Left Ventricular Peak Research Articles

Response of non-failing hypertrophic rat hearts to prostaglandin F2α.

BackgroundProstaglandin F2α (PGF2α) has a positively inotropic effect on right ventricular (RV) trabeculae from healthy adult rat hearts, and may therefore be therapeutically useful as a non-catecholaminergic inotrope. These provide additional contractile support for the heart without the added energetic demand of increased heart rate, and are also suitable for patients with reduced β adrenergic receptor (β-AR) responsiveness, or impaired mitochondrial energy supply. However, the response of hypertrophied rat hearts to PGF2α has not previously been examined. Our aim was therefore to determine the effect of PGF2α on isolated perfused rat hearts with RV hypertrophy following induction of pulmonary artery hypertension.MethodsMale Wistar rats (300 g) were injected with either 60 mg kg−1 of monocrotaline (MCT, n = 10) or sterile saline as control (CON, n = 11). Four weeks post injection; hearts were isolated and Langendorff-perfused in sinus rhythm. Measurement of left ventricular (LV) pressure and the electrocardiogram were made and the response to 0.3 μM PGF2α was determined.ResultsPGF2α increased LV developed pressure in CON and in 60% MCT hearts, with no change in heart rate. However, 40% of MCT hearts developed arrhythmias during the peak inotropic response. For comparison, the response to 0.03 μM isoproterenol (ISO) was also investigated. Peak LV pressure developed sooner in response to ISO compared to PGF2α in both rat groups, although the inotropic response to ISO was reduced in MCT hearts. Analysis of fixed ventricular tissue confirmed that only RV myocytes were hypertrophied in MCT hearts. Our study showed that PGF2α was positively inotropic for healthy hearts, but found it generated arrhythmias in 40% of MCT hearts at the dose investigated. However, a more physiological dose of PGF2α may be a useful alternative without the added energetic cost of catecholaminergic inotropes.

Left Ventricular Layer-Specific Myocardial Strains in Children with Recovered Primary Dilated Cardiomyopathy: What Lies Beneath the Iceberg?

We aimed to detect residual cardiac dysfunction-if any-in children with recovered primary dilated cardiomyopathy (DCM) by using the left ventricular (LV) layer-specific myocardial strains. Fifty children with recovered primary DCM both clinically and echocardiographically were included as the patient group. Fifty healthy children of matched age and sex served as the control group. Echocardiographic evaluation was performed for all included children in the form of conventional echocardiography, tissue Doppler imaging (TDI), two-dimensional speckle tracking echocardiography (2D-STE), and LV layer-specific myocardial strain. Both LV systolic and diastolic functions measured by conventional echocardiography were similar in children with recovered DCM and the control group. There was a significant reduction in LV systolic and diastolic functions measured by TDI in the patient group. Moreover, there was a significant reduction of LV global longitudinal systolic strain (GLSS) by 2D-STE in children with recovered DCM. Interestingly, there was a significant reduction of LV layer-specific myocardial strain from endocardium to epicardium in children with recovered DCM compared to the healthy control. There was a significant positive correlation between different layer-specific myocardial strains and LV GLSS, LV ejection fraction, and LV peak systolic velocity. Left ventricular layer-specific myocardial strain can be a promising tool for early identifications of LV dysfunction in children with DCM. Subtle cardiac dysfunction is present in patients with recovered DCM, so long-term follow-up is recommended in these patients.

Urocortin 2 Gene Transfer Improves Heart Function in Aged Mice.

Prevalence of left ventricular (LV) systolic and diastolic dysfunction increases with aging. We previously reported that urocortin 2 (Ucn2) gene transfer increases heart function in mice with heart failure with reduced ejection fraction. Here, we test the hypotheses that (1) Ucn2 gene transfer will increase LV function in aged mice and that (2) Ucn2 gene transfer given in early life will prevent age-related LV dysfunction. Nineteen-month-old (treatment study) and 3-month-old (prevention study) mice received Ucn2 gene transfer or saline. LV function was examined 3-4months (treatment study) or 20months (prevention study) after Ucn2 gene transfer or saline injection. In both the treatment and prevention strategies, Ucn2 gene transfer increased ejection fraction, reduced LV volume, increased LV peak -dP/dt and peak+dP/dt, and reduced global longitudinal strain. Ucn2 gene transfer-in both treatment and prevention strategies-was associated with higher levels of LV SERCA2a protein, reduced phosphorylation of LV CaMKIIa, and reduced LV α-skeletal actin mRNA expression (reflecting reduced cardiac stress). In conclusion, Ucn2 gene transfer restores normal cardiac function in mice with age-related LV dysfunction and prevents development of LV dysfunction.

P5499Coronary angioplasty for octogenarian acute coronary syndrome patients? Is it worth it?

