Global Systolic Performance Research Articles

The odyssey to dethrone LV ejection fraction continues: the prognostic value of LV global function index in heart failure

Abstract Background Left Ventricular (LV) Global Function index (LVGFi) is a parameter that combines data from global systolic performance and volumetric anatomical information, measurable by non-contrast Cardiac Magnetic Resonance (CMR). We aimed to evaluate whether LVGFi predicts major cardiovascular outcomes and outperforms LV ejection fraction (LVEF) in Heart Failure (HF). Methods We conducted a retrospective single-centre study of consecutive patients with HF who were referred to and had a LVEF <50% at CMR. Other than inadequate images for endocardial or epicardial border delineation, there were no exclusion criteria. LVEF was determined by 3D measurement. LVGFi was calculated as the LV stroke volume to the LV global volume ratio (Figure 1). The primary endpoint was a composite of time to all-cause death or HF hospitalization. Results The cohort was comprised of 433 HF patients (mean age 64±12 years, 74.1% male, ischaemic HF 53.1%, NYHA I-II 83.9%) with a mean LVEF of 33.5±10.0% and LVGFi of 22.8±7.4%. Over a median follow-up of 27 (17–37) months, 85 (19.6%) met the primary endpoint and 42 (9.7%) died. Patients with an event of the primary endpoint had markers of more severe HF, as noted by a reduced functional capacity (NYHA I-II: 63.5 vs. 89.0%; p<0.001) and increased natriuretic peptides [NT-proBNP: 2664 (1022–27242) vs. 791 (337–7258); p<0.001). Likewise, CMR showed higher LV volumes (e.g., LV end-diastolic volume index: 137±50 vs. 120±43mL/m2; p=0.001) and reduced LV performance indices, namely LVEF (29.2±10.6 vs 34.5±9.6%; p<0.001) and LVGFi (19.8±7.4 vs 23.6±7.3%; p<0.001). Both LVEF and LVGFi independently predicted the primary endpoint in multivariate analysis (separately imputed into a model adjusted for NYHA, NT-proBNP and creatinine). The LVEF model was more powerful than that of LVGFi. Similarly, LVGFi did not provide incremental prognostic information over LVEF in c-statistics analysis (0.653 vs. 0.622; p=0.645) (Figure 2). Conclusion While LVGFi independently predicted major outcomes in patients with HF and LVEF <50%, it did not surpass LVEF. Our findings contrast to those demonstrating LVGFi as a powerful variable that outperforms LVEF in hypertrophic cardiomyopathy, cardiac amyloidosis, and healthy subjects at risk of developing structural heart disease. We hypothesize that LVGFi might be primarily useful in the prognostic stratification of patients with preserved LVEF. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Magnetic Resonance Imaging of Cardiac Strain Pattern Following Transplantation of Human Tissue Engineered Heart Muscles.

The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance after such treatments are plagued by relatively low detection ability. Since the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility. Tissue engineered heart muscles (EHMs) were generated by casting human embryonic stem cell-derived cardiomyocytes with collagen in preformed molds. EHMs were transplanted (n=12) to cover infarct and border zones of recipient rat hearts 1 month after ischemia reperfusion injury. A control group (n=10) received only sham placement of sutures without EHMs. To assess the efficacy of EHMs, magnetic resonance imaging and ultrasound-based strain imaging were performed before and 4 weeks after transplantation. In addition to strain imaging, global cardiac performance was estimated from cardiac magnetic resonance imaging. Although no significant differences were found for global changes in left ventricular ejection fraction (control -9.6±1.3% versus EHM -6.2±1.9%; P=0.17), regional myocardial strain from tagged magnetic resonance imaging was able to detect preserved systolic function in EHM-treated animals compared with control (control 4.4±1.0% versus EHM 1.0±0.6%; P=0.04). However, ultrasound-based strain failed to detect any significant change (control 2.1±3.0% versus EHM 6.3±2.9%; P=0.46). This study highlights the feasibility of using cardiac strain from tagged magnetic resonance imaging to assess functional changes in rat models following localized regenerative therapies, which may not be detected by conventional measures of global systolic performance.

