Pulse arrival time variation as a non-invasive marker of acute response to cardiac resynchronization therapy.

AIMS: Successful cardiac resynchronization therapy (CRT) shortens the pre-ejection period (PEP) which is prolonged in the left bundle branch block (LBBB). In a combined animal and patient study, we investigated if changes in the pulse arrival time (PAT) could be used to measure acute changes in PEP during CRT implantation and hence be used to evaluate acute CRT response non-invasively and in real time. METHODS AND RESULTS: In six canines, a pulse transducer was attached to a lower limb and PAT was measured together with left ventricular (LV) pressure by micromanometer at baseline, after induction of LBBB and during biventricular pacing. Time-to-peak LV dP/dt (Td) was used as a surrogate for PEP. In twelve LBBB patients during implantation of CRT, LV and femoral pressures were measured at baseline and during five different pacing configurations. PAT increased from baseline (277 ± 9 ms) to LBBB (313 ± 16 ms, P < 0.05) and shortened with biventricular pacing (290 ± 16 ms, P < 0.05) in animals. There was a strong relationship between changes in PAT and Td in patients (r2 = 0.91). Two patients were classified as non-responders at 6 months follow-up. CRT decreased PAT from 320 ± 41 to 298 ± 39 ms (P < 0.05) in the responders, while PAT increased by 5 and 8 ms in the two non-responders. CONCLUSION: This proof-of-concept study indicates that PAT can be used as a simple, non-invasive method to assess the acute effects of CRT in real time with the potential to identify long-term response in patients.

Determinants of left atrial reservoir and pump strain and use of atrial strain for evaluation of left ventricular filling pressure.

AIMS: The aim of this study is to investigate determinants of left atrial (LA) reservoir and pump strain and if these parameters may serve as non-invasive markers of left ventricular (LV) filling pressure. METHODS AND RESULTS: In a multicentre study of 322 patients with cardiovascular disease of different aetiologies, LA strain and other echocardiographic parameters were compared with invasively measured LV filling pressure. The strongest determinants of LA reservoir and pump strain were LV global longitudinal strain (GLS) (r-values 0.64 and 0.51, respectively) and LV filling pressure (r-values -0.52 and -0.57, respectively). Left atrial volume was another independent, but weaker determinant of both LA strains. For both LA strains, association with LV filling pressure was strongest in patients with reduced LV ejection fraction. Left atrial reservoir strain <18% and LA pump strain <8% predicted elevated LV filling pressure better (P < 0.05) than LA volume and conventional Doppler parameters. Accuracy to identify elevated LV filling pressure was 75% for LA reservoir strain alone and 72% for pump strain alone. When combined with conventional parameters, accuracy was 82% for both LA strains. In patients with normal LV systolic function by GLS, LA pump strain >14% identified normal LV filling pressure with 92% accuracy. CONCLUSION: Left atrial reservoir and pump strain are determined predominantly by LV GLS and filling pressure. Accuracy of LA strains to identify elevated LV filling pressure was best in patients with reduced LV systolic function. High values of LA pump strain, however, identified normal LV filling pressure with good accuracy in patients with normal systolic function.

Noninvasive assessment of intraventricular pressure difference in left ventricular dyssynchrony using vector flow mapping.

Diastolic intraventricular pressure difference (IVPD) reflects left ventricular (LV) diastolic function. The relative pressure imaging (RPI) enables the noninvasive quantification of IVPD based on vector flow mapping (VFM) and visualization of regional pressure distribution. LV dyssynchrony causes deterioration of cardiac performance. However, it remains unclear how IVPD is modulated by LV dyssynchrony. LV dyssynchrony was created in ten open-chest dogs by right ventricular (RV) pacing. The other ten dogs undergoing right atrial (RA) pacing set at the similar heart rate with RV pacing were used as controls. Echocardiographic images were acquired at baseline and during pacing simultaneously with LV pressure measurement by a micromanometer. Pressure difference (ΔP) was computed between the apex and the base of the LV inflow tract during a cardiac cycle by RPI and ΔP during isovolumic relaxation time (ΔPIRT), a parameter of diastolic suction, and that during early filling phase (ΔPE) were measured. During RV pacing, stroke volume (SV) and ΔPIRT decreased significantly, while ΔPE did not change compared to the baseline. During RA pacing, SV, ΔPIRT and ΔPE did not change significantly. ΔPIRT tended to correlate with -dP/dtmin and end-systolic volume, and significantly correlated with ejection fraction. IVPD during isovolumic relaxation time was decreased by LV dyssynchrony, while IVPD during early filling phase was not. A reduction of diastolic suction is observed in LV dyssynchrony and is significantly related to a decrease in SV.