Abstract Background As the population ages, doctors are being challenged by the decision to offer intervention treatment in increasingly older and fragile patients. The comorbidity burden and performance status should be considered when making the decision. Purpose To assess the impact of optimal medical therapy (OMT) versus percutaneous coronary intervention (PCI) in non-ST elevation acute coronary syndrome (ACS) patients older than 80 years. Methods 182 patients older than 80 years old admitted to a single coronary care unit with a diagnosis of non-ST elevation ACS, who survived hospital stay were included. Clinical, laboratorial and echocardiographic data were evaluated. Two groups were created: Group A (OMT group) N=83; Group B (PCI group) N=99. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer curves and Cox regression were conducted to evaluate the impact of OMT versus PCI on the primary endpoint. The mean time of follow-up was 37±29 months. Results Groups were homogenous regarding gender, cardiovascular risk factors, heart failure diagnosis, left ventricular (LV) systolic function and peak troponin I. OMT group patients were older (85.1±3.7 vs 82.7±3.2 years old, P<0.01), had a higher prevalence of chronic kidney disease (CKD) (61.4% vs 46.5%, P<0.05), a lower haemoglobin (Hb) level (12.0±1.9 vs 12.6±1.7 g/dL, P<0.05) and were less likely to receive double antiplatelet therapy at discharge (80.8% vs 100%, P<0.001). 84 patients met the primary outcome. Kaplan-Meyer curves showed increased survival in the PCI group (36.5% vs 59.3%, Log Rank P<0.001 – Figure 1). Nevertheless, PCI was not associated with long-term mortality (HR 1.05, 95% CI 0.98–1.12) in a model adjusted for age, CKD, peak troponin, LV systolic function and Hb level. Only Hb (HR 0.81, 95% CI 0.73–0.93), peak troponin (HR 1.01, 95% CI 1.00–1.01) and LV function (slightly impaired [HR 1.89, 95% CI 1.03–3,48] and moderate/severely impaired [HR 1.96, 95% CI 1.14–3.36]) remained associated with the outcome. Conclusion Increased survival in older patients receiving PCI after a non-ST elevation ACS may be ascribed to the selection of patients with less comorbidities. This reinforces the idea it may be applied in well-fit patients regardless of age. In our elderly population, lower Hb level, peak troponin and impaired LV systolic function appear to be the main contributors to decreased survival, irrespective of intervention.

P1609Adverse left ventricular remodeling in descending thoracic vs ascending aorta banding in novel porcin model. cMRI study

Abstract Background Based on differences in the timing of left ventricular (LV) peak systolic pressure, distinction between early from late LV systolic loading is made. Reduced ascending aortic compliance results with chronic early LV systolic loading. Chronic late LV systolic loading associates with end-systolic wave refection's and developing earlier heart failure. The LV remodeling in chronic late vs early systolic loading has not been studied previously in a porcine model. Objective To develop novel porcin model and to study the LV hypertrophic remodeling in chronic late vs early LV systolic loading, during thoracic aorta banding. Methods Domestic male pigs (28±3.4kg, n=14) underwent thoracic aorta banding. Ascending aorta banding (PB, n=6) induced chronic early LV systolic loading. Descending thoracic aorta banding (DB n=8) provoked chronic late LV systolic loading. 3T cMRI with T1 mapping was performed at baseline, 4 and 8 weeks. Hemodynamic measurements were obtained using 5Fr Millar P-V catheter in LabChart, after 4 and 8 weeks. ANOVA two-way for repeated measurements was performed (R studio 3.5.1). Leven and Shapiro-Wilk normality testing was done. Analysis of variance of aligned rank transformed data was performed. Linear regression showed correlation between relevant parameters. Results Hemodynamic measurements are presented as means±se and means±sd for cMRI, for significant p<0.05. After 8 weeks of thoracic aorta banding, the timing of peak systolic LV pressure was prolonged in DB (PB 159±6 msec; DB 329±16 msec; p<0.01), correlating with LV dPdtmax (p=0.017, r=−0.8), Ea (p=0.04, r=0.73), LVEF (p=0.035, r=−0.74) and native T1 (p=0.01, r=−0.83) in DB. Tau was not different (p=0.8), correlated with the timing of peak LV pressure in DB (p=0.015, r=0.81). The gradients were not different (PB 25±5mmHg; DB 16±1mmHg; p=0.88) and LV systolic pressure (p=0.61). The isovolumic contraction phase was prolonged in DB (PB 34±4msec; DB 56±4msec, p<0.01). LV mass index increased (p=0.013) and was not different between the groups (PB 95±14g/m2; DB 89±12g/m2; p=0.89). RWT was different within (p<0.01) and between the groups (p=0.02),correlating with LVEFas dPdtmax (p=0.013, r=−0.82), whilst with dPdtmin (p=0.018, r=0.8) in DB. There was an interaction for site of aortic constriction and LV remodeling (RWT 0.067±0.08 in PB; 0.45±0.04 in DB, p=0.004; posterior LV wall thickness (PWT) p=0.012). RWT correlated with native T1 in PB (p=0.04) and DB (p<0.01, r=−0.8). Des. aorta banding in late LV loadining Conclusion The LV hypertrophic remodeling, defined by RWT, PWT and hemodynamic correlates is different between chronic late and early LV systolic loading, in this novel porcine model. The timing of peak LV afterload associates with increased LV afterload and adverse LV remodeling in presence of chronic late LV systolic loading, in the porcin model of descending thoracic aorta banding. Increased RWT ratio associates with adverse LV remodeling in the porcine model of descending thoracic aortic constriction.