Abstract 366: Cardiac Strain From Magnetic Resonance Imaging Offers Sensitive Detection of Therapeutic Efficacy Following Transplantation of Tissue Engineered Heart Muscles

Background: Myocardial infarction (MI) leads to gradually decreased cardiac contractility that can ultimately cause heart failure or sudden death. One potential therapy to recover this MI-impaired contractile function is the regenerative approach that integrates both tissue engineering and exogenously produced cardiomyocytes. Although this contractile recovery has been assessed by different imaging methods in previous studies, these assessments in global cardiac performance are plagued by their relatively low sensitivity. As this treatment is locally performed, the sensitivity of its therapeutic assessment can be improved by myocardial strain imaging that assesses regional contractility. Methods: We first made tissue engineered heart muscles (EHMs) by casting human embryonic stem cell-derived cardiomyocytes (ESC-CMs) with collagen in preformed molds. Then we transplanted these EHMs (n=12) into the post-MI rat hearts one month after this injure. We also performed sham surgeries on a control group (n=9) without EHM transplantation. Meanwhile, strain imaging from cardiac magnetic resonance imaging (MRI) and ultrasound were performed prior to and four weeks after EHM transplantations. In addition, global cardiac performance such as left ventricular ejection fraction (EF) was estimated from cardiac MRI. Results: Based on the measurements, regional myocardial strain measured from tagged MRI detected the preserved systolic function in the EHM-treated group compared to control group (P=0.04). In contrary, the global function EF was unable to detect this significant difference between both groups (P=0.38). Similarly, myocardial strain measured from cardiac ultrasound also failed to detect the significance between both treatment and control groups (P=0.24). Conclusions: This study for the first time confirmed that regional assessment of contractile function offered higher sensitivity compared to the conventional measure of global systolic performance. This finding highlights the feasibility and sensitivity of cardiac strain derived from tagged MRI as a sensitive method to assess the efficacy of regenerative therapies in both preclinical and clinical studies.

Intraoperative cardiac assessment with transesophageal echocardiography for decision-making in cardiac anesthesia

Transesophageal echocardiography is an invaluable hemodynamic monitoring modality. Extended and anatomically based evaluation of cardiac function with transesophageal echocardiography is essential to prompt and accurate decision-making in anesthetic management during cardiac surgery. Fractional shortening and fractional area changes are indices widely used to assess the global systolic performance of the left ventricle. Monitoring regional function using semi-quantitative scoring has been demonstrated to be a more sensitive indicator of myocardial ischemia. Assessment of left ventricular diastolic function should be performed in a systematic way, measuring transmitral flow, pulmonary venous flow, transmitral color M-mode flow propagation velocity, and mitral annulus tissue Doppler imaging. The unique anatomical features of the right ventricle make echocardiographic evaluation complicated and therefore less frequently employed. Right ventricular fractional area change, tricuspid annular plane systolic excursion, maximal systolic tricuspid annular velocity with tissue Doppler imaging, and myocardial performance index are indices successfully incorporated into intraoperative right ventricular assessment. Left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve may develop after cardiac procedures. Transesophageal echocardiography plays a central role in prevention as well as diagnosis of systolic anterior motion. Transesophageal echocardiography is extremely useful not only for detecting and locating intracardiac air, but also for guiding and evaluating the procedures to remove air. Air is likely to persist in the right and left superior pulmonary vein, left ventricular apex, left atrium, right coronary sinus of Valsalva, and ascending aorta. Accurate evaluation of cardiac function depends on performing TEE examination properly and obtaining optimal images.

