Evaluation of Myocardial Stiffness in Cardiac Amyloidosis Using Acoustic Radiation Force Impulse and Natural Shear Wave Imaging.

OBJECTIVE: Increased myocardial stiffness (MS) is an important hallmark of cardiac amyloidosis (CA) caused by myocardial amyloid deposition. Standard echocardiography metrics assess MS indirectly via downstream effects of cardiac stiffening. The ultrasound elastography methods acoustic radiation force impulse (ARFI) and natural shear wave (NSW) imaging assess MS more directly. METHODS: This study compared MS in 12 healthy volunteers and 13 patients with confirmed CA using ARFI and NSW imaging. Parasternal long-axis acquisitions of the interventricular septum were obtained using a modified Acuson Sequoia scanner and a 5V1 transducer. ARFI-induced displacements were measured through the cardiac cycle, and ratios of diastolic-over-systolic displacement were calculated. NSW speeds from aortic valve closure were extracted from echocardiography-tracked displacement data. RESULTS: ARFI stiffness ratios were significantly lower in CA patients than controls (mean ± standard deviation: 1.47 ± 0.27 vs. 2.10 ± 0.47, p < 0.001), and NSW speeds were significantly higher in CA patients than controls (5.58 ± 1.10 m/s vs. 3.79 ± 1.10 m/s, p < 0.001). A linear combination of the two metrics exhibited greater diagnostic potential than either metric alone (area under the curve = 0.97 vs. 0.89 and 0.88). CONCLUSION: MS was measured to be significantly higher in CA patients using both ARFI and NSW imaging. Together, these methods have potential utility to aid in clinical diagnosis of diastolic dysfunction and infiltrative cardiomyopathies.

Immersion-Induced Mitral Regurgitation: A Novel Risk Factor for Swimming-Induced Pulmonary Edema.

Immersion pulmonary edema, more commonly referred to as swimming-induced pulmonary edema (SIPE), is a well-documented condition believed to be a result of immersion physiologic condition that is characterized by a peripheral-to-central redistribution of blood volume. It disproportionally affects young, healthy athletes with no clinically overt cardiovascular or pulmonary conditions. We present four cases of healthy athletes with previously documented SIPE, who participated in Institutional Review Board-approved clinical studies that examined the pathophysiologic condition and prevention of SIPE. During standard recumbent echocardiography, trivial mitral regurgitation was observed in all four individuals. Acute exacerbation of their mitral regurgitation was observed during immersion with both immersed resting and immersed exercise echocardiography, contributing to the development of SIPE. These observations demonstrate that the occurrence of subclinical or trivial mitral valve regurgitation during dry rest is a novel risk factor for SIPE. We propose the use of immersion echocardiography as a useful investigative tool for otherwise healthy individuals with SIPE and no previously explainable cause.

Left bundle branch block without a typical contraction pattern is associated with increased risk of ventricular arrhythmias in cardiac resynchronization therapy patients.

Cardiac resynchronization therapy (CRT) reduces the risk of ventricular arrhythmias (VA) in heart failure (HF) patients with left bundle branch block (LBBB) while the effect is less clear among non-LBBB patients. This study aimed to investigate if absence of LBBB features whether by echocardiography or strict ECG criteria would identify patients at risk of developing VA in a cohort with LBBB according to conventional ECG criteria. Two hundred six CRT candidates were prospectively included from 2 centers. Prior to CRT presence of a typical LBBB contraction pattern was identified using longitudinal strain in the apical 4-chamber view. All preimplantation ECGs were categorized as LBBB or non-LBBB according to Strauss´ strict criteria. Primary end-point was defined as any appropriate antitachycardia pacing (ATP) or shock therapy within 2 years after CRT implantation. A total of 129 (63%) patients had a typical LBBB contraction pattern, while 134 (66%) met the strict ECG criteria. Over 2 years, 45 patients (22%) experienced VA. Absence of a typical LBBB contraction pattern was independently associated with an increased risk of VA (hazard ratio ([HR] 1.89; 95% CI 1.04 to 3.44; p: 0.036). Strict LBBB was not independently associated with the occurrence of VA. Fulfilling neither strict ECG nor echocardiographic criteria for LBBB was associated with a 3.3-fold increase in risk of VA ([HR] 3.34; 95% CI 1.75 to 6.94; (p < 0.001). The risk of VA was almost 2-fold higher if a typical LBBB contraction pattern was absent prior to CRT.