P5561MicroRNA-208b gene expression levels as a biomarkers of left ventricular dysfunction in patients with acute myocarditis

Abstract Purpose MicroRNAs (miRs) play a major role in protein regulation by post-transcriptional gene expression and cell to cell interaction. Recently, they have been emerged as important modulators in cardiovascular development and disease. Our aim was to determine whether cardiac related miRs such as miR-208b was differentially expressed in peripheral blood mononuclear cells from patients with acute myocarditis. We also evaluated their expression levels in peripheral blood mononuclear cells in relation with left ventricular global longitudinal peak strain (GLPS) in those patients. Methods We assessed the expression levels of miR-208b in 45 patients with acute myocarditis (38 men, mean age 31±10 years) and 22 healthy individuals (18 men, mean age 33±9 years). Blood samples were taken on admission and miR expression levels in peripheral blood mononuclear cells were quantified by real-time reverse transcription polymerase chain reaction. All patients were also underwent an assessment with standard conventional transthoracic and a two-dimensional speckle tracking echocardiography. Results GLPS was significantly reduced in the group of myocarditis compared to healthy individuals (from −13.7 ± −7.9% versus −22.2±6.7%, p<0.05). Myocarditis patients showed significantly higher miR-208b (28.5±6.6 versus 6.40±1.1, p<0.001) expression levels compared to control group. miR-208b gene expression levels at baseline revealed a significant negative correlation with GLPS on admission (r=−0.51, p<0.05). This correlation was independent of the patients' clinical parameters. Conclusions Our data reveal that miR-208b gene expression levels are upregulated in peripheral blood mononuclear cells from patients with acute myocarditis relative to healthy individuals. In addition, miR-208b levels have a prognostic value in the deterioration of left ventricular GLPS in those patients. Thus, miR-208b may represent a promising biomarkers in myocarditis or a potential therapeutic target in the future.

P3365Relationship between early diastolic intra-ventricular pressure gradient shortly after aortic valve closure estimated by vector flow mapping and left ventricular diastolic untwisting rate in humans

Abstract Background Early diastolic suction is an important determinant of early diastolic function. Previous studies using color Doppler M-mode and speckle-tracking echocardiography have shown left ventricular (LV) early diastolic LV untwisting rate is directly related to LV intra-ventricular pressure gradient (IVPG) between LV base and apex during early diastole. Recent introduction of vector flow mapping (VFM) using combination of color Doppler and speckle-tracking echocardiography provides noninvasive and feasible assessment of early diastolic IVPG shortly after aortic valve closure including isovolmic relaxation period (ED-IVPG) in humans. However, relationship between VFM–derived ED-IVPG and early diastolic LV untwisting rate has not been well investigated. Purpose The purpose of this study was to examine relationship between ED-IVPG estimated by VFM and LV untwisting rate by speckle-tracking echocardiography. Methods The study population consists of 66 patients without segmental wall motion abnormality, significant valvular diseases, and atrial fibrillation who underwent echocardiography for evaluation of LV function (age: 60±15 years, LVEF: 49±16%). From the apical long-axis views by color Doppler echocardiography, we analyzed peak ED-IVPG between LV base and apex just after aortic valve closure (figure) using commercially available VFM analysis software (DAS-RS1, Hitachi). We assessed peak early diastolic LV untwisting rate and LV torsion from LV basal and apical short-axis view by speckle-tracking echocardiography. We evaluated correlation between ED-IVPG and LV untwisting rate. We also evaluated correlation between ED-IVPG and peak systolic LV torsion, LV end-diastolic (EDV) and end-systolic volumes (ESV), ejection fraction (EF), early diastolic velocity (E) of LV inflow, average early diastolic velocity (e') of mitral annulus, and average E/e'. Results In all the study patients, ED-IVPG was successfully and quickly evaluated. 1) ED-IVPG correlated well with peak LV untwisting rate (r=0.64, p<0.0001). 2) ED-IVPG significantly correlated with LV torsion, LVEDV, LVESV, and LVEF (r=0.47, r=−0.48, r=−0.46, and r=0.48, respectively, p<0.001). 3) There were no significant correlations between ED-IVPG and other indexes including E, average e', and average E/e'. According to receiver operating characteristic analysis, the best cut-off value of ED-IVPG for determining impaired LV untwisting rate (<80 degrees/s) was found at 0.42 mmHg (sensitivity 81%, specificity 76%, and area under the curve 0.86) ED-IVPG measurement by VFM Conclusions The present results showed that noninvasive VFM-derived peak ED-IVPG shortly after aortic valve closure is related to early diastolic peak LV untwisting rate. ED-IVPG easily and quickly estimated by VFM may be used as an additional index for LV diastolic function.