Clinical Significance of Late Enhancement and Regional Wall Remodeling Assessed by 3T Magnetic Resonance Imaging.

BACKGROUND: Clinical follow-up studies comparing left ventricular (LV) function and late gadolinium enhancement (LGE) by high-field 3T cardiac magnetic resonance (CMR) are of general interest due to the increased use of 3T scanners. In this study, the occurrence of LGE and LV regional wall remodeling (RWR) was assessed by 3T CMR in patients undergoing coronary angiography for suspected stable coronary artery disease (CAD). MATERIALS AND METHODS: Analysis of myocardial viability by LGE was performed at the segmental level. LVRWR was identified by a significant reduction (≥50%) of the wall thickness. Major adverse cardiovascular events (MACE) were registered during a median follow-up time of 58 (45-62) months. RESULTS: Of the 87 patients (59 ± 9 years; 13 women) enrolled, nonviable myocardium was detected in 35 (40%) and significant CAD in 69 (79%). Nonviable myocardium was correlated to angiographic significant stenosis or occlusion. LVRWR was significantly related to a higher number of nonviable segments compared to those without LVRWR: ie, 6.0 ± 3.2 segments versus 2.6 ± 1.3; P < 0.001. In the nonviable group, LVEF was significantly reduced (P < 0.001) compared to the viable group: ie, 50 ± 16% versus 61 ± 8%, and LVEF was significantly correlated to the number of nonviable segments (r = -0.66, P < 0.001). The number of nonviable segments by LGE was significantly associated with MACE by an odds ratio of 1.25 (95% CI, 1.05-1.49; P = 0.013). CONCLUSION: The presence of nonviable myocardium as detected by LGE at 3T CMR is associated with angiographically significant CAD, and is associated with the development of LVRWR and reduced LVEF. Assessing the extent of nonviable myocardium by both LGE and LVRWR at the segmental level may therefore contribute to individualized risk stratification and treatment strategies.

Energy loss in the left ventricle obtained by vector flow mapping as a new quantitative measure of severity of aortic regurgitation: a combined experimental and clinical study.

AIMS: In aortic regurgitation (AR), energy loss (EL) produced by inefficient turbulent flow may be a burden to the heart predicting decompensation. We attempted to quantify EL in AR induced in an acute dog model and in patients with chronic AR using novel echocardiographic method vector flow mapping (VFM). METHODS AND RESULTS: In 11 anaesthetized open-chest dogs, AR was induced by distorting the aortic valve with a pigtail catheter, in totally 20 cases. Regurgitant fraction was determined using pulsed Doppler echocardiography, <30% considered mild to moderate (Group 1, n = 11) and ≥30% moderate to severe (Group 2, n = 9). The clinical study consisted of 22 patients with various degrees of AR; 11 mild to moderate (Group 1) and 11 moderate to severe (Group 2), and compared with 12 normals. VFM is based on continuity equation applied to colour Doppler and speckle tracking velocities, acquired from apical long-axis image. EL was calculated frame by frame, averaged from three beats. In the dog study, diastolic EL increased significantly with severity of AR (baseline vs. Group 1 vs. Group 2: 3.8 ± 1.6 vs. 13.0 ± 5.0 vs. 22.4 ± 14.0 [J/(m s)], ANOVA P = 0.0001). Similar to dogs, diastolic EL also increased in humans by the severity of AR (control vs. Group 1 vs. Group 2: 2.8 ± 1.5 vs. 14.3 ± 11.5 vs. 18.6 ± 2.3 [J/(m s)], ANOVA P = 0.001). CONCLUSION: VFM provides a promising method to quantify diastolic EL in AR. Diastolic EL increases in AR proportional to its severity. EL may be useful to determine the severity of disease from the aspect of cardiac load.