Left bundle-branch block is associated with asimilar dyssynchronous phenotype in heart failure patients with normal and reduced ejection fractions.

BACKGROUND: Few therapies improve outcomes in patients with heart failure with preserved ejection fraction (HFpEF). If left bundle-branch block (LBBB) is associated with left ventricular dyssynchrony and impaired cardiac performance in HFpEF, cardiac resynchronization therapy could be a promising treatment. METHODS: We performed a cross-sectional analysis of selected patients with HFpEF (ejection fraction ≥50%) with and without LBBB (normal conduction, NC) and patients with HFrEF and LBBB who were suitable cardiac resynchronization therapy candidates to describe and contextualize the mechanical phenotype of LBBB in HFpEF. Systolic and diastolic isovolumic times, ejection time(ET), and diastolic filling time(DFT) were measured on spectral tissue Doppler echocardiographic images and indexed to the heart rate. Dyssynchrony pattern was assessed using speckle-tracked longitudinal strain patterns. Comparisons were performed using analysis of variance and χ2 test with posthoc pairwise comparisons as indicated. RESULTS: Eighty-two HFpEF (50 with NC, 32 with LBBB) and 149 HFrEF (all with LBBB) patients met criteria. Overall, 84.4% with HFpEF/LBBB and 91.3% with HFrEF/LBBB had demonstrable mechanical dyssynchrony compared to 0% with HFpEF/NC. Compared to HFpEF/NC, HFpEF/LBBB had significantly prolonged isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and total isovolumetric time and significantly shorter ET (all indexed). LBBB/HFrEF patients, compared to LBBB/HFpEF patients, had increased ICT and IRT with decreased DFT but similar ET. CONCLUSIONS: Patients with HFpEF and LBBB frequently have an LBBB dyssynchrony phenotype, prolonged ICT and IRT, and reduced ET compared to HFpEF patients with NC. The electromechanical dyssynchrony and disordered cardiac timing of HFpEF with LBBB are similar to HFrEF with LBBB.

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.

Predicting the Development of Reduced Left Ventricular Ejection Fraction in Patients With Left Bundle Branch Block.

Left bundle branch block (LBBB) increases the likelihood of developing reduced left ventricular (LV) ejection fraction (EF) but predicting which patients with LBBB and normal LVEF will develop decreased LVEF remains challenging. Fifty patients with LBBB and normal LVEF were retrospectively identified. Clinical, electrocardiographic, and echocardiographic variables were compared between patients who developed a decreased LVEF and those who did not. A total of 16 of 50 patients developed reduced LVEF after 4.3 (SD = 2.8) years of follow-up. Baseline patient and electrocardiographic variables were similar between patients who did and did not develop decreased LVEF. Baseline LVEF was lower in patients who developed decreased LVEF than in those who did not (51.9% [SD = 2.2%] vs 54.9% [SD = 4.4%], p <0.01). Diastolic filling time (DFT) accounted for a significantly smaller percentage of the cardiac cycle in patients who developed decreased LVEF than in those who did not (35.9%, [SD = 6.9%] vs 44.4% [SD = 4.5%] p <0.01). In univariable logistic regression, DFT had a C-statistic of 0.86 (p <0.0001) for prediction of development of decreased LVEF. In conclusion, patients in whom DFT accounted for <38% of the cardiac cycle had a relative risk of developing decreased LVEF of 7.0 (95% confidence interval 3.0 to 16.0) compared to patients with DFT accounting for ≥38% of the cardiac cycle.

Concomitant changes in ventricular depolarization and repolarization and long-term outcomes of biventricular pacing.

