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Vasoactive drugs alter smooth muscle tone not only in arterial resistance vessels, but also in large conduit arteries. The resultant changes in smooth muscle tone alter both conduit vessel size and stiffness and hence influence pulsatile components of left ventricular afterload. The effects of smooth muscle relaxation and contraction on arterial elastic properties are complex and have not been fully characterized. Several recent studies have utilized a new intravascular ultrasound technique to study the effects of changes in smooth muscle tone on brachial artery elastic mechanics in normal human subjects in vivo. Smooth muscle relaxation with nitroglycerin improves isobaric brachial artery compliance without significantly altering arterial wall stiffness as measured by incremental elastic modulus (Einc). The improvement in compliance with smooth muscle relaxation is the net result of factors that: (1) increase wall stiffness (increased tension in parallel elastin and collagen fibers); (2) decrease wall stiffness (decreased tension in the smooth muscle and its associated series elastic component); and (3) increase vessel lumen size. Using a modified Maxwell model for the arterial wall, smooth muscle relaxation is also shown to shift the predominant elements contributing to wall stress and Einc from smooth muscle and the collagen fibers in series with the smooth muscle to collagen fibers in parallel with the smooth muscle. A better understanding of the mechanisms contributing to changes in arterial elastic mechanics following alterations in smooth muscle tone will help in developing pharmacologic therapies aimed at reducing pulsatile components of left ventricular afterload. [ABSTRACT FROM PUBLISHER]

Objective: The aim was to test the hypothesis that in normal humans angiotensin II would stimulate local release of noradrenaline under basal conditions or during a sympathetic stimulus provided by lower body negative pressure (LBNP). Methods: Nine healthy volunteers received intra-arterial infusions of angiotensin II, 5 ng·min−1, into the non-dominant forearm. Forearm blood flow (strain gauge plethysmography) and regional noradrenaline spillover (using the tracer methodology of Esler) were measured during angiotensin II alone, LBNP alone, and LBNP plus angiotensin II. Results: Angiotensin II and LBNP decreased forearm blood flow comparably: from 3.1(SD 1.5) to 2.4 (0.9) ml·100 g−1·min−1 during angiotensin II, p<0.05; and from 3.3(1.5) to 2.5(1.0) ml·100 g−1·min−1 during LBNP, p<0.05 (p = NS, A-II v LBNP). Angiotensin II had no effect on forearm venous noradrenaline or regional noradrenaline spillover. LBNP increased venous noradrenaline outflow from the forearm, from 1.6(0.40) to 2.1(0.6) nmol·min−1 (p<0.05), while regional noradrenaline spillover tended to increase, rising from 1.5(0.8) to 2.0(1.0) nmol·100 ml−1·min−1. Angiotensin II did not enhance forearm blood flow or noradrenaline responses to LBNP. Conclusions: In the human forearm, mildly vasoconstrictor infusions of angiotensin II do not increase local release of noradrenaline, either alone or during mild LBNP. At least under these conditions, angiotensin II would not appear to be a potent influence on local sympathetic activity.Cardiovascular Research 1994;28:663-666 [ABSTRACT FROM PUBLISHER]

There is an 80-90% mortality rate within the first 2 months of the occurrence of a post-infarction ventricular septal defect (VSD) with medical treatment alone. The muscular VSD presents a technical problem for the surgeon. Surgical treatment was unsuccessful in two patients. They were treated successfully using the Amplatzer Septal Occluder, with improvement in their condition. [ABSTRACT FROM AUTHOR]