Increased LV apical untwist during preload reduction in healthy humans: an echocardiographic speckle tracking study during lower body negative pressure.

We sought to investigate the effect of reduced preload on left ventricle (LV) untwist and early diastolic filling in healthy individuals. Twelve healthy men, 22 (22, 23) years of age, were examined at rest and during applied lower body negative pressure (LBNP) of -20 mmHg and -40 mmHg, respectively. Regional untwist and untwist rate during IVRT were calculated at LV basal, papillary, subpapillary, and apical short axis levels by two dimensional speckle tracking echocardiography. Left ventricle early diastolic filling was assessed by transmitral E-wave (E) peak velocity by pulsed Doppler and flow propagation velocity (Vp) by color M-mode Doppler and early diastolic pulsed Doppler tissue velocities (E') from septal and lateral mitral annulus. From rest to LBNP -40 mmHg, the LV untwist and untwist rate at subpapillary level increased from 2.3 (1.4, 3.5) to 4.5 (3.1, 7.6) degrees and from -36 (-51, -25) to -69 (-127, -42) °/s (P < 0.001, P = 0.003), respectively, while apical untwist and untwist rate increased from 3.9 (2.3, 4.3) to 7.6 (6.4, 10.5) degrees and from -51 (-69, -40) to -118 (-170, -84) °/s (P < 0.001, P < 0.001), respectively. Since untwist and untwist rate at the basal level were unchanged, this created markedly larger base to apical untwist and untwist rate gradients from rest to LBNP -40 mmHg. E, Vp, and E' were reduced by 34, 32, and 39%, respectively. LV untwist and untwist rate during IVRT were increased at apical levels, which might be a physiological mechanism to minimize the impairment in LV early diastolic filling during preload reduction.

Regional LV deformation in healthy individuals during isovolumetric contraction and ejection phases assessed by 2D speckle tracking echocardiography.

PURPOSE: The main purpose of the this human study was by speckle tracking imaging to characterize the regional and temporal distribution of normal left ventricular (LV) deformation and the LV geometry during isovolumetric contraction (IVC) and the ejection phase. METHODS: Twelve healthy young men [22 (2·3) years] were included. Longitudinal and circumferential strain and local twist angle were measured at four LV short-axis levels: basal, papillary, subpapillary and apical level during IVC and ejection phases. In addition, LV length from apex to the atrio-ventricular level, two diameters at LV basal short-axis level and atrio-ventricular plane displacement (AVPD) were measured to characterize LV shape during IVC. RESULTS: During IVC, longitudinal and circumferential shortening was demonstrated at all four short-axis levels from base to apex, while the LV made a basal counterclockwise and apical clockwise rotation representing untwist. In addition, there was a reduction in LV length and changes in short-axis diameters at basal level and AVPD from end-diastole to end-IVC, reflecting that the LV changed from an oval to a more spherical shape. At end-systole, longitudinal and circumferential shortening and local twist angle were significantly increased towards apex (P<0·05). CONCLUSION: This study demonstrated that the IVC in healthy humans is characterized by regional longitudinal and circumferential shortening and LV untwist, which occurs parallel to geometric changes of the LV into a spherical shape. During ejection, increased regional gradients of LV deformation towards apex in LV longitudinal and circumferential shortening and local and net twist angle were demonstrated.

Reduced preload elicits increased LV twist in healthy humans: an echocardiographic speckle-tracking study during lower body negative pressure.