BACKGROUND: Biventricular (BiV) pacing increases transmural repolarization heterogeneity due to epicardial to endocardial conduction from the left ventricular (LV) lead. However, limited evidence is available on concomitant changes in ventricular depolarization and repolarization and long-term outcomes of BiV pacing. Therefore, we investigated associations of BiV pacing-induced concomitant changes in ventricular depolarization and repolarization with mortality (i.e., LV assist device, heart transplantation, or all-cause mortality) and sustained ventricular arrhythmia endpoints. METHODS: Consecutive BiV-defibrillator recipients with digital preimplantation and postimplantation electrocardiograms recorded between 2006 and 2015 at Duke University Medical Center were included. We calculated changes in QRS duration and corrected JT (JTc) interval and split them by median values. For simplicity, these variables were named QRSdecreased (≤ -12 ms), QRSincreased (> -12 ms), JTcdecreased (≤22 ms), and JTcincreased (> 22 ms) and subsequently used to construct four mutually exclusive groups. RESULTS: We included 528 patients (median age, 68 years; male, 69%). No correlation between changes in QRS duration and JTc interval was observed (P = .295). Compared to QRSdecreased /JTcincreased , increased risk of the composite mortality endpoint was associated with QRSdecreased /JTcdecreased (hazard ratio [HR] = 1.62; 95% confidence interval [CI] = 1.09-2.43), QRSincreased /JTcdecreased (HR = 1.86; 95% CI = 1.27-2.71), and QRSincreased /JTcincreased (HR = 2.25; 95% CI = 1.52-3.35). No QRS/JTc group was associated with excess sustained ventricular arrhythmia risk (P = .400). CONCLUSION: Among BiV-defibrillator recipients, QRSdecreased /JTcincreased was associated with the most favorable long-term survival free of LV assist device, heart transplantation, and sustained ventricular arrhythmias. Our findings suggest that improved electrical resynchronization may be achieved by assessing concomitant changes in ventricular depolarization and repolarization.

Contractile Fronts In The Interventricular Septum: A Case For High Frame Rate Echocardiographic Imaging.

The real time high frame rate (HFR) 2-dimensional ultrasound system, T5, at Duke University is capable of imaging at up to 1000 images per second for adult cardiac imaging. A method for detecting and visualizing the mechanical contraction fronts using HFR echocardioagraphy-derived Strain Rate Image (SRI) was described in 26 patients. The Tissue Shortening Onset front durations for echocardiographic normal patients were significantly shorter than conduction disorder patients with left bundle branch block (LBBB) with intrinsic conduction and conduction disorder patients without LBBB (non-LBBB) with simulated LBBB (sLBBB). Echocardiographic normal patients had significantly higher correlation coefficients between their SRIs and spatially inverted versions of themselves compared to non-LBBB patients with intrinsic conduction and sLBBB. In conclusion, SRIs could spatially resolve contractile event fronts in patients.

Early cardiac dysfunction in children and young adults with perinatally acquired HIV.

OBJECTIVE: To define the prevalence of early cardiac dysfunction in children and young adults with perinatally acquired HIV and predictors of cardiac function. DESIGN: Cross-sectional design. METHODS: Early cardiac dysfunction was defined as left ventricular (LV) global longitudinal strain z-score less than -2 or myocardial performance index at least 0.5 with normal LV ejection fraction. Regression models were fitted to assess the relationship between measures of cardiac function and HIV RNA levels, clinical variables, and markers of inflammation. RESULTS: Six hundred and forty-three individuals (mean age 14.1 ±â€Š5.2 years) were enrolled. The average time on combination antiretroviral treatment was 6.8 ±â€Š3.6 years. Nearly 28% of individuals met criteria for early cardiac dysfunction. Individuals with early cardiac dysfunction were older (15.3 vs. 13.5 years, P < 0.001), had more frequently detectable HIV RNA (52.5 vs. 41.7%, P = 0.018), were more likely exposed to azidothymidine or zidovudine (ZDV) (55.6 vs. 41.2%, P = 0.002), and had higher median level of plasma IL-6 concentrations (1.00 vs. 0.88 pg/ml, P = 0.011). Multivariable models show LV ejection fraction negatively associated with HIV RNA levels [ß -0.18; 95% confidence interval (CI) -0.33, -0.03] and ZDV exposure (ß -1.75; 95% CI -2.62, -0.88) and positively associated with proportion of life on combination antiretroviral treatment (ß 2.65; 95% CI 0.90, 4.41). Higher myocardial performance index was positively associated with serum inflammation marker (IL-6 ß 0.01; 95% CI 0.0001, 0.001). Left ventricular global longitudinal strain was not significantly associated with clinical and laboratory variables of interest. CONCLUSION: Over one-quarter of children and young adults living with HIV demonstrated evidence of cardiac dysfunction, which may be associated with increasing levels of systemic inflammation.

Index of contractile asymmetry improves patient selection for CRT: a proof-of-concept study.

