Work Of Left Ventricle Research Articles

Effects of continuous positive airway pressure therapy on left ventricular performance in patients with severe obstructive sleep apnea

We investigated myocardial performance concerning obstructive sleep apnea (OSA) severity and the benefits of continuous positive airway pressure (CPAP) therapy. In this randomized sham-controlled trial, 52 patients (mean age, 49 years; 92%, males; mean AHI, 59) with severe OSA were randomly assigned to receive either CPAP or sham treatment for 3 months. The severity of OSA was determined using the apnea/hypopnea index (AHI), oxygen desaturation index (ODI), percentage of sleep time below 90% oxygen saturation (T90), and average O2 saturation during sleep (mean SpO2). We compared the changes in myocardial work after 3 months of CPAP (n = 26) versus the sham group (n = 26) at rest and during an exercise stress test. Unlike AHI or ODI, indices of hypoxemia including T90 and mean SpO2 were significantly correlated with global constructive work, as defined by work of left ventricle (LV) that contributes to LV ejection during systole (T90, β = 0.393, p = 0.012; mean SpO2, β = 0.331, p = 0.048), and global wasted work (GWW), as defined by work of LV that does not contribute to LV ejection (T90, β = 0.363, p = 0.015; mean SpO2, β = − 0.370, p = 0.019). After 3 months, GWW decreased (80.0 ± 49.2 to 60.8 ± 26.3, p = 0.009) and global work efficiency increased (94.0 ± 4.5 to 95.7 ± 2.0, p = 0.008) in the CPAP group compared to those in the sham group. At the 3-month follow-up exercise stress echocardiography, worsening of GWW during exercise was significantly decreased in the CPAP group compared to that in the sham group (p = 0.045 at 50 W). Hypoxemia indices were closely associated with myocardial performance in patients with severe OSA. CPAP treatment for 3 months improved left ventricular myocardial performance by decreasing wasted work and increasing work efficacy compared to the sham treatment.

S-37-4: TRANSCATHETER AORTIC VALVE REPLACEMENT DOES NOT RESULT IN SUSTAINED LOAD TRANSFER WITH INCREASED VASCULAR LOAD

Objectives: Transcatheter aortic valve replacement (TAVR) is an effective treatment for aortic stenosis (AS) by reducing the load placed on the left ventricle (LV) by the stenotic valve. Although systolic pressure is reported to increase in 50% of individuals after TAVR, its effects on steady and pulsatile vascular load represented by the systemic vascular resistance (SVR) and impedance of the proximal ascending aorta (Zc) respectively is less well understood. Using a previously validated non-invasive load estimation technique, we investigated the valvulo-arterial interaction in AS patients pre- and post-TAVR. Design and Method: In AS patients being assessed for TAVR, the proximal thoracic aorta flows, LV volume and function were recorded using 3T cardiac magnetic resonance (CMR) using phase-contrast velocity quantification. Simultaneous radial tonometric pressure was acquired during CMR and brachial cuff pressure was recorded. Aortic pressure was derived offline using SphygmoCor 8.1 (AtCor Medical, Sydney) from radial pressure, and calibrated to brachial pressure. Flow was acquired at 5 cm above the aortic valve at the level of the pulmonary artery bifurcation to avoid flow artefact from the TAVR prosthesis. Baseline and follow-up measurements were made before and after treatment with TAVR. Values pre- and post-TAVR were compared, and indices of pulsatile arterial load were calculated using frequency domain analysis. Results: A total of 17 patients (mean age 80 ± 6 years, 7 females) were recruited, with a median follow up of 54.5 days post-TAVR. In the post-TAVR measurements, a significant improvement in aortic peak volumetric flow (336 ± 79 ml/s vs 389 ± 110 ml, P = 0.011) was observed with an associated reduction in peak aortic velocity (189 ± 65 cm/s vs 126 ± 24 cm/s, P = 0.002). However, there was no statistical difference in heart rate (70 ± 9 beats per minute vs 68 ± 12 beats per minute), mean central aortic pressure (98 ± 13mmHg vs 99 ± 11mmHg), or the steady vascular load parameters of SVR (1860 ± 513 dynes.s/cm5 vs 1999 ± 561 dynes. s/cm5, P = 0.284) and pulsatile load Zc of the aorta (119 ± 51 dynes.s/cm5 vs 106 ± 43 dynes.s/cm5, P = 0.102). Conclusion: TAVR relieves valvular obstruction but does not result in significant alterations of vascular load in the short to medium term. The previously reported acute load transfer immediately following TAVR appears to resolve with time. Further study examining the effect of TAVR on external LV work may help to elucidate the energy consumption by the vascular system after correction of valvular obstruction from AS.