BACKGROUND: In normal left ventricles (LV), counterclockwise rotation (CCR) and net twist angle (NTA) have shown important roles during ejection. We investigated the effect of reduced preload by lower body negative pressure (LBNP) on CCR and NTA. METHODS AND RESULTS: Twelve healthy men were examined at rest, LBNP -20 and -40 mmHg. By two-dimensional speckle-tracking imaging, we measured rotation at four short-axis levels: basal, papillary, sub-papillary and apical. LV NTA was calculated as apex-to-base difference in rotation. Additionally, regional end-diastolic (EDA) and end-systolic area (ESA) were measured and regional area fraction (RAF) calculated [(EDA-ESA)/EDA] × 100). From rest to LBNP -40 mmHg, rotation at basal and papillary levels was unchanged. At sub-papillary level, rotation increased from 3·2 ± 3·6 to 5·8 ± 4·7° (P<0·05), while apical rotation increased from 9·3 ± 3·4 to 12·8 ± 4·7° (P<0·05). Correspondingly, LV NTA increased for each load reduction by 1·6 ± 1·8° (P<0·05) and 4·2 ± 2·3° (P<0·05). RAF increased at sub-papillary and apical levels from 57·6 ± 3·7 to 64·7 ± 8·8% and from 63·4 ± 8·8 to 74·8 ± 10·1%, respectively (P<0·05). From rest to LBNP -40 mmHg, changes in rotation and RAF correlated significantly at sub-papillary and apical levels (r = 0·94, P<0·01, and r = 0·63, P<0·05, respectively). CONCLUSIONS: Preload reduction in normal LV elicits increased systolic CCR and regional area fraction at sub-papillary and apical levels as well as net twist angle. These findings might be of physiological importance to minimize reduction in stroke volume and maintain arterial blood pressure.

Left ventricular systolic and diastolic function in asymptomatic patients with moderate aortic stenosis.

Tissue Doppler imaging (TDI) has improved the ability to detect subclinical changes in left ventricular (LV) function. The aim of this study was to investigate if asymptomatic patients with moderate aortic stenosis (AS) had impaired LV systolic and diastolic function. Fifty patients (mean age 65 +/- 12 years) recruited into the multicenter Simvastatin + Ezetimibe in Aortic Stenosis (SEAS) study with aortic peak velocities of 2.5 and 4.0 m/s were compared with 26 healthy subjects (mean age 64 +/- 12 years) (p = NS). Peak systolic tissue velocities and strain were measured at 8 LV locations and averaged. Early diastolic tissue velocity from the septal mitral annulus (E'sep) was measured as an index of LV relaxation. The ratio of early diastolic transmitral pulsed Doppler (E) to E'sep (E/E'sep) was calculated as an index of LV filling pressure. Peak systolic tissue velocity (4.1 +/- 1.0 vs 4.8 +/- 1.1 cm/s, p <0.01) and strain (-16.6 +/- 2.7% vs -17.9 +/- 2.0%, p <0.05) were decreased in patients with AS compared with controls. E'sep was decreased (4.9 +/- 1.0 vs 5.8 +/- 1.3 cm/s, p <0.01) and E/E'sep was increased (17.4 +/- 9.7 vs 11.7 +/- 3.8, p <0.01) in the AS group compared with the control group. In conclusion, asymptomatic patients with moderate AS have impaired LV systolic function as measured by reduced peak systolic tissue velocity and strain. Augmented LV filling pressure measured by E/E'sep and impaired LV relaxation measured by reduced E'sep also indicate diastolic dysfunction in these patients.

LV systolic impairment in patients with asymptomatic coronary heart disease and type 1 diabetes is related to coronary atherosclerosis, glycaemic control and advanced glycation endproducts.

AIMS: To evaluate whether heart failure in type 1 diabetes is linked to poor glycaemic control, coronary atherosclerosis or advanced glycation endproducts (AGEs). METHODS: Twenty six patients with type 1 diabetes (mean duration 32+/-5 years), and 16 age matched controls were recruited. Mean HbA(1c) through 18 years (HbA(1c)18), serum levels of AGEs and coronary atherosclerotic burden (CAB) were determined by IVUS. Peak tissue velocities and strain by tissue Doppler imaging were measured in 12 LV regions as an evaluation of LV function. RESULTS: Systolic tissue velocity was inversely correlated to CAB (r=0.53, p<0.01), to HbA(1c)18 (r=0.46, p<0.05) and to the duration of diabetes (r=0.46, p<0.05). Systolic strain was inversely correlated to HbA(1c)18 (r=0.45, p<0.05), to duration of diabetes (r=0.41, p<0.05), and tended to correlate with AGEs (r=0.37, p=0.07). In multiple regression analyses, CAB and HbA(1c)18 were significant independent predictors for systolic velocity, while AGEs and duration of diabetes were significant predictors of systolic strain. CONCLUSION: LV systolic function was impaired by increasing coronary atherosclerosis and worsening of glycaemic control. AGEs might be another mechanism for the increased risk of heart failure in type 1 diabetes.

