Racial and ethnic differences in left atrial appendage occlusion wait time, complications, and periprocedural management.

PURPOSE: Non-white patients are underrepresented in left atrial appendage occlusion (LAAO) trials, and racial disparities in LAAO periprocedural management are unknown. METHODS: We assessed sociodemographics and comorbidities of consecutive patients at our institution undergoing LAAO between 2015 and 2020, then in adjusted analyses, compared procedural wait time, procedural complications, and post-procedure oral anticoagulation (OAC) use in whites versus non-whites. RESULTS: Among 109 patients undergoing LAAO (45% white), whites had lower CHA2 DS2 VASc scores, on average, than non-whites (4.0 vs. 4.8, p = .006). There was no difference in median time from index event (IE) or initial outpatient cardiology encounter to LAAO procedure (whites 10.5 vs. non-whites 13.7 months, p = .9; 1.9 vs. 1.8 months, p = .6, respectively), and there was no difference in procedural complications (whites 4% vs. non-whites 5%, p = .33). After adjusting for CHA2 DS2 VASc score, OAC use at discharge tended to be higher in whites (OR 2.4, 95% CI [0.9-6.0], p = .07). When restricting the analysis to those with prior gastrointestinal (GI) bleed, adjusting for CHA2 DS2 VASc score and GI bleed severity, whites had a nearly five-fold odds of being discharged on OAC (OR 4.6, 95% CI [1-21.8], p = 0.05). The association between race and discharge OAC was not mediated through income category (total mediation effect 19% 95% CI [-.04-0.11], p = .38). CONCLUSION: Despite an increased prevalence of comorbidities amongst non-whites, wait time for LAAO and procedural complications were similar in whites versus non-whites. Among those with prior GI bleed, whites were nearly five-fold more likely to be discharged on OAC than non-whites, independent of income.

Cardiovascular safety of fenfluramine in the treatment of Dravet syndrome: Analysis of an ongoing long-term open-label safety extension study.

OBJECTIVE: Fenfluramine, which was previously approved as a weight loss drug, was withdrawn in 1997 when reports of cardiac valvulopathy emerged. The present study was conducted in part to characterize the cardiovascular safety profile of low-dose fenfluramine when used in a pediatric population to reduce seizure frequency in patients with Dravet syndrome. METHODS: Patients 2- to 18-years-old with Dravet syndrome who had completed any of three randomized, placebo-controlled clinical trials of fenfluramine were offered enrollment in this open-label extension (OLE) study. All patients were treated with fenfluramine starting at a dose of 0.2 mg/kg/day (oral solution dosed twice per day), which was titrated to maximal effect with a dose limit of 0.7 mg/kg/day (maximum 26 mg/day) or 0.4 mg/kg/day (maximum 17 mg/day) in patients receiving concomitant stiripentol. Standardized echocardiographic examinations were conducted at Week 4 or 6 and then every 3 months during the OLE study to monitor cardiac valve function and structure and pulmonary artery pressure. The primary end point for the echocardiography analysis was the number of patients who developed valvular heart disease or pulmonary artery hypertension (PAH) during treatment. RESULTS: A total of 232 patients were enrolled in the study. The average age of patients was 9.1 ± 4.7 years, and 55.2% were male. The median duration of treatment with fenfluramine was 256 days (range = 58-634 days), and the mean dose of fenfluramine was 0.41 mg/kg/day. No cases of valvular heart disease or PAH were observed. SIGNIFICANCE: Longitudinal echocardiography over a median 8.4 months of treatment with fenfluramine suggests a low risk of developing cardiac valvulopathy and PAH when used to treat pediatric patients with Dravet syndrome.

Evolution of Echocardiographic Measures of Cardiac Disease From CKD to ESRD and Risk of All-Cause Mortality: Findings From the CRIC Study.