Impact of metabolic substrate modification on myocardial efficiency in a rat model of obesity and diabetes

Abstract Background Congenic leptin receptor deficient rat generated by introgression of the Koletsky leptin receptor mutation into BioBreeding Diabetes Resistant rat (BBDR.lepr−/−) is a novel animal model combining obesity, systemic insulin resistance and diabetes. Systemic insulin resistance is associated with reduced myocardial glucose utilization, but its effect on myocardial external efficiency, i.e. the ability of the myocardium to convert energy into external stroke work, remains uncertain. Purpose To characterize cardiac energy metabolism and function in BBDR.lepr−/− rats and to study the effect of dipeptidyl peptidase 4 (DPP-4) inhibitor linagliptin in this model. Methods Cardiac phenotype was evaluated in six-month-old male BBDR.lepr−/− rats (n=11) and age-matched male non-diabetic lean control littermates (BBDR.lepr+/− or BBDR.lepr+/+ rats, n=14). Of these, 7 BBDR.lepr−/− rats and 6 controls underwent cardiac ultrasound, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), and [11C]acetate PET in order to evaluate cardiac structure and function as well as glucose and oxidative metabolism. In the remaining rats, fatty acid metabolism was evaluated by [18F]fluorothia-6-heptadecanoic acid ([18F]FTHA) PET/CT. In the linagliptin intervention study, 25 BBDR.lepr−/− male rats were randomly divided into control group (n=11) that received regular chow diet and linagliptin group (n=14) that received linagliptin (10mg/kg/d) mixed in the chow diet for three months. After the intervention, the rats underwent cardiac ultrasound, [18F]FDG PET/CT, and [11C]acetate PET. Results Compared with controls, BBDR.lepr−/− rats showed increased left ventricle (LV) mass (∼40%, p>0.001) and higher systolic blood pressure (∼10%, p=0.02). However, fractional shortening and cardiac output were similar in both groups. Myocardial fractional uptake rate of glucose measured with [18F]FDG PET was significantly reduced (∼86%, p=0.004) (Fig. 1A, E), whereas myocardial fatty acid uptake measured by [18F]FTHA PET was not significantly increased (free fatty acid (FFA) corrected standardized uptake value (SUV) ∼21%, p=0.54) (Fig. 1B) in BBDR.lepr−/− compared to controls. Myocardial oxygen consumption assessed by [11C]acetate PET was similar in both groups (Fig. 1C, E), but LV work per gram of myocardium was reduced (∼28%, p=0.001) resulting in reduced myocardial external efficiency (∼21%, p=0.03) (Fig. 1D) in BBDR.lepr−/− compared to controls. Treatment with linagliptin significantly enhanced myocardial fractional uptake rate of glucose (∼166%, p=0.006) (Fig. 2A, C), but had no effect on efficiency of cardiac work (Fig. 2B). Conclusions Obese and diabetic BBDR.lepr−/− rats demonstrate LV hypertrophy and markedly reduced myocardial glucose utilization associated with impaired myocardial external efficiency despite normal LV systolic function. Enhancement of myocardial glucose uptake by linagliptin did not improve efficiency of cardiac work. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): IMI-SUMMIT

Pulsatile Cardiac Efficiency May Improve Prior to Observable Left Ventricular Reverse Remodelling Following Transcatheter Aortic Valve Replacement for Aortic Stenosis

The excessive energy used by the left ventricle (LV) to overcome arterial stiffening and maintain steady flow within the circulation can be estimated by pulsatile LV work. Our study explored the effects of transcatheter aortic valve replacement (TAVR) on cardiac efficiency in aortic stenotic (AS) patients as estimated by the pulsatile LV work.

Echocardiographic assessment of myocardial function during His bundle and right ventricular pacing

In patients with pacemaker (PM) therapy, His bundle stimulation (HBS) may lead to amore synchronous activation of the left ventricle (LV) than conventional right ventricular stimulation (RVS). In this study, we investigated to which extent this effect can be objectified by means of contemporary echocardiographic functional imaging. In all, 15RVS patients (6women, mean age 76.6 ± 4.1years) and 15HBS patients (6women, mean age 74.6 ± 3.7years) underwent echocardiography with and without cardiac pacing. Besides LV end-diastolic volume (EDV), ejection fraction (EF), and global strain (GLS), we measured global and regional myocardial work and LV efficiency based on noninvasive pressure-strain loops. In all HBS patients, optimization of PM settings resulted in immediate changes in myocardial function parameters. With pacing, RVS patients showed ahigher decrease in EF and GLS than HBS patients. Global LV work and LV work efficiency decreased significantly only in RVS patients. Changes in regional and global myocardial function can by proven and quantified by functional echocardiography. In patients under PM therapy, HBS shows functional advantages in comparison to conventional RVS.

