Effects of mechanical limitation of apical rotation on left ventricular relaxation and end-diastolic pressure

Left ventricular (LV) twist is thought to play an important role in cardiac function. However, how twist affects systolic or diastolic function is not understood in detail. We acquired apical and basal short-axis images of dogs undergoing open-chest procedures (n = 15) using a GE Vivid 7 at baseline and during the use of an apical suction device (Starfish) to limit apical rotation. We measured LV pressure and stroke volume using a micromanometer-tipped catheter and an ultrasonic flow probe, respectively. Peak radial strain, peak rotation, peak twist, peak systolic twisting rate (TR), peak untwisting rate during isovolumic relaxation period (UR(IVR)), and peak early diastolic untwisting rate after mitral valve opening (UR(E)) were determined using speckle tracking echocardiography. Immobilizing the apex with gentle suction significantly decreased apical rotation (-50 ± 27%) and slightly increased basal rotation, resulting in a significant decrease in twist. The time constant of LV relaxation (τ) was prolonged, and LV end-diastolic pressure increased. TR and UR(IVR) decreased. LV systolic pressure, peak positive and negative first derivative of LV pressure (±dP/dt), stroke volume, radial strain, and UR(E) were not changed. The correlation between τ and UR(IVR) (r = 0.63, P = 0.0006) was stronger than that between peak +dP/dt and TR (r = 0.46, P = 0.01). Diastolic function was impaired with reduced apical rotation and UR(IVR) when the apex of the heart was immobilized using an apical suction device.     

Postsystolic shortening of ischemic myocardium: a mechanism of abnormal intraventricular filling

Acute myocardial ischemia has been associated with abnormal filling patterns in the left ventricular (LV) apex. We hypothesized that this may in part be due to postsystolic shortening of ischemic apical segments, which leads to reversal of early diastolic apical flow. Fourteen open-chest anesthetized dogs were instrumented with micromanometers in the LV apex and left atrium and myocardial sonomicrometers in the anterior apical LV wall. Intraventricular filling by color Doppler and wall motion by strain Doppler echocardiography (SDE) were assessed from an apical view. Measurements were taken before and after 5 min of left anterior descending coronary artery (LAD) occlusion. In four dogs, we measured the pressure difference between the LV apex and outflow tract. At baseline, peak early diastolic flow velocities in the distal one-third of the LV were directed toward apex (9.2 +/- 1.6 cm/s). After LAD occlusion, the velocities reversed (-2.3 +/- 0.4 cm/s, P < 0.01), indicating that blood was ejected from the apex toward the base during early filling. This interpretation was confirmed by wall motion analysis, which showed postsystolic shortening of apical myocardial segments. The postsystolic shortening represented 9.7 +/- 1.7% (P < 0.01) and 14.2 +/- 2.4% (P < 0.01) of end-diastolic segment length by SDE and sonomicrometry, respectively. Consistent with the velocity changes, we found reversal of the early diastolic pressure gradient from the LV apex to outflow tract. In the present model, acute LAD occlusion resulted in reversal of early diastolic apical flow, and this was attributed to postsystolic shortening of dyskinetic apical segments. The clinical diagnostic importance of this finding remains to be determined.     

Speckle-tracking echocardiography correctly identifies segmental left ventricular dysfunction induced by scarring in a rat model of myocardial infarction

Speckle-tracking echocardiography (STE) uses a two-dimensional echocardiographic image to estimate two orthogonal strain components. The aim of this study was to assess sensitivity of circumferential (S(circ)) and radial (S(rad)) strains to infarct-induced left ventricular (LV) remodeling and scarring of the LV in a rat. To assess the relationship among S(circ), S(rad), and scar size, two-dimensional echocardiographic LV short-axis images (12 MHz transducer, Vivid 7 echo machine) were collected in 34 Lewis rats 4 to 10 wk after ligation of the left anterior descending artery. Percent segmental fibrosis was assessed from histological LV cross sections stained by Masson trichrome. Ten normal rats served as echocardiographic controls. S(circ) and S(rad) were assessed by STE. Histological data showed consistent scarring of anterior and lateral segments with variable extension to posterior and inferior segments. Both S(circ) and S(rad) significantly decreased after myocardial infarction (P<0.0001 for both). As anticipated, S(circ) and S(rad) were lowest in the infarcted segments. Multiple linear regression showed that segmental S(circ) were similarly dependent on segmental fibrosis and end-systolic diameter (P<0.0001 for both), whereas segmental S(rad) measurements were more dependent on end-systolic diameter (P<0.0001) than on percent fibrosis (P<0.002). STE correctly identifies segmental LV dysfunction induced by scarring that follows myocardial infarction in rats.     