P888Left ventricular diastolic function and left atrial longitudinal function during exercise correlate with exercise capacity in patients with hypertrophic cardiomyopathy

Abstract Background The clinical course of hypertrophic cardiomyopathy (HCM) is heterogeneous and the development of heart failure (HF) is difficult to predict. Exercise echocardiography can provide information about mechanisms involved in the occurrence of HF symptoms: development of intraventricular obstruction, increase in mitral regurgitation (MR) severity, impaired left ventricular (LV) and left atrial (LA) function. Purpose To analyse the changes in LV and LA function during exercise and to identify the main correlates of exercise capacity in patients (pts) with HCM, in sinus rhythm and with normal LV ejection fraction. Methods We have prospectively enrolled 32 pts (48±17 years, 15 men) with HCM and no obstruction at rest. A symptom limited exercise echocardiogram was performed in all pts using a table ergometer. Maximum LV wall thickness (LVWT), indexed left atrial volume (LAVi), septal E', E/septal E' ratio, were measured at rest (r) and during exercise (e). Global longitudinal LV strain (GLS) and LA strain (LAɛ) were assessed by speckle tracking echocardiography at rest and during exercise. The peak LV outflow tract gradient, systolic pulmonary artery pressure (PAP), and MR degree were recorded at rest and during exercise. Exercise-related symptoms, peak exercise heart rate (HR) and exercise capacity calculated in metabolic equivalents (METs) were also recorded. Results The mean value of achieved METs was 5.9±1.4, the peak HR was 124±25 bpm, representing 72±12% of maximal HR, during a mean of 8.5±2.5 minutes of exercise. Thirteen pts developed LV gradients >30 mmHg. Fifteen pts were asymptomatic, while 17 pts reported dyspnea during exercise. There were no significant differences between pts with and without symptoms regarding: age, rE', rE/E', rGLS, rLAɛ, rMR, rPAP, LAVi, eE/e', eGLS, eMR, ePAP (p>0.05 for all). Symptomatic pts had lower values for eE' (p=0.01), eLAɛ (p=0.03) and tended to have higher values for LVWT (p=0.06) and a higher prevalence of eLV outflow tract obstruction (p=0.13) compared to asymptomatic pts. In symptomatic group of pts, E' (p=0.004), PAP (p<0.001) and GLS (p=0.04) significantly increased and LAɛ tended to decrease (p=0.18) during exercise. Age (r=−0.44, p=0.01), rE' (r=0.40, p=0.02), eE' (r=0.46, p=0.01), ePAP (r=−0.35, p=0.04) and LVWT (r=−0.32, p=0.07) significantly correlated with achieved METs in HCM pts overall. In multivariate analysis, eE' (β=0.60, 95% CI 0.122 to 0.009, p=0.003) was the only parameter independently correlated with exercise capacity (expressed in METs). Conclusions Symptomatic pts had a worse LV diastolic function (as expressed by E') and a severe LA longitudinal dysfunction (as expressed by LAɛ) during exercise. E' during exercise was the only parameter independently correlated with exercise capacity in pts with HCM. These suggest that a detailed analysis of LV and LA function during exercise could provide additional information to predict the occurrence of HF in HCM pts.

ALTERATIONS IN LEFT ATRIAL AND LEFT VENTRICULAR MYOCARDIAL FUNCTION IN MIXED AORTIC VALVE DISEASE

Patients with mixed aortic valve disease (MAVD; combined moderate or > aortic stenosis (AS) and moderate or > aortic regurgitation) have poorer outcomes compared to those with isolated severe AS. Little is known of the impact of MAVD on left atrial (LA) and left ventricular (LV) myocardial mechanics. We aim to characterize LA and LV myocardial function in MAVD patients. We retrospectively identified 184 patients, 35 moderate MAVD (moderate AS and moderate aortic regurgitation), 40 severe MAVD (severe AS and moderate aortic regurgitation), 33 isolated severe AS, 31 isolated severe aortic regurgitation, and 45 controls, who underwent transthoracic echocardiogram. Simultaneous speckle-tracking longitudinal strain (LS) analysis of the LA and LV were performed on the apical 4-chamber view (EchoInsight, Epsilon) to obtain LV peak LS and LA peak, contractile, and conduit strain. ANOVA with post-hoc Tukey’s test was used to compare groups. P < 0.05 was considered significant. Results are presented in Table 1. Compared to controls, LV peak LS was significantly reduced in moderate MAVD, severe MAVD and severe AS patients. LV peak LS was not significantly different between moderate MAVD and severe AS patients but was significantly lower in the severe MAVD group. Severe aortic regurgitation patients had higher peak LS compared to controls, moderate MAVD, severe MAVD and severe AS patients. LA peak, conduit and contractile strains were significantly reduced in moderate MAVD, severe MAVD and severe AS patients compared to controls and severe aortic regurgitation patients. LA peak and contractile strains were not different between the moderate MAVD, severe MAVD or severe AS groups. However, LA conduit strain was significantly reduced in those with severe MAVD compared to the moderate MAVD but not the severe AS group. The severe aortic regurgitation group had preserved LA peak, conduit and contractile strain compared to the other groups. Moderate MAVD patients have a reduction in LV and LA myocardial function comparable to isolated severe AS patients. Severe MAVD patients have a greater decline in LV peak LS and LA conduit strain compared to moderate MAVD or severe AS patients. These changes may contribute to the poorer outcomes observed in MAVD patients.

