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.

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.

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.

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.

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.

Hemodynamic outcomes of transcatheter aortic valve implantation with the CoreValve system: an early assessment.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) is an established method for the treatment of high-risk patients with aortic stenosis (AS). The beneficial effects of TAVI in cardiac hemodynamics have been described in recent studies, but those investigations were mostly performed after an interval of more than 6 months following aortic valve implantation. The aim of this study is to investigate the acute and short-term alterations in hemodynamic conditions using the echocardiography outcomes in patients undergoing TAVI. METHODS AND RESULTS: A total of 60 patients (26 males, 34 females; age 84·7 ± 5·8) who underwent TAVI with CoreValve system were included in the study. Echocardiography was performed before hospital discharge and at 3 months follow-up. As expected, TAVI was associated with an immediate significant improvement in aortic valve area (AVA) (from 0·64 ± 0·16 cm(2) to 1·67 ± 0·41 cm(2) , P-value<0·001) and mean gradient (from 51·9 ± 15·4 mmHg to 8·8 ± 3·8 mmHg, P-value<0·001). At 3-month follow-up, systolic LV function was augmented (EF: 50 ± 14% to 54 ± 11%, P-value = 0·024). Left ventricle (LV) mass and left atrium (LA) volume were significantly reduced (LV mass index from 126·5 ± 30·5 g m(-2) to 102·4 ± 32·4 g m(-2) ; LA index from 42·9 ± 17·3 ml m(-2) to 33·6 ± 10·6 ml m(-2) ; P-value<0·001 for both). Furthermore, a decrement in systolic pulmonary artery pressure (SPAP) from 47·5 ± 13·5 mmHg to 42·5 ± 11·2 mmHg, P-value = 0·02 was also observed. Despite the high incidence of paravalvular regurgitation (PVR) (80%), most of the patients presented mild or trace PVR and no significant progress of the regurgitation grade was seen after 3 months. CONCLUSION: This study demonstrates that the beneficial effects of TAVI in cardiac function and hemodynamics occur already after a short period following aortic valve implantation.

Prosthesis-patient mismatch after transcatheter aortic valve implantation: impact of 2D-transthoracic echocardiography versus 3D-transesophageal echocardiography.

To investigate the role of 2D-transthoracic echocardiography (2D-TTE) and 3D-transesophageal echocardiography (3D-TEE) in the determination of aortic annulus size prior transcatheter aortic valve implantation (TAVI) and its' impact on the prevalence of patient prosthesis mismatch (PPM). Echocardiography plays an important role in measuring aortic annulus dimension in patients undergoing TAVI. This has great importance since it determines both eligibility for TAVI and selection of prosthesis type and size, and can be potentially important in preventing an inadequate ratio between the prosthetic valvular orifice and the patient's body surface area, concept known as prosthesis-patient mismatch (PPM). A total of 45 patients were studied pre-TAVI: 20 underwent 3D-TEE (men/women 12/8, age 84.8 ± 5.6) and 25 2D-TTE (men/women 9/16, age 84.4 ± 5.4) in order to measure aortic annulus diameter. The presence of PPM was assessed before hospital discharge and after a mean period of 3 months. Moderate PPM was defined as indexed aortic valve area (AVAi) ≤ 0.85 cm(2)/m(2) and severe PPM as AVAi < 0.65 cm(2)/m(2). Immediately post-TAVI, moderate PPM was present in 25 and 28 % of patients worked up using 3D-TEE and 2D-TTE respectively p value = n.s) and severe PPM occurred in 10 % of the patients who underwent 3D-TEE and in 20 % in those with 2D-TTE (p value = n.s). The echocardiographic evaluation 3 months post-TAVI showed 25 % moderate PPM in the 3D-TEE group compared with 24 % in the 2D-TTE group (p value = n.s) and no cases of severe PPM in the 3DTEE group comparing to 20 % in the 2D-TTE group (p = 0.032). Our results indicate a higher incidence of severe PPM in patients who performed 2DTTE compared to those performing 3DTEE prior TAVI. This suggests that the 3D technique should replace the 2DTTE analysis when investigating the aortic annulus diameter in patients undergoing TAVI.

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.

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.

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.

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.

Thrombo-embolic renal infarction in a case of mid-ventricular takotsubo syndrome.

Thrombo-embolism is one of the serious complications of takotsubo syndrome (TS). It typically occurs in the classical mid-apical left ventricular ballooning form of TS. This complication has not been reported in cases of left mid-ventricular ballooning type of TS. We describe a 67-year-old woman who presented with 2-3 days of increasing signs and symptoms of heart failure. Echocardiography showed marked hypokinesia/akinesia in the mid-anterior, mid-anterolateral, and mid-inferior wall of the left ventricle and mild hypokinesia in the apical region. There was also hypokinesia of the mid and apical parts of the right ventricle. One day after admission, she developed acute left-sided renal infarction. Left ventriculography and coronary angiography 3 days after admission showed typical left mid-ventricular ballooning with no identifiable coronary lesion. Follow-up echocardiography showed complete resolution of left and right ventricular dysfunction. Takotsubo syndrome with right ventricular involvement complicated with heart failure and left renal embolic infarction was diagnosed. The mechanism of left renal embolic infarction is discussed.

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.

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.

Effects of prolonged exercise on left ventricular mechanical synchrony in long-distance runners: importance of previous exposure to endurance races.

BACKGROUND: Prolonged exercise has been shown to lead to elevated levels of cardiac troponin and altered cardiac function on echocardiography. It is not known if cardiac synchrony is altered by prolonged exercise. The aims of this study were to assess changes in intra-left ventricular mechanical synchrony and circulating levels of cardiac troponin following prolonged exercise and to evaluate the importance of prior exposure to endurance racing. METHODS: Forty-three male participants in a 30-km cross-country race (20 new participants at this event [median, 3 previous endurance races] age matched against 23 repeat participants [median, 31 previous endurance events]) were assessed prospectively 1 to 2 days before and 24 hours after the race using troponin T and Doppler tissue imaging analyzing the standard deviation of time to peak myocardial systolic velocity (T(s)-SD) in a six-basal, six-midventricular segment model measuring myocardial synchrony. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene was also analyzed, as I allele carriers reportedly have superior endurance performance, while the D allele predisposes to renin-angiotensin system-induced cardiac remodeling. RESULTS: Prerace troponin T was undetectable in all runners, and postrace levels were higher in new runners (median, 0.03 microg/L; interquartile range [IQR], 0.01-0.04 microg/L) than in repeat runners (median, 0.01 microg/L; IQR, 0.01-0.02 microg/L) (P = .03). Although new and repeat runners had similar T(s)-SD at baseline (32 msec [IQR, 22-43 msec] vs 34 msec [IQR, 29-45 msec], P = .13), dyssynchrony increased only in new runners (40 msec [IQR, 31-47 msec], P < .001; in repeat runners, median, 38 msec [IQR, 29-43 msec], P = .30; median relative difference, +13% vs +5%, P = .02). ACE genotype distribution was similar in both groups. Multivariate analysis showed that (1) a lack of prior endurance exposure; (2) more copies of the ACE D allele; and (3) lower peak systolic velocity were independent predictors of postrace dyssynchrony (P < .05 for all). CONCLUSION: Prolonged exertion increased ventricular mechanical dyssynchrony in new endurance participants and in ACE D allele carriers. The long-term impact of such changes warrants future study.

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.

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.