BACKGROUND: Nearly one-third of heart failure (HF) patients do not respond to cardiac resynchronization therapy (CRT) despite having left bundle branch block (LBBB). The aim of the study was to investigate a novel method of quantifying left ventricular (LV) contractile asymmetry in HF. METHODS: Patients with HF and LBBB undergoing CRT (n = 89, 37.1% females, 68 ± 9 years, ischemic etiology in 61%, LV ejection fraction 27.1 ± 7.1%) were analyzed. LV longitudinal systolic strain rate values were extracted from curved anatomical M-mode plots of standard long-axis 2D-echocardiography images and cubic spline interpolation was used to generate a 3D-phantom. Index of contractile asymmetry (ICA) was calculated based on standard deviation of differences in strain rate of opposing walls. Average ICA was individually assessed pairwise in 12 opposing 30-degree LV sectors. Reduction in LV end-systolic volume (ESV) ≥15% after 6 months was considered as positive response to CRT. RESULTS: CRT response was found in 66 (74.2%) patients. Responders with both ischemic and non-ischemic cardiomyopathy had a higher and more extensive contractile asymmetry at baseline and achieved a greater ICA reduction after CRT than non-responders. Higher baseline ICA predicted higher degree and wider extent of ICA improvement. Also, both ICA at baseline and reduction of ICA correlated with the degree of ESV reduction after CRT. CONCLUSIONS: Quantification of asymmetrical LV activation in 3D by ICA provides valuable insights into LV contraction in case of LBBB and is a promising tool for improved patient selection for CRT.

Non-invasively quantified changes in left ventricular activation predict outcomes in patients undergoing cardiac resynchronization therapy.

BACKGROUND: Changes in left ventricular (LV) activation after cardiac resynchronization therapy (CRT) influence survival but are difficult to quantify noninvasively. METHODS AND RESULTS: We studied 527 CRT patients to assess whether noninvasive quantification of changes in LV activation, defined by change (Δ) in QRS area (QRSA), can predict outcomes after CRT. The study outcome was time until LV assist device(LVAD), cardiac transplant, or death. The three-dimensional QRSA was measured from clinical 12 lead ECGs which were transformed into vectorcardiograms using the Kors method. QRSA was calculated as (QRSx2 + QRSy2 + QRSz2 )1/2 ; ΔQRSA was calculated as post-QRSA minus pre-QRSA, where a negative value represents a reduction in LV activation delay. Kaplan-Meier plots and multivariable Cox proportional hazards models were used to relate ΔQRSA area with outcomes after stratifying the population into quartiles of ΔQRSA. The median baseline QRSA of 93.6 µVs decreased to 59.7 µVs after CRT. Progressive reductions in QRSA with CRT were associated with a lower rate of LVAD, transplant, or death across patient quartiles (P < .001). In Cox regression analyses, ΔQRSA was associated with outcomes independent of QRS morphology and other clinical variables (Q1[greatest decrease] vs Q4[smallest change=reference], HR 0.45, CI, 0.30-0.70, P < .001). There was no interaction between ΔQRSA and QRS morphology. CONCLUSIONS: CRT induced ΔQRSA was associated with clinically meaningful changes in event-free survival. ΔQRSA may be a novel target to guide lead implantation and device optimization.

Echocardiographic Assessment of Right Ventricular Function and Response to Therapy in Pulmonary Arterial Hypertension.