Myocardial velocity, intra-, and interventricular dyssynchrony evaluated by tissue phase mapping in pediatric heart transplant recipients.

Endomyocardial biopsy (EMB) is the standard method for detecting allograft rejection in pediatric heart transplants (Htx). As EMB is invasive and carries a risk of complications, there is a need for a noninvasive alternative for allograft monitoring. To quantify left and right ventricular (LV & RV) peak velocities, velocity twist, and intra-/interventricular dyssynchrony using tissue phase mapping (TPM) in pediatric Htx compared with controls, and to explore the relationship between global cardiac function parameters and the number of rejection episodes to these velocities and intra-/interventricular dyssynchrony. Prospective. Twenty Htx patients (age: 16.0 ± 3.1 years, 11 males) and 18 age- and sex-matched controls (age: 15.5 ± 4.3 years, nine males). 5T; 2D balanced cine steady-state free-precession (bSSFP), TPM (2D cine phase contrast with three-directional velocity encoding). LV and RV circumferential, radial, and long-axis velocity-time curves, global and segmental peak velocities were measured using TPM. Short-axis bSSFP images were used to measure global LV and RV function parameters. A normality test (Lilliefors test) was performed on all data. For comparisons, a t-test was used for normally distributed data or a Wilcoxon rank-sum test otherwise. Correlations were determined by a Pearson correlation. Htx patients had significantly reduced LV (P < 0.05-0.001) and RV (P < 0.05-0.001) systolic and diastolic global and segmental long-axis velocities, reduced RV diastolic peak twist (P < 0.01), and presented with higher interventricular dyssynchrony for long-axis and circumferential motions (P < 0.05-0.001). LV diastolic long-axis dyssynchrony (r = 0.48, P = 0.03) and RV diastolic peak twist (r = -0.64, P = 0.004) significantly correlated with the total number of rejection episodes. TPM detected differences in biventricular myocardial velocities in pediatric Htx patients compared with controls and indicated a relationship between Htx myocardial velocities and rejection history. 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1212-1222.

Protease-activated receptor 2 protects against myocardial ischemia-reperfusion injury through the lipoxygenase pathway and TRPV1 channels.

This study tests the hypothesis that the lipoxygenase (LOX) pathway mediates protease-activated receptor (PAR) 2-induced activation of the transient receptor potential vanilloid receptor 1 (TRPV1) to protect the heart from ischemia/reperfusion (I/R) injury. SLIGRL, a PAR2 activating peptide, was administered prior to reperfusion following left anterior descending coronary artery ligation in wild type (WT) and TRPV1 knockout (TRPV1-/-) mice. In a Langendorffly perfused heart I/R model, hemodynamic parameters, including left ventricular end-diastolic pressure, left ventricular developed pressure, coronary blood flow and left ventricular peak +dP/dt were evaluated after I/R. SLIGRL reduced the cardiac infarct size in WT and TRPV1-/- mice with a greater effect in the former strain (P<0.05). SLIGRL increased plasma levels of calcitonin gene-related peptide (CGRP) and substance P in WT (both P<0.05) but not in TRPV1-/- mice. Pretreatment with CGRP8-37 (a CGRP receptor antagonist) or RP67580 (a neurokinin-1 receptor antagonist) alone had no effect on SLIGRL-induced cardiac protection in either strain. However, combined administration of CGRP8-37 and RP67580 abolished SLIGRL-induced cardiac protection in WT but not in TRPV1-/- mice. Nordihydroguaiaretic acid (a general LOX inhibitor) and baicalein (a 12-LOX inhibitor), but not indomethacin (a cyclooxygenase inhibitor) and hexanamide (a selective cytochrome P450 epoxygenase inhibitor), abolished the protective effects of SLIGRL in WT (all P<0.05) but not in TRPV1-/- hearts. These data suggested that PAR2, possibly via 12-LOX, activates TRPV1 and leads to CGRP and substance P release to prevent I/R injury in the heart, indicating that the 12-LOX-TRPV1 pathway conveys cardiac protection to alleviate myocardial infarction.

Evaluation of exercise on left ventricular function in patients with slow coronary flow by excercise-stress echocardiography

Objective To evaluate the role of treadmill exercise-stress echocardiography in the assessment of left ventricular (LV) function in patients with slow coronary flow (SCF), and discuss the possible mechanism of SCF. Methods Forty-six patients with diagnosis of SCF were enrolled as SCF group. Forty age and sex matched adults were included as control group. All subjects had underwent clinical evaluation and exercise stress echocardiography. LV diastolic and systolic functions were assessed by conventional echocardiography, tissue Doppler imaging and two-dimensional speckle tracking echocardiography at rest and during exercise. Results ①LV function in patients with SCF at rest: LV peak systolic longitudinal strain (LS) was lower in patients with SCF than that in controls (P 0.05). Early diastolic mitral annulus velocity (Mitral e′) and the ratio between the early mitral inflow velocity and Mitral e′(Mitral E/e′) were significantly decreased in SCF group(all P 0.05). Compared with control group, ΔLS and ΔMitral e′ were significantly higher in SCF group (all P<0.05). Conclusions LV systolic and diastolic function in patients with SCF are impaired at rest. LV systolic and diastolic function recover in patients with SCF during exercise. Key words: Echocardiography, stress; Slow coronary flow; Ventricular function, left