RATIONALE & OBJECTIVE: Abnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality. STUDY DESIGN: Prospective study. SETTING & PARTICIPANTS: We studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD. PREDICTOR: We measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD. OUTCOMES: All-cause mortality after dialysis therapy initiation. ANALYTICAL APPROACH: Cox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality. RESULTS: Over a mean of 2.9 years between pre- and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P<0.001) and LVESV (18.6 to 20.2mL/m2.7; P<0.001). During this time, there was improvement in left ventricular mass index (60.4 to 58.4g/m2.7; P=0.005) and diastolic relaxation (11.11% to 4.94% with moderately/severely abnormal; P=0.02). Changes in left atrial volume (4.09 to 4.15mL/m2; P=0.08) or LVEDV (38.6 to 38.4mL/m2.7; P=0.8) were not significant. Worsening from CKD to ESRD of LVEF (adjusted HR for every 1% decline in LVEF, 1.03; 95% CI, 1.00-1.06) and LVESV (adjusted HR for every 1mL/m2.7 increase, 1.04; 95% CI, 1.02-1.07) were independently associated with greater risk for postdialysis mortality. LIMITATIONS: Some missing or technically inadequate echocardiograms. CONCLUSIONS: In a longitudinal study of patients with CKD who subsequently initiated dialysis therapy, LVEF and LVESV worsened and were significantly associated with greater risk for postdialysis mortality. There may be opportunities for intervention during this transition period to improve outcomes.

Differences in right ventricular morphology, not function, indicate the nature of increased afterload in pulmonary hypertensive subjects with normal left ventricular function.

BACKGROUND: The aim of study was to assess whether a specific morphology of the right ventricle (RV) by 2D echo predicts the hemodynamic nature of pulmonary hypertension (PH). METHODS: We reviewed clinical, 2D echo, and hemodynamic data of 100 patients with PH: divided into three groups: PH from pulmonary vascular disease (PHPVD ; n = 34) with pulmonary vascular resistance (PVR) > 3 mm Hg/L/min (Wood unit [WU]) and pulmonary artery wedge pressure (PAWP) ≤ 15 mm Hg, pulmonary venous hypertension (PVH; n = 33) with PVR < 3 WU and PAWP > 15 mm Hg and PHMIXED (n = 33) with PVR > 3 WU and PAWP > 15 mm Hg. We analyzed several two-dimensional parameters of right heart morphology and function, including the degree of tapering of the RV diameter from base (just above tricuspid annulus) to apex (level of moderator band) in the apical four-chamber view. P = <.05. RESULTS: Baseline characteristics were similar in all three groups: age 62 ± 14.4 years, 69% females, 57% Caucasians. Hemodynamics and 2D echo data of PHPVD vs PVH vs PHMIXED were as follows: PVR 13 ± 6 vs 2 ± 1 vs 7 ± 2 WU, mean pulmonary artery pressure 53 ± 14 vs 34 ± 8 vs 49 ± 8 mm Hg and cardiac index 2.0 ± 0.5 vs 2.8 ± 0.7 vs 2.2 ± 0.7 L/m2 , RV base/apex ratio during systole (sRVb/a ) 1.3 ± 0.2 vs 2.6 ± 0.5 vs 1.5 ± 0.3. Thus, sRVb/a was twofold higher in the PVH vs PHPVD cohort. On ROC analysis, the AUC for sRVb/a for predicting PVR > 3 WU was 0.873, with optimal cutoff of 1.5. CONCLUSION: Systolic RV base/apex ratio is a simple 2D index of RV shape that powerfully predicts a PVR > 3 WU and provides powerful discriminating ability between PVH and PHPVD .

Sodium Excretion and the Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease.

IMPORTANCE: Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD. OBJECTIVE: To evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013. EXPOSURES: The cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion. MAIN OUTCOMES AND MEASURES: A composite of CVD events defined as congestive heart failure, stroke, or myocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication. RESULTS: Among 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (<2894 mg/24 hours) to highest (≥4548 mg/24 hours) quartile of calibrated sodium excretion, 174, 159, 198, and 273 composite CVD events occurred, and the cumulative incidence was 18.4%, 16.5%, 20.6%, and 29.8% at median follow-up. In addition, the cumulative incidence of CVD events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2% vs 13.3% for heart failure, 10.9% vs 7.8% for myocardial infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09-1.70; P = .007) for composite CVD events, 1.34 (95% CI, 1.03-1.74; P = .03) for heart failure, and 1.81 (95% CI, 1.08-3.02; P = .02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (P = .11) and indicated a significant linear association (P < .001). CONCLUSIONS AND RELEVANCE: Among patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD.

Left ventricular remodeling in human heart failure: quantitative echocardiographic assessment of 1,794 patients.

