Assessment of the correlation between Doppler derived dP/dt and aortic velocity-time integral during cardiac resynchronization therapy optimization.

PURPOSE: Suboptimal response to cardiac resynchronization therapy (CRT) may be improved by optimization of device parameters using echocardiography. For this purpose, the aortic velocity-time integral (aVTI) has been used as a target metric to define optimal velocity timings for each ventricle. dP/dt is a parameter used for the assessment of myocardial contractility. In this study, we aimed to evaluate the effectiveness of Doppler-derived dP/dt in optimization by assessing the possible correlation between aVTI and dP/dt. METHODS: Patients with CRT admitted for routine follow-up were included in the study. Aortic VTI and dP/dt measurements were recorded in four different standard pacing configurations during reprogramming. RESULTS: A total of 45 patients were included in the final analysis. No correlation was found between the aVTI and the delta dP/dt value in the two configurations where the change in dP/dt was maximum (p = 0.894). In the two configurations where the change in aVTI was maximum, there was also no correlation between the delta dP/dt and the delta aVTI (p = 0.715). When patients were dichotomized according to the median value of dP/dt, there were no differences in aVTI, NYHA classes, LVEF, and mitral regurgitation (MR) severity (p = 0.4; p = 0.5; p = 0.7; p = 0.3; respectively). The change in both dP/dt and aVTI was statistically significant when switching from RV-only to QRS width-targeted configuration (p = 0.001; p = 0.041; respectively). CONCLUSION: In conclusion, aVTI recorded at different pacing configurations did not correlate with dP/dt during interventricular optimization. However, both parameters consistently showed a positive effect of biventricular pacing on contractile synchronization and stroke volume.

Pulmonary Vein Flow Morphology After Transcatheter Mitral Valve Edge-to-Edge Repair as Predictor of Survival.

BACKGROUND: Data on the prognostic factors after mitral valve (MV) transcatheter edge-to-edge repair (TEER; MV-TEER) are limited. Pulsed-wave Doppler interrogation of pulmonary vein flow (PVF) is a convenient method to assess the hemodynamic burden of residual mitral regurgitation (MR), which could be of utility as a predictor of outcomes. METHODS: Patients that underwent MV-TEER between May 2014 and December 2021 at our institution were evaluated. Pulmonary vein flow patterns post-MV-TEER were reviewed on the procedural transesophageal echocardiogram and classified as normal (systolic dominant or codominant) or abnormal (systolic blunting or reversal). The PVF pattern was correlated with all-cause mortality at follow-up. RESULTS: Two-hundred sixty-five patients had diagnostic PVF post-MV-TEER, with 73 (27.5%) categorized as normal and 192 (72.5%) categorized as abnormal. Patients with abnormal PVF morphology were more likely to have atrial fibrillation (70% vs 42%, P < .001) and greater than moderate residual MR (16% vs 3%, P = .01) and had higher mean left atrial pressure (18.1 ± 5.0 vs 15.9 ± 4.2 mm Hg, P = .002) and left atrial V wave (26.6 ± 8.5 vs 21.4 ± 7.3 mm Hg, P < .001) postprocedure. In multivariable analysis, abnormal PVF morphology post-MV-TEER was independently associated with mortality at follow-up (hazard ratio = 1.70; 95% CI, 1.06-2.74; P = .03) after correction for end-stage renal disease, atrial fibrillation, and residual MR. Results were similar in subgroups of patients with moderate or less and those with mild or less residual MR. CONCLUSIONS: Pulmonary vein flow morphology is a simple and objective tool to assess MR severity immediately post-MV-TEER and offers important prognostic information to optimize procedural results. Additional studies are needed to determine whether patients with abnormal PVF pattern post-MV-TEER would benefit from more intensive goal-directed medical therapy postprocedure.

Reliable measurement methods for the isovolumic relaxation time: comparisons of dual gate Doppler and seven other methods.