Failure to prevent progressive dilation of ascending aorta by aortic valve replacement in patients with bicuspid aortic valve: comparison with tricuspid aortic valve.

BACKGROUND: Patients with bicuspid aortic valve (BAV) have been frequently complicated with ascending aortic dilation possibly because of hemodynamic burdens by aortic stenosis (AS) or regurgitation (AR) or congenital fragility of the aortic wall. METHODS AND RESULTS: To clarify if the aortic dilation could be prevented by aortic valve replacement (AVR) in BAV patients, we studied 13 BAV (8 AR dominant, 5 AS dominant) and 14 tricuspid aortic valve (TAV) patients (7 AR, 7 AS) by echocardiography before and after AVR (9.7+/-4.8 years). We also studied 18 BAV (11 AR, 7 AS) without AVR. Diameters of the sinuses of Valsalva, sinotubular junction and the proximal aorta were measured. The annual dilation rate was calculated by dividing changes of diameters during the follow-up period by the body surface area and the observation interval. We found that aortic dilation in BAV patients tended to be faster than that in TAV patients, although a significant difference was found only at the proximal aorta (0.18+/-0.08 versus -0.08+/-0.08 mm/(m2/year), P=0.03). BAV patients with and without AVR showed similar progressive dilation. AR dominant group showed tendency of more progressive dilation than AS dominant group in BAV, although it did not reach statistical significance. TAV patients did not show further aortic dilation after AVR. CONCLUSIONS: AVR could not prevent progressive aortic dilation in BAV. Since the aorta did not dilate in TAV, progressive aortic dilation in BAV seems mainly due to the fragility of the aortic wall rather than hemodynamic factors.

Quantitative assessment of short axis wall motion using myocardial strain rate imaging.

Although left ventricular wall motion has been usually assessed with four-point scale (1 = normal; 2 = hypokinesis; 3 = akinesis; 4 = dyskinesis) based on the visual assessment, this method is only qualitative and subjective. Recently, a new echocardiographic system that enables calculation of myocardial strain rate based on tissue Doppler information has been developed. We investigated whether myocardial strain rate could quantify regional myocardial contraction in 17 patients with and without wall motion abnormalities including 6 patients undergoing dobutamine stress echocardiography. Left ventricular short-axis wall motion was assessed with standard two-dimensional echocardiography at basal, mid-ventricular, and apical levels. The same levels were imaged with tissue Doppler method to determine regional myocardial strain rate. Sixty-four segments were judged normokinesis, 53 segments hypokinesis, and 18 segments akinesis at rest; 16 segments were judged normokinesis and 6 segments hypokinesis at stress. No segments characterized dyskinesis. Strain rates of normokinetic, hypokinetic, and akinetic wall segments at rest were significantly different each other (-2.0 +/- 0.6 for normokinesis,-0.6 +/- 0.5 for hypokinesis,P < 0.0001 vs. normokinesis, and-0.008 +/- 0.3 for akinesis, P < 0.0001 vs. normokinesis and hypokinesis). Further, strain rates well reflected the change in wall motion induced by dobutamine challenge: strain rates in the 15 segments revealing augmented wall motion changed from -2.0 +/- 0.7 to -4.7 +/- 1.7 (1/sec) (P < 0.0001) and those in the 7 segments revealing deteriorated or unchanged wall motion changed from -2.1 +/- 1.0 to -1.7 +/- 0.8 (1/sec) (P < 0.05). In conclusion, strain rate agreed well with assessed wall motion. Strain rate imaging may be a new powerful tool to quantify regional wall contraction.

Distinction between well-differentiated liposarcoma and intramuscular lipoma by power Doppler ultrasonography.

BACKGROUND: This study evaluates the feasibility of ultrasonography in the distinction between well-differentiated liposarcoma (WDLS) and intramuscular lipoma (IL). MATERIALS AND METHODS: Three WDLSs and 9 ILs were included. Gray scale images were assessed for echogenicity, textural pattern and margins. Power Doppler ultrasonography was used to assess the number of detectable flow velocity signals in a 3 x 3 cm area. Furthermore, the ratio of the area occupied by colour flow signals relative to the selected area was determined. RESULTS: Gray scale images showed no differences between WDLSs and ILs. However, power Doppler showed more than 2 flow velocity signals in all WDLSs, whereas only 11% of the ILs had 2 signals. In all WDLSs, colour flow signals occupied more than 30% of the selected area. In contrast, ILs were characterized by a low color-dot ratio. Histologically, increased vascularity was found close to malignant cell invasions. CONCLUSION: Power Doppler ultrasonography is feasible to evaluate increased vascularity and thus differentiate WDLSs from ILs.