Hemodynamic effects of positive end-expiratory pressure during abdominal hyperpression: A preliminary study in healthy volunteers

PurposeAn increase in abdominal pressure induces an increase in left ventricular afterload under clinical conditions. We tested the hypothesis that positive end-expiratory pressure (PEEP) could reverse the hemodynamic consequences of abdominal hyperpression by opposing the increase in left ventricular afterload. Materials and methodsEight healthy volunteers were investigated during 3 experimental conditions: (1) baseline, (2) increase in abdominal pressure by means of medical antishock trousers (MAST) inflation, and (3) addition of PEEP +10 cm H2O. Heart loading conditions and left ventricular systolic and diastolic function were assessed by transthoracic echocardiography. ResultsThe application of PEEP significantly reduced the prior increase in end-systolic wall stress: 45 ± 11 vs 55 ± 14 kdyn/cm2, P < .05. Medical antishock trousers inflation significantly altered the deceleration time of mitral E wave: 199 ± 23 vs 156 ± 38 milliseconds, P < .05. Left ventricular preload and global systolic performance were unaffected by MAST and PEEP applications. ConclusionsThe increase in left ventricular afterload induced by MAST inflation can be efficiently reduced by the use of a moderate PEEP. Potential clinical applications in the abdominal compartment syndrome or in the setting of laparoscopic surgery should be developed.

Left ventricular systolic torsion correlates global cardiac performance during dyssynchrony and cardiac resynchronization therapy

Left ventricular (LV) systolic torsion is a primary mechanism contributing to stroke volume (SV). We hypothesized that change in LV torsion parallels changes in global systolic performance during dyssynchrony and cardiac resynchronization therapy (CRT). Seven anesthetized open chest dogs had LV pressure-volume relationship. Apical, basal, and mid-LV cross-sectional echocardiographic images were studied by speckle tracking analysis. Right atrial (RA) pacing served as control. Right ventricular (RV) pacing simulated left bundle branch block. Simultaneous RV-LV free wall and RV-LV apex pacing (CRTfw and CRTa, respectively) modeled CRT. Dyssynchrony was defined as the time difference in peak strain between earliest and latest segments. Torsion was calculated as the maximum difference between the apical and basal rotation. RA pacing had minimal dyssynchrony (52 ± 36 ms). RV pacing induced dyssynchrony (189 ± 61 ms, P < 0.05). CRTa decreased dyssynchrony (46 ± 36 ms, P < 0.05 vs. RV pacing), whereas CRTfw did not (110 ± 96 ms). Torsion during baseline RA was 6.6 ± 3.7°. RV pacing decreased torsion (5.1 ± 3.6°, P < 0.05 vs. control), and reduced SV, stroke work (SW), and dP/dt(max) compared with RA (21 ± 5 vs. 17 ± 5 ml, 252 ± 61 vs. 151 ± 64 mJ, and 2,063 ± 456 vs. 1,603 ± 424 mmHg/s, respectively, P < 0.05). CRTa improved torsion, SV, SW, and dP/dt(max) compared with RV pacing (7.7 ± 4.7°, 23 ± 3 ml, 240 ± 50 mJ, and 1,947 ± 647 mmHg/s, respectively, P < 0.05), whereas CRTfw did not (5.1 ± 3.6°, 18 ± 5 ml, 175 ± 48 mJ, and 1,699 ± 432 mmHg/s, respectively, P < 0.05). LV torsion changes covaried across conditions with SW (y = 0.94x+12.27, r = 0.81, P < 0.0001) and SV (y = 0.66x+0.91, r = 0.81, P < 0.0001). LV dyssynchrony changes did not correlate with SW or SV (r = -0.12, P = 0.61 and r = 0.08, P = 0.73, respectively). Thus, we conclude that LV torsion is primarily altered by dyssynchrony, and CRT that restores LV performance also restores torsion.