PURPOSE: Isovolumic relaxation time (IVRT) is a useful indicator of diastolic dysfunction. However, a measurement method for IVRT has not been established. The Dual Gate Doppler method, which can record two separate pulse-wave Doppler signals simultaneously using two sample gates, may be ideal for measuring IVRT. This study aimed to evaluate the accuracy of IVRT measured using conventional methods versus that measured using the Dual Gate Doppler method. METHODS: A total of 104 patients (mean age 58 ± 21 years, 48 women) were examined using ultrasound equipment with Dual Gate Doppler at our hospital. In addition to Dual Gate Doppler method, IVRTs were measured using seven different methods: pulsed Doppler (PW method), continuous wave Doppler (CW method), and other methods. The IVRT values obtained using the Dual Gate Doppler method were compared with those measured using other methods. RESULTS: All IVRTs measured using conventional methods showed a strong correlation with the that measured using the Dual Gate Doppler method. However, there were slight deifferences among the IVRTs depending on the method. The PW method and the PW time difference method using only the PW showed small statistical bias and were not complicated. The IVRT measured using the CW method was significantly longer than that measured using the Dual Gate Doppler method. CONCLUSIONS: Among the conventional methods, the PW method was the simplest and most practical method for measuring the IVRT in any conditions as arrhythmias. It is important to recognize the characteristics of IVRTs based on the measurement method.

Poor Correlation between Fetal Tissue Doppler Imaging and Pulsed Wave Myocardial Performance Indices.

INTRODUCTION: Both tissue Doppler imaging (TDI) and pulsed wave Doppler (PWD) Myocardial Performance Indices (MPIs) have been proposed as tools for functional fetal cardiology. We wished to determine if there was any correlation between TDI-MPI and PWD-MPI. METHODS: A cohort of uncomplicated women with morphologically normal singleton fetuses between 22 and 39 weeks of gestation was recruited. A single sonologist acquired Doppler waveforms for evaluation of both left and right TDI-MPI and PWD-MPI. The PWD-MPI values were calculated using a previously published algorithm and the TDI-MPI time intervals were measured manually by a single operator. RESULTS: Achievability and repeatability were high for both modalities. TDI produced significantly lower right MPI values yet significantly higher left MPI values, potentially reflecting their evaluation of physiologically different events, blood flow versus myocardial contraction. CONCLUSION: This study demonstrates that MPIs measured from PWD and TDI have a weak correlation and cannot be used interchangeably, even with the exclusion of suboptimal TDI-MPI scans from the analysis. Given the lack of correlation between the two methods, the high variation in TDI waveform, and the lack of unified approach to TDI analysis, we feel further research is needed before adoption of this technique.

Does arterial stiffness mediate or suppress the associations of blood pressure with cardiac structure and function in adolescents?

There is limited understanding of the role of arterial stiffness in cardiovascular disease risk in the pediatric population, lagging behind strong evidence in the adult population. Arterial stiffness progression among adolescents with hypertension has been considered hypertension-mediated vascular damage. However, emerging pediatric reports suggest that arterial stiffness may precede increased blood pressure and hypertension, whereas increased blood pressure from childhood has been associated with signs of cardiac damage in mid-adulthood. Thus, this study used a third variable analytical approach to examine whether arterial stiffness mediates or suppresses the effects of increasing blood pressure on cardiac structure and function in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of 1,778 adolescents. After an adjustment for cardiometabolic and lifestyle factors, arterial stiffness measured as carotid-femoral pulse wave velocity partly suppressed the association of higher systolic blood pressure with higher left ventricular mass (standardized regression coefficient, ß = -0.012; P = 0.017; suppression effect = 4%), partly mediated the associations of higher systolic and diastolic blood pressure with higher relative ventricular wall thickness, and partly suppressed the association of higher diastolic blood pressure with lower left ventricular diastolic function (ß = -0.021; P = 0.003; suppression effect = 14.5%). In conclusion, increasing arterial stiffness could attenuate some of the adverse effects of increased blood pressure on cardiac structure and function in adolescents possibly by modifying the Windkessel effects.NEW & NOTEWORTHY The present study demonstrates that the associations of blood pressure with cardiac function and structure in adolescents may be mediated or suppressed by arterial stiffness depending on the blood pressure phenotype: systolic or diastolic. Arterial stiffness may be considered as an intermediate pathway to attenuate the effect of increased blood pressure on altered cardiac structure and function in youth.

Transthoracic Echocardiography to Assess Post-Resuscitation Left Ventricular Dysfunction After Acute Myocardial Infarction and Cardiac Arrest in Pigs.

