Left Ventricular Elastance Research Articles

Left ventricular mass is related to post-saline load plasma aldosterone levels in primary hypertension

The purpose of the study was to determine the prognostic value of ventricular-arterial coupling (VAC) in patients with arterial hypertension and stable heart failure with reduced ejection fraction (HFrEF). Methods: In prospective study (follow-up 12-24 months, median 18 months) prognosis of 93 stable patients (75% male, age 64 9 years (M SD), history of myocardial infarction 67%, diabetes mellitus 32%, heart rate 75 13/min) with controlled hypertension (blood pressure (BP) <160/100 mmHg, 131 14/80 10 mmHg), symptoms and signs of HF, left ventricular (LV) EF 100 pg/ml (650 679 pg/ml), II/III NYHA class 25/75% was evaluated. Adverse outcomes included all cause death or first HF hospitalization. 2-dimentional echocardiography was used to assess arterial elastance (Ea) and end-systolic LV elastance (Ees). VAC was assessed as the ratio Ea/Ees. Arterial stiffness was assessed using applanation tonometry. Clinical and demographic parameters, parameters of LV function, VAC and arterial stiffness were included in multivariate analysis. P<0.05 was considered significant. Results: Adverse outcomes were revealed in 39% of patients (15% deaths, 24% HF hospitalizations). The following factors increased the risk of adverse outcomes: LVEF <25% (odds ratio (OR) 26.1, 95% confidential interval (CI) 24.9-27.3), index of VAC 3.3 (OR 23.3, 95% CI 22.124.5), stroke work (SW)/pressure volume area (PVA) (LV work efficiency) <38% (OR 8.2, 95% CI 7.0-9.4), augmentation index (AI) 25% (OR 2.3, 95% CI 1.3-3.2), time to reflected wave (Tr) <135 ms (OR 2.1, 95% CI 1.2-3.0). Pulse wave velocity 15 m/s (OR 5.4, 95% CI 3.7-7.1), office systolic BP <120 mmHg (OR 5.1, 95% CI 4.2-6.0) were associated with increased risk of HF hospitalizations. AI 35% (OR 7.3, 95% CI 5.9-8.6), office systolic BP <120 mmHg (OR 3.4, 95% CI 1.3-5.5) and diastolic BP <70 mmHg (OR 3.4, 95% CI 1.3-5.5), Tr <116 ms (OR 2.3, 95% CI 1.1-3.5), SW/PVA <48% (OR 2.3, 95% CI 1.1-3.5) were associated with increased risk of all-cause death. Conclusions: Parameters of VAC, LV work efficiency and arterial stiffness have independent prognostic value as well as LVEF and BP in patients with arterial hypertension and HFrEF. Assessment of VAC via Ea/Ees, an additional noninvasively derived metric, can be used for risk stratification of patients with HFrEF.

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

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. 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 106subjects (32±8years, 72% female) with severe MS (0.8±0.2 cm(2) ) and 40age-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±0.3mmHgml(-1) ; P<0.001) and LV contractility (Ees : 4.1±1.6 vs. 2.4±0.5mmHgml(-1) ; P<0.001) as compared to controls, with higher Ea in subjects with smaller mitral valve area (≤ 0.8cm(2) ) and pronounced subvalvular fusion. Stroke volume (49±16 to 57±17ml; P<0.001) and indexed LV end-diastolic volume (LVEDVindex : 57±16 to 64±16mlm(-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.