Minor segmental wall motion abnormalities detected in patients with Chagas' disease have adverse prognostic implications

Recent data from our laboratory have shown that patients with the indeterminate form of Chagas' disease can have impairment of left ventricular contractility, as evaluated by the slope of the left ventricle end-systolic pressure-dimension relationship. We also showed that Chagas' disease patients with minimal baseline wall motion abnormalities detected by two-dimensional echocardiography have more intense contractility impairment when compared to patients with the indeterminate form of the disease without this abnormality. The prognostic implications of these findings have not been established. We evaluated 59 patients (37-76 years, mean = 55 years) with different clinical forms of Chagas' disease, who had normal left ventricular global systolic function at baseline (57.6 +/- 6.9%) and who had at least one additional echo during clinical follow-up (0.4-17.6; mean 4.6 years). Group 1 consisted of 14 patients with minor baseline left ventricle wall motion abnormalities and group 2 consisted of 45 patients without these abnormalities. During follow-up, global left ventricle systolic function deterioration was observed in 10 group 1 patients (71.4%) and in only 10 group 2 patients (22.2%; P < 0.005). Age and duration of follow-up were not independent determinants of left ventricular function deterioration in these patients. The present data indicate that mild segmental left ventricular wall motion abnormalities are associated with worsening of systolic function in Chagas' disease patients who have normal baseline global systolic performance.

Left ventricular hypertrophy in Caucasian master athletes: Differences with hypertension and hypertrophic cardiomyopathy

Aim To study, by conventional echocardiography, left ventricular remodelling and function in master athletes, hypertension and hypertrophic cardiomyopathy. Methods We studied 30 master athletes (MA; soccer players; mean age 43.9 ± 5.9), 24 subjects with essential hypertension (HYP; 46.6 ± 6), 20 patients with hypertrophic cardiomyopathy (HCM; 42.2 ± 9) and 30 normal individuals (CG; 43.4 ± 5). An integrated M-mode/two-dimensional echocardiographic analysis was performed to determine chambers dimensions, relative wall thickness (RWT) and left ventricular mass (LVM), indexed to height in meters raised to the power of 2.7 (LVM/ h 2.7). Cut-off levels for LVM/ h 2.7 and RWT were defined to assess 4 different patterns of LV geometric remodelling. In addition, we measured indexes of global systolic performance and indexes of global diastolic function. Results LV wall thickness and LV end-diastolic dimensions were higher in MA than controls, but significantly lower than other groups. LVH/h 2.7 was increased in 79% of HYP and in 95% of HCM, but was within the normal limits in MA. LV geometry was normal in 22 out of 30 MA (73%), while the remaining (8 athletes, 27%) showed a concentric remodelling. Systolic function (FS and EF) was normal in MA, but was slightly reduced in HYP and increased in HCM. Analysis of diastolic function showed an abnormal relaxation pattern in all HYP and 95% of HCM, but was normal in all MA. The ratio between peak filling rate and stroke volume (PFR / SV), a relatively independent index of diastolic function, was significantly greater in hypertensive patients with normal LV remodelling compared to those without it (4 ± 0.39 vs. 4.91 ± 0.19; P = 0.0002). Conclusion MA showed lower values of wall thickness, LV dimensions and LV mass compared with HYP and HCM. Despite an abnormal remodelling, all the athletes showed a normal systolic and diastolic function. The differential diagnosis between MA, HYP and HCM is feasible by accurate, comprehensive standard Doppler echocardiography.