One of the main causes of out-of-hospital cardiac arrest is acute myocardial infarction (AMI). After successful resuscitation from cardiac arrest, approximately 70% of patients die before hospital discharge due to post-resuscitation myocardial and cerebral dysfunction. In experimental models, myocardial dysfunction after cardiac arrest, characterized by an impairment in both left ventricular (LV) systolic and diastolic function, has been described as reversible but very little data are available in cardiac arrest models associated with AMI in pigs. Transthoracic echocardiography is the first-line diagnostic test for the assessment of myocardial dysfunction, structural changes and/or AMI extension. In this pig model of ischemic cardiac arrest, echocardiography was done at baseline and 2-4 and 96 hours after resuscitation. In the acute phase, the examinations are done in anesthetized, mechanically ventilated pigs (weight 39.8 ± 0.6 kg) and ECG is recorded continuously. Mono- and bi-dimensional, Doppler and tissue Doppler recordings are acquired. Aortic and left atrium diameter, end-systolic and end-diastolic left ventricular wall thicknesses, end-diastolic and end-systolic diameters and shortening fraction (SF) are measured. Apical 2-, 3-, 4-, and 5-chamber views are acquired, LV volumes and ejection fraction are calculated. Segmental wall motion analysis is done to detect the localization and estimate the extent of myocardial infarction. Pulsed Wave Doppler echocardiography is used to record trans-mitral flow velocities from a 4-apical chamber view and trans-aortic flow from a 5-chamber view to calculate LV cardiac output (CO) and stroke volume (SV). Tissue Doppler Imaging (TDI) of LV lateral and septal mitral anulus is recorded (TDI septal and lateral s', e', a' velocities). All the recordings and measurements are done according to the recommendations of the American and European Societies of Echocardiography Guidelines.

Tempo de aceleração na via de saída do ventrículo direito: correlação com a função diastólica do ventrículo esquerdo, sexo e idade / Right ventricular outflow tract acceleration time: correlation with left ventricular diastolic function, sex, and age

Fundamento: O tempo de aceleração na artéria pulmonar (TAP) pode ser utilizado para avaliação da hipertensão pulmonar na análise da função diastólica do ventrículo esquerdo. Objetivo: Avaliar se existe correlação entre o valor do tempo de aceleração na artéria pulmonar e parâmetros da função diastólica do ventrículo esquerdo em indivíduos com função sistólica do ventrículo esquerdo preservada e de acordo com sexo, idade e fatores de risco cardiovasculares. Métodos: Estudo observacional, transversal. Foram selecionados 119 pacientes (59 mulheres; 49,6%). Os indivíduos foram submetidos ao ecocardiograma transtorácico incluindo os valores de tempo de aceleração na artéria pulmonar; ondas E e A e relação E/A ao Doppler espectral do influxo mitral; ondas e' septal, e' lateral e relação E/e' ao Doppler tecidual do anel mitral; pressão sistólica na artéria pulmonar e volume atrial esquerdo. Resultados: No sexo feminino, foi encontrada correlação positiva (coeficiente de correlação de Spearman) entre o valor do tempo de aceleração na artéria pulmonar e e' lateral (coeficiente de correlação de Spearman de 0,47; p=0,002), relação E/A (coeficiente de correlação de Spearman de 0,32; p=0,04) e e' septal (coeficiente de correlação de Spearman de 0,36; p=0,023) e uma correlação negativa entre o valor do tempo de aceleração na artéria pulmonar e pressão sistólica na artéria pulmonar (coeficiente de correlação de Spearman de -0,43; p=0,034). No sexo masculino, não foi encontrada correlação significativa. Foram encontrados menores valores de tempo de aceleração na artéria pulmonar em mulheres com hipertensão arterial sistêmica quando comparadas a mulheres sem hipertensão arterial sistêmica (0,13±0,03 segundos versus 0,16±0,03 segundos; p = 0,015). Conclusão: O presente estudo mostrou correlação significativa dos valores do TAP com alguns parâmetros da função diastólica do ventrículo esquerdo apenas no sexo feminino, sendo que mulheres hipertensas apresentaram menores valores de TAP. (AU)