Echocardiography is a key tool in the management of patients with pulmonary arterial hypertension (PAH), but many potential parameters could be used to assess response to therapy. In this retrospective study of 48 patients with severe PAH at baseline, we examined echocardiographic variables before and after initiation of PAH-specific therapy to evaluate which measures of right ventricular (RV) function best correlated with clinical response to therapy as assessed by 6-minute walk distance (6MWD) and 3-year all-cause mortality. Tricuspid annular plane systolic excursion (TAPSE), mid-RV and basal-RV diameters, RV systolic pressure, and RV global longitudinal strain were all found to significantly improve after initiation of a PAH therapy. Decreases in right atrial area (r = -0.50, p = 0.002) and mid-RV diameter (r = -0.36, p = 0.03) were most strongly correlated with improvement in 6MWD. Pretreatment values of RA area (hazard ratio [HR] per 1 SD: 2.72; 95% confidence interval [CI] 1.58, 4.69), mid-RV diameter (HR 2.03; 1.20, 3.45), basal-RV diameter (HR 2.27; 1.40, 3.70), and RV global longitudinal strain (HR 2.36; 1.22, 4.56) were all associated with mortality risk. 6MWD and TAPSE were the 2 variables for which pretreatment measures (6MWD - HR 0.35; 0.17, 0.72; TAPSE - HR 0.41; 0.21, 0.82) and change with treatment (6MWD - HR 0.26; 0.10, 0.64; TAPSE - HR 0.40; 0.21, 0.77) were both significantly associated with 3-year mortality. Change in RV systolic pressure with treatment was significantly associated with mortality (HR 2.55; 1.23, 5.28,) but pretreatment baseline had no association (HR 1.48; 0.72, 3.06). Although many echocardiographic parameters change with initiation of PAH treatment, the strong association of both baseline TAPSE and change in TAPSE with mortality supports the ongoing use of TAPSE as an important measure in the assessment of disease severity and treatment response in PAH.

PR Prolongation predicts inadequate resynchronization with biventricular pacing in left bundle branch block.

BACKGROUND: PR interval prolongation is associated with poor outcome after cardiac resynchronization therapy (CRT) among patients with left bundle branch block (LBBB) but the mechanisms are unknown. We investigated clinical outcomes, electrocardiogram (ECG), and echocardiogram changes after CRT by PR interval. METHODS: This is a retrospective study of CRT recipients with a baseline ejection fraction ≤35% and ECG showing sinus rhythm and LBBB. Patients were stratified by baseline PR interval quartile and the primary combined endpoint was time to heart transplantation, left ventricular assist device (LVAD) implantation, or death. ECG, echocardiogram, and clinical variables were compared to identify mechanisms for observed differences in outcomes. RESULTS: Of 291 eligible patients, the mean age was 65 years, 60% were male, and 19% had prior atrial fibrillation. Patients with PR prolongation (quartile 4, PR > 200 ms) more frequently had a history of atrial fibrillation, coronary artery bypass graft surgery, prior implantable cardioverter defibrillator implantation, and use of amiodarone than patients in PR quartiles 1-3. A PR > 200ms was associated with an adjusted hazard ratio of 1.7 (95% CI: 1.1-2.5) for the primary endpoint. Patients with PR > 200 ms had less reduction in QRS duration and QRS area after CRT while having more increase in QT and QTc intervals than patients with PR ≤ 200 ms. No major differences were observed in echocardiography by baseline PR interval quartiles. CONCLUSIONS: PR prolongation predicts shorter survival free of heart transplantation or LVAD implantation in patients with LBBB. This may be due to inadequate ventricular resynchronization.

The Association of a classical left bundle Branch Block Contraction Pattern by vendor-independent strain echocardiography and outcome after cardiac resynchronization therapy.

BACKGROUND: The association of a Classical left bundle branch block (LBBB) contraction pattern and better outcome after cardiac resynchronization therapy (CRT) has only been studied using vendor-specific software for echocardiographic speckle-tracked longitudinal strain analysis. The purpose of this study was to assess whether a Classical LBBB contraction pattern on longitudinal strain analysis using vendor-independent software is associated with clinical outcome in CRT recipients with LBBB. METHODS: This was a retrospective cohort study including CRT recipients with LBBB, heart failure, and left ventricular (LV) ejection fraction ≤35%. Speckle-tracked echocardiographic longitudinal strain analysis was performed retrospectively on echocardiograms using vendor-independent software. The presence of a Classical LBBB contraction pattern was determined by consensus of two readers. The primary end point was a composite of time to death, heart transplantation or LV assist device implantation. Secondary outcome was ≥15% reduction in LV end-systolic volume. Intra- and inter-reader agreement of the longitudinal strain contraction pattern was assessed by calculating Cohen's κ. RESULTS: Of 283 included patients, 113 (40%) were women, mean age was 66 ± 11 years, and 136 (48%) had ischemic heart disease. A Classical LBBB contraction pattern was present in 196 (69%). The unadjusted hazard ratio for reaching the primary end point was 1.93 (95% confidence interval, 1.36-2.76, p < 0.001) when comparing patients without to patients with a Classical LBBB contraction pattern. Adjusted for ischemic heart disease and QRS duration < 150 milliseconds the hazard ratio was 1.65 (95% confidence interval, 1.12-2.43, p = 0.01). Of the 123 (43%) patients with a follow-up echocardiogram, 64 of 85 (75%) of patients with a Classical LBBB contraction pattern compared to 13 of 38 (34%) without, had ≥15% reduction in LV end-systolic volume (p < 0.001). Cohen's κ were 0.86 (95% confidence interval, 0.71-1.00) and 0.42 (95% confidence interval, 0.30-0.54) for intra- and inter-reader agreement, respectively. CONCLUSION: Using vendor-independent strain software, a Classical LBBB contraction pattern is associated with better outcome in CRT recipients with LBBB, but inter-reader agreement for the classification of contraction pattern is only moderate.

