Effects of alcohol septal ablation on coronary microvascular function and myocardial energetics in hypertrophic obstructive cardiomyopathy.

This study investigated the effects of alcohol septal ablation (ASA) on microcirculatory function and myocardial energetics in patients with hypertrophic cardiomyopathy (HCM) and left ventricular outflow tract (LVOT) obstruction. In 15 HCM patients who underwent ASA, echocardiography was performed before and 6 mo after the procedure to assess the LVOT gradient (LVOTG). Additionally, [(15)O]water PET was performed to obtain resting myocardial blood flow (MBF) and coronary vasodilator reserve (CVR). Changes in LV mass (LVM) and volumes were assessed by cardiovascular magnetic resonance imaging. Myocardial oxygen consumption (MVo(2)) was evaluated by [(11)C]acetate PET in a subset of seven patients to calculate myocardial external efficiency (MEE). After ASA, peak LVOTG decreased from 41 ± 32 to 23 ± 19 mmHg (P = 0.04), as well as LVM (215 ± 74 to 169 ± 63 g; P < 0.001). MBF remained unchanged (0.94 ± 0.23 to 0.98 ± 0.15 ml·min(-1)·g(-1); P = 0.45), whereas CVR increased (2.55 ± 1.23 to 3.05 ± 1.24; P = 0.05). Preoperatively, the endo-to-epicardial MBF ratio was lower during hyperemia compared with rest (0.80 ± 0.18 vs. 1.18 ± 0.15; P < 0.001). After ASA, the endo-to-epicardial hyperemic (h)MBF ratio increased to 1.03 ± 0.26 (P = 0.02). ΔCVR was correlated to ΔLVOTG (r = -0.82; P < 0.001) and ΔLVM (r = -0.54; P = 0.04). MEE increased from 15 ± 6 to 20 ± 9% (P = 0.04). Coronary microvascular dysfunction in obstructive HCM is at least in part reversible by relief of LVOT obstruction. After ASA, hMBF and CVR increased predominantly in the subendocardium. The improvement in CVR was closely correlated to the absolute reduction in peak LVOTG, suggesting a pronounced effect of LV loading conditions on microvascular function of the subendocardium. Furthermore, ASA has favorable effects on myocardial energetics.

Increased left ventricular torsion in hypertrophic cardiomyopathy mutation carriers with normal wall thickness.

BACKGROUND: Increased left ventricular (LV) torsion has been observed in patients with manifest familial hypertrophic cardiomyopathy (HCM), and is thought to be caused by subendocardial dysfunction. We hypothesize that increased LV torsion is already present in healthy mutation carriers with normal wall thickness. METHODS: Seventeen carriers with an LV wall thickness <10 mm, and seventeen age and gender matched controls had cardiovascular magnetic resonance (CMR) cine imaging and tissue tagging. LV volumes and mass were calculated from the cine images. LV torsion, torsion rate, endocardial circumferential strain and torsion-to-endocardial-circumferential-shortening (TECS) ratio, which reflects the transmural distribution in contractile function, were determined using tissue tagging. RESULTS: LV volumes, mass and circumferential strain were comparable between groups, whereas LV ejection fraction, torsion and TECS-ratio were increased in carriers compared to controls (63 ± 3% vs. 60 ± 3%, p = 0.04, 10.1 ± 2.5° vs. 7.7 ± 1.2°, p = 0.001, and 0.52 ± 0.14°/% vs. 0.42 ± 0.10°/%, p = 0.02, respectively). CONCLUSIONS: Carriers with normal wall thickness display increased LV torsion and TECS-ratio with respect to controls, which might be due to subendocardial myocardial dysfunction. As similar abnormalities are observed in patients with manifest HCM, the changes in healthy carriers may be target for clinical intervention to delay or prevent the onset of hypertrophy.

Determinants of myocardial energetics and efficiency in symptomatic hypertrophic cardiomyopathy.

