserver analysis. There were significant differences when calculating the LV volumes (p < 0.001) and EF (p < 0.05) with SB in comparison to 4B in group B. CONCLUSION: Single-beat three-dimensional full volume acquisition seems to be superior to four-beat ECG-gated acquisition in measuring left ventricular volumes and ejection fraction in patients having atrial fibrillation. The variability is significantly lower both for ejection fraction and left ventricular volumes.

Direct measurement of left ventricular outflow tract area using three-dimensional echocardiography in biplane mode improves accuracy of stroke volume assessment.

AIMS: The aim of the study was to investigate whether left ventricular stroke volume (LVSV) assessment using direct measurement of left ventricular outflow tract area (LVOT(A)) is superior to conventional methods for SV calculation. METHODS AND RESULTS: Thirty patients were included in the study (39 ± 12 years). LVSV was assessed by multiplying LVOT velocity time integral (VTI) by LVOT(A) provided by direct planimetrical measurements from real time three-dimensional echocardiography (RT3DE) in biplane mode (SV2). These measurements were compared to conventional methods using either the LVOT diameter for LVOT(A) multiplied with VTI (SV1) or biplane Simpson (SV3). Direct SV measurements by RT3DE were used as gold standard (SV(ref)). There was an excellent correlation and agreement between SV determined by SV2 and 3DE (r = 0.98, mean difference 0.5 ± 3.3 mL). However, the concordance of the traditional methods (SV1 and SV3) with 3DE was weaker (r = 0.38, mean difference -2.0 ± 17.6 mL, r = 0.84, mean difference -7.6 ± 8.7 mL, respectively). Furthermore, cardiac output (CO) measurements performed by the different modalities were not concordant with wide limits of agreement, except by SV2 the mean difference of CO by SV1 was -0.12 ± 1.05 L/min, 0.03 ± 0.20 L/min by SV2, and -0.45 ± 0.52 L/min by SV3. CONCLUSIONS: SV and CO calculations using direct measurement of LVOT area is a feasible, accurate and reproducible method and correlates extremely well with 3DE volume measurements. SV and CO calculation by LVOT(A) is therefore an appealing method for LVSV assessment in clinical routine.

Comparison between colour-coded and spectral tissue Doppler measurements of systolic and diastolic myocardial velocities: effect of temporal filtering and offline gain setting.

AIMS: Colour tissue Doppler (TD) has been reported to underestimate the longitudinal myocardial motion velocities measured with spectral TD. This study evaluates the effect of temporal smoothing and offline gain settings on the results of velocity measurements with these two methods and the difference between them. METHODS AND RESULTS: In 57 patients, 2D data and left ventricular velocity profiles were acquired using spectral and colour TD for a subsequent offline analysis. Longitudinal myocardial velocities were measured at unsaturated, 50%-saturated and fully saturated gain, and before and after temporal smoothing using 30, 50, and 70 ms filters, respectively. Gain level and filter width altered significantly the measured velocities. Peak systolic and early diastolic velocities were significantly higher (P < 0.001) and E/E' ratio was significantly lower (P < 0.001) with spectral TD than with colour TD, although there was a good correlation between the results of both TD modalities. The differences between the methods increased at increasing filter width and gain level. CONCLUSION: Despite good correlation of the results, spectral TD produces significantly higher myocardial velocity values and lower E/E' ratio than colour TD modality. Increasing gain and temporal smoothing alter significantly the results of velocity measurements and accentuate the difference between the two TD methods.

Measurements of left ventricular myocardial longitudinal systolic displacement using spectral and colour tissue Doppler: time for a reassessment?

BACKGROUND: Echocardiographic measurements of left ventricular (LV) myocardial displacement may produce different results depending on the choice of employed modality and subjective adjustments during data acquisition and analysis. METHODS: In this study, left ventricular longitudinal systolic displacement was quantified in 57 patients (31 women and 26 men, 50 +/- 16 years) using colour (colour TD) and spectral tissue Doppler (spectral TD) before and after temporal filtering (30 to 70 milliseconds in 20-millisecond steps) and changed offline gain saturation (0%, 50% and 100%), respectively. The results were compared with those obtained with anatomic M-mode. RESULTS: Whereas only minor differences occurred between the results of colour TD and anatomic M-mode measurements, spectral TD significantly overestimated the results obtained with both these methods. However, the limits of agreement between the results produced by all three studied methods were not clinically acceptable in any of the cases. The spectral TD displacement values increased along with increasing offline gain saturation whereas the effect of temporal filtering on colour Doppler measurements was insignificant. CONCLUSION: Measurements of LV myocardial longitudinal displacement employing spectral TD, colour TD or anatomic M-mode produce different results, thus discouraging interchangeable use of these modalities. Whereas the results of spectral TD measurements can be significantly altered by changing offline gain setting, the effect of temporal filtering on colour TD measurements is insignificant, a fact that increases clinical practicality of the latter method.