P909 Diagnostic evaluation of rheumatic heart disease in aborigonal population

Abstract Background Among Indigenous Australians, rates of Acute Rheumatic Fever (ARF) continue to be among the highest in the world. Diagnosis remains a clinical decision based on identification of major and minor manifestations of the illness. Treatment involves lengthy prophylaxis and should continue for a minimum of 10 years. ARF can cause permanent damage to the heart known as rheumatic heart disease (RHD). We therefore utilised echocardiography as a diagnostic tool incorporating Tissue Quantification Backscatter expressed in decibels (dB) and global LV work efficiency estimated from left ventricle (LV) pressure-strain loops to identify rheumatic changes of the Mitral Valve and help improve early diagnosis of RHD. Method Data from patients with suspected RHD (n = 14), and age matched controls (n = 10) underwent Mitral Valve Backscatter Analysis (MVBS). MVBS was expressed as a ratio % (MVBS ratio %) by dividing the average MVBS and the average blood pool value expressed in decibels (dB). Furthermore LV function was utilised via 2D longitudinal strain and indices of myocardial work were derived. Result MVBS ratio % was significantly higher in the control group as compared to the RHD group (p = 0.001) (fig1). Of the RHD group echocardiography parameters showed there were no significant mitral valve stenosis or regurgitation. Correlates of LV function included: Global work Index (GWI), Global longitudinal Strain (GLS) and Global work efficiency (GWE). Of the above correlates the control group showed Backscatter vs GLS (r= -0.89, p = 0.001), the RHD group: Backscatter vs GLS (r = 0.52. p = 0.12). Within the RHD group the ratio vs GWE (r= 0.57, p = 0.09) these results showed a trend to significance. Conclusions Currently diagnosis of RHD remains a clinical decision based on the identification of major and minor manifestations. In addition treatment involves prophylaxis injections for a minimum of ten years. Of this group there were no significant echocardiography changes, rather clinical manifestation to derive RHD. This study shows that calibrated MVBS ratio % and determinants of myocardial work may be a promising quantitative tool to detect early manifestation of RHD potentially aiding an early treatment plan and thus reducing the clinical burden of monthly penicillin injections for a ten year period. Abstract P909 Figure. RHD and Myocardial correlates

553 Acute re-distribution of regional left ventricular work by cardiac resynchronization therapy determines long-term remodelling

Abstract Background In patients with dilated cardiomyopathy and left bundle branch block (LBBB), different regions of the left ventricle (LV) have been shown to perform different amounts of work. In this study, we investigate the acute impact of cardiac resynchronization therapy (CRT) on regional LV work distribution and its relation to long-term reverse-remodelling. Methods We recruited 140 heart failure patients, referred for CRT. Regional myocardial work was calculated from non-invasive echocardiographic segmental stress-strain-loop-area before and immediately after CRT. The magnitude of volumetric reverse-remodelling was determined from the change in LV end-systolic volume (ESV), 11 ± 3 months after implantation. Characteristics of patients with the lowest and highest quartile of LV ESV reverse remodelling (LV ESV reduction of less than 10% and LV ESV reduction of more than -48%) were compared. Results Before CRT, myocardial work showed significant differences among the walls of the LV (Figure A). CRT caused an acute re-distribution of myocardial work, on average with most increase in the septum and most decrease laterally (all walls p < 0.05) and lead to a homogeneous work distribution (Figure B). The acute change in the difference between lateral and septal wall work (Δ Lateral-to-septal work) correlated significantly with LV ESV reverse-remodelling (r = 0.63, p < 0.0001). The smallest changes in work were seen in the patients with the least LV ESV reverse remodelling (Figure C, red markers), while patients with the most LV ESV reverse remodelling showed the largest changes in work (Figure C, green markers). In multivariate linear regression analysis, including conventional parameters such as pre-implant QRS duration, LV ejection fraction, LV end-diastolic volume and global longitudinal strain, the re-distribution of work across the septal and lateral walls appeared as the strongest determinant of volumetric reverse-remodelling after CRT (R²=0.393, p < 0.0001). Conclusions The acute re-distribution of regional myocardial work between the septal and lateral wall of the left ventricle is an important determinant of long term reverse-remodelling after CRT-implantation. Our data suggest that modification of regional loading is the mode of action of CRT treatment. Abstract 553 Figure.

