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.

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.

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.

Cardiac perturbations after high-intensity exercise are attenuated in middle-aged compared with young endurance athletes: diminished stress or depleted stimuli?

Strenuous exercise elicits transient functional and biochemical cardiac imbalances. Yet, the extent to which these responses are altered owing to aging is unclear. Accordingly, echocardiograph-derived left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) and high-sensitivity cardiac troponin I (hs-cTnI) were assessed before (pre) and after (post) a 60-min high-intensity cycling race intervention (CRIT60) in 11 young (18-30 yr) and 11 middle-aged (40-65 yr) highly trained male cyclists, matched for cardiorespiratory fitness. LV and RV GLS were measured at rest and during a semirecumbent exercise challenge performed at the same intensity (young: 93 ± 10; middle-aged: 85 ± 11 W, P = 0.60) pre- and post-CRIT60. Augmentation (change from rest-to-exercise challenge) of LV GLS (pre: -2.97 ± 0.65; post: -0.82 ± 0.48%, P = 0.02) and RV GLS (pre: -2.08 ± 1.28; post: 3.08 ± 2.02%, P = 0.01) was attenuated and completely abolished, in the young following CRIT60, while augmentation of LV GLS (pre: -3.21 ± 0.41; post: -3.99 ± 0.55%, P = 0.22) and RV GLS (pre: -3.47 ± 1.44; post: -1.26 ± 1.00%, P = 0.27) was preserved in middle-aged following CRIT60. While serum hs-cTnI concentration increased followingCRIT60 in the young (pre: 7.3 ± 1.6; post: 17.7 ± 1.6 ng/L, P < 0.01) and middle-aged (pre: 4.5 ± 0.6; post: 10.7 ± 2.0 ng/L, P < 0.01), serum hs-cTnI concentration increased to a greater extent in the young than in the middle-aged following CRIT60 (P < 0.01). These findings suggest that functional and biochemical cardiac perturbations induced by high-intensity exercise are attenuated in middle-aged relative to young individuals. Further study is warranted to determine whether acute exercise-induced cardiac perturbations alter the adaptive myocardial remodeling response.NEW & NOTEWORTHY High-intensity endurance exercise elicits acute cardiac imbalances that may be an important stimulus for adaptive cardiac remodeling. This study highlights that following a bout of high-intensity exercise that is typical of routine day-to-day cycling training, exercise-induced autonomic, biochemical, and functional cardiac imbalances are attenuated in middle-aged relative to young well-trained cyclists. These findings suggest that aging may alter exercise-induced stress stimulus response that initiates cardiac remodeling in athlete's heart.

Effects of liraglutide on diastolic function parameters in patients with type 2 diabetes and coronary artery disease: a randomized crossover study.

BACKGROUND: Diastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, thus modulating factors associated with diastolic dysfunction. We have previously reported the effects of liraglutide on systolic function, and in this current study we explore the effects of liraglutide on diastolic function parameters in patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM. METHODS: Thirty subjects were randomized to liraglutide or placebo intervention for 12 + 12-weeks in this double-blind cross-over study. 2D-echocardiography using tissue velocity imaging was used for assessment of diastolic function parameters. Early diastolic filling velocity (E), late atrial filling velocity (A), E-wave deceleration time (EDT) and E/A ratio was assessed from the pulse wave (PW)-Doppler velocity recording of the mitral inflow. Peak early diastolic annular velocities (e') was measured from color tissue doppler images. RESULTS: Liraglutide, when compared to placebo, induced a significant reduction in average e' and lateral e' velocities (- 0.57 cm/s [- 1.05 to - 0.08] and -0.74 cm/s [-1.32 to -0.15], respectively). Adjusted for the concomitant increase in HR (+ 6.16 bpm [0.79 to 11.54], the changes were not significant. No significant changes in other diastolic function parameters were observed. CONCLUSIONS: Liraglutide therapy did not improve any diastolic function parameters in subjects with T2DM, CAD, and preserved LVEF. Instead, a deterioration in e' was observed, which was associated to an increase in heart rate induced by liraglutide therapy. Trial registration Clinical Trial Registration: http://www.clinicaltrials.gov (unique identifier: NCT01595789) (first submitted May 8, 2012).

