Left Ventricular Contractile Performance Research Articles

Evaluation of Left Ventricular Systolic Function Using Layer-Specific Strain in Rats Performing Endurance Exercise: A Pilot Study.

The functional characteristics of exercise-induced myocardial hypertrophy were studied in a rat model in conjunction with ultrasound layered strain technique to investigate the hidden changes in the heart brought about by exercise. Forty specific pathogen free (SPF) adult Sprague-Dawley rats were selected and randomly divided into two groups of 20 exercise and 20 control rats. The longitudinal and circumferential strain parameters were measured using the ultrasonic stratified strain technique. The differences between the two groups and the predictive effect of stratified strain parameters on left ventricular systolic function were analyzed. The exercise group had significantly higher global endocardial myocardial longitudinal strain (GLSendo), global mid-myocardial global longitudinal strain (GLSmid) and global endocardial myocardial global longitudinal strain (GCSendo) values than the control group (p < 0.05). Even though global mid-myocardial circumferential strain (GCSmid) and global epicardial myocardial circumferential strain (GCSepi) were higher in the exercise group than in the control group, statistical significance was not reached (p > 0.05). Conventional echocardiography parameters were well correlated with GLSendo, GLSmid, and GCSendo (p < 0.05). GLSendo was the best predictor of left ventricular myocardial contractile performance in athletes determined using the receiver operating characteristic curve, with an area under the curve of 0.97, sensitivity of 95% and specificity of 90%. Rats performing endurance exercise exhibited subclinical changes in the heart after prolonged high-intensity exercise. A stratified strain parameter, GLSendo, played an important role in the evaluation of LV systolic performance in exercising rats.

The prognostic value of left atrial and left ventricular strain in patients after ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

Global longitudinal strain (GLS) based on two-dimensional speckle-tracking echocardiography (2D-STE) might better reflect left ventricular (LV) contractile performance than conventional parameters. Recently, left atrial (LA) strain has been used as a more accurate alternative to assessing LA performance. The aim in this study was to assess the clinical prognostic value of left ventricular GLS (LV GLS) and peak atrial longitudinal strain (PALS) in patients after ST-segment elevation myocardial infarction (STEMI). The study enrolled 199 patients who underwent primary percutaneous coronary intervention (pPCI) for first STEMI. Conventional and 2D-STE were performed within 48 h after pPCI. LV GLS and PALS were related to LV remodeling at 6-month follow-up and to adverse events. Diabetes mellitus, GLS and PALS independently predicted LV remodeling. With multivariable Cox proportional hazards, diabetes mellitus, GLS and PALS were predictive of adverse clinical outcomes. However, PALS did not add significant incremental value beyond LV GLS in the prediction of LV remodeling (increase in area under the receiver-operator characteristic curve [AUC]: 0.05, p = 0.24) and clinical events (even a decrease in AUC: 0.03, p = 0.69). Both GLS and PALS provide independent prognostic value for adverse LV remodeling and clinical outcomes after STEMI. However, the ability of the combination of PALS and GLS to predict LV remodeling and clinical outcomes may not be superior to that of a single indicator.

Correlation Between Longitudinal Strain in the Apical Segments of the Left Ventricle at End-Systole Obtained by 2-Dimensional Speckle-Tracking Echocardiography and Left Ventricular Relaxation.

It is well acknowledged that left ventricular (LV) contractile performance affects LV relaxation via LV elastic recoil. Accordingly, we aimed to investigate whether global longitudinal strain (GLS), particularly longitudinal strain at LV apical segments at end-systole (ALS), obtained by 2-dimensional speckle-tracking echocardiography could be used to assess LV relaxation. We enrolled 121 patients with suspected or definite coronary artery disease in whom echocardiography and diagnostic cardiac catheterization were performed on the same day. We obtained conventional echo-Doppler parameters and GLS, as well as ALS prior to catheterization. LV functional parameters were obtained from the LV pressure recorded using a catheter-tipped micromanometer. In all patients, GLS and ALS were significantly correlated with the time constant τ of LV pressure decay during isovolumetric relaxation (r=0.63 [P<0.001] and r=0.66 [P<0.001], respectively). Receiver operating characteristic curve analysis for identifying impaired LV relaxation (τ ≥48 ms) revealed that ALS greater than -22.3% was an optimal cut-off value, with 81.7% sensitivity and 82.4% specificity. Even in patients with preserved LV ejection fraction, the same ALS cut-off value enabled the identification of impaired LV relaxation with 70% sensitivity and 87.5% specificity. The findings indicate that contractile dysfunction at LV apical segments slows LV relaxation via loss of LV elastic recoil, even in patients with preserved LVEF.