Echocardiographic assessment at rest and during stress in patients with intermittent claudication

Objective. Skeletal muscle perfusion during walking relies on complex interactions between cardiac activity and vascular control mechanisms, why cardiac dysfunction may contribute to intermittent claudication (IC) symptoms. The study aims were to describe cardiac function at rest and during stress in consecutive IC patients, to explore the relations between cardiac function parameters and treadmill performance, and to test the hypothesis that clinically silent myocardial ischemia during stress may contribute to IC limb symptomatology. Design. Patients with mild to severe IC (n = 111, mean age 67 y, 52% females, mean treadmill distance 195 m) underwent standard echocardiography, dobutamine stress echocardiography (SE) and treadmill testing. The patient cohort was separated in two groups based on treadmill performance (HIGH and LOW performance). Results. Ten patients (9%) had regional wall motion abnormalities of which three had left ventricular ejection fraction <50% at standard echocardiography. A majority had lower than expected systolic- and diastolic ventricular volumes. LOW performers had smaller diastolic left ventricular volumes and lower global peak systolic velocity during dobutamine stress. No patient demonstrated significant cardiac dysfunction during dobutamine provocation that was not also evident at standard echocardiography. Conclusions. Most IC patients were without signs of ischemic heart disease or cardiac failure. The majority had small left ventricular volumes. The hypothesis that clinically silent myocardial ischemia impairing left ventricular function during stress may contribute to IC limb symptomatology was not supported.Trial registration: ClinicalTrials.gov identifier: NCT01219842.

Subclinical biventricular systolic dysfunction in patients with systemic sclerosis.

ObjectiveSilent myocardial involvement is associated with poor prognosis in patients with systemic sclerosis (SSc). Here we aimed to evaluate the subclinical left ventricular (LV) and right ventricular (RV) systolic dysfunction in patients with SSc without any cardiovascular diseases, by using both strain imaging methods, speckle tracking echocardiography (STE) and real-time 3D echocardiography (RT3DE).MethodsA total of 47 patients with SSc and 20 age- and gender-matched healthy controls (HC) were studied. Conventional echocardiography, STE-based strain imaging, and real-time 3D echocardiography (Bothell, WA, USA) were performed to assess the biventricular deformation. Clinical and serological findings were sought.ResultsConventional echocardiographic LV measurements were similar between SSc and HC. Both the LV and RV longitudinal peak systolic strain/strain rates were significantly impaired in SSc, demonstrating subclinical LV and RV systolic dysfunction (p≤0.001). Systolic pulmonary artery pressure (SPAP) was negatively correlated with both the LV and RV longitudinal peak systolic strain/strain rates (LV, r=−0.554 and r=−0.642, respectively, p<0.001; and RV, r=−0.554 and r=−0.642, respectively, p=0.001). There was a trend for decreasing LV strain and increasing LEVSV in a 1-year analysis of patients with SSc.ConclusionSSc is associated with myocardial systolic dysfunction. A deformation scrutiny conducted by both the STE-based strain imaging and end-systolic LV volume analysis by real-time 3D echocardiography are promising modalities that allow us for non-invasive, comprehensive investigation of subtle deterioration in the biventricular systolic function of patients with SSc.

Urocortin 2 Gene Transfer Reduces the Adverse Effects of a Western Diet on Cardiac Function in Mice.

Diabetes mellitus is associated with increased risk of heart failure. It has been previously demonstrated in mice that a single injection of adeno-associated virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal in models of insulin resistance and improves the function of the failing heart. The present study tested the hypothesis that UCn2 gene transfer would reduce diabetes-related left ventricular (LV) dysfunction. Eight-week-old C57BL6 male mice were fed a Western diet (WD; 45% fat, 35% carbohydrate) for 40 weeks. At week 30, they received saline or AAV8.UCn2 (2 × 1013 genome copies/kg) via intravenous injection. Ten weeks after gene transfer, fasting blood glucose, glucose tolerance, and cardiac function were measured via echocardiography and in vivo measurement of LV contractile function, and the results were compared to those of mice fed normal chow (NC; 10% fat; 70% carbohydrate). The contents of key LV signaling proteins were also measured to probe mechanisms. WD increased 12 h fasting glucose (WD: 190 ± 11 mg/dL, n = 8; NC: 105 ± 12 mg/dL, n = 7; p = 0.0004). WD tended to reduce LV peak +dP/dt (p = 0.08) and LV peak -dP/dt (p = 0.05). LV ejection fraction was unchanged. Among WD-fed mice, UCn2 gene transfer reduced 12 h fasting glucose (WD-UCn2: 149 ± 6 mg/dL, n = 8; WD-Saline: 190 ± 11 mg/dL, n = 8; p = 0.012), increased LV peak +dP/dt (p < 0.001) and LV peak -dP/dt (p = 0.013), and reduced Tau (p < 0.02), indicating beneficial effects on systolic and diastolic LV function. In addition, among WD-fed mice, UCn2 gene transfer increased LV ejection fraction (p < 0.005) and the velocity of circumferential fiber shortening (p = 0.0005). Finally, a reduction was seen in fatty infiltration of the liver in WD-fed mice that had received UCn2 gene transfer. LV samples from WD-UCn2 mice showed increased phosphorylation of the protein kinase A catalytic domain (p = 0.03). In conclusion, UCn2 gene transfer increased LV systolic and diastolic function and reduced blood glucose in mice with diabetes-related LV dysfunction, indicating that UCn2 gene transfer may be of potential therapeutic benefit.