Acute Impact of Pacing at Different Cardiac Sites on Left Ventricular Rotation and Twist in Dogs

Objectives

We evaluated the acute impact of different cardiac pacing sites on two-dimensional speckle-tracking echocardiography (STE) derived left ventricular (LV) rotation and twist in healthy dogs.

Methods

Twelve dogs were used in this study. The steerable pacing electrodes were positioned into right heart through the superior or inferior vena cava, into LV through aorta across the aortic valve. The steerable pacing electrodes were positioned individually in the right atrium (RA), right ventricular apex (RVA), RV outflow tract (RVOT), His bundle (HB), LV apex (LVA) and LV high septum (LVS), individual pacing mode was applied at 10 minutes interval for at least 5 minutes from each position under fluoroscopy and ultrasound guidance and at stabilized hemodynamic conditions. LV short-axis images at the apical and basal levels were obtained during sinus rhythm and pacing. Offline STE analysis was performed. Rotation, twist, time to peak rotation (TPR), time to peak twist (TPT), and apical-basal rotation delay (rotational synchronization index, RSI) values were compared at various conditions. LV pressure was monitored simultaneously.

Results

Anesthetic death occurred in 1 dog, and another dog was excluded because of bad imaging quality. Data from 10 dogs were analyzed. RVA, RVOT, HB, LVA, LVS, RARV (RA+RVA) pacing resulted in significantly reduced apical and basal rotation and twist, significantly prolonged apical TPR, TPT and RSI compared to pre-pacing and RA pacing (all P<0.05). The apical and basal rotation and twist values were significantly higher during HB pacing than during pacing at ventricular sites (all P<0.05, except basal rotation at RVA pacing). The apical TPR during HB pacing was significantly shorter than during RVOT and RVA pacing (both P<0.05). The LV end systolic pressure (LVESP) was significantly lower during ventricular pacing than during pre-pacing and RA pacing.

Conclusions

Our results show that RA and HB pacing results in less acute reduction on LV twist, rotation and LVESP compared to ventricular pacing.     

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.     

Age-related changes in the biomechanics of left ventricular twist measured by speckle tracking echocardiography

The increasing number and proportion of aged individuals in the population warrants knowledge of normal physiological changes of left ventricular (LV) biomechanics with advancing age. LV twist describes the instantaneous circumferential motion of the apex with respect to the base of the heart and has an important role in LV ejection and filling. This study sought to investigate the biomechanics behind age-related changes in LV twist by determining a broad spectrum of LV rotation parameters in different age groups, using speckle tracking echocardiography (STE). The final study population consisted of 61 healthy volunteers (16-35 yr, n=25; 36-55 yr, n=23; 56-75 yr, n=13; 31 men). LV peak systolic rotation during the isovolumic contraction phase (Rot(early)), LV peak systolic rotation during ejection (Rot(max)), instantaneous LV peak systolic twist (Twist(max)), the time to Rot(early), Rot(max), and Twist(max), and rotational deformation delay (defined as the difference of time to basal Rot(max) and apical Rot(max)) were determined by STE using QLAB Advanced Quantification Software (version 6.0; Philips, Best, The Netherlands). With increasing age, apical Rot(max) (P<0.05), time to apical Rot(max) (P<0.01), and Twist(max) (P<0.01) increased, whereas basal Rot(early) (P<0.001), time to basal Rot(early) (P<0.01), and rotational deformation delay (P<0.05) decreased. Rotational deformation delay was significantly correlated to Twist(max) (R(2)=0.20, P<0.05). In conclusion, Twist(max) increased with aging, resulting from both increased apical Rot(max) and decreased rotational deformation delay between the apex and the base of the LV. This may explain the preservation of LV ejection fraction in the elderly.     