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.

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.

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.

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.

Echocardiographic Parameters and Mortality in Pediatric Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to investigate the prognostic value of echocardiographic parameters in pediatric septic patients. DATA SOURCES: MEDLINE, PubMed, and EMBASE (last update April 5, 2020). STUDY SELECTION: Observational studies of pediatric sepsis providing echocardiographic parameters in relation to mortality. DATA EXTRACTION: Echocardiography data were categorized as those describing left ventricular systolic or diastolic function, right ventricular function, and strain echocardiography parameters. Data from neonates and children were considered separately. Analysis is reported as standardized mean difference and 95% CI. DATA SYNTHESIS: We included data from 14 articles (n = 5 neonates, n = 9 children). The fractional shortening was the most commonly reported variable (11 studies, n = 555 patients) and we did not identify an association with mortality (standardized mean difference 0.22, 95% CI [-0.02 to 0.47]; p = 0.07, I2 = 28%). In addition, we did not find any association with mortality also for left ventricular ejection fraction (nine studies, n = 417; standardized mean difference 0.06, 95% CI [-0.27 to 0.40]; p = 0.72, I2 = 51%), peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave (four studies, n = 178; standardized mean difference -0.01, 95% CI [-0.34 to 0.33]; p = 0.97, I2 = 0%), and myocardial performance index (five studies, n = 219; standardized mean difference -0.51, 95% CI [-1.10 to 0.08]; p = 0.09, I2 = 63%). However, in regard to left ventricular diastolic function, there was an association with mortality for higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging ratio (four studies, n = 189, standardized mean difference -0.45, 95% CI [-0.80 to -0.10]; p = 0.01, I2 = 0%) or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging wave (three studies, n = 159; standardized mean difference 0.49, 95% CI [0.13-0.85]; p = 0.008, I2 = 0%). We did not find any association with mortality for early wave of transmitral flow/late (atrial) wave of trans-mitral flow ratio (six studies, n = 273; standardized mean difference 0.28, 95% CI [-0.42 to 0.99]; p = 0.43, I2 = 81%) and peak velocity of systolic mitral annular motion determined by tissue Doppler imaging wave measured at the tricuspid annulus (three studies, n = 148; standardized mean difference -0.18, 95% CI [-0.53 to 0.17]; p = 0.32, I2 = 0%). Only a few studies were conducted with strain echocardiography. CONCLUSIONS: This meta-analysis of echocardiography parameters in pediatric sepsis failed to find any association between the measures of left ventricular systolic or right ventricular function and mortality. However, mortality was associated with higher early wave of transmitral flow/peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging or lower peak velocity of early diastolic mitral annular motion determined by tissue Doppler imaging, indicating possible importance of left ventricular diastolic dysfunction. These are preliminary findings because of high clinical heterogeneity in the studies to date.

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.

Ultrasound targeted microbubble destruction assisted exosomal delivery of miR-21 protects the heart from chemotherapy associated cardiotoxicity.

Chemotherapy related cardiotoxicity is now becoming one of the biggest hurdles for the prognosis of cancer patients. Therapeutically delivering protective small RNAs holds promise for the cardiotoxicity prevention and therapy. However, heart is intrinsically refractory to the nanoparticle-mediated drug delivery. In this study, we found that the exosome-mediated miRNA delivery into the heart could be significantly augmented with the aid of ultrasound targeted microbubble destruction (UTMD). Moreover, we found that UTMD assisted exosomal miR-21 delivery into the heart significantly decreased the cell death, and restored the cardiac function in a doxorubicin induced cardiotoxicity mouse model. Our study here not only provides a promising strategy to protect the heart from the chemotherapy related cardiotoxicity, but also sheds light on gene therapy of other heart diseases.