P1238Acute re-distribution of myocardial work by cardiac resynchronization therapy determines long-term remodelling of the left ventricle

Abstract Background In patients with dilated cardiomyopathy and left bundle branch block (LBBB), different regions of the left ventricle (LV) have been shown to perform different amounts of work. In this study, we investigate the acute impact of cardiac resynchronization therapy (CRT) on regional LV work distribution and its relation to long-term reverse-remodelling. Methods We recruited 130 heart failure patients, referred for CRT. Regional myocardial work was calculated from non-invasive echocardiographic segmental stress-strain-loop-area before and immediately after CRT. The magnitude of volumetric reverse-remodelling was determined from the change in LV end-systolic volume (ESV), 11±2 months after implantation. Characteristics of patients with the lowest and highest quartile of LV ESV reverse remodelling (ΔLV ESV <−9% and ΔLV ESV >−48%) were compared. Results Before CRT, myocardial work showed significant differences among the walls of the LV (Figure 1A). CRT caused an acute re-distribution of myocardial work, on average with most increase in the septum and most decrease laterally (all walls p<0.05) and lead to a homogeneous work distribution (Figure 1B). The acute change in the difference between lateral and septal wall work (Δlateral − septal work) correlated best and significantly with LV ESV reverse-remodelling (r=0.62, p<0.0001). The smallest changes in work were seen in the patients with the least LV ESV reverse remodelling (Figure 1C, red markers), while patients with the most LV ESV reverse remodelling showed the largest changes in work (Figure 1C, green markers). In a multivariate-linear-regression-analysis, including pre-implant QRS duration, LVEF, LV EDV and GLS, the re-distribution of work remained as the strongest determinant of volumetric reverse-remodelling after CRT (r=0.63, p<0.0001). Figure 1 Conclusions The acute re-distribution of regional myocardial work between the septal and lateral wall of the left ventricle is the main determinant of long term reverse-remodelling after CRT-implantation. Our data suggest that modification of regional loading is the mode of action of CRT treatment.

PP.18.01] VENTRICULAR-ARTERIAL COUPLING MAY BE AN EARLY MARKER OF CARDIAC REMODELING AFTER MYOCARDIAL INFARCTION TREATED WITH PERCUTANEOUS CORONARY INTERVENTION

Objective: Ventricular remodeling may occur following myocardial infarction (MI) of the left ventricle (LV) and such remodeling has been shown to be correlated with increased patient morbidity and mortality. It is important to estimate the likelihood of remodeling from the state of the infarcted LV. The aim of the study was to assess the ventricular-arterial coupling (VAC) in patients with ST segment elevation (STEMI) and non ST segment elevation MI (NSTEMI) treated with percutaneous coronary intervention (PCI). Design and method: In 93 patients with acute coronary syndrome and PCI (70% male, age 61,5 ± 10,1 years (M ± SD), 57 (61,3%) with STEMI, smokers 25%, arterial hypertension 20.4%, blood pressure (BP) 129 ± 6/82 ± 7 mmHg, LVEF 47,4 ± 4,3%) 2-dimentional echocardiography was performed to assess arterial elastance (Ea) and end-systolic LV elastance (Ees) on admission and in 4 weeks. VAC was assessed as the ratio Ea/Ees. Results: Baseline LF EF was 47.4 ± 4.3, E/A 0.95 ± 0,18, Ea 1.9 ± 0.3 mmHg/ml/m2, Ees 2.1 ± 0.4 mmHg/ml/m2, VAC 0.89 ± 0.1. At baseline all patients had LVEF >40% and VAC in optimal range. In 4 weeks after PCI VAC >1.2 (upper optimal level) was revealed in 19% of patients with STEMI and 44% with NSTEMI. In patients with achieved VAC >1.2 Ees (2.1 ± 0.4 vs 1.6 ± 0.2 mmHg/ml/m2, p < 0.001), stroke work (SW) (6254 ± 1516 vs 6112 ± 1059 mmHg*ml/m2, p>0.05), potential energy (PE) (62.8 ± 4.3 vs 56.3 ± 5.4 mmHg*ml/m2, p < 0.001), pressure-volume area (PVA) (6317 ± 2136 vs 6179 ± 1060 mmHg*ml/m2, p < 0.001), LV work efficiency (SW/PVA) significantly decreased (p < 0.001) while Ea (1.9 ± 0.3 to 2.1 ± 0.4 mmHg/ml/m2, p > 0.05) did not change. In patients with VAC in optimal range in 4 weeks Ees decreased from 2.3 ± 0.3 to 2.1 ± 0.4 mmHg/ml/m2 (p < 0.001), Ea (p < 0.001) and VAC (p < 0.001) did not change. Conclusions: Impairment of functioning of cardio-vascular system assessed by increased value of VAC > 1.2 was revealed in 27% of patients with acute coronary syndrome. Increase of VAC is associated predominantly with decrease of Ees and LV work efficiency (SW/PVA). Increased in the VAC index > 1.2 indicating LV-arterial uncoupling may be an early marker of cardiovascular remodeling in MI or systolic dysfunction.