Background: Pulmonary artery acceleration time (PAAT) can be used as a parameter in the evaluation of pulmonary hypertension and aids left ventricular diastolic function (LVDF) analyses. Objective: To assess whether there is a correlation between PAAT and LVDF parameters in individuals with a preserved left ventricular systolic function and by sex, age, and cardiovascular risk factors. Method: Observational cross-sectional study. One hundred nineteen patients were selected (59 women [49.6%]). The subjects underwent transthoracic echocardiography including measurements of PAAT, E and A waves and E/A ratio, e' septal and e' lateral waves and E/e' ratio, pulmonary artery systolic pressure (PASP), and left atrial volume. Results: In female patients, a positive correlation (Spearman's correlation coefficient ­ Spearman correlation coefficient [SCC]) was found between the PAAT value and the lateral e' (SCC, 0.47; p = 0.002), with the E/A ratio (SCC, 0.32; p = 0.04), and with septal e' (SCC, 0.36; p = 0.023), and a negative correlation between PAAT and PASP (SCC, -0.43; p = 0.034). In men, no correlation was found between PAAT. and any parameters. Lower PAAT values were found in women with systemic arterial hypertension (hypertension) than in women without hypertension (0.13 ± 0.03 s versus 0.16 ± 0.03 s; p = 0.015). Conclusion: The present study showed a significant correlation between PAAT and some LVDF parameters in female patients only. Hypertension was correlated with lower PAAT values in women. (AU)

Impact of Flow on Prosthesis-Patient Mismatch Following Transcatheter and Surgical Aortic Valve Replacement.

BACKGROUND: Severe prosthesis-patient mismatch (PPM) is diagnosed by an indexed effective orifice area <0.65 cm2/m2, which is derived from stroke volume index. We examined the impact of flow, determined by stroke volume index, on severe PPM following transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). METHODS: We included SAVR patients from the PARTNER 2A trial (Placement of Aortic Transcatheter Valve 2A) and TAVR patients from the PARTNER 2 S3i (Placement of Aortic Transcatheter Valve 2 S3i) registry. The primary end point was the separate analysis of all-cause death, cardiac death, and rehospitalization at 5 years. Following TAVR and SAVR, we compared the primary end points between severe versus no-severe PPM in all patients, in low flow (LF), and in normal flow. Multivariable analysis was performed to determine variables associated with the end points. RESULTS: Nine hundred fifty-four TAVR and 726 SAVR patients with PPM and flow data were included. Severe PPM following TAVR was significantly lower compared with SAVR in all patients (9% versus 28%, P<0.0001), in normal flow (5% versus 8%, P=0.04), and in LF (20% versus 42%, P<0.0001). Severe PPM was associated with rehospitalization following TAVR (odds ratio, 1.52 [95% CI, 1.01-2.29], P=0.0456) and SAVR (odds ratio, 1.51 [95% CI, 1.06-2.16], P=0.0237). Severe PPM in LF was independently associated with cardiac death following TAVR (odds ratio, 1.85 [95% CI, 1.06-3.23], P=0.0308). Following SAVR, severe PPM in LF and low ejection fraction was associated with increased cardiac death (35.26% versus 12.51%, P=0.01) and rehospitalization (37.59% versus 15.46%, P=0.006) compared with severe PPM in LF and preserved ejection fraction, respectively. Severe PPM in normal flow was not associated with clinical outcomes despite higher gradients and smaller valves compared with severe PPM in LF. CONCLUSIONS: Severe PPM is more common following SAVR compared with TAVR. Regardless of the implanted valve size or gradient, severe PPM impacts mortality only in patients with LF following TAVR and LF and low ejection fraction following SAVR. Severe PPM in normal flow is not associated with poor outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01314313 and NCT02687035.

Inhaled nitric oxide preserves ventricular function during resuscitation using a percutaneous mechanical circulatory support device in a porcine cardiac arrest model: an echocardiographic myocardial work analysis.