Association between adipocyte fatty acid-binding protein with left ventricular remodelling and diastolic function in type 2 diabetes: a prospective echocardiography study.

BACKGROUND: The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM. METHODS: Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively. RESULTS: The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e' (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (ß = 0.89, P < 0.01) and worsening of average E/e' (ß = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16-6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease. CONCLUSION: Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.

New insights to the potential mechanisms driving coronary flow reserve impairment in Cushing's syndrome: A pilot noninvasive study by transthoracic Doppler echocardiography.

BACKGROUND: The contribution of functional and/or structural remodeling to reduced coronary flow velocity reserve (CFVR), reflecting impaired coronary microcirculation in Cushing's syndrome (CS), has not been clearly elucidated. We aimed to identify the potential mechanisms of coronary microvascular impairment in CS. METHODS: We studied 15 CS patients (11 female, age 50 ±â€¯9 years) without clinical evidence of cardiovascular disease. Coronary flow velocity in the left anterior descending coronary artery was measured by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. Average peak flow velocities, CFVR, and microvascular resistance in baseline (BMR) and hyperemic conditions (HMR) were assessed. CFVR ≤2.5 was considered a marker of microvascular disease (CMD). Diastolic function (E/e'), global longitudinal strain (GLS) and fractional pulse pressure (fPP), an index of arterial stiffness, were also assessed. RESULTS: CMD was present in 5 patients (33.3%). CMD was primarily driven by increased baseline peak flow velocity (29 ±â€¯12 versus 19.6 ±â€¯4.2 cm/s, p = .03) in the presence of decreased BMR (3.62 ±â€¯0.6 versus 5.46 ±â€¯1.4 mm Hg·s/cm, p = .03). Moreover, urinary cortisol and E/e' were higher (p = .001 and p = .001, respectively) and GLS was lower (p = .009) in patients with CMD. fPP was higher in patients with CMD (p = .01). Urinary cortisol correlated to CFVR (p = .008), E/e' (p < .0001) and GLS (p < .0001). fPP directly correlated to average peak flow velocities at rest (p = .01) and inversely to BMR (p = .03). CONCLUSIONS: Functional microvascular regulatory impairment seems to be the potential mechanism of CMD in CS. CMD seems to be related to decreased myocardial contractility and diastolic dysfunction associated with cortisol excess.

TAVR outcome after reclassification of aortic valve stenosis by using a hybrid continuity equation that combines computed tomography and echocardiography data.

BACKGROUND: In the continuity equation, assumption of a round-shaped left ventricular outflow tract (LVOT) leads to underestimation of the true aortic valve area in two-dimensional echocardiography. The current study evaluated whether inclusion of the LVOT area, as measured by computed tomography (CT), reclassifies the degree of aortic stenosis (AS) and assessed the impact on patient outcome after transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Four hundred and twenty-two patients with indexed aortic valve area index (AVAi) of <0.6 cm2 /m2 , assessed by using the classical continuity equation (mean age: 81.5 ± 6.1 years, 51% female, mean left ventricular ejection fraction: 53.2 ± 13.6%), underwent TAVR and were included. After inclusion of the CT measured LVOT area into the continuity equation, the hybrid AVAi led to a reclassification of 30% (n = 128) of patients from severe to moderate AS. Multivariate predictors for reclassification were male sex, lower mean aortic gradient, and lower annulus/LVOT ratio (all p < .01). Reclassified patients had significantly higher sST2 at baseline and higher NT-proBNP values at baseline and 6 months follow-up compared to non-reclassified patients. Acute kidney injury was experienced more frequently after TAVR by reclassified patients, but no significant mortality difference occurred during 2 years of follow-up. CONCLUSION: The hybrid AVAi reclassifies a significant portion of low-gradient severe AS patients into moderate AS. Reclassified patients showed increased fibrosis and heart failure markers at baseline compared to non-reclassified patients. But reclassification had no significant impact on mortality up to 2 years after TAVR. Routine assessment of hybrid AVAi seems not to improve further risk stratification of TAVR patients.