Assessment of biventricular function in patients with hepatopulmonary syndrome.

Cardiac function impairment in the setting of hepatopulmonary syndrome (HPS) in patients with end stage liver disease remains an issue of debate. The current study evaluated possible correlations between HPS and biventricular systolic function in patients with decompensated cirrhosis. Consecutive liver transplantation candidates with stable decompensated cirrhosis were prospectively evaluated. HPS was defined as the presence of an elevated alveolar-arterial oxygen gradient and intrapulmonary vasodilatation, detected by contrast enhanced echocardiography. HPS severity was determined based on arterial blood oxygen pressure values, while shunt size was assessed with a semi-quantitative method. Demographic, clinical and laboratory parameters were also prospectively collected. In total, 130 patients (mean age 56.5, M/F: 94/36, MELD score 14.6 ± 5.6) were enrolled, of whom 45 (34.6%) fulfilled the criteria for HPS diagnosis (mild: 57.7%, moderate: 33.3%, severe 4.4% and very severe 4.4%). Significantly lower absolute left ventricular (LV) global longitudinal strain (GLS) values (- 21.6 ± 2.3 vs. - 22.6 ± 2.5%, p = 0.041) were measured in patients with HPS compared to cirrhotic patients without HPS, while there was no statistically significant difference regarding right ventricular GLS (- 22.1 ± 3.3 vs. - 23.2 ± 3.5%, p = 0.061) between the two groups. Lower LV ejection fraction values were also recorded in the HPS group (53.9 ± 3.5 vs. 56.3 ± 4.5%, p < 0.01). No other echocardiographic parameter was correlated to HPS. Intrapulmonary shunt grading was correlated to HPS classification (χ2 = 19.8, p < 0.01), with lower arterial oxygen values being recorded in higher stages of intrapulmonary shunt. In patients with cirrhosis, the presence of HPS is associated with worse LV contractile performance.

V alidity of Assessing in vivo Cardiac Contractility Using A “Less‐Invasive” Approach during Mechanical Ventilation: Insights from Small and Large Animal Models

Background and Aims End-systolic elastance (Ees) derived from sequential pressure-volume (PV) loops acquired during inferior vena cava occlusion (IVCO) is the reference for quantification of in vivo left ventricular (LV) contractile performance. Given the challenges associated with midline laparotomy surgeries in animal models and the barriers of performing such measures in clinical practice, a number of single-beat estimations of LV contractile function have been proposed. Here, we examined the agreement between two single-beat estimates of Ees obtained from basal LV and arterial hemodynamics in rats and pigs and the Ees obtained from IVCO (Ees(IVC)). We also tested whether a novel approach of leveraging the respiratory-induced oscillations in cardiac PV (i.e., changes in intrathoracic pressure) during mechanical ventilation enables a “naturally” occurring change in cardiac preload and the subsequent estimation of Ees (Ees(RES)). Methods 38 Wistar rats (300-350g; aged 10 wks) and 22 Yucatan mini-pigs (20-25 kg, aged 8-12 wks) were used. Once anesthetized and ventilated, animals were instrumented with 1) a LV PV catheter for assessments of LV Ees(IVC) during IVCO and LV hemodynamics, and 2) a femoral arterial catheter to record basal systemic hemodynamics. Basal LV and arterial indices, including end-systolic volume (ESV), end-systolic pressure (ESP), and arterial systolic blood pressure (SBP), were averaged over a 30s (rats) or 60s period (pigs). Ees(IVC) was measured as the slope of end-systolic PV relationship (ESPVR). From the basal LV and arterial data we then calculated single-beat estimation of Ees(IVC), including the ESP and ESV ratio (EesSB1), and the ESP (SBP × 0.9) and EDV ratio (EesSB2). Estimation of Ees(RES) was analogous to Ees(IVC) however, respiratory-induced oscillations in cardiac preload, rather than an IVCO, was used to calculate the slope of the ESPVR. Absolute agreement between metrics was examined using intra-class correlation coefficients (ICC). Results In rats, while we found a moderate agreement between Ees(SB1) (ICC = 0.685, P < 0.001), Ees(SB2) (ICC = 0.685, P < 0.001) and Ees(IVC), there was excellent agreement between Ees(RES) and Ees(IVC) (ICC = 0.934 P < 0.001). In pigs, although a moderate agreement was observed between Ees(RES) and Ees(IVC) (ICC = 0.572, P = 0.033), no agreements were noted between Ees(SB1) (ICC = 0.352, P = 0.101), Ees(SB2) (ICC = 0.320, P = 0.0741) and Ees(IVC). Conclusion Thesefindings demonstrate that the single-beat estimates of Ees show moderate agreement with Ees(IVC) in rats. Utilizing the respiratory-induced changes in cardiac preload during mechanical ventilation, however, may provide a better less-invasive approach for estimation of cardiac contractile performance, especially in a small animal model.