BACKGROUND: An interatrial shunt may provide an autoregulatory mechanism to decrease left atrial pressure and improve heart failure (HF) symptoms and prognosis. METHODS: Patients with symptomatic HF with any left ventricular ejection fraction (LVEF) were randomized 1:1 to transcatheter shunt implantation versus a placebo procedure, stratified by reduced (≤40%) versus preserved (>40%) LVEF. The primary safety outcome was a composite of device-related or procedure-related major adverse cardiovascular or neurological events at 30 days compared with a prespecified performance goal of 11%. The primary effectiveness outcome was the hierarchical composite ranking of all-cause death, cardiac transplantation or left ventricular assist device implantation, HF hospitalization, outpatient worsening HF events, and change in quality of life from baseline measured by the Kansas City Cardiomyopathy Questionnaire overall summary score through maximum 2-year follow-up, assessed when the last enrolled patient reached 1-year follow-up, expressed as the win ratio. Prespecified hypothesis-generating analyses were performed in patients with reduced and preserved LVEF. RESULTS: Between October 24, 2018, and October 19, 2022, 508 patients were randomized at 94 sites in 11 countries to interatrial shunt treatment (n=250) or a placebo procedure (n=258). Median (25th and 75th percentiles) age was 73.0 years (66.0, 79.0), and 189 patients (37.2%) were women. Median LVEF was reduced (≤40%) in 206 patients (40.6%) and preserved (>40%) in 302 patients (59.4%). No primary safety events occurred after shunt implantation (upper 97.5% confidence limit, 1.5%; P <0.0001). There was no difference in the 2-year primary effectiveness outcome between the shunt and placebo procedure groups (win ratio, 0.86 [95% CI, 0.61–1.22]; P =0.20). However, patients with reduced LVEF had fewer adverse cardiovascular events with shunt treatment versus placebo (annualized rate 49.0% versus 88.6%; relative risk, 0.55 [95% CI, 0.42–0.73]; P <0.0001), whereas patients with preserved LVEF had more cardiovascular events with shunt treatment (annualized rate 60.2% versus 35.9%; relative risk, 1.68 [95% CI, 1.29–2.19]; P =0.0001; P interaction<0.0001). There were no between-group differences in change in Kansas City Cardiomyopathy Questionnaire overall summary score during follow-up in all patients or in those with reduced or preserved LVEF. CONCLUSIONS: Transcatheter interatrial shunt implantation was safe but did not improve outcomes in patients with HF. However, the results from a prespecified exploratory analysis in stratified randomized groups suggest that shunt implantation is beneficial in patients with reduced LVEF and harmful in patients with preserved LVEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03499236. [ABSTRACT FROM AUTHOR]

Carvedilol does not worsen glycemic control in patients with type 2 diabetes mellitus (T2DM) and possesses anti-oxidant properties that might provide vascular protection. We sought to compare the effects of carvedilol and metoprolol tartrate on endothelial function and oxidative stress in a head to head trial. Thirty-four patients with T2DM and hypertension were randomized to receive either carvedilol (n = 16) or metoprolol (n = 18) in addition to their current anti-hypertensive medications for five months. The following variables were "measured pre- and post-treatment: blood pressure, fasting glucose and insulin, homeostasis model assessment, hemoglobin A1c, lipids, C-reactive protein (CRP), 8-isoprostane, asymmetric dimethylarginine, oxidized LDL cholesterol, ultrasound assessment of brachial artery flow-mediated dilation (FMD), nitroglycerin-induced endothelium-independent dilation (EID), brachial and carotid artery distension, distensibility, and compliance. Changes in variables between groups over time were compared with 2X2 (group by time) ANOVA. Background medications were similar between groups. Both carvedilol and metoprolol treatment resulted in significant and equivalent decreases in systolic (p<0.05) and diastolic (p<0.0001) blood pressure. There were no differences between groups for any of the glycemic or lipid variables except HDL cholesterol, which significantly decreased (p<0.05) in the metoprolol compared to carvedilol group. No differences were observed between groups for CRP or the markers of oxidative stress. However, compared to metoprolol, carvedilol significantly improved FMD (carvedilol: 3.5 ± 0.8% to 6.2 ± 0.1% vs. metoprolol: 5.5 ± 0.9% to 4.1 ± 0.9%, p<0.001). There were no differences between groups for EID or arterial stiffness. Compared to metoprolol, carvedilol significantly improves endothelial function in patients with T2DM. Differences in glycemic control and oxidative stress do not seem to explain the observed improvements in FMD, suggesting other mechanisms may be involved. [ABSTRACT FROM AUTHOR]