Amplitudes, Durations, and Timings of Apically Directed Left Ventricular Myocardial Velocities: II. Systolic and Diastolic Asynchrony in Patients with Left Ventricular Hypertrophy

Background: Regional myocardial dysfunction may be the earliest manifestation of myocardial disease and can occur in the absence of abnormalities of global left ventricular (LV) function. The LV long-axis function, which is mainly due to subendocardial muscle fibers, may become abnormal in the presence of normal short-axis function. This study investigates the temporal and spatial characteristics of the LV long-axis function in patients with secondary LV hypertrophy in the presence of normal systolic function. Methods and Results: LV long-axis myocardial velocities were recorded in 18 patients with LV hypertrophy and preserved regional and global systolic function with Doppler tissue imaging. Apically directed myocardial velocities were recorded from the basal, mid, and apical segments of the four LV walls, and their amplitudes, timings, and durations were measured. The abnormalities uncovered by the analysis of regional myocardial velocities included (1) asynchrony in the onset of myocardial contraction circumferentially, (2) presence of postejection LV shortening, (3) asynchrony in the onset of early myocardial lengthening circumferentially, (4) reduced early myocardial lengthening velocity, (5) reduced early to late myocardial lengthening velocity and extents circumferentially, and (6) lack of variation in the basal myocardial velocities circumferentially in contrast to normal individuals. Conclusions:Patients with secondary LV hypertrophy with preserved regional and global systolic performance have distinct abnormalities in the timings and amplitudes of apically directed myocardial velocities. These abnormalities may explain some of the changes in LV global diastolic behavior and may also serve as markers of early regional myocardial dysfunction. (J Am Soc Echocardiogr 1998;11:112-8.)

998-120 Left Ventricular Systolic Performance Changes in Mild Hypertensive Subjects Treated with Antihypertensive Monotherapy or Placebo: The Treatment of Mild Hypertension Study (TOMHS)

Few large scale studies have evaluated long term effects of antihypertensive monotherapy (MT) versus placebo (P) on left ventricular (LV) systolic performance. Over a period of 4 years, 844 subjects with mild hypertension (mean BP: 140/91) without cardiac disease were treated with one of 5 MTs or P, all receiving nutritional-hygienic intervention. 2-D directed M-mode echocardiograms evaluated LV function at baseline, 3 months and annually through 4 years. Average changes over 4 years were compared between combined MT groups and P. Average decrease in BP was 15.9/12.3 mmHg in the MT group and 9.1/8.6 mmHg in the P group. for global systolic performance, stroke volume, ejection fraction, and fractional shortening (FS) increased with MT but decreased in P (p &lt; 0.01 (MT vs P). Average change from baseline in stroke volume was –3.0% with P and +1.7% with MT. Cardiac output, stroke work index and minute work index decreased similarly in both MT and P. Peak-and end-systolic stress (ESS) increased significantly more in P than MT (p &lt; 0.01). Total peripheral resistance decreased more in the MT group (p &lt; 0.001). For indexes of contractility, ESS/ES volume index increased more in the P group, FS/ESS increased in MT and decreased in P, and SBP/ES dimension decreased more in the MT group (p &lt; 0.02 for each). These findings suggest that even in mild hypertensives without underlying LV dysfunction, the addition of MT to nutritional-hygienic therapy can produce small, though significant changes in LV performance characteristics.

Effects of cardioplegic arrest on left ventricular systolic and diastolic function of the intact neonatal heart

The effects of cardiopulmonary bypass and cardioplegic arrest on left ventricular systolic and diastolic function were studied in 20 intact neonatal lambs instrumented with ultrasonic dimension transducers and micromanometers for collection of left ventricular pressure-dimension data. Group I lambs underwent 2 hours of hypothermic cardiopulmonary bypass (25 degrees C) alone; group II lambs underwent 2 hours of hypothermic cardiopulmonary bypass (25 degrees C) with 1 hour of multidose, cold, crystalloid cardioplegic arrest (St. Thomas' Hospital No. 2 solution). The control neonatal lamb left ventricle was found to be relatively stiff, with the limit of diastolic filling reached at physiologic left ventricular filling pressures, resulting in apparent descending limbs of left ventricular function. After cardiopulmonary bypass, identical results were obtained in groups I and II. A significant loss of left ventricular compliance limited left ventricular performance via two mechanisms. First, left ventricular preload was significantly decreased, with a concomitant diminution in left ventricular stroke work; afterload (pressure work) was maintained at the expense of volume work (flow), which declined significantly. Second, preload behaved as though fixed, resulting in a loss of impedance matching (afterload mismatch). Although contractility as assessed by the end-systolic pressure-dimension relationship was significantly increased (because of increased levels of circulating catecholamines), global systolic performance as quantified by the stroke work/end-diastolic length relationship remained unchanged, reflecting the afterload sensitivity of the latter parameter in the face of fixed preload. We conclude that cardiopulmonary bypass in the intact neonate results in a loss of compliance and impedance matching rather than a loss of contractility; however, the addition of 1 hour of cold, crystalloid cardioplegic arrest results in no dysfunction beyond that attributable to cardiopulmonary bypass alone.