Effect of acute nitrate ingestion on central hemodynamic load in hypoxia

Acute hypoxia results in local vasodilation that may temporarily unload the left ventricle (LV) through nitric oxide (NO)-mediated mechanisms. Whether increasing NO levels augments LV unloading and improves ventricular-vascular coupling in hypoxia remains unknown. PurposeInvestigate the effect of acute nitrate ingestion on central hemodynamic load in hypoxia. Methods20 Healthy men (23 ± 3 yrs, BMI 24.6 ± 2.8 kg m−2) consumed 70 mL of either a) 0.45 g nitrate (NIT) or b) an inert placebo (PLA) prior to 105 min of normobaric hypoxia (11.6 ± 0.1%) in this randomized, double-blind, crossover-design study. Wave reflection index (RIX; ratio of forward to reflected wave pressure), augmentation index (AIX75) and pulse wave velocity were calculated as measures of wave reflection magnitude and aortic stiffness, respectively, from the aortic blood pressure (BP) waveform. LV wasted pressure effort (WPE) was calculated as an index of LV work due to wave reflections. Subendocardial viability ratio (SEVR) was assessed a measure of myocardial O2 supply/demand ratio. ResultsAortic diastolic BP decreased in hypoxia compared to normoxia (p < 0.05). Aortic RIX, AIX75, and LV WPE significantly decreased in hypoxia compared to normoxia (p < 0.05). Aortic systolic BP, SEVR, and PWV were unaffected by hypoxia (p > 0.05). Compared to placebo, nitrate ingestion did not significantly alter central hemodynamics in hypoxia (p > 0.05). ConclusionsAcute hypoxic exposure unloads the LV (WPE, AIX75, and RIX) without disturbing myocardial O2 supply-demand ratio (SEVR). Reductions in LV work with hypoxia are likely due to reductions in pressure from wave reflections as hypoxia had negligible effects on aortic stiffness. Nitrate ingestion did not affect the central hemodynamic response to acute systemic hypoxia.

Cardiac remodeling in a new pig model of chronic heart failure: Assessment of left ventricular functional, metabolic, and structural changes using PET, CT, and echocardiography

AimsLarge animal models are needed to study disease mechanisms in heart failure (HF). In the present study we characterized the functional, metabolic, and structural changes of myocardium in a novel pig model of chronic myocardial infarction (MI) by using multimodality imaging and histology. Methods and ResultsMale farm pigs underwent a two-step occlusion of the left anterior descending coronary artery with concurrent distal ligation and implantation of a proximal ameroid constrictor (HF group), or sham operation (control group). Three months after the operation, cardiac output and wall stress were measured by echocardiography. Left ventricle (LV) volumes and mass were measured by computed tomography (CT). Myocardial perfusion was evaluated by [15O]water and oxygen consumption using [11C]acetate positron emission tomography, and the efficiency of myocardial work was calculated. Histological examinations were conducted to detect MI, hypertrophy, and fibrosis. Animals in the HF group had a large anterior MI scar. CT showed larger LV diastolic volume and lower ejection fraction in HF pigs than in controls. Perfusion and oxygen consumption in the remote non-infarcted myocardium were preserved in HF pigs as compared to controls. Global LV work and efficiency were significantly lower in HF than control pigs and was associated with increased wall stress. Histology showed myocyte hypertrophy but not increased interstitial fibrosis in the remote segments in HF pigs. ConclusionsThe chronic post-infarction model of HF is suitable for studies aimed to evaluate LV remodeling and changes in oxidative metabolism and can be useful for testing new therapies for HF.