PURPOSE: Next to hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by alterations in myocardial energetics. A small number of studies have shown that myocardial external efficiency (MEE), defined by external work (EW) in relation to myocardial oxidative metabolism (MVO(2)), is reduced. The present study was conducted to identify determinants of MEE in patients with HCM by use of dynamic positron emission tomography (PET) and cardiovascular magnetic resonance imaging (CMR). METHODS: Twenty patients with HCM (12 men, mean age: 55.2 + or - 13.9 years) and 11 healthy controls (7 men, mean age: 48.1 + or - 10 years) were studied with [(11)C]acetate PET to assess MVO(2). CMR was performed to determine left ventricular (LV) volumes and mass (LVM). Univariate and multivariate analyses were employed to determine independent predictors of myocardial efficiency. RESULTS: Between study groups, MVO(2) (controls: 0.12 + or - 0.04 ml x min(-1) x g(-1), HCM: 0.13 + or - 0.05 ml x min(-1) x g(-1), p = 0.64) and EW (controls: 9,139 + or - 2,484 mmHg x ml, HCM: 9,368 + or - 2,907 mmHg x ml, p = 0.83) were comparable, whereas LVM was significantly higher (controls: 99 + or - 21 g, HCM: 200 + or - 76 g, p < 0.001) and MEE was decreased in HCM patients (controls: 35 + or - 8%, HCM: 21 + or - 10%, p < 0.001). MEE was related to stroke volume (SV), LV outflow tract gradient, NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP) and serum free fatty acid levels (all p < 0.05). Multivariate analysis revealed that SV (ss = 0.74, p < 0.001) and LVM (ss = -0.43, p = 0.013) were independently related to MEE. CONCLUSION: HCM is characterized by unaltered MVO(2), impaired EW generation per gram of myocardial tissue and subsequent deteriorated myocardial efficiency. Mechanical external efficiency could independently be predicted by SV and LVM.

How do hypertrophic cardiomyopathy mutations affect myocardial function in carriers with normal wall thickness? Assessment with cardiovascular magnetic resonance.

BACKGROUND: Clinical data on myocardial function in HCM mutation carriers (carriers) is sparse but suggests that subtle functional abnormalities can be measured with tissue Doppler imaging before the development of overt hypertrophy. We aimed to confirm the presence of functional abnormalities using cardiovascular magnetic resonance (CMR), and to investigate if sensitive functional assessment could be employed to identify carriers. RESULTS: 28 carriers and 28 controls were studied. Global left atrial (LA) and left ventricular (LV) dimensions, segmental peak systolic circumferential strain (SCS) and peak diastolic circumferential strain rate (DCSR), as well as the presence of late Gadolinium enhancement (LGE) were determined with CMR. Septal and lateral myocardial velocities were measured with echocardiographic tissue Doppler imaging. LV mass and volumes were comparable between groups. Maximal septal to lateral wall thickness ratio (SL ratio) was larger in carriers than in controls (1.3+/-0.2 versus 1.1+/-0.1, p<0.001). Also, LA volumes were larger in carriers compared to controls (p<0.05). Both peak SCS (p<0.05) and peak DCSR (p<0.01) were lower in carriers compared to controls, particularly in the basal lateral wall. Focal LGE was present in 2 carriers and not in controls. The combination of a SL ratio>1.2 and a peak DCSR<105%.s-1 was present in 45% of carriers and in none of the controls, yielding a positive predictive value of 100%. Two carriers and 18 controls had a SL ratio<1.2 and peak DCSR>105%.s-1, yielding a negative predictive value of 90%. With multivariate analysis, HCM mutation carriership was an independent determinant of reduced peak SCS and peak DCSR. CONCLUSIONS: HCM mutation carriership is an independent determinant of reduced peak SCS and peak DCSR when LV wall thickness is within normal limits, and is associated with increased LA volumes and SL ratio. Using SL ratio and peak DCSR has a high accuracy to identify carriers. However, since carriers also display structural abnormalities and focal LGE, we advocate to also evaluate morphology and presence of LGE when screening for carriers.