Differential effects of left ventricular pacing sites in an acute canine model of contraction dyssynchrony

The goal of the present study was to assess the effects of left ventricular (LV) pacing sites (apex vs. free wall) on radial synchrony and global LV performance in a canine model of contraction dyssynchrony. Ultrasound tissue Doppler imaging and hemodynamic (LV pressure-volume) data were collected in seven anesthetized, opened-chest dogs. Right atrial (RA) pacing served as the control, and contraction dyssynchrony was created by simultaneous RA and right ventricular (RV) pacing to induce a left bundle-branch block-like contraction pattern. Cardiac resynchronization therapy (CRT) was implemented by adding simultaneous LV pacing to the RV pacing mode at either the LV apex (CRTa) or free wall (CRTf). A new index of synchrony was developed via pair-wise cross-correlation analysis of tissue Doppler radial strain from six midmyocardial cross-sectional regions, with a value of 15 indicating perfect synchrony. Compared with RA pacing, RV pacing significantly decreased radial synchrony (11.1 +/- 0.8 vs. 4.8 +/- 1.2, P < 0.01) and global LV performance (cardiac output: 2.0 +/- 0.3 vs. 1.4 +/- 0.1 l/min and stroke work: 137 +/- 22 vs. 60 +/- 14 mJ, P < 0.05). Although both CRTa and CRTf significantly improved radial synchrony, only CRTa markedly improved global function (cardiac output: 2.1 +/- 0.2 l/min and stroke work: 113 +/- 13 mJ, P < 0.01 vs. RV pacing). Furthermore, CRTa decreased LV end-systolic volume compared with RV pacing without any change in LV end-systolic pressure, indicating an augmented global LV contractile state. Thus, LV apical pacing appears to be a superior pacing site in the context of CRT. The dissociation between changes in synchrony and global LV performance with CRTf suggests that regional analysis from a single plane may not be sufficient to adequately characterize contraction synchrony.     

Structure and torsion of the normal and situs inversus totalis cardiac left ventricle. I. Experimental data in humans

In 1926, the famous American pediatric cardiologist, Dr. Helen B. Taussig, observed that in situs inversus totalis (SIT) main gross anatomical structures and the deep muscle bundles of the ventricles were a mirror image of the normal structure, while the direction of the superficial muscle bundles remained unchanged (H. B. Taussig, Bull Johns Hopkins Hosp 39: 199-202, 1926). She and we wondered about the implication of this observation for left ventricular (LV) deformation in SIT. We used magnetic resonance tagging to obtain information on LV deformation, rotation, and torsion from a series of tagged images in five evenly distributed, parallel, short-axis sections of the heart of nine controls and eight persons with SIT without other structural (cardiac) defect. In the controls, during ejection, the apex rotated counterclockwise with respect to the base, when looking from the apex. Furthermore, the base-to-apex gradient in rotation (torsion) was negative and similar at all longitudinal levels of the LV. In SIT hearts, torsion was positive near the base, indicating mirrored myofiber orientations compared with the normal LV. Contrary to expectations, torsion in the apical regions of SIT LVs was as in normal ones, reflecting a normal internal myocardial architecture. The transition zone with zero torsion, found between the apex and base, suggests that the heart structure in SIT is essentially different from that in the normal heart. This provides a unique possibility to study regulatory mechanisms for myocardial fiber orientation and mechanical load, which has been dealt with in the companion paper by Kroon et al.     

Early impairment of myocardial deformation assessed by regional speckle-tracking echocardiography in the indeterminate form of Chagas disease without fibrosis detected by cardiac magnetic resonance