BACKGROUND: The left ventricle (LV) undergoes significant architectural remodeling in heart failure (HF). However, the fundamental associations between cardiac function and LV size and performance have not been thoroughly characterized in this population. We sought to define the adaptive remodeling that occurs in chronic human HF through the detailed analyses of a large quantitative echocardiography database. METHODS: Baseline echocardiograms were performed in 1,794 patients with HF across a broad range of ejection fraction (EF), from less than 10% to greater than 70%. Core lab measurements of LV volumes and length were made, from which EF, mass, sphericity indices, stroke volume (SV), and stroke work were derived. Spearman correlation coefficients and linear regression methods were used to determine the relationships between remodeling parameters. RESULTS: The median EF was 28.6% (IQR 21.9-37.0). Across a multitude of parameters of cardiac structure and function, indexed end-systolic volumes (ESVs) explained the greatest proportion of the variance in EF (R =-0.87, P < 0.0001). Systolic sphericity index and LV mass were also strongly correlated with EF (R =-0.62 and -0.63, P < 0.0001), reflective of the alterations in LV shape and size that occur as EF declines. SV was rigorously maintained across a broad spectrum of EF, until the EF fell below 20%, at which point SV decreased significantly (P < 0.0001). CONCLUSIONS: In chronic HF, the LV undergoes extensive structural adaptive remodeling in order to maintain SV across a broad range of EF. However, when the EF falls below 20%, further modulation of SV is no longer possible through alterations in ventricular architecture.

EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease.

The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing transcatheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease.

Impact of Racial Disparities in Preoperative Cardiovascular Evaluation and Surgical Outcomes in Patients Undergoing Metabolic and Bariatric Surgery: A Retrospective Cohort Analysis.

Background We investigated preoperative referral patterns, rates of cardiovascular testing, surgical wait times, and postoperative outcomes in White versus Black, Hispanic, or other racial or ethnic groups of patients undergoing metabolic and bariatric surgery. Methods and Results This was a single center retrospective cohort analysis of 797 consecutive patients undergoing metabolic and bariatric surgery from January 2014 to December 2018; 86% (n=682) were Black, Hispanic, or other racial or ethnic groups. White versus Black, Hispanic, or other racial or ethnic groups had similar baseline comorbidities and were referred for preoperative cardiovascular evaluation in similar proportion (65% versus 68%, P=0.529). Black, Hispanic, or other racial or ethnic groups of patients were less likely to undergo preoperative cardiovascular testing (unadjusted odds ratio [OR], 0.56; 95% CI, 0.33-0.95; P=0.031; adjusted for Revised Cardiac Risk Index OR, 0.59; 95% CI, 0.35-0.996; P=0.049). White patients had a shorter wait time for surgery (unadjusted hazard ratio [HR], 0.7; 95% CI, 0.58-0.87; P=0.001; adjusted HR, 0.7; 95% CI, 0.56-0.95; P=0.018). Reduction in body mass index at 6 months was greater in White patients (12.9 kg/m2 versus 12.0 kg/m2, P=0.0289), but equivalent at 1 year (14.9 kg/m2 versus 14.3 kg/m2, P=0.330). Conclusions White versus Black, Hispanic, or other racial or ethnic groups of patients were referred for preoperative cardiovascular evaluation in similar proportion. White patients underwent more preoperative cardiac testing yet had a shorter wait time for surgery. Early weight loss was greater in White patients, but equivalent between groups at 12 months.

Automated analysis of limited echocardiograms: Feasibility and relationship to outcomes in COVID-19.

Background: As automated echocardiographic analysis is increasingly utilized, continued evaluation within hospital settings is important to further understand its potential value. The importance of cardiac involvement in patients hospitalized with COVID-19 provides an opportunity to evaluate the feasibility and clinical relevance of automated analysis applied to limited echocardiograms. Methods: In this multisite US cohort, the feasibility of automated AI analysis was evaluated on 558 limited echocardiograms in patients hospitalized with COVID-19. Reliability of automated assessment of left ventricular (LV) volumes, ejection fraction (EF), and LV longitudinal strain (LS) was assessed against clinically obtained measures and echocardiographic findings. Automated measures were evaluated against patient outcomes using ROC analysis, survival modeling, and logistic regression for the outcomes of 30-day mortality and in-hospital sequelae. Results: Feasibility of automated analysis for both LVEF and LS was 87.5% (488/558 patients). AI analysis was performed with biplane method in 300 (61.5%) and single plane apical 4- or 2-chamber analysis in 136 (27.9%) and 52 (10.7%) studies, respectively. Clinical LVEF was assessed using visual estimation in 192 (39.3%), biplane in 163 (33.4%), and single plane or linear methods in 104 (21.2%) of the 488 studies; 29 (5.9%) studies did not have clinically reported LVEF. LV LS was clinically reported in 80 (16.4%). Consistency between automated and clinical values demonstrated Pearson's R, root mean square error (RMSE) and intraclass correlation coefficient (ICC) of 0.61, 11.3% and 0.72, respectively, for LVEF; 0.73, 3.9% and 0.74, respectively for LS; 0.76, 24.4ml and 0.87, respectively, for end-diastolic volume; and 0.82, 12.8 ml, and 0.91, respectively, for end-systolic volume. Abnormal automated measures of LVEF and LS were associated with LV wall motion abnormalities, left atrial enlargement, and right ventricular dysfunction. Automated analysis was associated with outcomes, including survival. Conclusion: Automated analysis was highly feasible on limited echocardiograms using abbreviated protocols, consistent with equivalent clinically obtained metrics, and associated with echocardiographic abnormalities and patient outcomes.