Loss of opposite left ventricular basal and apical rotation predicts acute response to cardiac resynchronization therapy and is associated with long-term reversed remodeling.

BACKGROUND: Normal left ventricular (LV) torsion is caused by opposite basal and apical rotation. Opposite rotation can be lost in heart failure, but might be restored by pacing; therefore, the predictive value of the loss of opposite base-apex rotation in heart failure patients for the response to cardiac resynchronization therapy (CRT) was studied. METHODS AND RESULTS: In 34 CRT candidates and 12 controls, basal and apical LV rotations were calculated using magnetic resonance image tagging. Loss of opposite rotation was quantified by the correlation between both rotation curves: a negative correlation indicates normal, opposite rotation and a positive correlation indicates that base and apex rotate in the same direction. In patients, LV pressure was measured invasively during biventricular stimulation. Acute response to CRT was defined by >10% increase in dP/dt(max) relative to baseline. LV volume was determined at baseline and 8 months follow-up using echocardiography. The base-apex rotation correlation (BARC) was significantly higher in acute responders (n=22) than in nonresponders (n=12) and controls (0.64+/-0.51, -0.23+/-0.67, and -0.68+/-0.22, respectively; P=.001). The sensitivity and specificity for prediction of acute response were 82% and 83%, respectively, at a cutoff value of 0.5. At follow-up, volumes could be analyzed in 18 patients. In the group with BARC >0.5, end-diastolic volume decreased by 7% (NS), end-systolic volume by 16%, and ejection fraction increased by 28% (both P=.02), whereas in the group with BARC <0.5, no significant changes were observed. CONCLUSIONS: The loss of opposite base-apex rotation in patients eligible for CRT is an excellent predictor of acute response and is associated with LV reverse remodeling.

Comparison of 2D and 3D calculation of left ventricular torsion as circumferential-longitudinal shear angle using cardiovascular magnetic resonance tagging.

PURPOSE: To compare left ventricular (LV) torsion represented as the circumferential-longitudinal (CL) shear angle between 2D and 3D quantification, using cardiovascular magnetic resonance (CMR). METHODS: CMR tagging was performed in six healthy volunteers. From this, LV torsion was calculated using a 2D and a 3D method. The cross-correlation between both methods was evaluated and comparisons were made using Bland-Altman analysis. RESULTS: The cross-correlation between the curves was r2 = 0.97 +/- 0.02. No significant time-delay was observed between the curves. Bland-Altman analysis revealed a significant positive linear relationship between the difference and the average value of both analysis methods, with the 2D results showing larger values than the 3D. The difference between both methods can be explained by the definition of the 2D method. CONCLUSION: LV torsion represented as CL shear quantified by the 2D and 3D analysis methods are strongly related. Therefore, it is suggested to use the faster 2D method for torsion calculation.

Regional assessment of left ventricular torsion by CMR tagging.

PURPOSE: To introduce a standardized method for calculation of left ventricular torsion by CMR tagging and to determine the accuracy of torsion analysis in regions using an analytical model. METHODS: Torsion between base and apex, base and mid, and mid and apex levels was calculated using CSPAMM tagging and Harmonic Phase tracking. The accuracy of torsion analysis on a regional basis (circumferential segments and transmural layers) was analyzed using an analytical model of a deforming cylinder with a displaced axis of rotation (AoR). Regional peak torsion values from twelve healthy volunteers calculated by the described method were compared to literature. RESULTS: The deviation from the analytical torsion per % AoR-displacement (of the radius) was 0.90 +/- 0.44% for the circumferential segments and only 0.05% for the transmural layers. In the subjects, circumferentially, anterolateral torsion was larger than inferior (12.4 +/- 3.9 degrees vs. 5.0 +/- 3.3 degrees , N.S.). Transmurally, endocardial torsion was smaller than epicardial (7.5 +/- 1.3 degrees vs. 8.0 +/- 1.5 degrees , p < 0.001). CONCLUSION: Variability in the position of the AoR causes a large variability in torsion in circumferential segments. This effect was negligible for global torsion, and torsion calculated in transmural layers. Results were documented for the healthy human heart and are in agreement with data from literature.