Aims Right ventricular pacing ( RVp) results in an electrocardiographic left bundle branch block pattern and can lead to heart failure. This study aimed to evaluate echocardiographic and clinical outcomes of heart failure patients with RVp upgraded to cardiac resynchronization therapy ( CRT), as they are frequently excluded from multicentre studies. Methods and results This observational study assessed 655 consecutive patients with QRS ≥120 ms and left ventricular ejection fraction ≤35%. There were 465 patients without significant previous RVp and 190 with RVp >40%. Echocardiograms were analysed pre- CRT and ∼ 1 year post- CRT. Death and heart failure hospitalizations were analysed using Cox regression, adjusted for baseline characteristics. The RVp patients had smaller end-systolic volume ( P = 0.002), were older ( P < 0.001), and had more atrial fibrillation ( P < 0.001) pre- CRT. Ejection fraction and proportion of ischaemic aetiology were similar. One year following CRT implantation the ejection fraction response was greater in the RVp group (8.3 ± 9 vs. 5.8 ± 9 units, P = 0.005). The RVp patients had an adjusted 33% lower risk of death or heart failure hospitalization [hazard ratio ( HR) 0.67 95% confidence interval ( CI) 0.51-0.89, P = 0.005], while tending to have an adjusted lower risk of death ( HR 0.73 95% CI 0.53-1.01, P = 0.055). Conclusion Despite similar ejection fraction pre- CRT, patients upgraded to CRT with previous RVp have smaller end-systolic volume and respond to CRT at least as well as, if not better than, other wide QRS heart failure patients. A greater improvement in ejection fraction and a lower risk of death or heart failure hospitalization when adjusted for baseline characteristics were seen in those with previous RVp. [ABSTRACT FROM AUTHOR]

Aims: Right ventricular (RV) pacing can impair left ventricular (LV) function. When timed with native RV activation, LV-only pacing may cause greater improvements in LV function than biventricular pacing. This study compared the chronic effects of cardiac resynchronization therapy (CRT) on LV mechanics between biventricular pacing and LV-only pacing in patients with normal atrioventricular (AV) conduction.Methods and Results: The Adaptive CRT (aCRT) algorithm provides LV-only pacing timed with native RV activation when the AV interval is normal (≤200 ms during sinus rhythm). We studied patients from the aCRT trial with normal AV conduction at their baseline visit and compared changes in cardiac function after 12 months of treatment with conventional biventricular or mostly (≥80%) LV-only pacing. Speckle tracking echocardiography was used to assess LV myocardial strain before and after treatment. Despite similar improvements in Packer's clinical composite scores and LV volumes, LV-only paced patients (n = 70) had a greater improvement in LV ejection fraction (8.5 ± 11.3% vs. 5.5 ± 10.3%, P = 0.038) and global LV radial strain (6.3 ± 8.6% vs. 4.0 ± 10.1%, P = 0.046) than those randomized to biventricular pacing (n = 91). Strain was improved to a greater extent near the RV pacing lead, in septal and apical regions (P < 0.05 for both regions), in patients receiving LV-only pacing.Conclusion: In heart failure patients with normal AV conduction, LV-only pacing timed with native RV activation may result in greater improvements in LV ejection fraction and myocardial strain compared with biventricular pacing due to better apical and septal function. [ABSTRACT FROM AUTHOR]

Habitual intake of black tea has been associated with relatively lower serum cholesterol concentrations in observational studies. However, clinical trial results evaluating the effects of black tea on serum cholesterol have been inconsistent. Several factors could explain these mixed results, in particular, uncontrolled confounding caused by lifestyle factors (eg, diet). This diet-controlled clinical trial estimates the effect of black tea flavonoid consumption on cholesterol concentrations in 57 borderline hypercholesterolemic individuals (total cholesterol concentrations between 190 and 260 mg/dL [4.9 and 6.7 mmol/L]). A double-blind, randomized crossover trial was conducted in Minneapolis, MN, from April 2002 through April 2004 in which key conditions were tightly controlled to minimize possible confounding. Participants consumed a controlled low-flavonoid diet plus 5 cups per day of black tea or tea-like placebo during two 4-week treatment periods. The flavonoid-free caffeinated placebo matched the tea in color and taste. Differences in cholesterol concentrations at the end of each treatment period were evaluated via linear mixed models. Differences among those treated with tea vs placebo were 3.43 mg/dL (0.09 mmol/L) (95% CI −7.08 to 13.94) for total cholesterol, −1.02 mg/dL (−0.03 mmol/L) (95% CI −11.34 to 9.30) for low-density lipoprotein cholesterol, 0.58 mg/dL (0.02 mmol/L) (95% CI −2.98 to 4.14) for high-density lipoprotein cholesterol, 15.22 mg/dL (0.17 mmol/L) (95% CI −40.91 to 71.35) for triglycerides, and −0.39 mg/dL (−0.01 mmol/L) (95% CI −11.16 to 10.38) for low-density lipoprotein plus high-density lipoprotein cholesterol fraction. The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio decreased by −0.1 units (95% CI −0.41 to 0.21). No results were statistically or clinically significant. The intake of 5 cups of black tea per day did not alter the lipid profile of borderline hypercholesterolemic subjects significantly. [ABSTRACT FROM AUTHOR]