The impact of mitral regurgitation on patients undergoing catheter ablation of atrial fibrillation.

AIMS: Mitral regurgitation (MR) causes left atrium (LA) enlargement and subsequent atrial fibrillation (AF). The presence of MR may increase recurrence rates after AF ablation. The purpose of this study was to determine the impact of MR on recurrence rates after catheter ablation of AF. METHODS AND RESULTS: We compared 95 patients with moderate or greater baseline MR (defined by MR jet area to LA area ratio ≥ 0.2) and AF undergoing ablation to 95 randomly selected patients without significant MR undergoing AF ablation. Electrocardiographic recurrence at 1-year follow-up was the primary outcome. Patients in the MR cohort had mean MR/LA ratio 0.37 vs. 0.09 in controls (P< 0.0001). Mitral regurgitation patients had larger LA dimension (4.5 vs. 4.1 cm, P< 0.0001) and more persistent AF (71 vs. 28%, P< 0.0001). Mitral regurgitation patients had higher recurrence rates than controls (61 vs. 46%, P= 0.04). The degree of MR was higher in patients with recurrence (MR/LA ratio 0.25 vs. 0.20, P= 0.03), as was LA dimension (4.5 vs. 4.1 cm, P< 0.0001). In multivariate analyses, only LA size was an independent predictor of recurrence (odds ratio 2.9 per centimetre increase in LA dimension, P= 0.005). Fifty-five percent of MR patients had normal leaflet motion, with MR likely due to atrial remodelling secondary to AF. CONCLUSION: Mitral regurgitation was associated with increased AF recurrence after AF ablation, but its impact was mediated by LA size. Left atrium size was the only independent predictor of AF recurrence. The high percentage of MR that was likely secondary to AF may have impacted our findings and deserves further study.

EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease.

The introduction of devices for transcatheter aortic valve implantation, mitral repair, and closure of prosthetic paravalvular leaks has led to a greatly expanded armamentarium of catheter-based approaches to patients with regurgitant as well as stenotic valvular disease. Echocardiography plays an essential role in identifying patients suitable for these interventions and in providing intra-procedural monitoring. Moreover, echocardiography is the primary modality for post-procedure follow-up. The echocardiographic assessment of patients undergoing transcatheter interventions places demands on echocardiographers that differ from those of the routine evaluation of patients with native or prosthetic valvular disease. Consequently, the European Association of Echocardiography in partnership with the American Society of Echocardiography has developed the recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. It is intended that this document will serve as a reference for echocardiographers participating in any or all stages of new transcatheter treatments for patients with valvular heart disease.

The utility of prescreening transesophageal echocardiograms: a prospective study.

BACKGROUND: Recent emphasis on the judicious use of imaging prompted the publication of the 2007 ACC/ASE Appropriateness Use Criteria (AUC) for Echocardiography. However, the intersection of the AUC with the safety and clinical use of transesophageal echocardiography (TEE) is not well established. METHODS: We reviewed 490 consecutive orders for TEEs for appropriateness, significant findings, and reasons for cancellation. RESULTS: We found that 79% (389/490) of ordered studies were performed and 21% (101/490) were not. The number of TEEs cancelled for safety reasons (n = 29) was similar to that cancelled for inappropriateness (n = 36). Only 2% (6/389) of those performed were inappropriate vs. 16% of those that were cancelled. New or unsuspected findings were obtained in half of all performed TEEs; the majority of which were ordered to detect cardiac source of embolism (CSE). CONCLUSIONS: The AUC should specifically consider the utility of clinician-based prescreening of TEEs to encourage appropriate use and safety. Furthermore, given the incremental value of TEE over transthoracic echocardiography in detection of CSE, in some cases, TEE may be considered an appropriate initial test for this indication.