Mechanisms of diastolic intraventricular regional pressure differences and flow in the inflow and outflow tracts.

OBJECTIVES: We sought to investigate the mechanisms of left ventricular (LV) intracavitary early diastolic flow during changes in contractility and loading. BACKGROUND: There is limited understanding of how intracavitary flow velocities relate to intraventricular driving pressures. METHODS: In 12 anesthetized dogs, we measured pressures in the left atrium (LA), LV at the mitral tip, apex, and subaortic region; intraventricular velocities by color M-mode Doppler echocardiography (CMD); and volume by sonomicrometry. We also investigated responses to isoprenaline, ischemic failure, and volume loading. RESULTS: During rapid, early filling, the mitral to apical pressure gradient (LVP(mitral-apex)) correlated with the peak mitral to apical velocity (r = 0.92). The LVP(mitral-apex) increased from 1.4 +/- 0.6 (SD) to 3.2 +/- 1.8 mm Hg during isoprenaline (p < 0.05) and decreased to 0.6 +/- 0.5 during ischemic failure (p < 0.01). The pressure gradient correlated positively with the time constant of isovolumic relaxation (tau) (r = 0.82) and negatively with LV end-systolic volume (ESV) (r = -0.77). Volume loading increased LA pressure, tau, and ESV, but caused no significant change in LVP(mitral-apex). At baseline and during isoprenaline, tau was shorter (p < 0.05) at the apex than at the base. When the mitral to apical gradient approached zero, filling velocities were directed toward the LV outflow tract, and a pressure gradient was established between the apex and subaortic region. CONCLUSIONS: Changes in LVP(mitral-apex) induced by inotropic stimuli, loading, and ischemia appeared to reflect dependency of the pressure gradient on the rate of relaxation, ESV, and LA pressure. Regional differences in the rate of relaxation may also contribute to intraventricular pressure gradients. These findings have implications for how to interpret intraventricular filling in a clinical context.

Postsystolic shortening in ischemic myocardium: active contraction or passive recoil?

BACKGROUND: Postsystolic shortening in ischemic myocardium has been proposed as a marker of tissue viability. Our objectives were to determine if postsystolic shortening represents active fiber shortening or passive recoil and if postsystolic shortening may be quantified by strain Doppler echocardiography (SDE). METHODS AND RESULTS: In 15 anesthetized dogs, we measured left ventricular (LV) pressure, myocardial long-axis strains by SDE, and segment lengths by sonomicrometry before and during LAD stenosis and occlusion. Active contraction was defined as elevated LVP and stress during postsystolic shortening when compared with the fully relaxed ventricle at similar segment lengths. LAD stenosis decreased systolic shortening from 10.4+/-1.2% to 5.9+/-0.9% (P<0.05), whereas postsystolic shortening increased from 1.1+/-0.3% to 4.2+/-0.7% (P<0.05). In hypokinetic and akinetic segments, LV pressure-segment length and LV stress-segment length loop analysis indicated that postsystolic shortening was active. LAD occlusion resulted in dyskinesis, and postsystolic shortening increased additionally to 8.2+/-1.0% (P<0.05). After 3 to 5 minutes with LAD occlusion, the dyskinetic segment generated no active stress, and the postsystolic shortening was attributable to passive recoil. Elevation of afterload caused hypokinetic segments to become dyskinetic, and postsystolic shortening remained partly active. Postsystolic shortening by SDE correlated well with sonomicrometry (r=0.83, P<0.01). CONCLUSIONS: Postsystolic shortening is a relatively nonspecific feature of ischemic myocardium and may occur in dyskinetic segments by an entirely passive mechanism. However, in segments with systolic hypokinesis or akinesis, postsystolic shortening is a marker of actively contracting myocardium. SDE was able to quantify postsystolic shortening and might represent a clinical method for identifying actively contracting and hence viable myocardium.