Abstract 13027: Differential Direct Effects of Equal Hypotensive Natriuretic Peptides (NPs) of ANP, BNP and CNP on Left Ventricular Contractile Performance in Heart Failure: Assessment by Left Ventricular Pressure-Volume Analysis

Background: Natriuretic peptides (NPs) play a crucial role in maintaining cardiovascular homeostasis. NPs stimulate the production and release of cGMP, leading to the vasodilating and natriuretic actions. In heart failure (HF), circulating and cardiac ANP, BNP, and CNP are increased and exhibit a range of actions. However, although they serve as therapeutic agents, their direct cardiac effects in HF are uncertain due to the confounding influence of NPs-produced changes in loading condition on conventional measures of LV function. We test the hypothesis that equal hypotensive 3 NPs may have different inotropic effects on LV contractility and relaxation in HF. Methods: We assessed the cardiac effects of intravenous infusion (20 min) of ANP (2 μg/kg plus 0.5 μg/kg/min), BNP (2 μg/kg plus 0.04 μg/kg/min) and CNP (2 μg/kg plus 0.4 μg/kg/min) on different days in 6 instrumented conscious dogs with pacing-induced HF by using pressure (P)-volume (V) analysis, a load-independent measure of LV contractility. Results: Versus baselines, 3 NPs produced arterial vasodilation with similar and significant decreases in LV end-systolic pressure (10 to 12 mmHg) with relatively unchanged heart rate. ANP caused significant reductions (13%) of E ES (4.2 vs 4.8 mmHg/ml) and M SW (54.6 vs 62.8 mmHg). The time constant of LV relaxation (τ, 45.1 vs 37.6 ms) was lengthened. The LV-arterial coupling, E ES / E A (arterial elastance) (0.57 vs 0.58) was unaltered. The peak mitral flow, dV/dt max was only increased by 7% (178 vs 166 ml/s). With BNP, there were no significant changes in E ES (5.1 vs 4.9 mmHg/ml) and M SW, but E ES /E A was improved 30% (0.74 vs 0.57) due to decreased E A . τ (33.4 vs 37.9 ms) was significantly shortened and dV/dt max increased 15% (189 vs 165 ml/s). In contrast, CNP produced significant increases (~30%) in E ES (6.3 vs 4.8 mmHg/ml) and M SW (80.5 vs 62.4 mmHg) with enhanced increase in E ES /E A (50%, 0.87vs 0.58), but decrease in τ (25%, 28.4 vs 38.1 ms) and significantly greater augmented dV/dt max (25%, 205 vs 164 ml/s). Similar observations of NPs were made at constant heart rate, or after autonomic blockade. Conclusion: In conscious dogs with HF, equal hypotensive ANP, BNP and CNP have negative, no effect, and positive inotropic effects on LV contractility and relaxation, respectively.

Assessment of left ventricular systolic function by non-invasive pressure-strain loop area in young male strength athletes

BackgroundThe health of athletes has been recognized as a worldwide public concern with more reported sudden cardiac deaths (SCD). Therefore, early detection of abnormal heart function in athletes can help reduce the risk of exercise. A novel valid non-invasive method to evaluate left ventricular (LV) myocardial work (MW) using LV pressure-strain loop (PSL), was used in this paper to explore LV systolic function in young male strength athletes.MethodsThirty-six professional young male strength athletes (the athlete group) and 32 healthy, age-matched young men (the control group) were involved in the study. The LVMW parameters were calculated as the area of PSL by two-dimensional speckle tracking echocardiography (2D-STE) and peak systolic LV pressure. The differences between two groups of data and the predictive efficacy of MW parameters for LV systolic function were analyzed.ResultsThe athlete group had significantly higher values of global wasted myocardial work (GWW) and peak strain dispersion (PSD) than did the control group (P<0.05). Global myocardial work index (GWI), global constructive myocardial work (GCW) and global longitudinal strain (GLS) were lower in the athlete group than that in the control group, although statistical significance was not reached (P>0.05). Due to the proportion of GWW and GCW, statistically significant reduction was found in global myocardial work efficiency (GWE) in the athlete group. Conventional echocardiography parameters were well correlated with GWW and GWE (P<0.05). The best predictor of LV myocardial contractile performance in the athletes using receiver operating characteristic curve (ROC) was GWE, with the area under ROC (AUC) of 0.733, sensitivity of 83.3% and specificity of 59.4%.ConclusionsSubclinical changes have appeared in the hearts of young male strength athletes after long-term intensive exercise and LVMW parameters by PSL play an important role in the evaluation of athlete’s LV contractile performance.