Background: The adaptive cardiac resynchronization therapy (CRT) (aCRT) algorithm provides an important clinical benefit. However, a significant number of patients are nonresponders., Objectives: The goals of this study were to quantify electrical synchrony in patients programmed with aCRT and to assess the echocardiographic effects of optimization in CRT nonresponders and incomplete responders., Methods: We studied 125 patients programmed with aCRT and measured electrical synchrony at multiple device settings using novel electrical dyssynchrony mapping (EDM) technology. Electrical synchrony was quantified as cardiac resynchronization index (CRI), a measure that analyzes areas between multiple pairs of anterior and posterior electrograms and calculates synchrony normalized to native rhythm., Results: CRI improved from baseline aCRT settings to optimal settings on the basis of EDM (56%±29% vs 92%±12%; P<.001). Patients programmed with left ventricle (LV)-only aCRT (group 1, n=68 [54%]) had a higher CRI (62%±25% vs 48%±31%; P=.014) than did patients programmed with biventricular aCRT (group 2, n=57 [46%]). In group 1 and group 2, optimal CRI during sequential biventricular (92%±13% and 93%±9%, respectively) and LV-only (92%±6% and 91%±7%, respectively) pacing was significantly (P<.001) higher than CRI at baseline aCRT setting. In a subset of 53 nonresponders optimized using EDM, there were significant improvements in CRI (37%±25%; P<.0001), LV ejection fraction (6.2%±6.6%; P<.0001), end-diastolic volume (9.5±28.2 mL; P=.015), end-systolic volume (13.4±24.9 mL; P<.001), and transverse (1.5%±4.4%; P=.014), longitudinal (1.0%±2.5%; P=.003), and circumferential (2.6%±8.5%; P=.047) strain., Conclusion: Electrical synchrony improves 56% with CRT using aCRT programming and 92% with EDM optimization. Optimization of aCRT-programmed nonresponders results in significant improvements in LV size and systolic function, offering the possibility of converting CRT nonresponders into responders., Competing Interests: Disclosures Dr Bank, Mr Brown, Dr Burns, and Dr Czeck received research grant support and/or consulting payments from Medtronic. Dr Bank is a cofounder of Myochron, which owns the patents related to the methods and technologies used in this study. The rest of the authors report no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Optimization of atrial-ventricular delay (AVD) during atrial sensing (SAVD) and pacing (PAVD) provides the most effective cardiac resynchronization therapy (CRT). We demonstrate a novel electrocardiographic methodology for quantifying electrical synchrony and optimizing SAVD/PAVD., Methods: We studied 40 CRT patients with LV activation delay. Atrial-sensed to RV-sensed (As-RVs) and atrial-paced to RV-sensed (Ap-RVs) intervals were measured from intracardiac electrograms (IEGM). LV-only pacing was performed over a range of SAVD/PAVD settings. Electrical dyssynchrony (cardiac resynchronization index; CRI) was measured at each setting using a multilead ECG system placed over the anterior and posterior torso. Biventricular pacing, which included multiple interventricular delays, was also conducted in a subset of 10 patients., Results: When paced LV-only, peak CRI was similar (93 ± 5% vs. 92 ± 5%) during atrial sensing or pacing but optimal PAVD was 61 ± 31 ms greater than optimal SAVD. The difference between As-RVs and Ap-RVs intervals on IEGMs (62 ± 31 ms) was nearly identical. The slope of the correlation line (0.98) and the correlation coefficient r (0.99) comparing the 2 methods of assessing SAVD-PAVD offset were nearly 1 and the y-intercept (0.63 ms) was near 0. During simultaneous biventricular (BiV) pacing at short AVD, SAVD and PAVD programming did not affect CRI, but CRI was significantly (p < .05) lower during atrial sensing at long AVD., Conclusions: A novel methodology for measuring electrical dyssynchrony was used to determine electrically optimal SAVD/PAVD during LV-only pacing. When BiV pacing, shorter AVDs produce better electrical synchrony., (© 2024 Wiley Periodicals LLC.)