BACKGROUND: Resuscitation using a percutaneous mechanical circulatory support device (iCPR) improves survival after cardiac arrest (CA). We hypothesized that the addition of inhaled nitric oxide (iNO) during iCPR might prove synergistic, leading to improved myocardial performance due to lowering of right ventricular (RV) afterload, left ventricular (LV) preload, and myocardial energetics. This study aimed to characterize the changes in LV and RV function and global myocardial work indices (GWI) following iCPR, both with and without iNO, using 2-D transesophageal echocardiography (TEE) and GWI evaluation as a novel non-invasive measurement. METHODS: In 10 pigs, iCPR was initiated following electrically-induced CA and 10 min of untreated ventricular fibrillation (VF). Pigs were randomized to either 20 ppm (20 ppm, n = 5) or 0 ppm (0 ppm, n = 5) of iNO in addition to therapeutic hypothermia for 5 h following ROSC. All animals received TEE at five pre-specified time-points and invasive hemodynamic monitoring. RESULTS: LV end-diastolic volume (LVEDV) increased significantly in both groups following CA. iCPR alone led to significant LV unloading at 5 h post-ROSC with LVEDV values reaching baseline values in both groups (20 ppm: 68.2 ± 2.7 vs. 70.8 ± 6.1 mL, p = 0.486; 0 ppm: 70.8 ± 1.3 vs. 72.3 ± 4.2 mL, p = 0.813, respectively). LV global longitudinal strain (GLS) increased in both groups following CA. LV-GLS recovered significantly better in the 20 ppm group at 5 h post-ROSC (20 ppm: - 18 ± 3% vs. 0 ppm: - 13 ± 2%, p = 0.025). LV-GWI decreased in both groups after CA with no difference between the groups. Within 0 ppm group, LV-GWI decreased significantly at 5 h post-ROSC compared to baseline (1,125 ± 214 vs. 1,835 ± 305 mmHg%, p = 0.011). RV-GWI was higher in the 20 ppm group at 3 h and 5 h post-ROSC (20 ppm: 189 ± 43 vs. 0 ppm: 108 ± 22 mmHg%, p = 0.049 and 20 ppm: 261 ± 54 vs. 0 ppm: 152 ± 42 mmHg%, p = 0.041). The blood flow calculated by the Impella controller following iCPR initiation correlated well with the pulsed-wave Doppler (PWD) derived pulmonary flow (PWD vs. controller: 1.8 ± 0.2 vs. 1.9 ± 0.2L/min, r = 0.85, p = 0.012). CONCLUSIONS: iCPR after CA provided sufficient unloading and preservation of the LV systolic function by improving LV-GWI recovery. The addition of iNO to iCPR enabled better preservation of the RV-function as determined by better RV-GWI. Additionally, Impella-derived flow provided an accurate measure of total flow during iCPR.

Nifedipine disturbs fetal cardiac function during hypoxemia in a chronic sheep model at near term gestation.

BACKGROUND: Nifedipine is a widely used drug in pregnancies complicated by maternal hypertensive disorders that can be associated with placental insufficiency and fetal hypoxemia. The evidence regarding fetal myocardial responses to nifedipine in hypoxemia is limited. OBJECTIVE: We hypothesized that nifedipine would not impair fetal sheep cardiac function under hypoxemic environment. In particular, we investigated the effects of nifedipine on fetal ventricular functional parameters and cardiac output. STUDY DESIGN: A total of 21 chronically instrumented fetal sheep at 122 to 134 gestational days (term, 145 days) were included in this study. Fetal cardiac function was evaluated by measuring global longitudinal strain, indices describing ventricular systolic and diastolic function, and cardiac outputs using two-dimensional speckle tracking and tissue and spectral pulsed-wave Doppler echocardiography. Fetal carotid artery blood pressure and blood gas values were invasively monitored. After baseline data collection, fetal hypoxemia was induced by maternal hyperoxygenation. After hypoxemia phase data collection, 9 fetuses received nifedipine infusion, and 12 fetuses received saline infusion. Data were collected 30 and 120 minutes after the infusion was started. After 120 minutes of data collection, maternal and fetal oxygenation were normalized, and normoxemia phase data were collected, while infusion was continued. RESULTS: Hypoxemia decreased fetal carotid artery mean arterial pressure from 40 (8) mm Hg to 35 (8) mm Hg (P<.007), and left ventricular global longitudinal strain showed less deformation than at baseline (P=.001). Under hypoxemia, nifedipine caused a reduction in right ventricular global longitudinal strain (P<.05), a decrease in right ventricular isovolumic relaxation velocity and its deceleration (P<.01) indicating diastolic dysfunction, and a drop in right ventricular cardiac output (P<.05). Nifedipine did not alter fetal left ventricular functional parameters or cardiac output. When normoxemia was restored, fetal right ventricular functional parameters and cardiac output returned to baseline level. CONCLUSION: In hypoxemic fetus, nifedipine impaired right ventricular function and reduced its cardiac output. The detrimental effects of nifedipine on fetal right ventricular function were abolished, when normoxemia was restored. Our findings suggest that in a hypoxemic environment nifedipine triggers detrimental effects on fetal right ventricular function.

Impact of pulsed-wave-Doppler velocity-envelope tracing techniques on classification of complete fetal cardiac cycles.