Time-varying myocardial stress and systolic pressure-stress relationship: role in myocardial-arterial coupling in hypertension.

BACKGROUND: Myocardial afterload depends on left ventricular (LV) cavity size, pressure, and wall thickness, all of which change markedly throughout ejection. We assessed the relationship between instantaneous ejection-phase pressure and myocardial stress and the effect of arterial wave reflections on myocardial stress in hypertensive and normotensive adults. METHODS AND RESULTS: We studied 42 untreated hypertensive, 42 treated hypertensive, and 42 normotensive adults with normal LV ejection fraction. Time-resolved central pressure, flow, and LV geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography for computation of arterial load and time-varying circumferential and longitudinal myocardial stress. In all 3 groups, peak myocardial stress typically occurred in early systole (within the first 100 milliseconds of ejection), followed by a marked midsystolic shift in the pressure-stress relationship, which favored lower late systolic stress values (P<0.001) relative to pressure. The mean magnitude of this midsystolic shift was quantitatively important in all 3 groups (circumferential stress, 144 to 148 kdynes/cm(2)) and was independently predicted by a higher LV ejection fraction and ratio of LV end-diastolic cavity to wall volume. Time of peak myocardial stress independently correlated with time of the first systolic but not with time of the second systolic central pressure peak. CONCLUSIONS: Peak myocardial stress occurs in early systole, before important contributions of reflected waves to central pressure. In the presence of normal LV ejection fraction, a midsystolic shift in the pressure-stress relationship protects cardiomyocytes against excessive late systolic stress (despite pressure augmentation associated with wave reflections), a coupling mechanism that may be altered in various disease states.

Akt pathway is hypoactivated by synergistic actions of diabetes mellitus and hypercholesterolemia resulting in advanced coronary artery disease.

Atherosclerosis is an inflammatory process leading to enhanced cellular proliferation, apoptosis, and vasa vasorum (VV) neovascularization. While both diabetes mellitus (DM) and hypercholesterolemia (HC) predispose to atherosclerosis, the precise interaction of these risk factors is unclear. Akt is a central node in signaling pathways important for inflammation, and we hypothesized that DM/HC would lead to aberrant Akt signaling and advanced, complex atherosclerosis. DM was induced in pigs by streptozotocin and HC by a high-fat diet. Animals were randomized to control (non-DM, non-HC), DM only, HC only, and DM/HC groups. Coronary artery homogenates were analyzed by immunoblotting for proteins involved in the Akt pathway, including phosphorylated (p)-Akt (Ser473), p-GSK-3beta (Ser9), activated NF-kappaB p65, and VEGF. Immunohistochemical staining for Ki67 (cell proliferation), terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) (apoptosis), and von Willebrand factor (vWF) (neovascularization) was performed. Neovascularization was visualized with micro-computerized tomography (CT). Only DM/HC animals developed advanced atherosclerosis and showed decreased p-Akt (Ser473) and p-GSK-3beta (Ser9) levels (P < 0.01 and P < 0.05, respectively). DM/HC arteries demonstrated increased cellular proliferation (P < 0.001), apoptosis (P < 0.01), and activation of NF-kappaB p65 (P < 0.05). Induction of DM/HC also resulted in significant VV neovascularization by enhanced VEGF expression (P < 0.05), increased vWF staining (P < 0.01), and increased density by micro-CT. In conclusion, DM and HC synergistically resulted in complex atherosclerosis associated with attenuated p-Akt (Ser473) levels. Aberrant Akt signaling correlated with increased inflammation, cellular proliferation, apoptosis, and VV neovascularization. Our results revealed a synergistic effect of DM and HC in triggering abnormal Akt signaling, resulting in advanced atherosclerosis.

Arterial pulsatile hemodynamic load induced by isometric exercise strongly predicts left ventricular mass in hypertension.

Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P < or = 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (beta = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (beta = -17.85; P < 0.0001) during handgrip, Zc during handgrip (beta = -150; P < 0.0001), and the change in the timing of wave reflections during handgrip (beta = -0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension.

Intracoronary delivery of mesenchymal stem cells at high flow rates after myocardial infarction improves distal coronary blood flow and decreases mortality in pigs.