Left Ventricular End-Systolic Volume Is a Reliable Predictor of New-Onset Heart Failure with Preserved Left Ventricular Ejection Fraction.

Background Left ventricular (LV) ejection fraction (EF) and LV volumes were reported to have prognostic efficacy in cardiac diseases. In particular, the end-systolic volume index (LVESVI) has been featured as the most reliable prognostic indicator. However, such efficacy in patients with LVEF ≥ 50% has not been elucidated. Methods We screened the patients who received cardiac catheterization to evaluate coronary artery disease concomitantly with both left ventriculography and LV pressure recording using a catheter-tipped micromanometer and finally enrolled 355 patients with LVEF ≥ 50% and no history of heart failure (HF) after exclusion of the patients with severe coronary artery stenosis requiring early revascularization. Cardiovascular death or hospitalization for HF was defined as adverse events. The prognostic value of LVESVI was investigated using a Cox proportional hazards model. Results A univariable analysis demonstrated that age, log BNP level, tau, peak − dP/dt, LVEF, LV end-diastolic volume index (LVEDVI), and LVESVI were associated with adverse events. A correlation analysis revealed that LVESVI was significantly associated with log BNP level (r = 0.356, p < 0.001), +dP/dt (r = −0.324, p < 0.001), −dP/dt (r = 0.391, p < 0.001), and tau (r = 0.337, p < 0.001). Multivariable analysis with a stepwise procedure using the variables with statistical significance in the univariable analysis revealed that aging, an increase in BNP level, and enlargement of LVESVI were significant prognostic indicators (age: HR: 1.071, 95% CI: 1.009–1.137, p=0.024; log BNP : HR : 1.533, 95% CI: 1.090–2.156, p=0.014; LVESVI : HR : 1.051, 95% CI: 1.011–1.093, p=0.013, respectively). According to the receiver-operating characteristic curve analysis for adverse events, log BNP level of 3.23 pg/ml (BNP level: 25.3 pg/ml) and an LVESVI of 24.1 ml/m2 were optimal cutoff values (BNP : AUC : 0.753, p < 0.001, LVESVI : AUC : 0.729, p < 0.001, respectively). Conclusion In patients with LVEF ≥ 50%, an increased LVESVI is related to the adverse events. LV contractile performance even in the range of preserved LVEF should be considered as a role of a prognostic indicator.

Left ventricular contractile performance and heart failure in patients with left ventricular ejection fraction more than 40%

Heart failure (HF) with mid-range left ventricular ejection fraction (LVEF) (HFmrEF) is considered a new category of HF and LVEF < 50%, which is the upper threshold of LVEF for HFmrEF, is thought to represent a mild decrease in LV contractile performance. We aimed to consider an LVEF threshold value to be taken as a surrogate for impairment of LV contractile performance, resulting in new-onset HF. We enrolled 398 patients with LVEF ≥ 40% that underwent cardiac catheterization. Using the LV pressure recording with a catheter-tipped micromanometer, we calculated the inertia force of late systolic aortic flow (IFLSAF), which was sensitive to the slight impairment in LV contractile performance. We evaluated the utility of the IFLSAF for predicting future cardiovascular death or hospitalization for HF. We performed a receiver operating characteristic (ROC) curve analysis to determine the best LVEF threshold value for distinguishing whether the LV maintained the IFLSAF. A multivariate Cox proportional-hazards model revealed that the loss of IFLSAF was significantly associated with the future adverse events (HR: 7.798, 95%CI 2.174–27.969, p = 0.002). According to the ROC curve analysis, an LVEF ≥ 58% indicated that the LV could maintain the IFLSAF. We concluded that the loss of IFLSAF, which could reflect even slight impairment in LV contractile performance, was a reliable indicator for new-onset HF in patients with LVEF ≥ 40%. LVEF ≥ 58% could be taken as a surrogate for the IFLSAF maintenance; this threshold could be useful for risk stratification of new-onset HF in patients with preserved LVEF.