Closing the Loop: Modelling of Heart Failure Progression from Health to End-Stage Using a Meta-Analysis of Left Ventricular Pressure-Volume Loops

IntroductionThe American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for the classification of heart failure (HF) are descriptive but lack precise and objective measures which would assist in categorising such patients. Our aim was two fold, firstly to demonstrate quantitatively the progression of HF through each stage using a meta-analysis of existing left ventricular (LV) pressure-volume (PV) loop data and secondly use the LV PV loop data to create stage specific HF models.Methods and ResultsA literature search yielded 31 papers with PV data, representing over 200 patients in different stages of HF. The raw pressure and volume data were extracted from the papers using a digitising software package and the means were calculated. The data demonstrated that, as HF progressed, stroke volume (SV), ejection fraction (EF%) decreased while LV volumes increased. A 2-element lumped parameter model was employed to model the mean loops and the error was calculated between the loops, demonstrating close fit between the loops. The only parameter that was consistently and statistically different across all the stages was the elastance (Emax).ConclusionsFor the first time, the authors have created a visual and quantitative representation of the AHA/ACC stages of LVSD-HF, from normal to end-stage. The study demonstrates that robust, load-independent and reproducible parameters, such as elastance, can be used to categorise and model HF, complementing the existing classification. The modelled PV loops establish previously unknown physiological parameters for each AHA/ACC stage of LVSD-HF, such as LV elastance and highlight that it this parameter alone, in lumped parameter models, that determines the severity of HF. Such information will enable cardiovascular modellers with an interest in HF, to create more accurate models of the heart as it fails.

Abstract 17241: Impaired Left Atrioventricular Coupling Compromises Cardiac Performance in Heart Failure With Preserved Ejection Fraction

Background: In heart failure with preserved ejection fraction (HFpEF), left ventricular (LV) systolic elastance (Ees) increases in tandem with increases in arterial elastance (Ea), which maintains ejection fraction but limits systolic reserve and precipitates volume sensitivity. The left atrium (LA) lies in series with the LV and contributes to LV stroke volume. We hypothesized that HFpEF is associated with increased LA systolic elastance (E LA ) and deranged atrioventricular (AV) coupling which may additionally compromise cardiac performance. Methods: HFpEF was modeled by experimental hypertension (bilateral renal wrap + DOCA) in elderly dogs (n=9). LA and LV structure, function (echo, MRI) and invasively assessed pressure-volume relationships (PVR, open-chest; pericardiotomy; admittance catheter) were compared to sham-operated young dogs (control; n=13). Results: As compared to controls, HFpEF dogs displayed concentric remodeling, with increased diastolic stiffness, Ea and Ees (p&lt;0.05 for all) and reduced Ea/Ees (p=0.03). LA maximum volume (28±3 vs 23±3mL, p=0.007), LA stroke volume (4±1 vs2±1mL, p=0.006), LA active emptying fraction (18±6 vs 12±2%, p=0.03) and LA ejection rate (51±14 vs 30±16mL/s) were higher in HFpEF versus controls, suggesting increased LA stroke work and inotropy. At matched heart rate and LA pressure, E LA was steeper in HFpEF than control (2.7±0.9 vs 1.5±0.6mmHg/mL, p=0.01) and positively correlated with Ees (r=0.6, p=0.005) and Ea (r=0.66, p=0.002). However AV mismatch occurred as increases in E LA were not proportionate to increases in Ees (Ees/E LA 1.3±0.4 HFpEF vs 0.8±0.4 control, p&lt;0.05). On linear regression, worse AV coupling (i.e. higher Ees/E LA ) was associated with lower LV stroke volume ( Figure ). Conclusion: In experimental HFpEF, despite enhanced LA contractility, AV coupling was deranged. Worse AV coupling may further contribute to reserve dysfunction, LA pressure rise, and susceptibility to pulmonary edema in HFpEF.

Impact of chronic changes in arterial compliance and resistance on left ventricular ageing in humans.