Non-invasive Measurement of Dynamic Myocardial Stiffness Using Acoustic Radiation Force Impulse Imaging.

Myocardial stiffness exhibits cyclic variations over the course of the cardiac cycle. These trends are closely tied to the electromechanical and hemodynamic changes in the heart. Characterization of dynamic myocardialstiffness can provide insights into the functional state of the myocardium, as well as allow for differentiation between the underlying physiologic mechanisms that lead to congestive heart failure. Previous work has revealed the potential of acoustic radiation force impulse (ARFI) imaging to capture temporal trends in myocardial stiffness in experimental preparations such as the Langendorff heart, as well as on animals in open-chest and intracardiac settings. This study was aimed at investigating the potential of ARFI to measure dynamic myocardial stiffness in human subjects, in a non-invasive manner through transthoracic imaging windows. ARFI imaging was performed on 12 healthy volunteers to track stiffness changes within the interventricular septum in parasternal long-axis and short-axis views. Myocardial stiffness dynamics over the cardiac cycle was quantified using five indices: stiffness ratio, rates of relaxation and contraction and time constants of relaxation and contraction. The yield of ARFI acquisitions was evaluated based on metrics of signal strength and tracking fidelity such as displacement signal-to-noise ratio, signal-to-clutter level, temporal coherence of speckle and spatial similarity within the region of excitation. These were quantified using the mean ARF-induced displacements over the cardiac cycle, the contrast between the myocardium and the cardiac chambers, the minimum correlation coefficients of radiofrequency signals and the correlation between displacement traces across simultaneously acquired azimuthal beams, respectively. Forty-one percent of ARFI acquisitions were determined to be "successful" using a mean ARF-induced displacement threshold of 1.5 µm. "Successful" acquisitions were found to have higher (i) signal-to-clutter levels, (ii) temporal coherence and (iii) spatial similarity compared with "unsuccessful" acquisitions. Median values of these three metrics, between the two groups, were measured to be 13.42dB versus 5.42dB, 0.988 versus 0.976 and 0.984 versus 0.849, respectively. Signal-to-clutter level, temporal coherence and spatial similarity were also found to correlate with each other. Across the cohort of healthy volunteers, the stiffness ratio measured was 2.74 ± 0.86; the rate of relaxation, 7.82 ± 4.69/s; and the rate of contraction, -7.31±3.79 /s. The time constant of relaxation was 35.90 ± 20.04ms, and that of contraction was 37.24 ± 19.85ms. ARFI-derived indices of myocardial stiffness were found to be similar in both views. These results indicate the feasibility of using ARFI to measure dynamic myocardial stiffness trends in a non-invasive manner and also highlightthe technical challenges of implementing this method in the transthoracic imaging environment.

Quantitative Parameters of High-Frame-Rate Strain in Patients with Echocardiographically Normal Function.

Recently, we developed a high-frame-rate echocardiographic imaging system capable of acquiring images at rates up to 2500 per second. High imaging rates were used to quantify longitudinal strain parameters in patients with echocardiographically normal function. These data can serve as a baseline for comparing strain parameters in disease states. The derived timing data also reveal the propagation of mechanical events in the left ventricle throughout the cardiac cycle. High-frame-rate echocardiographic images were acquired from 17 patients in the apical four-chamber view using Duke University's phased array ultrasound system, T5. B-Mode images were acquired at 500-1000 images per second by employing 16:1 or 32:1 parallel processing in receive, a scan depth ≤14 cm and an 80° field of view with a 3.5-MegaHertZ (MHz), 96-element linear array. The images were analyzed using a speckle tracking algorithm tailored for high-frame-rate echocardiographic images developed at Aalborg and Duke University. Four specific mechanical events were defined using strain curves from six regions along the myocardial contour of the left ventricle. The strain curves measure the local deformation events of the myocardium and are independent of the overall cardiac motion. We observed statistically significant differences in the temporal sequence among different myocardial segments for the first mechanical event described, myocardial tissue shortening onset (p < 0.01). We found that the spatial origin of tissue shortening was located near the middle of the interventricular septum in patients with echocardiographically normal function. The quantitative parameters defined here, based on high-speed strain measurements in patients with echocardiographically normal function, can serve as a means of assessing degree of contractile abnormality in the myocardium and enable the identification of contraction propagation. The relative timing pattern among specific events with respect to the Q wave may become an important new metric in assessing cardiac function and may, in turn, improve diagnosis and prognosis.