Reversal of angiotensin-(1–12)-caused positive modulation on left ventricular contractile performance in heart failure: Assessment by pressure-volume analysis

BackgroundAngiotensin-(1–12) [Ang-(1–12)] is a renin-independent precursor for direct angiotensin-II production by chymase. Substantial evidence suggests that heart failure (HF) may alter cardiac Ang-(1–12) expression and activity; this novel Ang-(1–12)/chymase axis may be the main source for angiotensin-II deleterious actions in HF. We hypothesized that HF alters cardiac response to Ang-(1–12). Its stimulation may produce cardiac negative modulation and exacerbate left ventricle (LV) systolic and diastolic dysfunction. Methods and resultsWe assessed the effects of Ang-(1–12) (2 nmol/kg/min, iv, 10 min) on LV contractility, LV diastolic filling, and LV-arterial coupling (AVC) in 16 SD male rats with HF-induced by isoproterenol (3 mo after 170 mg/kg sq. for 2 consecutive days) and 10 age-matched male controls. In normal controls, versus baseline, Ang-(1–12) increased LV end-systolic pressure, without altering heart rate, arterial elastance (EA), LV end-diastolic pressure (PED), the time constant of LV relaxation (τ) and ejection fraction (EF). Ang-(1–12) significantly increased the slopes (EES) of LV end-systolic pressure (P)-volume (V) relations and the slopes (MSW) of LV stroke wok-end-diastolic V relations, indicating increased LV contractility. AVC (quantified as EES/EA) improved. In contrast, in HF, versus HF baseline, Ang-(1–12) produced a similar increase in PES, but significantly increased τ, EA, and PED. The early diastolic portion of LV PV loop was shifted upward with reduced in EF. Moreover, Ang-(1–12) significantly decreased EES and MSW, demonstrating decreased LV contractility. AVC was decreased by 43%. ConclusionsIn both normal and HF rats, Ang-(1–12) causes similar vasoconstriction. In normal, Ang-(1–12) increases LV contractile function. In HF, Ang-(1–12) has adverse effects and depresses LV systolic and diastolic functional performance.

Biomechanics and Myocardial Damage in Chronic Mitral Regurgitation

The 2014 ACC/AHA guidelines for surgery for asymptomatic chronic mitral regurgitation states as a class IIa recommendation that mitral valve (MV) repair could be considered if the left ventricular ejection fraction (LVEF) is greater than 0.60 and the LVESD less than 40 mm if there is a 95% probability of a durable repair with an expected mortality of less than 1%. However, adhering to these guideline surgical triggers uncovers a subset of patients (20% incidence) where the LVEF decreases post repair. Is this due to changing loading conditions or impaired myocyte contractility? In a study at University of Alabama at Birmingham of patients undergoing (MV) repair for chronic mitral regurgitation MRI derived left ventricular (LV) volumes demonstrated reverse diastolic remodelling while left ventricular end systolic remodelling was essentially unchanged following surgery. Myocardial strain rates were normal prior to mitral valve repair. However, in the face of unchanging left ventricular end systolic wall stress, strain rates decreased below normal following MV repair suggesting a decrease in left ventricular contractile performance. LV biopsies of these patients taken at the time of MV repair demonstrated deposition of lipofuscin which is composed of protein and lipid degradation residues. Lipofuscin accumulation may have a deleterious effect on myocyte function. These biopsies also demonstrated extensive myofibrillar degeneration. The desmin cytoskeleton in the myocardium forms a continuous network maintaining a spatial relationship between the contractile apparatus and mitochondria. The LV biopsies demonstrated desmin loss indicating substantial underlying cellular and molecular damage. Implications: At the time of correction of mitral regurgitation substantial LV damage has occurred. This suggests that an even earlier repair of mitral regurgitation should be considered.