Association of Local Epicardial Adipose Tissue Depots and Left Ventricular Diastolic Performance in Patients With Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Although full-volume quantification of epicardial adipose tissue (EAT) is a predictor of LV diastolic dysfunction (LVDD), how localized EAT depots are linked to LVDD remains unclear. We evaluated the effect of local EAT depots on LV diastolic function parameters in patients with preserved LV ejection fraction (LVEF).Methods and Results:From 423 consecutive patients who underwent cardiac CT angiography, we recruited 252 with sinus rhythm and normal LVEF. The EAT volume index (EATV/body surface area) and the localized EAT thickness around the right coronary artery (EATRCA), left anterior descending artery (EATLAD), left circumflex artery (EATLCX), right ventricle (EATRV), left ventricle (EATLV), right atrium (EATRA), and left atrium (EATLA) were measured using cardiac CT. In the LVDD group (n=71), the EATV index (75±30 vs. 64±28 mL/m2, P=0.010), EATLCX(10.7±3.8 vs. 9.4±3.4 mm, P=0.008), and EATLV(2.6±1.6 vs. 2.1±1.4 mm, P=0.024) were greater than in the non-LVDD group (n=181). In contrast, EATLCXand EATLVwere markedly associated with decreased lateral e' and increased lateral E/e'. Multiple regression analysis indicated that EATLCXand EATLVwere strongly associated with LV diastolic function parameters. CONCLUSIONS: Localized EAT depots are linked to altered mitral annular motion. Further study is warranted to clarify whether localized EAT depots are functionally linked to the clinical manifestations of LVDD.

Low left ventricular outflow tract velocity time integral is associated with poor outcomes in acute pulmonary embolism.

The left ventricular outflow tract (LVOT) velocity time integral (VTI) is an easily measured echocardiographic stroke volume index analog. Low values predict adverse outcomes in left ventricular failure. We postulate the left ventricular VTI may be a signal of right ventricular dysfunction in acute pulmonary embolism, and therefore a predictor of poor outcomes. We retrospectively reviewed echocardiograms on all Pulmonary Embolism Response Team activations at our institution at the time of pulmonary embolism diagnosis. Low LVOT VTI was defined as ⩽ 15 cm. We examined two composite outcomes: (1) in-hospital death or cardiac arrest; and (2) shock or need for primary reperfusion therapies. Sixty-one of 188 patients (32%) had a LVOT VTI of ⩽ 15 cm. Low VTI was associated with in-hospital death or cardiac arrest (odds ratio (OR) 6, 95% CI 2, 17.9; p = 0.0014) and shock or need for reperfusion (OR 23.3, 95% CI 6.6, 82.1; p < 0.0001). In a multivariable model, LVOT VTI ⩽ 15 remained significant for death or cardiac arrest (OR 3.48, 95% CI 1.02, 11.9; p = 0.047) and for shock or need for reperfusion (OR 8.12, 95% CI 1.62, 40.66; p = 0.011). Among intermediate-high-risk patients, low VTI was the only variable associated with the composite outcome of death, cardiac arrest, shock, or need for reperfusion (OR 14, 95% CI 1.7, 118.4; p = 0.015). LVOT VTI is associated with adverse short-term outcomes in acute pulmonary embolism. The VTI may help risk stratify patients with intermediate-high-risk pulmonary embolism.

Acute rupture of a sinus of Valsalva aneurysm into the right atrium: a case report and a narrative review.