CONTRIBUTION OF AORTIC REGURGITATION TO LEFT VENTRICLE LOAD IN PATIENTS WITH AORTIC STENOSIS: A MATHEMATICAL MODEL ANALYSIS

The prognosis of mixed aortic stenosis (AS) and aortic regurgitation (AR), or aortic valve disease (AVD) is worse than isolated AS. It is unclear though which component of AVD affects more myocardial dynamics and work-load, AS or AR. Better understanding of left ventricle (LV) work-load induced by AVD is essential for adequate risk stratification. The objectives of this study are: 1) To evaluate the LV overload induced by AVD; 2) To propose a modified form for the Valvulo-Arterial Impedance (Zav) applicable to associated AVD, since LV work can not be determined non-invasively, We developed a mathematical model for AS and AR based on non-invasive parameters (prograde effective orifice area (pEOA), retrograde effective orifice area (rEOA), brachial blood pressure, stroke volume). The range of the parameters used in the model were based on data from pediatric subjects obtained during a pilot clinical study comparing [Group#1: moderate AS + mild AR] where pEOA = 1.0 -1.4 cmˆ2 and rEOA = 0.1-0.2 cmˆ2 to [Group#2: mild AS + moderate AR] where pEOA =1.5 -1.9 cmˆ2 and rEOA =0.2-0.4 cmˆ2. For each group, LV stroke work and valvulo-arterial impedance using the original formulation Zav = (SAP+MeanTPG)/SV and a modified formulation modZav = (SV/(SV-SVregurgitant))*[(SAP+MeanTPG)/(SV-SVregurgitant)] were computed and compared, where SAP: peak systolic arterial pressure; TPG: trans-valvular pressure gradient; SV: stroke volume (forward); SVregurgitant: regurgitant stroke volume. Figure 1 shows typical pressure-volume loops obtained using the model for each group. LV stroke work was significantly higher in Group#2 compared to Group#1 (2.37±0.28 vs. 2.08±0.21 Joules; p<0.01) despite a lower mean AS gradient (24±4 vs. 32±8 mmHg; p<0.01). Zav correlated weakly with LV stroke work (Rˆ2=0.39), whereas modZav significantly improved the correlation with LV stroke work (Rˆ2=0.95). This in silico study suggests that patients with mild AS + moderate AR experience high work-load compared to patients with moderate AS + mild AR. This load supported by the LV can be evaluated using the proposed modified version of valvulo-arterial-impedance. Patients with associated AVD should carefully be evaluated for the combined contribution of valvular disease with various component severity.View Large Image Figure ViewerDownload (PPT)

Cardiac hypertrophy and oxidative metabolism in novel congenic leptin receptor deficient BBDR.cg‐lepr.cp rats (1155.10)

Congenic BBDR.cg‐lepr.cp rats generated by introgression of the Koletsky leptin receptor mutation into the BioBreeding Diabetes Resistant (BBDR) rat develop obesity and diabetes mellitus, known risk factors for heart failure. Here we studied cardiac function and myocardial oxidative metabolism in these rats by non‐invasive imaging. Myocardial glucose utilization (18F‐fluorodeoxyglucose uptake) and oxygen consumption (washout constant for 11C‐acetate derived from monoexponential fitting) were measured by positron emission tomography (PET); left ventricle (LV) mass, systolic function and cardiac output by echocardiography. Compared with non‐diabetic littermates, diabetic rats were obese (body weight 463±36 vs. 706±65 g, p&lt;0.01), hyperglycemic (6±1 vs. 22±10 mM, p&lt;0.01), had elevated blood pressure (136±5 vs. 151±13 mmHg, p=0.02), comparable systolic function (fractional shortening 49 vs. 48%), but higher LV mass (0,6±0,1 vs. 0,9±0,1 g, p&lt;0.01). Diabetic rats had lower fasting myocardial glucose uptake (p=0.04) and lower efficiency of myocardial forward work (LV work / oxygen consumption * myocardial mass; 69000±8000 vs. 54000±12000 mmHg L/min; p=0.03), despite having comparable resting myocardial oxygen consumption in fasting state. Results suggest that BBDR.cg‐lepr.cp rats should prove a useful new model to study the adverse effects of obesity and diabetes on cardiac metabolism.Grant Funding Source: Supported by: VR 2011‐3900; EFSD, SSMF, the SUMMIT consortium (IMI‐2008/115006).