Effects of glucagon-like peptide-1 agents on left ventricular function: Systematic review and meta-analysis

Background. The cardiovascular safety of many glucagon-like peptide-1 agents (GLP-1 agents) is unclear. In this study, we assess the effects of the GLP-1 agents on left ventricular function in patients with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD).Methods. PubMed, EMBASE, and the Cochrane Library were searched for the relevant publications up to May 2013 without restriction by language. All clinical controlled trials assessing left ventricular function and cardiovascular outcomes with the GLP-1 agents were selected for eligibility. Fourteen trials (415 patients) were identified as eligible between 1966 and 2013. Twelve of the studies were randomized controlled trials (RCT).Results. The results showed that GLP-1 agent treatment in patients with T2DM and/or CVD led to significantly improved regional left ventricular contractile parameters (including peak left systolic tissue velocity and strain) and global left ventricular performance (including stroke volume, ejection fraction, and left ventricular chambers) compared with patients receiving placebo.Conclusions. GLP-1 agent treatment in T2DM and/or CVD patients is associated with a modest but significant increase in the odds of left ventricular contractile parameters and left ventricular performance compared with patients having received placebo, which may be indicative of additional cardiovascular benefits for these patients.

Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury

We have previously identified exosomes as the paracrine factor secreted by mesenchymal stem cells. Recently, we found that the key features of reperfusion injury, namely loss of ATP/NADH, increased oxidative stress and cell death were underpinned by proteomic deficiencies in ischemic/reperfused myocardium, and could be ameliorated by proteins in exosomes. To test this hypothesis in vivo, mice (C57Bl6/J) underwent 30min ischemia, followed by reperfusion (I/R injury). Purified exosomes or saline was administered 5min before reperfusion. Exosomes reduced infarct size by 45% compared to saline treatment. Langendorff experiments revealed that intact but not lysed exosomes enhanced viability of the ischemic/reperfused myocardium. Exosome treated animals exhibited significant preservation of left ventricular geometry and contractile performance during 28days follow-up. Within an hour after reperfusion, exosome treatment increased levels of ATP and NADH, decreased oxidative stress, increased phosphorylated-Akt and phosphorylated-GSK-3β, and reduced phosphorylated-c-JNK in ischemic/reperfused hearts. Subsequently, both local and systemic inflammation were significantly reduced 24h after reperfusion. In conclusion, our study shows that intact exosomes restore bioenergetics, reduce oxidative stress and activate pro-survival signaling, thereby enhancing cardiac function and geometry after myocardial I/R injury. Hence, mesenchymal stem cell-derived exosomes are a potential adjuvant to reperfusion therapy for myocardial infarction.

New Insights into Mechanisms of Action of Carvedilol Treatment in Chronic Heart Failure Patients—A Matter of Time for Contractility

BackgroundIt is unclear whether improvement in left ventricular (LV) ejection fraction (LVEF) following treatment with a combined α1,β1,β2-blockade can be attributed to improvement in LV contractility, to a reduction in afterload, and/or to improvements in LV remodeling and chamber size. We aimed to examine whether the observed improvement in LVEF following carvedilol treatment is due to changes in intrinsic myocardial contractility beyond changes in LV chamber size or loading conditions. Methods and ResultsIn 49 consecutive patients with chronic heart failure (HF), LVEF ≤35%, NYHA functional class II–IV, on angiotensin-converting enzyme inhibitors but not on ß-blockers, LV contractile performance and remodeling were assessed by comprehensive echocardiography at baseline and after 3 and 6 months of treatment with carvedilol. Carvedilol treatment resulted in significant improvements in LVEF, shortening fraction, and velocity of circumferential shortening (VCFc). There were no significant changes in the mean arterial blood pressure or systemic vascular resistance index; but LV end-systolic wall stress (LVESS), effective arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end-systolic dimensions and volumes were significantly reduced. Estimated end-systolic elastance, VCFc-to-LVESS ratio, and pulsatile arterial compliance significantly improved after 6 months of treatment with carvedilol. The slope of the VCFc relationship to LVESS worsened from 0 to 3 months, but significantly improved from 3 to 6 months. ConclusionsDespite an initial transient negative inotropic effect from 0 to 3 months, carvedilol treatment was associated with a positive inotropic effect with significant improvement in load-independent indexes of myocardial contractility beyond what can be attributed to changes in LV chamber size and load after 3 months. There were no changes in systemic vascular resistance with carvedilol treatment; however, improvement in pulsatile arterial compliance and ventriculoarterial coupling suggested enhanced cardiac mechanoenergetic performance along with improved systemic arterial compliance.