In vivo dosimetry with MOSFETs and GAFCHROMIC films during electron IORT for Accelerated Partial Breast Irradiation.

PURPOSE: The purpose of this study was to compare the delivered dose to the expected intraoperative radiation therapy (IORT) dose with in vivo dosimetry. For IORT using electrons in accelerated partial breast irradiation, this is especially relevant since a high dose is delivered in a single fraction. METHODS: For 47 of breast cancer patients, in vivo dosimetry was performed with MOSFETs and/or GAFCHROMIC EBT2 films. A total dose of 23.33 Gy at dmax was given directly after completing the lumpectomy procedure with electron beams generated with an IORT dedicated mobile accelerator. A protection disk was used to shield the thoracic wall. RESULTS: The results of in vivo MOSFET dosimetry for 27 patients and GAFROMIC film dosimetry for 20 patients were analysed. The entry dose for the breast tissue, measured with MOSFETs, (mean value 22.3 Gy, SD 3.4%) agreed within 1.7% with the expected dose (mean value 21.9 Gy). The dose in breast tissue, measured with GAFCHROMIC films (mean value 23.50 Gy) was on average within 0.7% (SD = 3.7%, range -5.5% to 5.6%) of the prescribed dose of 23.33 Gy. CONCLUSIONS: The dose measured with MOSFETs and GAFROMIC EBT2 films agreed well with the expected dose. For both methods, the dose to the thoracic wall, lungs and heart for left sided patents was lower than 2.5 Gy even when 12 MeV was applied. The positioning time of GAFCHROMIC films is negligible and based on our results we recommend its use as a standard tool for patient quality assurance during breast cancer IORT.

Fast 3D coronary artery contrast-enhanced magnetic resonance angiography with magnetization transfer contrast, fat suppression and parallel imaging as applied on an anthropomorphic moving heart phantom.

A magnetic resonance sequence for high-resolution imaging of coronary arteries in a very short acquisition time is presented. The technique is based on fast low-angle shot and uses fat saturation and magnetization transfer contrast prepulses to improve image contrast. GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) is implemented to shorten acquisition time. The sequence was tested on a moving anthropomorphic silicone heart phantom where the coronary arteries were filled with a gadolinium contrast agent solution, and imaging was performed at varying heart rates using GRAPPA. The clinical relevance of the phantom was validated by comparing the myocardial relaxation times of the phantom's homogeneous silicone cardiac wall to those of humans. Signal-to-noise ratio and contrast-to-noise ratio were higher when parallel imaging was used, possibly benefiting from the acquisition of one partition per heartbeat. Another advantage of parallel imaging for visualizing the coronary arteries is that the entire heart can be imaged within a few breath-holds.

Comparison between three-dimensional speckle-tracking echocardiography and cardiac magnetic resonance imaging for quantification of left ventricular volumes and function.

AIMS: We evaluated the accuracy of three-dimensional speckle-tracking echocardiography (3DSTE) to evaluate left ventricular (LV) volumes, ejection fraction (EF), and global circumferential strain (CS) in comparison with cardiac magnetic resonance imaging (MRI) in a healthy population. METHODS AND RESULTS: A total of 45 out of 50 consecutive healthy subjects (38 males, age 45 ± 15 years) successfully underwent both 3DSTE and MRI on the same day. Three-dimensional echocardiography data sets were analysed using speckle tracking to measure LV end-diastolic and end-systolic volumes, EF, and global CS. With MRI, the method of discs approximation was used to obtain volumes and the EF, whereas CS was acquired using myocardial tissue tagging. Inter-technique comparisons included regression and the Bland-Altman analysis. For quantification of LV volumes, 3DSTE correlated well with MRI (r: 0.75-0.81), but volumes were significantly underestimated with relatively large biases (13-34 mL) and wide limits of agreement (SD: 11-25 mL). However, excellent accuracy was revealed for measurement of EF by 3DSTE with a good correlation (r: 0.91), minimal bias, and narrow limits of agreement (0.6 ± 1.7%) compared with MRI. For measurement of CS, a large mean bias was found between techniques (10.0%), despite narrow limits of agreement (SD: 1.7%) and a good correlation between techniques (r: 0.80). CONCLUSION: Although 3DSTE-derived LV volumes are underestimated in most patients compared with MRI, measurement of the LVEF revealed excellent accuracy. Measurements of CS were systematically greater (i.e. more negative) with 3DSTE than MRI, which likely reflects various inter-technique differences that preclude direct comparability of their measurements.