Left ventricular energetics: new insight into the plasticity of regional contributions at rest and during exercise

Although the human left ventricle (LV) operates as a functional syncytium and previous studies have reported a single value for LV stroke work at rest, more intricate plasticity of regional LV energetics may be required during enhanced cardiovascular demand. We compared kinetic energy of the LV base and apex, respectively, during ventricular contraction and relaxation at rest and during continuous and discontinuous incremental exercise. At rest, prior to both exercise trials, the accumulated kinetic energy during contraction and relaxation was significantly higher at the LV base compared with the apex (P ≤ 0.05). With increasing exercise intensity, kinetic energy during contraction increased significantly more at the LV base (interaction effect: P < 0.0001), while kinetic energy during relaxation increased significantly more at the apex during high-intensity exercise (interaction effect: P < 0.001). Total kinetic energy produced over the entire cardiac cycle was significantly greater at the LV apex during high exercise intensities (P < 0.05). We further show that the region-specific differences in kinetic energy at rest and during exercise are explained by significantly different wall mechanics, showing heterogenic contributions from radial, circumferential, and angular components at the base and apex, respectively. In conclusion, the present findings provide unique insight into human LV function by demonstrating that within this functional syncytium, significant differences in the regional contributions of kinetic energy to overall LV work exist. Importantly, regional contributions are not fixed but highly plastic and the underpinning LV wall energetics adjust according to the prevailing cardiovascular demand.

Comparative Electromechanical and Hemodynamic Effects of Left Ventricular and Biventricular Pacing in Dyssynchronous Heart Failure: Electrical Resynchronization Versus Left–Right Ventricular Interaction

The purpose of this study was to enhance understanding of the working mechanism of cardiac resynchronization therapy by comparing animal experimental, clinical, and computational data on the hemodynamic and electromechanical consequences of left ventricular pacing (LVP) and biventricular pacing (BiVP). It is unclear why LVP and BiVP have comparative positive effects on hemodynamic function of patients with dyssynchronous heart failure. Hemodynamic response to LVP and BiVP (% change in maximal rate of left ventricular pressure rise [LVdP/dtmax]) was measured in 6 dogs and 24 patients with heart failure and left bundle branch block followed by computer simulations of local myofiber mechanics during LVP and BiVP in the failing heart with left bundle branch block. Pacing-induced changes of electrical activation were measured in dogs using contact mapping and in patients using a noninvasive multielectrode electrocardiographic mapping technique. LVP and BiVP similarly increased LVdP/dtmax in dogs and in patients, but only BiVP significantly decreased electrical dyssynchrony. In the simulations, LVP and BiVP increased total ventricular myofiber work to the same extent. While the LVP-induced increase was entirely due to enhanced right ventricular (RV) myofiber work, the BiVP-induced increase was due to enhanced myofiber work of both the left ventricle (LV) and RV. Overall, LVdP/dtmax correlated better with total ventricular myofiber work than with LV or RV myofiber work alone. Animal experimental, clinical, and computational data support the similarity of hemodynamic response to LVP and BiVP, despite differences in electrical dyssynchrony. The simulations provide the novel insight that, through ventricular interaction, the RV myocardium importantly contributes to the improvement in LV pump function induced by cardiac resynchronization therapy.

High Risk Percutaneous Coronary Intervention and Intra-Aortic Balloon Pumps

The goal of percutaneous coronary intervention (PCI) is to decrease the coronary obstruction in a durable manner without compromising or damaging the myocardium so that patients may obtain the clinical benefits from the procedure, namely potentially improved survival in the setting of acute myocardial infarction interventions and improvement in health status for elective interventions. Interventional cardiologists make decisions each day aimed at improving the likelihood of both procedural success and resultant patient outcomes. These wide-ranging decisions include procedural planning, adjunctive pharmacotherapy, and device therapy for both coronary devices and possible use of various hemodynamic support devices. It is in this framework that the effectiveness of intra-aortic balloon pump (IABP) counterpulsation devices must be considered because they represent a common tool that interventional cardiologists use for procedure and patient support. Article see p 21 IABP counterpulsation was first reported in 1968 as a cardiac-assist device in a patient with cardiogenic shock,1 which supported the patient as shock resolved. As an adjunctive hemodynamic support device, the intra-aortic balloon is timed with the cardiac cycle to inflate at the start of diastole, augmenting diastolic pressure, which increases coronary perfusion and oxygen delivery to the myocardium. It is timed to deflate just before the start of systole, thereby reducing afterload. This facilitates ejection of blood from the left ventricle (LV) by decreasing LV work and reducing myocardial oxygen demands,2 resulting in increased cardiac output. …