ATP Production Rate via Creatine Kinase or ATP Synthase In Vivo

Rationale: 31 P magnetization saturation transfer (MST) experiment is the most widely used method to study ATP metabolism kinetics. However, its lengthy data acquisition time greatly limits the wide biomedical applications in vivo, especially for studies requiring high spatial and temporal resolutions. Objective: We aimed to develop a novel superfast MST method that can accurately quantify ATP production rate constants ( k f ) through creatine kinase (CK) or ATP synthase (ATPase) with 2 spectra. Methods and Results: The T 1 nom (T 1 nominal) method uses a correction factor to compensate the partially relaxed MST experiments, thus allowing measurement of enzyme kinetics with an arbitrary repetition time and flip angle, which consequently reduces the data acquisition time of a transmurally differentiated CK k f measurement by 91% as compared with the conventional method with spatial localization. The novel T 1 nom method is validated theoretically with numeric simulation, and further verified with in vivo swine hearts, as well as CK and ATPase activities in rat brain at 9.4 Tesla. Importantly, the in vivo data from swine hearts demonstrate, for the first time, that within an observation window of 30 minutes, the inhibition of CK activity by iodoacetamide does not limit left ventricular chamber contractile function. Conclusions: A novel MST method for superfast examination of enzyme kinetics in vivo has been developed and verified theoretically and experimentally. In the in vivo normal heart, redundant multiple supporting systems of myocardial ATP production, transportation, and utilization exist, such that inhibition of one mechanism does not impair the normal left ventricular contractile performance.

Glucose Tolerance and Left Ventricular Pressure‐Volume Relationships in Frequently Used Mouse Strains

We investigated glucose tolerance and left ventricular contractile performance in 4 frequently used mouse strains (Swiss, C57BL/6J, DBA2, and BalbC) at 24 weeks. Glucose tolerance was tested by measuring blood glucose levels in time after intraperitoneal glucose injection (2 mg/g body weight). Left ventricular contractility was assessed by pressure-conductance analysis. Peak glucose levels and glucose area under the curve were higher (all P < .05) in C57BL/6J (418 ± 65 mg/dL and 813 ± 100 mg·h/dL) versus Swiss (237 ± 66 mg/dL and 470 ± 126 mg·h/dL), DBA2 (113 ± 20 mg/dL and 304 ± 49 mg·h/dL, P < .01), and BalbC mice (174 ± 55 mg/dL and 416 ± 70 mg·h/dL). Cardiac output was higher (all P < .05) in Swiss (14038 ± 4530 μL/min) versus C57BL/6J (10405 ± 2683 μL/min), DBA2 (10438 ± 3251 μL/min), and BalbC mice (8466 ± 3013 μL/min). Load-independent left ventricular contractility assessed as recruitable stroke work (PRSW) was comparable in all strains. In conclusion, glucose tolerance and load-dependent left ventricular performance parameters were different between 4 mice background strains, but PRSW was comparable.

Longitudinal and Circumferential Strain Rate, Left Ventricular Remodeling, and Prognosis After Myocardial Infarction

We sought to investigate the clinical prognostic value of longitudinal and circumferential strain (S) and strain rate (SR) in patients after high-risk myocardial infarction (MI). Left ventricular (LV) contractile performance after MI is an important predictor of long-term outcome. Tissue deformation imaging might more closely reflect myocardial contractility than traditional measures of systolic functions. The VALIANT (Valsartan in Acute Myocardial Infarction Trial) Echo study enrolled 603 patients with LV dysfunction, heart failure, or both 5 days after MI. We measured global peak longitudinal S and systolic SR (SRs) from apical 4- and 2-chamber views and global circumferential S and SRs from parasternal short-axis view with speckle tracking software (Velocity Vector Imaging, Siemens, Inc., Mountain View, California). We related global S and SRs to LV remodeling at 20-month follow-up and to clinical outcomes. Both longitudinal (mean: -5.1 ± 1.6 100/ms) and circumferential SRs (mean: -8.0 ± 2.8 100/ms) were predictive of death or hospital stay for heart failure (hazard ratio: 2.4, 95% confidence interval [CI]: 2.0 to 3.1, p < 0.001; hazard ratio: 1.3, 95% CI: 1.2 to 1.4, p < 0.001, respectively) after adjustment for clinical covariates by Cox proportional hazards, and longitudinal SRs further improved in predicting 18-month survivor on a model based on clinical and standard echocardiographic measures (increase in area under the receiver-operator characteristic curve: 0.13, p = 0.009). With multivariable logistic regression, circumferential SRs, but not longitudinal SRs, was strongly predictive of remodeling (odds ratio: 1.3, 95% CI: 1.1 to 1.4, p < 0.001). Both longitudinal and circumferential SRs were independent predictors of outcomes after MI, whereas only circumferential SRs was predictive of remodeling, suggesting that preserved circumferential function might serve to restrain ventricular enlargement after MI.