Left ventricular systolic elastance (Ees) and diastolic elastance (Eed) correlate with arterial elastance (Ea), but it is unknown how chronic changes in arterial compliance and resistance, which determine Ea, might differentially affect cardiac properties with ageing. We sought to characterize chronic changes in pulsatile and resistive arterial load and correlate them with longitudinal changes in LV structure and function in a prospective, community-based study. Comprehensive echocardiography was performed in 722 subjects participating in a randomly selected community-based study at two examinations separated by 4 years, allowing for assessment of LV Ees, Eed, and end-diastolic volume (EDV), Ea, total arterial compliance, and systemic vascular resistance at both examinations. Chronic changes in resistance and heart rate were the dominant contributors to change in Ea. Changes in arterial compliance had little impact on changes in Ea, but were strongly associated with changes in Ees. The combination of increased resistance and decreased compliance was associated with the largest increase in LV diastolic stiffness, an effect that was mediated by a decrease in LVEDV. In contrast, subjects with both improved arterial compliance and decreased resistance displayed an increase in LVEDV over time, with no increase in LV Eed. Increases in pulsatile arterial load with ageing contribute more to LV systolic stiffening, while combined pulsatile and resistive loading changes are associated with positive and negative chamber remodelling and diastolic stiffness. Therapies designed to improve arterial resistance and particularly to enhance aortic compliance may hold promise to prevent or reverse cardiac ageing and its sequelae.

Emax monitoring by aortic pressure waveform analysis.

Emax- the maximal left ventricular elastance- is perhaps the best available scalar index of contractility. However, the conventional method for its measurement involves obtaining multiple ventricular pressure-volume loops at different loading conditions and is thus impractical. We previously proposed a more practical technique for tracking Emax from just a single beat of an aortic pressure waveform based on a lumped parameter model of the left ventricle and arteries. Here, we tested the technique against the conventional Emax measurement method in animals during inotropic interventions. Our results show that the estimated Emax changes corresponded fairly well to the reference changes, with a correlation coefficient of 0.793. With further development and testing, the technique could ultimately permit continuous and less invasive monitoring of Emax.

Abstract 159: Ablation of the Hypertension Candidate Gene ATP2B1 Leads To Deficient Calcium Cycling, Systolic Dysfunction and Heart Failure Following Pressure Overload

Mutations in ATP2B1 encoding the ubiquitous calcium extrusion pump Plasma Membrane Calcium ATPase 1 (PMCA1) have recently identified it as having the strongest association of any gene to hypertension, yet the role of PMCA1 in the pressure-overloaded heart is not known. To investigate this we generated a novel mouse line carrying cardiomyocyte-specific deletion of PMCA1 (PMCA1 cko ) and challenged them with transverse aortic constriction (TAC) alongside littermate ‘floxed’ controls (PMCA1 f/f ). After two weeks, echocardiographic analysis revealed signs of systolic dysfunction and left ventricular (LV) dilation in PMCA1 cko hearts as evidenced by reduced fractional shortening and increased diastolic diameter (both p&lt;0.05), whilst function in PMCA1 f/f TAC controls remained preserved. This was accompanied by an increase in normalised lung weight in PMCA1 cko mice compared to sham operated and TAC controls (p&lt;0.05) indicative of pulmonary congestion and a progression into LV failure, despite comparable hypertrophic growth amongst the two TAC cohorts. Hemodynamic analysis following LV catheterisation revealed contractility, as measured by left ventricular elastance (E es ), to be increased in controls after TAC (PMCA1 f/f TAC 12.69 ± 1.63 vs sham 7.02 ± 1.11 mmHg/μl, p&lt;0.05), a change which was not reciprocated in knockout hearts (PMCA1 cko TAC 7.70 ± 1.19 vs sham 7.22 ± 1.55 mmHg/μl). To examine whether altered calcium handling could be the underlying cause of the observed phenotype, cardiomyocytes were isolated following one week TAC and loaded with Indo-1, prior to the onset of failure in PMCA1 cko hearts. Compatible with an increase in E es , systolic calcium levels were higher in PMCA1 f/f myocytes following pressure overload compared to sham controls (p&lt;0.05), whilst PMCA1 cko TAC myocytes displayed equivalent peak calcium levels to their respective sham controls. These results suggest that PMCA1 may play a necessary role in enhancing calcium cycling during the early response to pressure overload, and that disrupting this gene may increase the susceptibility to heart failure under these conditions. This may provide first evidence of a novel genetic basis for the development of heart failure in a proportion of hypertensive patients.