Chagas disease (CD) will account for 200,000 cardiovascular deaths worldwide over the next 5 years. Early detection of chronic Chagas cardiomyopathy (CCC) is a challenge. We aimed to test if speckle-tracking echocardiography (STE) can detect incipient myocardial damage in CD. METHODS: Among 325 individuals with positive serological tests, 25 (age 55±12yrs) were selected to compose the group with indeterminate form of Chagas disease (IFCD), based on stringent criteria of being asymptomatic and with normal EKG/X-ray studies. This group was compared with a group of 20 patients with CCC (55±11yrs) and a group of 20 non-infected matched control (NC) subjects (48±10yrs). CD patients and NC were submitted to STE and CD patients were submitted to cardiac magnetic resonance (CMR) with late gadolinium administration to detect cardiac fibrosis by the late enhancement technique. Global longitudinal strain (GLS), circumferential (GCS) and radial strain (GRS) were defined as the average of segments measured from three apical view (GLS) and short axis views (GRS and GCS). Regional left ventricular (LV) longitudinal strain (Reg LS) was measured from each of the 17 segments. Twist was measured as systolic peak difference between basal and apical rotation and indexed to LV length to express torsion. RESULTS: STE global indices (GLS, GCS, twist and torsion) were reduced in CCC vs NC (GLS: -14±6.3% vs -19.3±1.6%, p = 0.001; GCS: -13.6±5.2% vs -17.3 ±2.8%; p = 0.008; twist: 8±7° vs 14±7°, p = 0.01 and torsion: 0.96±1°/cm vs 1.9±1°/cm, p = 0.005), but showed no differences in IFCD vs NC. RegLS was reduced in IFCD vs NC in four LV segments: basal-inferior (-16.3±3.3% vs -18.6±2.2%, p = 0.013), basal inferoseptal (-13.1±3.4 vs -15.2±2.7, p = 0.019), mid-inferoseptal (-17.7±3.2 vs -19.4±2, p = 0.032) and mid-inferolateral (-15.2±3.5 vs -17.8±2.8, p = 0.014). These abnormalities in RegLS occurred in the absence of myocardial fibrosis detectable with CMR in nearly 92% of subjects with IFCD, while myocardial fibrosis was present in 65% with CCC. CONCLUSION: RegLS detects early regional impairment of myocardial strain that is independent from fibrosis in IFCD subjects.     

New insights in LV torsion for the selection of cardiac resynchronisation therapy candidates

Recent literature indicates that torsion of the left ventricle (LV) is a promising predictor for response to cardiac resynchronisation therapy (CRT). Among patients with severe heart failure, 45 to 75% of patients show rigid body rotation, where the base and apex rotate in the same direction, instead of normal, opposite rotation. The occurrence of this phenomenon seems to be a good indicator for response to CRT. From this review, it can be concluded that LV torsion might be a welcome addition to current selection criteria.     

Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study

Background and Aims

Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX.

Methods and Results

Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B-type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 ± 7.8 vs 32.7 ± 8.9 degrees, p = 0.04). Serum creatinine and PIIINP levels were increased [1.1 (0.9–1.3) mg/dL, and 5.8 (5.4–7.6)] μg/L, respectively), while urinary cGMP was reduced [270 (250–355) vs 581 (437–698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.

Conclusions

Long-term kidney donors have no apparent structural myocardial abnormalities as assessed by contrast enhanced CMR. However, myocardial deformation of the apical segments, as well as apical rotation, and LV torsion are reduced. The concomitant increase in circulating PIIINP level is suggestive of fibrosis. Further studies, focused on US and EU patients are warranted to evaluate whether these early functional modifications will progress to a more compromised cardiac function and structure at a later time.     

Ischemic cardiomyopathy in pigs with two-vessel occlusion and viable, chronically dysfunctional myocardium

A chronic left anterior descending coronary artery (LAD) stenosis leads to the development of hibernating myocardium with severe regional hypokinesis but normal global ventricular function after 3 mo. We hypothesized that two-vessel occlusion would accelerate the progression to hibernating myocardium and lead to global left ventricular (LV) dysfunction and heart failure. Pigs were instrumented with a fixed 1.5-mm constrictor on the proximal LAD and circumflex arteries. After 2 mo, there were no overt signs of right-heart failure and triphenyl tetrazolium chloride infarction was trivial (1.4 +/- 0.1% of the LV). Compared with shams, regional function [myocardial systolic excursion (DeltaWT); 2.1 +/- 0.3 vs. 4.6 +/- 0.4 mm, P < 0.05] and resting perfusion (0.90 +/- 0.13 vs. 1.32 +/- 0.09 ml small middle dot min(-1) small middle dot g(-1), P < 0.05) were reduced, consistent with hibernating myocardium. Pulmonary systolic (45.9 +/- 3.3 vs. 36.5 +/- 2.2 mmHg, P < 0.05) and wedge pressures (19.1 +/- 1.6 vs. 11.2 +/- 0.9 mmHg, P < 0.05) were increased with global ventricular dysfunction (ejection fraction 43 +/- 2 vs. 50 +/- 2%, P < 0.05). Early LV remodeling was present with increased cavity size and mass. Reductions in sarcoplasmic reticulum Ca(2+)-ATPase and phospholamban were confined to the dysfunctional LAD region with no change in calsequestrin. Thus combined stenoses of the LAD and circumflex arteries accelerate the development of hibernating myocardium and result in compensated heart failure.     