Intramyocardial injection of autologous bone marrow mononuclear cells for patients with chronic ischemic heart disease and left ventricular dysfunction ( First M ononuclear Cells injected in the US [FOCUS]): Rationale and design

The increasing worldwide prevalence of coronary artery disease (CAD) continues to challenge the medical community. Management options include medical and revascularization therapy. Despite advances in these methods, CAD is a leading cause of recurrent ischemia and heart failure, posing significant morbidity and mortality risks along with increasing health costs in a large patient population worldwide. The Cardiovascular Cell Therapy Research Network (CCTRN) was established by the National Institutes of Health to investigate the role of cell therapy in the treatment of chronic cardiovascular disease. FOCUS is a CCTRN-designed randomized, phase II, placebo-controlled clinical trial that will assess the effect of autologous bone marrow mononuclear cells delivered transendocardially to patients with left ventricular (LV) dysfunction and symptomatic heart failure or angina. All patients need to have limiting ischemia by reversible ischemia on single-photon emission computed tomography assessment. After thoughtful consideration of both statistical and clinical principles, we will recruit 87 patients (58 cell treated and 29 placebo) to receive either bone marrow-derived stem cells or placebo. Myocardial perfusion, LV contractile performance, and maximal oxygen consumption are the primary outcome measures. The designed clinical trial will provide a sound assessment of the effect of autologous bone marrow mononuclear cells in improving blood flow and contractile function of the heart. The target population is patients with CAD and LV dysfunction with limiting angina or symptomatic heat failure. Patient safety is a central concern of the CCTRN, and patients will be followed for at least 5 years.

CARDIAC CONTRACTILITY MEASURES OF LEFT VENTRICULAR SYSTOLIC FUNCTIONAL ASSESSMENT OF NORMAL AND DISEASED HEARTS

Left ventricular (LV) contraction is the basis of LV systolic function, impairment of which underlies heart failure pathophysiology. Its accurate quantification in the form of LV contractility indices is imperative for diagnostic and follow-up assessment of LV systolic function in heart failure. Herein, we analyze LV contractile performance by focusing on LV contractility indices at different physiological organizational levels: from sarcomere dynamics to LV myocardial properties (such as elastic modulus and elastance), and from LV wall contractile stress development to the generation of intra-LV blood flow velocities and pressure distributions. Further, we present the development analyses of these indices and their medical applications. Using improved development of invasive and noninvasive techniques for measuring ventricular pressure, geometry, and volume, we show how these indices have become more amenable for clinical usage to obtain better patient assessment. The purpose of this paper is to present a comprehensive coverage of LV contraction physiology, indices to qualify LV contraction, formulation, and medical applications of some major intrinsic LV contractility indices, so as to provide the basis of functional assessment of normal versus diseased hearts.

Pattern and Impact of Altered Regional Myocardial Excursion on Global Ventricular Performance After First-Time Acute Anterior Wall Myocardial Infarction by Real-Time Three-Dimensional Echocardiography

The regional wall motion score index obtained by two-dimensional echocardiography in myocardial infarction (MI) has a significant impact on left ventricular (LV) global contractility and is of extraordinary prognostic value, whereas data regarding real-time three-dimensional echocardiography (RT-3DE) are lacking. We sought to clarify the relationship between RT-3DE and LV contractility in patients after MI. RT-3DE was performed in 50 patients with anterior wall acute myocardial infarction and 30 normal controls. Global (16 segments) and regional ring-based LV systolic excursions were analyzed offline using the commercially available software Q-Lab version 5.0. The correlations between the LV global and regional systolic excursions and the global LV contractile performance were examined in the MI patients, and further compared with the control group. The global and regional (basal and middle ring-based) LV systolic excursions were lower in the MI patients (age, 61.8 ± 13.1 years) than in the normal controls (age, 40.0 ± 15.4 years). Global excursion showed inverse linear relationships with LV end-systolic volume ( r =-0.26, p < 0.05) and end-diastolic volume ( r =-0.22, p < 0.05) but no significant relationships with LV ejection fraction ( p = 0.08) and stroke volume ( p = 0.49). Regional wall motion abnormalities quantified by RT-3DE are clinically convenient and feasible in both MI patients and the normal population. This rapid and objective quantification may also help discriminate abnormal from normal regional and global functions after infarction and, therefore, has the potential to be an attractive solution for clinical diagnosis.