Gender differences in myocardial function and arterio-ventricular coupling in response to maximal exercise in adolescent floor-ball players.

BackgroundThe hemodynamic and cardiac responses to exercise have been widely investigated in adults. However, little is known regarding myocardial performance in response to a short bout of maximal exercise in adolescents. We therefore sought to study alterations in myocardial function and investigate sex-influences in young athletes after maximal cardiopulmonary testing.Methods51 adolescent (13-19 years old) floor-ball players (24 females) were recruited. All subjects underwent a maximal exercise test to determine maximal oxygen uptake (VO2max) and cardiac output. Cardiac performance was investigated using conventional and tissue velocity imaging, as well as 2D strain echocardiography before and 30 minutes following exercise. Arterio-ventricular coupling was evaluated by means of single beat ventricular elastance and arterial elastance.ResultsCompared to baseline the early diastolic myocardial velocity (E′LV) at the basal left ventricular (LV) segments declined significantly (females: E′LV: 14.7 +/- 2.6 to 13.6 +/- 2.9 cm/s; males: 15.2 +/- 2.2 to 13.9 +/- 2.3 cm/s, p < 0.001 for both). Similarly, 2D strain decreased significantly following exercise (2D strain LV: from 21.5 +/- 2.4 to 20.2 +/- 2.7% in females, and from 20 +/- 1 to 17.9 +/- 1.5% in males, p < 0.05 for both). However, there were no significant changes in LV contractility estimated by elastance in either sex following exercise (p > 0.05). Arterial elastance) Ea) at baseline was identified as the only predictor of VO2max in males (r = 0.76, p < 0.001) but not in females (p > 0.05).ConclusionsThe present study demonstrates that vigorous exercise of short duration results in a significant decrease of longitudinal myocardial motion in both sexes. However, in view of unaltered end systolic LV elastance (Ees), these reductions most probably reflect changes in the loading conditions and not an attenuation of myocardial function per se. Importantly, we show that arterial load at rest acts as a strong predictor of VO2max in males but not in female subjects.

Ultrasound study of carotid and cardiac remodeling and cardiac-arterial coupling in normal pregnancy and preeclampsia: a case control study.

BackgroundCardiovascular adaptions, such as cardiac and uterine spiral arterial remodeling, and aortic arterial stiffening during pregnancy have been extensively investigated, while the interactions between the elastic artery and the left ventricle are poorly understood. This study was to evaluate the cardiac-arterial coupling in both normal pregnancy and preeclampsia using ultrasound techniques.MethodsTwenty-three preeclamptic women with no antihypertensive treatment prior to admission, and 40 age- (27.2 ± 3.0 y vs. 29.1 ± 5.7 y, p = 0.0805) and gestational week- (35.6 ± 3.4 wk vs. 34.8 ± 3.6 wk, p = 0.3573) matched normotensive pregnant women were included. All women signed informed consent. All were nulliparas, had singleton pregnancies, and had no other risk factors for arterial stiffening. Carotid and cardiac ultrasound was performed using a MylabTwice ultrasound unit (Esaote, Italy). Cardiac and carotid remodeling and their associations were analyzed. Left ventriculo-carotid coupling was characterized by the ratio between the arterial elastance (Ea) and the left ventricular systolic elastance (Ees). Follow-up study was performed 16–20 months after parturition.ResultsLeft ventricular and carotid arterial remodeling was seen more frequently in preeclamptic women than in normal pregnant controls (96% vs. 40%, 82% vs. 48%, both p < 0.0001). The relative carotid arterial wall thickness showed no significant difference between the two groups. However, the carotid cross-sectional area, a surrogate for carotid arterial mass, was significantly greater in preeclampsia than that in normal controls (11.23 ± 0.17 mm2 vs. 8.58 ± 1.88 mm2, p < 0.00001). Carotid arterial stiffness and intima-media thickness correlated significantly with cardiac diastolic function parameters and blood pressures (p < 0.05). Both Ea and Ees were significantly greater in preeclampsia, compared with values in normal pregnant controls (Ea: 2.41 ± 0.57 mmHg/ml vs. 1.98 ± 0.46 mmHg/ml, p = 0.0005; Ees: 11.68 ± 9.51 m/s2 vs. 6.91 ± 6.13 m/s2, p = 0.002). However, there was no significant difference in the left ventriculo-carotid coupling index, Ea/Ees, between the two groups. Carotid remodeling persisted in both preeclamptic women and normal pregnant controls 16–20 months after parturition.ConclusionsSignificant cardiac and carotid remodeling and similar left ventriculo-carotid coupling were observed in both preeclampsia and normal pregnancy. Carotid remodeling may persist postpartum. Further studies with larger populations are needed to confirm these findings.