OBJECTIVES: Evaluate the effects of pressure and duration of intracoronary (IC) infusion of mesenchymal stem cells (MSCs) on delivery efficiency and safety after myocardial infarction (MI). BACKGROUND: Standard IC delivery of MSCs can lead to intravascular plugging and reduced coronary blood flow. The optimal delivery pressure and duration is unknown. METHODS: Immediately after MI pigs were randomized to 1 of 3 delivery protocols of 5 x 10(7) iron-fluorescent microspheres labeled MSCs, control received 2 ml infusions at 1 ml/min (five times), very high flow rate (VHFR) a single 10 ml infusion at 60 ml/min and the high flow rate (HFR) group a single 10 ml infusion at 20 ml/min. TIMI grade flow was assessed throughout the procedure and at sacrifice (day 14). MSCs distribution was analyzed in isolated hearts by 4.7T MRI. Delivery efficiency was quantified via fluorescent microsphere recovery using a magnetic separation technique and by light microscopy. RESULTS: TIMI grade flow did not change following MI (all groups TIMI 3). However, following MSCs delivery only 18% (2/11) of control animals had TIMI 3 blood flow vs. 56% (5/9) in VHFR and 67% (4/6) in HFR (P = 0.03). As a consequence, 63% of control animals died within 24 hr, 33% in VHFR and none in HFR (P = 0.02). MSCs delivery in the infarct tissue did not differ between the groups (P = 0.06). CONCLUSIONS: A single MSCs infusion at 20 ml/min resulted in improved coronary blood flow and decreased mortality, without sacrificing delivery efficiency.

Clinical utility of automated assessment of left ventricular ejection fraction using artificial intelligence-assisted border detection.

BACKGROUND: Ejection fraction (EF) calculated from 2-dimensional echocardiography provides important prognostic and therapeutic information in patients with heart disease. However, quantification of EF requires planimetry and is time-consuming. As a result, visual assessment is frequently used but is subjective and requires extensive experience. New computer software to assess EF automatically is now available and could be used routinely in busy digital laboratories (>15,000 studies per year) and in core laboratories running large clinical trials. We tested Siemens AutoEF software (Siemens Medical Solutions, Erlangen, Germany) to determine whether it correlated with visual estimates of EF, manual planimetry, and cardiac magnetic resonance (CMR). METHODS: Siemens AutoEF is based on learned patterns and artificial intelligence. An expert and a novice reader assessed EF visually by reviewing transthoracic echocardiograms from consecutive patients. An experienced sonographer quantified EF in all studies using Simpson's method of disks. AutoEF results were compared to CMR. RESULTS: Ninety-two echocardiograms were analyzed. Visual assessment by the expert (R = 0.86) and the novice reader (R = 0.80) correlated more closely with manual planimetry using Simpson's method than did AutoEF (R = 0.64). The correlation between AutoEF and CMR was 0.63, 0.28, and 0.51 for EF, end-diastolic and end-systolic volumes, respectively. CONCLUSION: The discrepancies in EF estimates between AutoEF and manual tracing using Simpson's method and between AutoEF and CMR preclude routine clinical use of AutoEF until it has been validated in a number of large, busy echocardiographic laboratories. Visual assessment of EF, with its strong correlation with quantitative EF, underscores its continued clinical utility.

Failure of digital echocardiography to accurately diagnose intracardiac shunts.

BACKGROUND: Intravenous agitated saline injection during transthoracic echocardiography assists in the detection of right to left intracardiac and intrapulmonary shunts. Whether digital echocardiography offers comparable sensitivity and specificity to analog tape recording to assess shunts is unknown. Technical differences between methods could lead to significant differences in shunt detection. METHODS: Agitated saline was injected intravenously at rest and with Valsalva in 189 consecutive patient studies (406 injections). Echocardiographers assessed presence and degree of left ventricle contrast on simultaneously recorded analog tape and digital echocardiography images in blinded fashion. RESULTS: Digital echocardiography had low overall sensitivity (rest 0.50, valsalva 0.63, late 0.39) compared to analog tape. Longer clip lengths improved sensitivity for detection of late contrast passage (rest 0.50, valsalva 0.67, late 0.46). CONCLUSION: Digital echocardiography saline contrast studies have poor sensitivity for assessment of intracardiac shunts versus analog tape, and increasing clip length only modestly increases sensitivity. Joint Photographic Experts Group digital compression losses may be an important cause of failure to detect intracardiac shunts, including patent foramen ovale.