Cardiac-Directed Expression of Adenylyl Cyclase Catalytic Domain (C1C2) Attenuates Deleterious Effects of Pressure Overload.

A fusion protein (C1C2) constructed by fusing the intracellular C1 and C2 segments of adenylyl cyclase type 6 (AC6) retains beneficial effects of AC6 expression, without increasing cyclic adenosine monophosphate generation. The effects of cardiac-directed C1C2 expression in pressure overload is unknown. Left ventricular (LV) pressure overload was induced by transverse aortic constriction (TAC) in C1C2 mice and in transgene negative (TG-) mice. Four weeks after TAC, LV systolic function and diastolic function were measured, and Ca2+ handling was assessed. Four weeks after TAC, TG- animals showed reduced LV peak +dP/dt. LV peak +dP/dt in C1C2 mice was statistically indistinguishable from that of normal mice and was higher than that seen in TG- mice 4 weeks after TAC (p = 0.02), despite similar and substantial cardiac hypertrophy. In addition to higher LV peak +dP/dt in vivo, cardiac myocytes from C1C2 mice showed shorter time-to-peak Ca2+ transient amplitude (p = 0.002) and a reduced time constant of cytosolic Ca2+ decline (Tau; p = 0.003). Sarcomere shortening fraction (p < 0.03) and the rate of sarcomere shortening (p < 0.02) increased in C1C2 cardiac myocytes. Myofilament sensitivity to Ca2+ was increased in systole (p = 0.02) and diastole (p = 0.04) in C1C2 myocytes. These findings indicate enhanced Ca2+ handling associated with C1C2 expression. Favorable effects on Ca2+ handling and LV function were associated with increased LV SERCA2a protein content (p = 0.015) and reduced LV fibrosis (p = 0.008). Cardiac-directed C1C2 expression improves Ca2+ handling and increases LV contractile function in pressure overload. These data provide a rationale for further exploration of C1C2 gene transfer as a potential treatment for heart failure.

An Echocardiographic Comparison of Sutureless and Conventional Aortic Valve Replacement: a Matched Case-Control Study

Background Patients at a high operative risk for conventional aortic valve replacement (AVR) may be offered sutureless valve implantation. Sutureless valves resemble conventional valves but incorporate an anchoring mechanism without using annular sutures. Methods Pre-operative and six month post-operative echocardiography data from our first year, single centre experience of sutureless valves was compared to conventional aortic valve replacements in patients matched for operative risk. Left ventricular ejection fraction, mean and peak AV gradients and inter-ventricular septal thickness, effective orifice area (EOA) and indexed effective orifice area (iEOA) were measured. Results The drops in mean and peak pre- to post-operative gradients were greater in the sutureless group, p=0.039 and p=0.001 respectively. Post-operative EOA was 1.69 cm2 and 1.26 cm2 (p=0.001) in the sutureless and conventional groups. Similarly iEOA was 0.93 cm2 and 0.74 cm2 (p=0.001) in the sutureless and conventional groups. There was also a reduction in patient prosthesis mismatch (PPM) in the sutureless group as compared to the conventional group (Chi square test p=0.026). Post-operative inter-ventricular septal thickness was 1.13 cm2 in the sutureless group and 1.35 cm2 in the conventional group (p=0.011). Conclusions Use of sutureless valves with a stent framework resulted in larger EOA and iEOA and a diminution in PPM; and lead to a statistically significant faster regression in inter-ventricular septal thickness that is a measure of left ventricular mass. The rate and extent of regression in left ventricular hypertrophy after AVR is important since it determines long-term survival including mortality, heart failure and decreased admission rates.

Left Atrial Dysfunction as an Independent Correlate of Heart Failure Symptoms in Patients With Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction

Data regarding the contribution of left atrial (LA) dysfunction to the occurrence of heart failure in patients with severe aortic stenosis (AS) are scarce. The aim of this study was to assess the relationship between LA deformation and symptomatic status in this clinical setting. A total of 361 consecutive patients with severe AS (aortic valve area [AVA] index≤0.6cm2/m2) referred to the echocardiography laboratory were prospectively screened. Two hundred forty-eight patients with preserved left ventricular (LV) ejection fraction (≥50%), in sinus rhythm, and with no more than mild aortic or mitral regurgitation (202 symptomatic and 46 asymptomatic) were enrolled. Asymptomatic status was confirmed by exercise echocardiography or electrocardiography, as clinically indicated. All patients underwent comprehensive echocardiography, including speckle-tracking analysis of LV and LA deformation. No significant differences were found between the two groups regarding age and cardiovascular risk factors. LV ejection fraction and geometric parameters were similar between groups despite higher indexed AVA in asymptomatic patients. In symptomatic patients, brain natriuretic peptide values, average E/e' ratio, and LA size were higher, whereas LV global longitudinal strain and peak LA longitudinal strain and strain rate parameters were lower compared with asymptomatic patients. AVA and peak systolic LA longitudinal strain rate were the only independent correlates of heart failure symptoms (P=.04 and P=.01, respectively). LA systolic strain rate, in addition to AVA, emerged as an independent correlate of the presence of heart failure in patients with severe AS and preserved LV ejection fraction. The echocardiographic evaluation of LA function by speckle-tracking may become useful for risk stratification in patients with asymptomatic AS, but larger prospective studies are needed.

Study of left ventricular torsional mechanics in patients with premature ventricular complexes from right ventricular outflow tract

Objective To assess alternations in left ventricular(LV) torsion parameters in healthy subjects and patients with premature ventricular complexes (PVCs) from the right ventricular outflow tract (RVOT). Methods Thirty patients with PVCs from RVOT and 31 healthy subjects were included. Two-dimensional speckle tracking imaging(2D-STI) was applied to evaluate LV torsion parameters, including LV rotational degrees in basal and apical levels respectively, LV total torsional degrees, and time to peak rotational and torsional degrees. All values of patients with PVCs were recorded during both sinus beats (PVC-S) and premature ventricular beats (PVC-V). Results No significant difference was observed in left ventricular ejection fraction(LVEF) between PVC-S group and control subjects(P>0.05), while LV rotational degrees in apical levels[(8.47±3.54)° vs (9.50±3.21)°, P=0.042] and LV total torsional degrees [(11.25±6.31)° vs (14.00±4.07)°, P=0.046] were significantly reduced in PVC-S group. In addition to the reduction of LV rotational degrees in apical levels[(3.93±7.23)° vs (9.50±3.21)°, P=0.000] and LV total torsional degrees[ (4.35±9.62)° vs (14.00±4.07)°, P=0.000], lower apical levels [(-0.57±4.44)° vs (-5.26±3.84)°, P=0.000] and advanced LV rotational degrees [(40.5±18.6)% vs (48.0±9.1)%, P=0.05] in basal levels were observed in PVC-V group in comparison with the control subjects. Compared with the PVC-S group, PVC-V group showed lower LV rotational degrees in basal levels [(-0.57±4.44)° vs (-4.57±4.57)°, P=0.000] and advanced time to peak rotational degrees [(40.5±18.6)% vs (48.1±12.6)%, P=0.018], as well as advanced time to peak and lower LV total torsional degrees [(39.3±15.4)% vs (46.7±13.8)%, P=0.007; (4.35±9.62)° vs (11.25±6.31)°, P=0.001]. Conclusions As to RVOT-PVC patients, LV myocardial torsional motion has changed in PVC-S mainly manifested as a decrease of rotation degrees in apical levels even if the LVEF is still in the normal range. During PVC-V the rotation and twist degree is further reduced, and the time sequence altered, accompanied with significantly decreased LVEF. Key words: Echocardiography; Ventricular premature complexes; Ventricular function, left; Torsion

Decreased biventricular longitudinal strain in patients with systemic sclerosis is mainly caused by pulmonary hypertension and not by systemic sclerosis per se.

SummaryPurposePatients with pulmonary arterial hypertension (PAH) due to systemic sclerosis (SSc) have high mortality. Left ventricular (LV) peak global longitudinal strain (GLS) is decreased in SSc. It is unknown whether low GLS is due to SSc or PAH. Therefore, our primary aim was to evaluate both LV and right ventricular free wall GLS (RVFW GLS) in SSc, with and without PAH, using cardiac magnetic resonance with feature tracking. Secondary aim was to relate GLS to invasive mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR).MethodsThirty‐eight patients with SSc, 19 patients with SSc‐PAH and 19 healthy controls for comparison, were included. Endocardial and epicardial borders were delineated in cine images (short‐axis stack and three long‐axis views) for volumetric and strain calculations.ResultsSystemic sclerosis‐PAH had lower LV and RVFW GLS than SSc (LV: P = 0·01, RV: P<0·001) and controls (LV: P = 0·02; RV: P<0·001), with no difference between SSc and controls. LV strain correlated with mPAP (R = 0·42, P = 0·03) and PVR (R = 0·52, P = 0·006). RVFW GLS correlated with mPAP (R = 0·68, P<0·001) and PVR (R = 0·59, P = 0·001). ROC curves for predicting PAH had AUC 0·73 for LV strain (P = 0·003) and 0·86 for RVFW GLS (P<0·001).ConclusionsLower GLS is mainly determined by increased pulmonary pressure and not by SSc per se. Low LV and RVFW GLS are indicative of increased mPAP and PVR, which opens for improved non‐invasive methods to select patients eligible for right heart catheterization and to monitor the effects of PAH therapy.