Impact of positive end-expiratory pressure application on ventriculo-arterial coupling in decompensated left ventricles after cardiac surgery: a non-invasive echocardiographic study

The management of ICU patients following heart surgery can be hustling when coping with severe left ventricular (LV) dysfunction. Single beat (Sb) measurements of ventriculo- arterial coupling (VAc) can be used by the intensivist when dealing with altered hemodynamic states [1]. LV elastance (Ees) and arterial elastance (Ea) can be measured by trasthoracic echocardiography (TTE) in a Sb fashion [2], so allowing quick assessment of VAc. PEEP application is common practice in the ICU but can have hemodynamic consequences and lead to instability. Speckle tracking analysis by TTE has been recently reported to help titrating PEEP in critically ill patients [3]. However, this can be demanding and require specific ultrasound tools. In this study we aimed to assess whether standard TTE can be useful in evaluating the effect of respiratory treatment with PEEP on cardiovascular efficiency by measuring VAc after coronary artery bypass surgery (CABG).

The Frank-Starling relationship of the heart revealed in a large animal study utilizing real-time undersampled radial MRI at variable inotropic state and heart rate

Background LV performance is coupled to loading conditions (i.e. preload and afterload) and myocardial contractility (1,2). Therefore load-independence is an important means to isolate and study LV contractility in preclinical studies of cardiovascular pharmaceuticals and devices (3). Precise and rapid assessment of LV pressure is achieved with high fidelity catheter-based pressure transducers but measurements of LV volume are more difficult and less reliable. Thus far, MRI has not demonstrated sufficient spatiotemporal resolution to measure beat-to-beat changes of the pressure-volume (PV) loop to measure left ventricular (LV) elasticity or preload-recruitable stroke work (PRSW). Our aim was to develop a realtime (rtMRI) approach to measure PV and FrankStarling relationships in a preclinical model of heart disease under normal and stressed physiologic conditions.

Cardiovascular changes in children with coarctation of the aorta treated by endovascular stenting

The aim of this study was to investigate the echocardiographic, biochemical short- and mid-term effects of the stenting procedure on left ventricular function, aortic stiffness, elasticity and systemic hypertension in children with coarctation of the aorta (CoA). Fifteen patients with native or recurrent CoA and 30 healthy controls who were sex and age matched were included in the study. The blood pressure values, echocardiographic measurements, elastic functions of ascending aorta and serum N-Terminal ProBNP (NT-ProBNP) levels were recorded prospectively before and at the first and sixth month after stenting. The mean arterial pressure recorded before stenting was 134.4±16.3 mm Hg; at the sixth month it was 115.5±9.5 mm Hg and in the control group it was 107.3±9.4 mm Hg. Although blood pressure levels were lower compared with the pre-stenting measurements (P<0.05), they were still significantly higher compared with the control group (P<0.05). Although a significant reduction was detected in the LVMIz at the end of the sixth month (50.4±14.3 g m(-2.7)) compared with the baseline (66.6±17.9 g m(-2.7); P<0.05), it was still higher compared with the control group (35.7±6.2 g m(-2.7); P<0.05). The baseline aortic elasticity (6.4±3.4 cm(2) dyn(-1) 10(-6)) was lower compared with the control group (10.0±1.7 cm(2) dyn(-1) 10(-6); P<0.05), and prestenting aortic stiffness was higher than that of the control group (5.6±1.6 dyn(-1) 10(-6); 2.5±0.45 dyn(-1) 10(-6); P<0.05). A statistically significant negative correlation was detected between the pressure gradient at the lesion site and aortic elasticity (r: -0.53, P: 0.04). Although resolution of the coarctation by endovascular stenting led to a reduction in the arteriopathy that had already begun before treatment, it was demonstrated that these children did not completely return to normal.