Regional nonuniformity of normal adult human left ventricle

Regional nonuniformity is a feature of both diseased and normal left ventricles (LV). With the use of magnetic resonance (MR) myocardial tagging, we performed three-dimensional strain analysis on 87 healthy adults in local cardiac and fiber coordinate systems (radial, circumferential, longitudinal, and fiber strains) to characterize normal nonuniformities and to test the validity of wall thickening as a parameter of regional function. Regional morphology included wall thickness and radii of curvature measurements. With respect to transmural nonuniformity, subendocardial strains exceeded subepicardial strains. Going from base to apex, wall thickness and circumferential radii of curvature decreased, whereas longitudinal radii of curvature increased. All of the strains increased from LV base to apex, resulting in a higher ejection fraction (EF) at the apex than at the base (70.9 +/- 0.4 vs. 62.4 +/- 0.4%; means +/- SE, P < 0.0001). When we looked around the circumference of the ventricle, the anterior part of the LV was the flattest and thinnest and showed the largest wall thickening (46.6 +/- 1.2%) but the lowest EF (64.7 +/- 0.5%). The posterior LV wall was thicker, more curved, and showed a lower wall thickening (32.8 +/- 1.0%) but a higher EF (71.3 +/- 0.5%). The regional contribution of the LV wall to the ejection of blood is thus highly variable and is not fully characterized by wall thickening alone. Differences in regional LV architecture and probably local stress are possible explanations for this marked functional nonuniformity.     

Impact of acute hypoxic pulmonary hypertension on LV diastolic function in healthy mountaineers at high altitude

In pulmonary hypertension right ventricular pressure overload leads to abnormal left ventricular (LV) diastolic function. Acute high-altitude exposure is associated with hypoxia-induced elevation of pulmonary artery pressure particularly in the setting of high-altitude pulmonary edema. Tissue Doppler imaging (TDI) allows assessment of LV diastolic function by direct measurements of myocardial velocities independently of cardiac preload. We hypothesized that in healthy mountaineers, hypoxia-induced pulmonary artery hypertension at high altitude is quantitatively related to LV diastolic function as assessed by conventional and TDI Doppler methods. Forty-one healthy subjects (30 men and 11 women; mean age 41 +/- 12 yr) underwent transthoracic echocardiography at low altitude (550 m) and after a rapid ascent to high altitude (4,559 m). Measurements included the right ventricular to right atrial pressure gradient (DeltaP(RV-RA)), transmitral early (E) and late (A) diastolic flow velocities and mitral annular early (E(m)) and late (A(m)) diastolic velocities obtained by TDI at four locations: septal, inferior, lateral, and anterior. At a high altitude, DeltaP(RV-RA) increased from 16 +/- 7 to 44 +/- 15 mmHg (P < 0.0001), whereas the transmitral E-to-A ratio (E/A ratio) was significantly lower (1.11 +/- 0.27 vs. 1.41 +/- 0.35; P < 0.0001) due to a significant increase of A from 52 +/- 15 to 65 +/- 16 cm/s (P = 0.0001). DeltaP(RV-RA) and transmitral E/A ratio were inversely correlated (r(2) = 0.16; P = 0.0002) for the whole spectrum of measured values (low and high altitude). Diastolic mitral annular motion interrogation showed similar findings for spatially averaged (four locations) as well as for the inferior and septal locations: A(m) increased from low to high altitude (all P < 0.01); consequently, E(m)/A(m) ratio was lower at high versus low altitude (all P < 0.01). These intraindividual changes were reflected interindividually by an inverse correlation between DeltaP(RV-RA) and E(m)/A(m) (all P < 0.006) and a positive association between DeltaP(RV-RA) and A(m) (all P < 0.0009). In conclusion, high-altitude exposure led to a two- to threefold increase in pulmonary artery pressure in healthy mountaineers. This acute increase in pulmonary artery pressure led to a change in LV diastolic function that was directly correlated with the severity of pulmonary hypertension. However, in contrast to patients suffering from some form of cardiopulmonary disease and pulmonary hypertension, in these healthy subjects, overt LV diastolic dysfunction was not observed because it was prevented by augmented atrial contraction. We propose the new concept of compensated diastolic (dys)function.     