Relation of coronary microvascular dysfunction in hypertrophic cardiomyopathy to contractile dysfunction independent from myocardial injury.

We studied the spatial relations among hyperemic myocardial blood flow (hMBF), contractile function, and morphologic tissue alterations in 19 patients with hypertrophic cardiomyopathy (HC). All patients were studied with oxygen-15 water positron emission tomography during rest and adenosine administration to assess myocardial perfusion. Cardiovascular magnetic resonance was performed to derive delayed contrast-enhanced images and to calculate contractile function (E(cc)) with tissue tagging. Eleven healthy subjects underwent similar positron emission tomographic and cardiovascular magnetic resonance scanning protocols and served as a control group. In the HC group, hMBF averaged 2.46 ± 0.91 ml/min/g and mean E(cc) was -14.7 ± 3.4%, which were decreased compared to the control group (3.97 ± 1.48 ml/min/g and -17.7 ± 3.2%, respectively, p <0.001 for the 2 comparisons). Delayed contrast enhancement (DCE) was present only in patients with HC, averaging 6.2 ± 10.3% of left ventricular mass. In the HC group, E(cc) and DCE in the septum (-13.7 ± 3.6% and 10.2 ± 13.6%) significantly differed from the lateral wall (-16.0 ± 2.8% and 2.4 ± 5.9%, p <0.001 for the 2 comparisons). In general, hMBF and E(cc) were decreased in segments displaying DCE compared to nonenhanced segments (p <0.001 for the comparisons). In the HC group, univariate analysis revealed relations of hMBF to E(cc) (r = -0.45, p <0.001) and DCE (r = -0.31, p <0.001). Multivariate analysis revealed that E(cc) was independently related to hMBF (beta -0.37, p <0.001) and DCE (beta 0.28, p <0.001). In conclusion, in HC hMBF is impaired and related to contractile function independent from presence of DCE. When present, DCE reflected a progressed disease state as characterized by an increased perfusion deficit and contractile dysfunction.

Left ventricular torsion: an expanding role in the analysis of myocardial dysfunction.

During left ventricular (LV) torsion, the base rotates in an overall clockwise direction and the apex rotates in a counterclockwise direction when viewed from apex to base. LV torsion is followed by rapid untwisting, which contributes to ventricular filling. Because LV torsion is directly related to fiber orientation, it might depict subclinical abnormalities in heart function. Recently, ultrasound speckle tracking was introduced for quantification of LV torsion. This fast, widely available technique may contribute to a more rapid introduction of LV torsion as a clinical tool for detection of myocardial dysfunction. However, knowledge of the exact function and structure of the heart is fundamental for understanding the value of LV torsion. LV torsion has been investigated with different measurement methods during the past 2 decades, using cardiac magnetic resonance as the gold standard. The results obtained over the years are helpful for developing a standardized method to quantify LV torsion and have facilitated the interpretation and value of LV torsion before it can be used as a clinical tool.

Relation between three-dimensional echocardiography derived left ventricular volume and MRI derived circumferential strain in patients eligible for cardiac resynchronization therapy.