Longitudinal Changes in Left Ventricular Stiffness

Background— Cross-sectional studies suggest that left ventricular (LV) and arterial elastance (stiffness) increase with age, but data examining longitudinal changes within human subjects are lacking. In addition, it remains unknown whether age-related LV stiffening is merely a reaction to arterial stiffening or caused by other processes. Methods and Results— Comprehensive echo-Doppler cardiography was performed in 1402 subjects participating in a randomly selected community-based study at 2 examinations separated by 4 years. From this population, 788 subjects had adequate paired data to determine LV end-systolic elastance (Ees), end-diastolic elastance (Eed), and effective arterial elastance. Throughout 4 years, blood pressure, arterial elastance, and LV mass decreased, coupled with significantly greater use of antihypertensive medications. However, despite reductions in arterial load, Ees increased by 14% (2.10±0.67–2.26±0.70 mm Hg/mL; P &lt;0.0001) and Eed increased by 8% (0.13±0.03–0.14±0.04 mm Hg/mL; P &lt;0.0001). Increases in Eed were greater in women than men, whereas Ees changes were similar. Age-related increases in Ees and Eed were correlated with changes in body weight, but were similar in subjects with or without cardiovascular disease. Changes in Ees were correlated with Eed ( r =0.5; P &lt;0.0001), but not with other measures of contractility, indicating that the increase in Ees was reflective of passive stiffening rather than enhanced systolic function. Conclusions— Despite reductions in arterial load with medical therapy, LV systolic and diastolic stiffness increase over time in humans, particularly in women. In addition to blood pressure control, therapies targeting load-independent ventricular stiffening may be effective to treat and prevent age-associated cardiovascular diseases, such as heart failure.

Low-Sodium DASH Diet Improves Diastolic Function and Ventricular–Arterial Coupling in Hypertensive Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFPEF) involves failure of cardiovascular reserve in multiple domains. In HFPEF animal models, dietary sodium restriction improves ventricular and vascular stiffness and function. We hypothesized that the sodium-restricted dietary approaches to stop hypertension diet (DASH/SRD) would improve left ventricular diastolic function, arterial elastance, and ventricular-arterial coupling in hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD (target sodium, 50 mmol/2100 kcal) for 21 days. We measured baseline and post-DASH/SRD brachial and central blood pressure (via radial arterial tonometry) and cardiovascular function with echocardiographic measures (all previously invasively validated). Diastolic function was quantified via the parametrized diastolic filling formalism that yields relaxation/viscoelastic (c) and passive/stiffness (k) constants through the analysis of Doppler mitral inflow velocity (E-wave) contours. Effective arterial elastance (Ea) end-systolic elastance (Ees) and ventricular-arterial coupling (defined as the ratio Ees:Ea) were determined using previously published techniques. Wilcoxon matched-pairs signed-rank tests were used for pre-post comparisons. The DASH/SRD reduced clinic and 24-hour brachial systolic pressure (155 ± 35 to 138 ± 30 and 130 ± 16 to 123 ± 18 mm Hg; both P=0.02), and central end-systolic pressure trended lower (116 ± 18 to 111 ± 16 mm Hg; P=0.12). In conjunction, diastolic function improved (c=24.3 ± 5.3 to 22.7 ± 8.1 g/s; P=0.03; k=252 ± 115 to 170 ± 37 g/s(2); P=0.03), Ea decreased (2.0 ± 0.4 to 1.7 ± 0.4 mm Hg/mL; P=0.007), and ventricular-arterial coupling improved (Ees:Ea=1.5 ± 0.3 to 1.7 ± 0.4; P=0.04). In patients with hypertensive HFPEF, the sodium-restricted DASH diet was associated with favorable changes in ventricular diastolic function, arterial elastance, and ventricular-arterial coupling. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00939640.