The End-Systolic Pressure-Volume Relationship in the Newborn Lamb: Effects of Loading and Inotropic Interventions

Indices of global systolic performance of the newborn left ventricle exceed those of the adult, despite isolated tissue studies showing immature contractile mechanisms. To evaluate contractility in situ, we investigated the end-systolic pressure-volume relationship (ESPVR) by the conductance technique in nine newborn lambs. After percutaneous placement of catheters, we generated ESPVR by inferior vena cava occlusion, aortic occlusion, and volume infusion in two control states, during three levels of dobutamine infusion, and after propranolol. We performed linear and nonlinear regression analyses of the end-systolic points and derived the slope (Ees) and volume at 14 kPa pressure. We found that reliable ESPVR could be obtained in almost all inferior vena cava and aortic occlusions (50 of 51 in each), but in only 18 of 27 volume infusions. Overall, linear regressions adequately defined the ESPVR (75 of 102 were not statistically different than nonlinear regressions; of those different, the mean linear R2 was 0.934 +/- 0.048). By multiple regression analysis, neither Ees nor volume at 14 kPa significantly changed with dobutamine, but both changed after propranolol (23% less than control and 54% greater, respectively), supporting previous studies showing a limited contractile reserve in the newborn secondary to high resting beta-adrenergic tone. Neither Ees nor volume at 14 kPa was different between control states. However, Ees was 25% less steep when generated by inferior vena cava than by aortic occlusion. We conclude that the ESPVR can be generated reliably and reproducibly in the newborn lamb and is relatively linear and sensitive to changes in contractility, but that it is also sensitive to the technique of load intervention.

Physiologic role of the mitral apparatus in left ventricular regional mechanics, contraction synergy, and global systolic performance

In animal models, severing the chordae tendineae of the mitral valve reduces the maximum global left ventricular elastance (Emax,g), a load-independent measure of left ventricular systolic performance; moreover, chamber geometry is altered with systolic bulging in the region of the papillary muscle insertions. This suggests that forces transmitted by the mitral apparatus increase the regional volume elastance (Emax,r) of segments subtending the insertions of the papillary muscles, and these regions contribute substantially to overall left ventricular systolic function (Emax,g). To test this hypothesis, we developed a method to evaluate changes in the magnitude and uniformity of Emax,r as quantitated by the slopes (E'max,i) of regional left ventricular isovolumetric pressure-dimension relations. Such measurements were obtained before and after all chordal attachments of the mitral valve were surgically divided in seven open-chest swine preparations. Significant declines in E'max,i were limited to the region of the posteromedial papillary muscle insertion. Although the mean E'max,i of all ventricular regions (E'max,ave) was unchanged, regional left ventricular elastances were less uniform after the mitral chordae tendineae were severed, which indicated a less synergistic contraction, and Emax,g fell by 21% from 7.1 +/- 2.0 to 5.6 +/- 1.2 mm Hg/ml (p less than 0.05). These data demonstrate that the mitral apparatus contributes importantly to the magnitude and uniformity of regional left ventricular elastances and suggest that such alterations in regional mechanics underlie the deterioration in global left ventricular systolic performance (Emax,g) after excision of the mitral apparatus.