Visually estimated ejection fraction by two dimensional and triplane echocardiography is closely correlated with quantitative ejection fraction by real-time three dimensional echocardiography.

BACKGROUND: Visual assessment of left ventricular ejection fraction (LVEF) is often used in clinical routine despite general recommendations to use quantitative biplane Simpsons (BPS) measurements. Even thou quantitative methods are well validated and from many reasons preferable, the feasibility of visual assessment (eyeballing) is superior. There is to date only sparse data comparing visual EF assessment in comparison to quantitative methods available. The aim of this study was to compare visual EF assessment by two-dimensional echocardiography (2DE) and triplane echocardiography (TPE) using quantitative real-time three-dimensional echocardiography (RT3DE) as the reference method. METHODS: Thirty patients were enrolled in the study. Eyeballing EF was assessed using apical 4-and 2 chamber views and TP mode by two experienced readers blinded to all clinical data. The measurements were compared to quantitative RT3DE. RESULTS: There were an excellent correlation between eyeballing EF by 2D and TP vs 3DE (r = 0.91 and 0.95 respectively) without any significant bias (-0.5 +/- 3.7% and -0.2 +/- 2.9% respectively). Intraobserver variability was 3.8% for eyeballing 2DE, 3.2% for eyeballing TP and 2.3% for quantitative 3D-EF. Interobserver variability was 7.5% for eyeballing 2D and 8.4% for eyeballing TP. CONCLUSION: Visual estimation of LVEF both using 2D and TP by an experienced reader correlates well with quantitative EF determined by RT3DE. There is an apparent trend towards a smaller variability using TP in comparison to 2D, this was however not statistically significant.

Head to head comparisons of two modalities of perfusion adenosine stress echocardiography with simultaneous SPECT.

BACKGROUND: Real-time perfusion (RTP) contrast echocardiography can be used during adenosine stress echocardiography (ASE) to evaluate myocardial ischemia. We compared two different types of RTP power modulation techniques, angiomode (AM) and high-resolution grayscale (HR), with 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) for the detection of myocardial ischemia. METHODS: Patients with known or suspected coronary artery disease (CAD), admitted to SPECT, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using AM and HR during Sonovue(R) infusion, before and throughout the adenosine stress, also used for SPECT. Analysis of myocardial perfusion and wall motion by RTP-ASE were done for AM and HR at different time points, blinded to one another and to SPECT. Each segment was attributed to one of the three main coronary vessel areas of interest. RESULTS: In 50 patients, 150 coronary areas were analyzed by SPECT and RTP-ASE AM and HR. SPECT showed evidence of ischemia in 13 out of 50 patients. There was no significant difference between AM and HR in detecting ischemia (p = 0.08). The agreement for AM and HR, compared to SPECT, was 93% and 96%, with Kappa values of 0.67 and 0.75, respectively (p < 0.001). CONCLUSION: There was no significant difference between AM and HR in correctly detecting myocardial ischemia as judged by SPECT. This suggests that different types of RTP modalities give comparable data during RTP-ASE in patients with known or suspected CAD.

Quantitative detection of myocardial ischaemia by stress echocardiography; a comparison with SPECT.

AIMS: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique angio-mode (AM), provides images for off-line perfusion quantification using Qontrast software, generating values of peak signal intensity (A), myocardial blood flow velocity (beta) and myocardial blood flow (Axbeta). By comparing rest and stress values, their respective reserve values (A-r, beta-r, Axbeta-r) are generated. We evaluated myocardial ischaemia by RTP-ASE Qontrast quantification, compared to visual perfusion evaluation with 99mTc-tetrofosmin single-photon emission computed tomography (SPECT). METHODS AND RESULTS: Patients admitted to SPECT underwent RTP-ASE (SONOS 5500) using AM during Sonovue infusion, before and throughout adenosine stress, also used for SPECT. Visual myocardial perfusion and wall motion analysis, and Qontrast quantification, were blindly compared to one another and to SPECT, at different time points off-line.We analyzed 201 coronary territories (left anterior descendent [LAD], left circumflex [LCx] and right coronary [RCA] artery territories) in 67 patients. SPECT showed ischaemia in 18 patients and 19 territories. Receiver operator characteristics and kappa values showed significant agreement with SPECT only for beta-r and Axbeta-r in all segments: area under the curve 0.678 and 0.665; P < 0.001 and < 0.01, respectively. The closest agreements were seen in the LAD territory: kappa 0.442 for both beta-r and Axbeta-r; P < 0.01. Visual evaluation of ischaemia showed good agreement with SPECT: accuracy 93%; kappa 0.67; P < 0.001; without non-interpretable territories. CONCLUSION: In this agreement study with SPECT, RTP-ASE Qontrast quantification of myocardial ischaemia was less accurate and less feasible than visual evaluation and needs further development to be clinically useful.