The incremental diagnostic value of regional wall motion, coronary flow reserve and left ventricular elastance during high-dose dipyridamole stress echocardiography

The incremental diagnostic value of regional wall motion, coronary flow reserve and left ventricular elastance during high-dose dipyridamole stress echocardiography

The incremental diagnostic value of coronary flow reserve and left ventricular elastance during high-dose dipyridamole stress echocardiography in patients with normal wall motion at rest

A “normal” dipyridamole stress echocardiogram by wall motion criteria identifies a subset of patients at low risk of experiencing hard events in the follow-up [1]. The sensitivity for identifying significant coronary artery disease (CAD) is suboptimal, and can be increased by adding coronary flow reserve (CFR) assessment by Doppler echocardiography [2] or myocardial contrast echo [3]. Another possible variable of incremental value over wall motion is the assessment of contractile reserve (CR) via the end-systolic pressure–volume relationship (PVR), which has been used with pacing [4], exercise [5] or dobutamine [6] — not yet with dipyridamole. We prospectively enrolled 111 patients (60men; age 68, SD 10 years) with normal baseline function who underwent dipyridamole (0.84 mg/ kg over 6 min) stress echocardiography with CFR evaluation of LAD by Doppler [7] and CR calculated as peak stress ESP (end-systolic pressure)/ ESV (end-systolic volume)− rest ESP/ESV [6]. All patients underwent quantitative coronary angiography performed independently of test results. Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. All continuous data are reported as mean values ± standard deviation (SD). Known normal vs abnormal cutoff values of variation with stress (i.e., positive ESP/ESV index changes; CFR N 2) were tested as predictor of obstructive coronary disease in patients without inducible ischemia. Receiver operator characteristic curve analysis was used to determine potentially useful threshold values of ΔESP/ ESV derived predictors for identification of coronary artery disease in negative stress echo. Contingency tables were constructed to assess the sensitivity and specificity of the method. SPSS 13.0 (SPSS, Inc., Chicago, IL, USA) was used for the analysis. Stress echocardiogramwas positive for ischemia in 23 patients (21%). One or more significant coronary stenoses (≥50% luminal narrowing) were present in 51 patients (46%). Regional wall motion abnormalities (WMA) showed a sensitivity of 45% (95% CI 31% to 60%), which rose to 88% (95% CI 76% to 96%) with the combination of CFR positivity (LAD flow reserve≤ 2.0) and CR (b0.36 mmHg/mL/m) criteria (Fig. 1). Contractile reserve was negative (−3.6 SD 3 mmHg/mL/m) in patients with positive stress. In the subset with negative stress, contractile reserve was +3.5 SD 3 mmHg/mL/m in the 42 negative patients without, vs−1.4 SD 3.6 mmHg/mL/m in the 28 negative patients with ≥50% coronary stenosis diagnosis. With a receiver operating characteristic analysis, a ΔESP/ESV index b0.36 mmHg/mL/m from baseline to peak stress was the best value to identify angiographic evidence of significant (≥50%) coronary stenosis patient population (area under curve 0.9, 95% CI 0.84 to 0.96; Younden index= 1.73). This criterion showed good sensitivity (86%, 95% CI 74% to 94%) and specificity (87%, 95% CI 75% to 94%) for ≥50% coronary stenosis diagnosis. Specificity was 100% (95% CI 94% to 100%) with WMA and fell to 83% (95% CI 71% to 92%) with the combination of CFR and CR criteria. At individual patient analysis, all patients with wall motion abnormalities showed CAD, with high prevalence of CFR and CR impairment. In patients without wall motion abnormalities, CAD was more frequent in the presence of a depressed CR and/or CFR. The likelihood of underlying CAD was higher when both were altered (Fig. 2).