Fetal echocardiography is an operator-dependent examination technique requiring a high level of expertise. Pulsed-wave Doppler (PWD) is often used as a reference for the mechanical activity of the heart, from which several quantitative parameters can be extracted. These aspects suggest the development of software tools that can reliably identify complete and clinically meaningful fetal cardiac cycles that can enable their automatic measurement. Several scientific works have addressed the tracing of the PWD velocity envelope. In this work, we assess the different steps involved in the signal processing chains that enable PWD envelope tracing. We apply a supervised classifier trained on envelopes traced by different signal processing chains for distinguishing complete and measurable PWD heartbeats from incomplete or malformed ones, which makes it possible to determine the impact of each of the different processing steps on the detection accuracy. In this study, we collected 43 images and labeled 174,319 PWD segments from 25 pregnant women volunteers. By considering seven envelope tracing techniques and the 23 different processing steps involved in their implementation, the results of our study reveal that, compared to the steps investigated in most other works, those that achieve binarisation and envelope extraction are significantly more important (p < 0.05). The best approaches among those studied enabled greater than 98% accuracy on our large manually annotated dataset.

Personalized physiologic flow waveforms improve wave reflection estimates compared to triangular flow waveforms in adults.

Central aortic pressure waveforms contain valuable prognostic information in addition to central systolic pressure. Using pressure-flow relations, wave separation analysis can be used to decompose aortic pressure waveforms into forward- (Pf) and backward-traveling (Pb) components. Reflection magnitude, the ratio of pressure amplitudes (RM = Pb/Pf), is a predictor of heart failure and all-cause mortality. Aortic flow can be measured via Doppler echocardiography or estimated using a triangular flow waveform; however, the latter may underestimate the flow waveform convexity and overestimate Pb and RM. We sought to determine the accuracy of a personalized synthetic physiologic flow waveform, compared with triangular and measured flow waveforms, for estimating wave reflection indices in 49 healthy young (27 ± 6 yr) and 29 older adults [66 ± 6 yr; 20 healthy, 9 chronic kidney disease (CKD)]. Aortic pressure and measured flow waveforms were acquired via radial tonometry and echocardiography, respectively. Triangular and physiologic flow waveforms were constructed from aortic pressure waveforms. Compared with the measured flow waveform, the triangular waveform underestimated Pf in older, but not young, adults and overestimated Pb and RM in both groups. The physiologic waveform was equivalent to measured flow in deriving all wave reflection indices and yielded smaller mean absolute biases than the triangular waveform in all instances (P < 0.05). Lastly, central pulse pressure was associated with triangular, but not physiologic, mean biases for Pb and RM independent of age or central arterial stiffness (P < 0.05). These findings support the use of personalized physiologic flow waveforms as a more robust alternative to triangular flow waveforms when true flow cannot be measured.NEW & NOTEWORTHY We demonstrate that triangular flow waveforms overestimate wave reflection indices, particularly at higher central pulse pressures independent of age or carotid-femoral pulse wave velocity. In contrast, personalized physiologic flow waveforms provide equivalent wave reflection estimates as measured flow waveforms, thereby offering a more robust alternative to triangulation when aortic flow cannot be measured.

Left Atrial Appendage Flow Velocity and Multiple Infarcts in Cryptogenic Stroke.

BACKGROUND: To validate the hypothesis that cryptogenic stroke with multiple infarcts included embolic stroke due to left atrial appendage (LAA) dysfunction, the present retrospective observational study was aimed to clarify the association between LAA flow velocity (LAA-FV) and multiple infarcts in patients with cryptogenic stroke. METHODS: From consecutive patients with cryptogenic stroke admitted to our hospital within 7 days after onset, patients without brain magnetic resonance imaging (MRI) on admission or without transesophageal echocardiography (TEE) during acute hospitalization were excluded, and the remaining patients were enrolled. Multiplicity of fresh infarcts was assessed using diffusion-weighted images from brain MRI. LAA-FV was defined as LAA peak emptying flow velocity on TEE. RESULTS: Of 786 enrolled patients, 522 patients (66%) had a single infarct, and the remaining 264 patients (34%) had multiple infarcts. The percentage of multiple infarcts decreased with increasing quartiles of LAA-FV (p for trend <0.001). The adjusted odds ratio for multiple infarcts decreased with increasing quartiles of LAA-FV (adjusted odds ratio in the fourth quartile, 0.39; 95% confidence interval, 0.25-0.60; compared with the first quartile). LAA-FV as a continuous variable was negatively associated with multiple infarcts (adjusted odds ratio per 10 cm/s, 0.87; 95% confidence interval, 0.81-0.92). CONCLUSIONS: Reduced LAA-FV on TEE was associated with multiple infarcts in patients with cryptogenic stroke. The present findings indicate that cryptogenic stroke with multiple infarcts includes embolic stroke due to LAA dysfunction.