Predictors and Changes in Cardiac Hemodynamics and Geometry With Transcatheter Aortic Valve Implantation.

The introduction of transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of patients with severe aortic stenosis (AS). However, despite the great clinical success of TAVI, less is known about the cardiac hemodynamics and structural changes to post-TAVI. We analyzed patients with AS who had a transthoracic echocardiography at most 6 months before index TAVI and follow-up transthoracic echocardiography 9 to 18 months later, performed at Duke University Medical Center from 2012 to 2014. A total of 152 TAVI patients with a median age of 81 years (median interquartile range 74 to 86) were included. TAVI resulted in the reduction of left ventricle (LV) mass index (g/m2), median (interquartile range) 130 (115 to 157) pre versus 106 (85 to 135) post, p <0.001; LV end-diastolic volume (ml) 127 (105 to 143) pre versus 120 (100 to 143) post, p = 0.013; and LV end-systolic volume (ml) 55 (38 to 77) pre versus 45 (40 to 65) post, p = 0.027. TAVI also significantly improved LV global longitudinal strain (%) -14.4 (-11.3, -15.5) pre versus -14.8 (-12.2, -16.6) post (p <0.001, respectively). Post-TAVI LV mass regression was predicted by baseline LV mass and LV global longitudinal strain whereas post-TAVI LV ejection fraction was predicted by baseline LV ejection fraction, LV mass, and post-TAVI paravalvular leak. In conclusion, TAVI results in significant cardiac hemodynamic, geometrical, and functional changes at approximately 1-year postprocedure for patients with AS. Better baseline myocardial structure and function leads to more reverse remodeling.

Vectorcardiographic QRS area is associated with long-term outcome after cardiac resynchronization therapy.

BACKGROUND: Recent studies have suggested that vectorcardiographic measures predict left ventricular (LV) reverse remodeling and clinical outcome in patients receiving cardiac resynchronization therapy (CRT). OBJECTIVES: The objectives of this study were to compare predictive abilities of different vectorcardiographic measures (QRS area and sum absolute QRS-T integral) and transformation methods (Kors and inverse Dower) and to assess the independent association between the best predictor and outcomes in CRT recipients. METHODS: This retrospective study included CRT recipients with a digital baseline electrocardiogram, QRS duration ≥120 ms, and ejection fraction ≤35%. The end point was a composite of heart transplantation, LV assist device implantation, or all-cause death. Analyses were performed for the overall cohort and for a prespecified subgroup of patients with left bundle branch block (LBBB). RESULTS: Of 705 included patients with a mean age of 66.6 ± 11.5 years, 492 (70%) were men, 374 (53%) had ischemic heart disease, and 465 (66%) had LBBB. QRS area from vectorcardiograms derived via the Kors transformation demonstrated the best predictive value. In multivariable Cox regression, patients with a smaller QRS area (≤ 95 µVs) had an increased hazard in the overall cohort (adjusted hazard ratio 1.65; 95% CI 1.25-2.18 P < .001) and in the LBBB subgroup (adjusted hazard ratio 1.95; 95% CI 1.38-2.76 P < .001). QRS area was associated with outcome in patients with QRS duration <150 ms (unadjusted hazard ratio 3.85; 95% CI 2.02-7.37 P < .001) and in patients with QRS duration ≥150 ms (unadjusted hazard ratio 1.76; 95% CI 1.32-2.34 P < .001). CONCLUSION: Vectorcardiographic QRS area is associated with survival free from heart transplantation and LV assist device implantation in CRT recipients.