OBJECTIVES: To compare regional left ventricular (LV) volume curves obtained with real time three-dimensional echocardiography (RT3DE) with two-dimensional circumferential strain curves obtained by MRI in cardiac resynchronization therapy candidates. BACKGROUND: Several methods using either ultrasound or MRI are used to quantify mechanical dyssynchrony (MD). Theoretically, LV volume and circumferential strain seem related, since both measures are connected to the radius of the ventricle. METHODS: In 21 patients with chronic heart failure, RT3DE and tagged MRI were performed subsequently. Regional LV volume was computed from the ultrasound images. From the MR images, regional circumferential strain was calculated. Cross-correlations with time lags of 1% of the cardiac cycle were performed to compare the curves in corresponding LV segments. Furthermore, peak septal to lateral (SL) delays were compared between modalities. RESULTS: High correlations were found between the curves (r(2) = 0.65 +/- 0.19), but regional differences in time delay between modalities were observed. In the septum, the volume curve was earlier than the strain curve by 1.8 +/- 17.0 time-lags (n.s.), while in the lateral wall, the volume curve was earlier by 3.3 +/- 12.0 time-lags (P < 0.02). There was a non-significant difference between SL delays in the two modalities (volume: -1.0 +/- 8.6%, strain: 3.0 +/- 12.7%, P = 0.17, a positive sign indicates that the lateral wall is delayed). CONCLUSIONS: High correlations were observed between both modalities, but regional differences in time-delay were found. This is possibly inherent to the method of echocardiographic volume calculation and hampers the comparison of both measures for the quantification of MD.

Mechanical dyssynchrony or myocardial shortening as MRI predictor of response to biventricular pacing?

PURPOSE: To investigate whether mechanical dyssynchrony (regional timing differences) or heterogeneity (regional strain differences) in myocardial function should be used to predict the response to cardiac resynchronization therapy (CRT). MATERIALS AND METHODS: Baseline mechanical function was studied with MRI in 29 patients with chronic heart failure. Using myocardial tagging, two mechanical dyssynchrony parameters were defined: the standard deviation (SD) in onset time (T onset) and in time to first peak (T peak,first) of circumferential shortening. Electrical dyssynchrony was described by QRS width. Further, two heterogeneity parameters were defined: the coefficient of variation (CV) in end-systolic strain and the difference between peak septal and lateral strain (DiffSLpeakCS). The relative increase in maximum rate of left ventricle pressure rise (dP/dt max) quantified the acute response to CRT. RESULTS: The heterogeneity parameters correlated better with acute response (CV: r = 0.58, DiffSLpeakCS: r = 0.63, P < 0.005) than the mechanical dyssynchrony parameters (SD(T onset): r = 0.36, SD(T peak,first) r = 0.47, P = 0.01, but similar to electrical dyssynchrony (r = 0.62, P < 0.001). When a heterogeneity parameter was combined with electrical dyssynchrony, the correlation increased (r > 0.70, P incr < 0.05). CONCLUSION: Regional heterogeneity in myocardial shortening correlates better with response to CRT than mechanical dyssynchrony, but should be combined with electrical dyssynchrony to improve prediction of response beyond the prediction from electrical dyssynchrony only.

Myocardial strain and torsion quantified by cardiovascular magnetic resonance tissue tagging: studies in normal and impaired left ventricular function.

Accurate quantification and timing of regional myocardial function allows early identification of dysfunction, and therefore becomes increasingly important for clinical risk assessment, patient management, and evaluation of therapeutic efficacy. For this purpose, the application of tissue Doppler echocardiography has rapidly increased. However, echocardiography has some major inherent limitations. Cardiovascular magnetic resonance imaging with tissue tagging provides highly reproducible data on myocardial function, not only in longitudinal and radial directions, but also in the circumferential direction. Because of the development of faster imaging protocols, improved temporal resolution, less time-consuming postprocessing procedures, and the potential of quantifying myocardial deformation in 3 dimensions at any point in the heart, this technique may serve as an alternative for tissue Doppler echocardiography and is now ready for more widespread clinical use. This review discusses the clinical use of cardiovascular magnetic resonance tissue tagging for quantitative assessment of regional myocardial function, thereby underlining the specific features and emerging role of this technique.