Structure and torsion in the normal and situs inversus totalis cardiac left ventricle. II. Modeling cardiac adaptation to mechanical load

Mathematical models provide a suitable platform to test hypotheses on the relation between local mechanical stimuli and responses to cardiac structure and geometry. In the present model study, we tested hypothesized mechanical stimuli and responses in cardiac adaptation to mechanical load on their ability to estimate a realistic myocardial structure of the normal and situs inversus totalis (SIT) left ventricle (LV). In a cylindrical model of the LV, 1) mass was adapted in response to myofiber strain at the beginning of ejection and to global contractility (average systolic pressure), 2) cavity volume was adapted in response to fiber strain during ejection, and 3) myofiber orientations were adapted in response to myofiber strain during ejection and local misalignment between neighboring tissue parts. The model was able to generate a realistic normal LV geometry and structure. In addition, the model was also able to simulate the instigating situation in the rare SIT LV with opposite torsion and transmural courses in myofiber direction between the apex and base [Delhaas et al. (6)]. These results substantiate the importance of mechanical load in the formation and maintenance of cardiac structure and geometry. Furthermore, in the model, adapted myocardial architecture was found to be insensitive to fiber misalignment in the transmural direction, i.e., myofiber strain during ejection was sufficient to generate a realistic transmural variation in myofiber orientation. In addition, the model estimates that, despite differences in structure, global pump work and the mass of the normal and SIT LV are similar.     

Impaired subendocardial contractile myofiber function in asymptomatic aged humans, as detected using MRI

With aging, structural and functional changes occur in the myocardium without obvious impairment of systolic left ventricular (LV) function. Transmural differences in myocardial vulnerability for these changes may result in increase of transmural inhomogeneity in contractile myofiber function. Subendocardial fibrosis and impairment of subendocardial perfusion due to hypertension might change the transmural distribution of contractile myofiber function. The ratio of LV torsion to endocardial circumferential shortening (torsion-to-shortening ratio; TSR) during systole reflects the transmural distribution of contractile myofiber function. We investigated whether the transmural distribution of systolic contractile myofiber function changes with age. Magnetic resonance tissue tagging was performed to derive LV torsion and endocardial circumferential shortening. TSR was quantified in asymptomatic young [age 23.2 (SD 2.6) yr, n = 15] and aged volunteers [age 68.8 (SD 4.4) yr, n = 16]. TSR and its standard deviation were significantly elevated in the aged group [0.47 (SD 0.12) aged vs. 0.34 (SD 0.05) young; P = 0.0004]. In the aged group, blood pressure and the ratio of LV wall mass to end-diastolic volume were mildly elevated but could not be correlated to the increase in TSR. There were no significant differences in other indexes of systolic LV function such as end-systolic volume and ejection fraction. The elevated systolic TSR in the asymptomatic aged subjects suggests that aging is associated with local loss of contractile myofiber function in the subendocardium relative to the subepicardium potentially caused by subclinical pathological incidents.     

Relation of arterial stiffness to left ventricular structure and function in healthy women

Background

Interactions between the left ventricular (LV) and the arterial system, (ventricular-arterial coupling) are key determinants of cardiovascular function. However, most of studies covered multiple cardiovascular risk factors, which also contributed to the morphological and functional changes of LV. The aim of this study was to examine the relationship between arterial stiffness and LV structure and function in healthy women with a low burden of risk factors.

Methods

Healthy women from the Twins UK cohort (n?=?147, mean age was 54.07?±?11.90 years) were studied. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV). LV structure and function were assessed by two-dimensional speckle tracking echocardiography.

Results

cf-PWV was significantly associated with most measures of LV geometry and function, including relative wall thickness (RWT), E/e’ ratio, global circumferential and radial strain, apical rotation and LV twist (each p?<? 0.05), but bore no relation to global longitudinal strain. After adjustment for age, body mass index, blood pressure and heart rate, cf-PWV was significantly correlated with RWT, global circumferential strain, apical rotation and LV twist (β?=?0.011, ??0.484, 1.167 and 1.089, respectively, each p?≤? 0.05).

Conclusions

In healthy women with a low burden of risk factors, elevated arterial stiffness was intimately interwoven with increased LV twisting even before LV dysfunction becomes clinically evident.