BACKGROUND: Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which has potential for spontaneous rupture into other cardiac chambers or the pericardial space (depending on its location). A ruptured SVA has a very poor prognosis with high morbidity and mortality. The development of a shunt between the sinus of Valsalva and right-sided cardiac chambers results in a continuous murmur on examination. Our case report is a case of SVA rupture into the right atrium. CASE PRESENTATION: In this case report, we describe a 23-year-old patient with an acute onset of chest pain, shortness of breath, palpitations and dizziness starting 2 days prior to presentation to the emergency department. The patient was initially treated for presumed pulmonary embolism overnight while awaiting CTPA the next morning. However, further examination by the inpatient medical team demonstrated a continuous machinery cardiac murmur. Subsequent echocardiography demonstrated an acutely ruptured SVA with shunting to the right atrium. Emergency surgical repair resulted in an excellent outcome for the patient. CONCLUSION: A thorough clinical history and physical examination is the cornerstone of all medical encounters. An SVA could be asymptomatic until acute rupture. Echocardiography is the preferred initial diagnostic tool. Additional imaging techniques can be used to confirm the diagnosis. In cases of rupture, prognosis is poor and surgical repair is always required.

Continuous LVAD monitoring reveals high suction rates in clinically stable outpatients.

Suction of the left ventricle can lead to potentially life-threatening events in left ventricular assist device (LVAD) patients. With the resolution of currently available clinical LVAD monitoring healthcare professionals are unable to evaluate patients' suction occurrences in detail. This study investigates occurrences and durations of suction events and their associations with tachycardia in stable outpatients. Continuous high-resolution LVAD data from HVAD patients were analyzed in the early outpatient period for 15 days. A validated suction detection from LVAD signals was used. Suction events were evaluated as suction rates, bursts of consecutive suction beats, and clusters of suction beats. The occurrence of tachycardia was analyzed before, during, and after suction clusters. Furthermore, blood work, implant strategy, LVAD speed setting, inflow cannula position, left ventricular diameters, and adverse events were evaluated in these patients. LVAD data of 10 patients was analyzed starting at 78 ± 22 postoperative days. Individuals' highest suction rates per hour resulted in a median of 11% (range 3%-61%). Bursts categorized as consecutive suction beats with n = 2, n = 3-5, n = 6-15, and n > 15 beats were homogenously distributed with 10.3 ± 0.8% among all suction beats. Larger suction bursts were followed by shorter suction-free periods. Tachycardia during suction occurred in 12% of all suction clusters. Significant differences in clinical parameters between individuals with high and low suction rates were only observed in left ventricular end-diastolic and end-systolic diameters (P < .02). Continuous high-resolution LVAD monitoring sheds light on outpatient suction occurrences. Interindividual and intraindividual characteristics of longitudinal suction rates were observed. Longer suction clusters have higher probabilities of tachycardia within the cluster and more severe types of suction waveforms. This work shows the necessity of improved LVAD monitoring and the implementation of an LVAD speed control to reduce suction rates and their concomitant burden on the cardiovascular system.

The impact of different geometric assumption of mitral annulus on the assessment of mitral regurgitation volume by Doppler method.

BACKGROUND: Mitral regurgitation volume (MRvol) by quantitative pulsed Doppler (QPD) method previously recommended suffers from geometric assumption error because of circular geometric assumption of mitral annulus (MA). Therefore, the aim of this study was to evaluate the impact of different geometric assumption of MA on the assessment of MRvol by two-dimensional transthoracic echocardiographic QPD method. METHODS: This study included 88 patients with varying degrees of mitral regurgitation (MR). The MRvol was evaluated by QPD method using circular or ellipse geometric assumption of MA. MRvol derived from effective regurgitant orifice area by real time three-dimensional echocardiography (RT3DE) multiplied by MR velocity-time integral was used as reference method. RESULTS: Assumption of a circular geometry of MA, QPD-MAA4C and QPD-MAPLAX overestimated the MRvol by a mean difference of 10.4 ml (P < 0.0001) and 22.5 ml (P < 0.0001) compared with RT3DE. Assumption of an ellipse geometry of MA, there was no significant difference of MRvol (mean difference = 1.7 ml, P = 0.0844) between the QPD-MAA4C + A2C and the RT3DE. CONCLUSIONS: Assuming that the MA was circular geometry previously recommended, the MRvol by QPD-MAA4C was overestimated compared with the reference method. However, assuming that the MA was ellipse geometry, the MRvol by the QPD-MAA4C + A2C has no significant difference with the reference method.