Improving the diagnosis of heart failure in patients with atrial fibrillation.

OBJECTIVE: To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval. METHODS: Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides. RESULTS: 160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e' with natriuretic peptide levels. CONCLUSIONS: Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF.

Value of quantitative analysis of left ventricular systolic function in patients on maintenance hemodialysis based on myocardial work technique.

BACKGROUND: This study aimed to determine the left ventricular (LV) systolic function in patients on maintenance hemodialysis (MHD) using the myocardial work (MW) technique and investigate the clinical value of the MW technique for the quantitative analysis of left ventricular (LV) systolic function in MHD patients with left ventricular hypertrophy (LVH). METHODS: A total of 68 MHD patients and 35 controls were registered in this study. The MHD patients were divided into the non-left ventricular hypertrophy (NLVH) group (n = 35) and the LVH group (n = 33) according to the LV mass index (LVMI). MW was used to generate the LV global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), and global wasted work (GWW), global work efficiency (GWE). GLS and the MW parameters (GWI, GCW, GWW, GWE) were compared between groups and the correlations between these parameters and the LV ejection fraction (LVEF) in the LVH group were examined. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of MW parameters and GLS for the assessment of LV systolic dysfunction in MHD with LVH patients. RESULTS: The LVH group had significantly lower GWE, GWI, GCW, and GLS but higher GWW than the control and NLVH groups. Compared with the control group, the NLVH group had significantly lower GWE and GLS and higher GWW, but no significant differences in GWI, GCW were observed between these two groups. The LVEF was negatively correlated with GWW in MHD patients, but positively correlated with GWI, GWE, and GCW in the LVH group. Receiver operating characteristic curve (ROC) analysis revealed that GWE, GWW, GWI, and GCW had appreciable area under the curve (AUC), sensitivity, and specificity for evaluating LV function in LVH patients on MHD. CONCLUSIONS: The MW parameters can quantitatively represent the LV myocardial work in MHD patients. Thus, the technique provides a new method for the quantitative evaluation of LV systolic function in MHD with LVH patients.

Scaffold-free tissue-engineered arterial grafts derived from human skeletal myoblasts.

Tissue-engineered vascular grafts (TEVGs) are in urgent demand for both adult and pediatric patients. Although several approaches have utilized vascular smooth muscle cells (SMCs) and endothelial cells as cell sources for TEVGs, these cell sources have a limited proliferative capacity that results in an inability to reconstitute neotissues. Skeletal myoblasts are attractive cell sources as they possess high proliferative capacity, and they are already being tested in clinical trials for patients with ischemic cardiomyopathy. Our previous study demonstrated that periodic hydrostatic pressurization (PHP) promoted fibronectin fibrillogenesis in vascular SMCs, and that PHP-induced extracellular matrix (ECM) arrangements enabled the fabrication of implantable arterial grafts derived from SMCs without using a scaffold material. We assessed the molecular response of human skeletal myoblasts to PHP exposure, and aimed to fabricate arterial grafts from the myoblasts by exposure to PHP. To examine the PHP-response genes, human skeletal myoblasts were subjected to bulk RNA-sequencing after PHP exposure. Gene-set enrichment analysis revealed significant positive correlations between PHP exposure and vascular development-related genes. Real-time polymerase chain reaction (RT-PCR) demonstrated that PHP significantly upregulated collagen and elastic fiber formation-related gene expression, such as fibronectin, lysyl oxidase, collagen type I α1, collagen type IV α1, and tropoelastin. Based on these findings showing the potential role of PHP in vessel formation, we fabricated arterial grafts by repeated cell seeding and exposure to PHP every 24 hours. The resultant 15-layered myoblast grafts had high collagen content, which provided a tensile rupture strength of 899 ± 104 mm Hg. Human skeletal myoblast grafts were implanted as patch grafts in the aorta of immunosuppressed rats and found to be endothelialized and completely patent until the endpoint of 60 postoperative days. Implanted human myoblasts were gradually replaced by host-derived cells, which successfully formed vascular neotissues with layered elastic fibers. These findings suggest that human skeletal myoblasts have the potential to be a feasible cell source for scaffold-free implantable arterial grafts under PHP culture conditions.