     

Quantification of interventricular asynchrony during LBBB and ventricular pacing

The quantification of mechanical interventricular asynchrony (IVA) was investigated. In 12 dogs left bundle branch block (LBBB) was induced by radio frequency ablation. Left ventricular (LV) and right ventricular (RV) pressures were recorded before and after induction of LBBB and during LBBB + LV apex pacing at different atrioventricular (AV) delays. Four IVA measures were validated using computer simulations on experimentally obtained pressure signals. The most robust measure for IVA was the time delay between the upslope of the LV and RV pressure signals (DeltaT(up)), estimated by cross correlation. The induction of experimental LBBB decreased DeltaT(up) from -6.9 +/- 7.0 ms (RV before LV) to -33.9 +/- 7.6 ms (P < 0.05) in combination with a significant decrease of LV maximal first derivative of pressure development over time (dP/dt(max)). During LV apex pacing, DeltaT(up) increased with decreasing AV delay up to +20.9 +/- 14.6 ms (P < 0.05). Interventricular resynchronization (DeltaT(up) = 0 ms) significantly improved LV dP/dt(max) by 15.1 +/- 5.9%. QRS duration increased significantly after induction of LBBB but did not change during LV apex pacing. In conclusion, DeltaT(up) is a reliable measure of mechanical IVA, which adds valuable information concerning the nature of asynchronous activation of the ventricles.     

Theoretical analysis of the effects of a radial activation wave and twisting motion on the mechanics of the left ventricle

The mechanical effects resulting from the normal transmural delay of electrical depolarization of the myocardium are investigated. An activation sequence having a finite radial propagation velocity is introduced into the equations of ventricular mechanics. The resulting system of coupled integral equations is solved using a perturbation method based on the small ratio of transmural propagation time to cardiac period. Numerical calculations are performed using cavity pressure and volume waveforms characteristic of the canine left ventricle (LV), for both simultaneous and delayed activation of fiber layers. The results show that a finite transmural electrical propagation velocity tends to: (i) equalize the transmural distribution of sarcomere length during systole; (ii) equalize the transmural distribution of fiber external work/vol; and (iii) insignificantly affect myocardial tissue pressure. Calculations are also performed to investigate the mechanical effects resulting from the application of an externally applied moment that prevents LV torsion. Those results are highly dependent on the transmural distribution of sarcomere length in the stress-free reference state (unloaded diastole). When we assume a uniform distribution, then normal torsion acting with normal activation delay tends to: (i) increase the magnitude of fiber strain in the subendocardium and decrease it in the subepicardium; (ii) equalize the transmural distribution of fiber external work/vol; and (iii) lower myocardial tissue pressure. The normally occurring transmural delay of activation tends to lessen endocardial O2 demand, while the normally occurring torsion further lessens that demand and improves O2 supply.     

Aging alters patterns of regional nonuniformity in LV strain relaxation: a 3-D MR tissue tagging study

Although age-related impairment of diastolic function is well documented, patterns of regional tissue relaxation impairment with age have not been characterized. MRI tissue tagging with a regional three-dimensional (3-D) analysis was performed in 15 younger (age 19-26 yr) and 16 older (age 60-74 yr) normal, healthy volunteers. The peak rate of relaxation of circumferential strain (RC) was decreased in the older group (on average, 105 +/- 28 vs. 163 +/- 18 %/s for older vs. younger, mean +/- SD, P < 0.001) to a greater extent in the lateral wall than in the septum (P = 0.016) and to a greater extent in the apex than in the base (P < 0.001). Peak rate of relaxation of longitudinal strain (RL) was also reduced with age (94 +/- 27 vs. 155 +/- 18 %/s, P < 0.001) to a greater extent in the apex than in the base (P < 0.001). Both RC and RL were greater in the apex than in the base only in the younger subjects (P < 0.001 for each). Peak rate of torsion reversal (RT) was reduced with age (74 +/- 16 vs. 91 +/- 15 degrees/s, P = 0.006) to a greater extent in the base than in the apex (P = 0.035). An increase in regional asynchrony in time to RC and time to RL (P < 0.001 for each), but not time to RT, occurred with age. Thus patterns of regional nonuniformity of myocardial relaxation are altered in a consistent fashion with aging.