Modeling the impact of concomitant aortic stenosis and coarctation of the aorta on left ventricular workload

Coarctation of the aorta (COA) is an obstruction of the aorta and is usually associated with bicuspid and tricuspid aortic valve stenosis (AS). When COA coexists with AS, the left ventricle (LV) is facing a double hemodynamic load: a valvular load plus a vascular load. The objective of this study was to develop a lumped parameter model, solely based on non-invasive data, allowing the description of the interaction between LV, COA, AS and the arterial system. First, a formulation describing the instantaneous net pressure gradient through the COA was introduced and the predictions were compared to in vitro results. The model was then used to determine LV work induced by coexisting AS and COA with different severities. The results show that LV stroke work varies from 0.98 J (no-AS; no-COA) up to 2.15 J (AS: 0.61 cm 2+COA: 90%). Our results also show that the proportion of the total flow rate that will cross the COA is significantly reduced with the increasing COA severity (from 85% to 40%, for a variation of COA severity from 0% to 90%, respectively). Finally, we introduced simple formulations capable of, non-invasively, estimating both LV peak systolic pressure and workload. As a conclusion, this study allowed the development of a lumped parameter model, based on non-invasive measurements, capable of accurately investigating the impact of coexisting AS and COA on LV workload. This model can be used to optimize the management of patients with COA and AS in terms of the sequence of lesion repair.

Why the left ventricle is not a sphere

Abstract In this study, we have tried to understand why the left ventricle (LV) is not a homogeneous sphere. An experimental model of a spherical ventricle was developed. The chamber was configured as a mathematical model, and the wall properties were represented by isolated cardiac muscles. The stroke work of the spherical LV when modelling different types of inhomogeneity in the wall structure was investigated. It was found that the emergence of even slight inhomogeneity in a spherical ventricle inevitably results in a diminution of pump function. It was concluded that at a given level of the myocardial contractility, a homogeneous spherical LV would not have any functional reserve, ie no ability to maintain pump function in case of additional load. Functional reserve can be achieved only with a certain degree of inhomogeneity. Thus, inhomogeneity in the normal left ventricular wall structure constitutes a strategic functional reserve that is absent in a homogeneous spherical ventricle.

Why the Left Ventricle Is Not a Sphere

In this study, we have tried to understand why the left ventricle (LV) is not a homogeneous sphere. An experimental model of a spherical ventricle was developed. The chamber was configured as a mathematical model, and the wall properties were represented by isolated cardiac muscles. The stroke work of the spherical LV when modelling different types of inhomogeneity in the wall structure was investigated. It was found that the emergence of even slight inhomogeneity in a spherical ventricle inevitably results in a diminution of pump function. It was concluded that at a given level of the myocardial contractility, a homogeneous spherical LV would not have any functional reserve, ie no ability to maintain pump function in case of additional load. Functional reserve can be achieved only with a certain degree of inhomogeneity. Thus, inhomogeneity in the normal left ventricular wall structure constitutes a strategic functional reserve that is absent in a homogeneous spherical ventricle.

Effectiveness of transaortic venting from a failing left ventricle during venoarterial bypass.

Insufficient unloading of the left ventricle (LV) is a limitation of percutaneous cardiopulumonary support (PCPS). We previously reported the unloading effect of transaortic catheter venting (TACV) during venoarterial bypass (VAB) in normal hearts. The aim of this study was to assess the effectiveness of TACV with VAB in a heart failure (HF) model. Seven adult mongrel dogs underwent TACV with VAB, and isolated LV failure was induced by multiple ligation of left coronary arteries. With standard hemodynamic monitoring, slope of the LV end-systolic pressure-volume relationship (Emax; mm Hg/ml), aortic elastance (Ea; mm Hg/ml), LV stroke work (SW; 10(-4)J), preload recruitable stroke work (PRSW; 10(-4)J/ ml), LV pressure-volume area (PVA; 10(-4)J), and potential energy (PE; 10(-4)J) were assessed using a micro-tip manometer and a conductance catheter. In addition to evaluation of LV function, myocardial adenosine 5'-triphosphate (ATP) was measured in each condition. The TACV combined support significantly reduced LV total energy (PVA) and LV work (SW). The LV energetic charge (PE/PVA, myocardial ATP) was significantly increased by TACV. These results suggest that TACV might be an effective technique for LV recovery during VAB or PCPS in patients with severe heart failure.