LONGITUDINAL CHANGES IN LEFT VENTRICULAR STIFFNESS: A COMMUNITY-BASED STUDY

In cross sectional studies, left ventricular (LV) and arterial elastance (stiffness) increase with age and are correlated with one another. LV stiffening is a key mechanism causing heart failure with preserved ejection fraction (HFpEF) that is widely felt to be the consequence of arterial stiffening

Increased left ventricular elastance at end-ejection is associated with lower arterial compliance and reduced ventricular relaxation

Increased left ventricular elastance at end-ejection is associated with lower arterial compliance and reduced ventricular relaxation

Assessment of cardiovascular function by combining clinical data with a computational model of the cardiovascular system

A sufficient understanding of patients' cardiovascular status is necessary for doctors to make the best decisions with regard to the treatment of cardiovascular disease; however, it is often not available because of the limitation of clinical measurements. The objective of this study was to examine whether cardiovascular function can be assessed quantitatively and for specific patients by combining clinical data with a computational model of the cardiovascular system. Seven consecutive patients undergoing off-pump coronary artery bypass grafting were enrolled in this study. The clinical data were collected both during the preoperative diagnosis and during the operation. Sensitivity analysis was performed to select the major model parameters most relevant to the measured data. The major model parameters were then estimated through a data-fitting procedure, enabling a patient-specific quantitative assessment of various aspects of cardiovascular function. The results revealed the prevalence of left ventricular diastolic dysfunction in the patients, although the severity of dysfunction exhibits significant interpatient variability (the estimated left ventricular passive elastance varies from 194% to 540% of its reference value). Moreover, 4 of the 7 patients studied had impaired left ventricular systolic function. The current study demonstrates the feasibility of assessing cardiovascular function quantitatively by combining clinical data with a cardiovascular model. In particular, the assessment utilizes the measurements already in use or available in clinical settings, enhancing the clinical potential of the proposed method.

Role of ER Stress in Ventricular Contractile Dysfunction in Type 2 Diabetes

BackgroundDiabetes mellitus (DM) is associated with an increased risk of ischemic heart disease and of adverse outcomes following myocardial infarction (MI). Here we assessed the role of endoplasmic reticulum (ER) stress in ventricular dysfunction and outcomes after MI in type 2 DM (T2DM).Methodology and Principal FindingsIn hearts of OLETF, a rat model of T2DM, at 25∼30 weeks of age, GRP78 and GRP94, markers of ER stress, were increased and sarcoplasmic reticulum calcium ATPase (SERCA)2a protein was reduced by 35% compared with those in LETO, a non-diabetic control. SERCA2a mRNA levels were similar, but SERCA2a protein was more ubiquitinated in OLETF than in LETO. Left ventricular (LV) end-diastolic elastance (Eed) was higher in OLETF than in LETO (53.9±5.2 vs. 20.2±5.6 mmHg/µl), whereas LV end-systolic elastance and positive inotropic responses to β-adrenergic stimulation were similar in OLETF and LETO. 4-Phenylbutyric acid (4-PBA), an ER stress modulator, suppressed both GRP up-regulation and SERCA2a ubiquitination and normalized SERCA2a protein level and Eed in OLETF. Sodium tauroursodeoxycholic acid, a structurally different ER stress modulator, also restored SERCA2a protein level in OLETF. Though LV dysfunction was modest, mortality within 48 h after coronary occlusion was markedly higher in OLETF than in LETO (61.3% vs. 7.7%). Telemetric recording showed that rapid progression of heart failure was responsible for the high mortality rate in OLETF. ER stress modulators failed to reduce the mortality rate after MI in OLETF.ConclusionsER stress reduces SERCA2a protein via its augmented ubiquitination and degradation, leading to LV diastolic dysfunction in T2DM. Even at a stage without systolic LV dysfunction, susceptibility to lethal heart failure after infarction is markedly increased, which cannot be explained by ER stress or change in myocardial response to sympathetic nerve activation.