Background: The wearable cardioverter-defibrillator (WCD) prevents sudden cardiac death due to ventricular tachycardia (VT) or ventricular fibrillation (VF) but does not pace for post-shock asystole (PS-A) or bradycardia (PS-B;<50 beats/ min)., Objectives: The purpose of this study was to assess PS-A and PS-B in patients dying out of hospital (OOH) while wearing a WCD., Methods: The database of the U.S. Food and Drug Administration Manufacturers and User Facility Device Experience (MAUDE) was queried for manufacturers' reports of OOH deaths while patients were wearing a WCD. Excluded were patients who did not receive a shock or were initially shocked for asystole or during resuscitation., Results: From January 2017 to March 2022, 313 patients received an initial WCD shock for VF (n = 150), VT (n = 90), and non-VF/VT rhythms (n = 73). PS-A occurred in 204 patients (65.2%), and PS-B occurred in 111 (35.5%); 85 (41.7%) PS-A patients also had PS-B. Most PS-A patients (n = 185; 90.7%) had an initial shocked rhythm of VF or VT, but 19 patients (9.3%) were initially inappropriately shocked for atrial fibrillation/supraventricular tachycardia (n = 7) and idioventricular (n = 8) or sinus (n = 4) rhythm. PS-A occurred after the first WCD shock in 118 (63.8%) and after the first, second, or third shocks in 159 patients (85.9%). Seven patients had post-shock heart block. Eight patients had permanent pacemakers; 1 became nonfunctional after 1 shock, and 7 showed noncapture and/or asystole after 1 to 4 shocks., Conclusions: Post-shock asystole appears to be common in patients who die OOH after being shocked by a WCD for VF or VT. PS-A also occurs after inappropriate WCD shocks for non-VF/VT rhythms. Implanted pacemakers may not prevent PS-A after a WCD shock. WCD backup pacing should be explored., Competing Interests: Funding Support and Author Disclosures The Minneapolis Heart Institute Foundation funded this study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The LifeVest® wearable cardioverter-defibrillator (WCD) prevents sudden cardiac death in at-risk patients who are not candidates for an implantable defibrillator. The safety and efficacy of the WCD may be impacted by inappropriate shocks (IAS)., Objective: The purpose of this study was to assess the causes and clinical consequences of WCD IAS in survivors of IAS events., Methods: The Food and Drug Administration's Manufacturers and User Facility Device Experience database was searched for IAS adverse events (AE) that were reported during 2021 and 2022., Results: A total of 2568 IAS-AE were found (average number of IAS per event: 1.5 ± 1.9; range 1-48). IAS were caused by tachycardias (1255 [48.9%]), motion artifacts (840 [32.7%]), and oversensing (OS) of low-level electrical signals (473 [18.4%]) (P <.001). Tachycardias included atrial fibrillation (AF) (828 [32.2%]), supraventricular tachycardia (SVT) (333 [13.0%]), and nonsustained ventricular tachycardia/fibrillation (NSVT/VF) (87 [3.4%]). Activities responsible for motion-induced IAS included riding a motorcycle, lawnmower, or tractor (n = 128). In 19 patients, IAS induced sustained ventricular tachycardia or ventricular fibrillation that subsequently were terminated by appropriate WCD shocks. Thirty patients fell and suffered physical injuries. Conscious patients (n = 1905) did not use the response buttons to abort shocks (47.9%) or used them improperly (20.2%). IAS resulted in 1190 emergency room visits or hospitalizations, and 17.3% of patients (421/2440) discontinued the WCD after experiencing IAS, especially multiple IAS., Conclusions: The LifeVest WCD may deliver IAS caused by AF, SVT, NSVT/VF, motion artifacts, and oversensing of electrical signals. These shocks may be arrhythmogenic, result in injuries, precipitate WCD discontinuation, and consume medical resources. Improved WCD sensing, rhythm discrimination, and methods to abort IAS are needed., (Copyright © 2023. Published by Elsevier Inc.)

Background: Nonresponse to cardiac resynchronization therapy (CRT) occurs in ∼30%-50% of patients. There are no well-accepted clinical approaches for optimizing CRT in nonresponders., Objective: The purpose of this study was to demonstrate the effect of CRT optimization using electrical dyssynchrony mapping on left ventricular (LV) function, size, and dyssynchrony in selected patients with nonresponse/incomplete response to CRT., Methods: We studied 39 patients with underlying left bundle branch block or interventricular conduction delay who had an LV ejection fraction of ≤40% after receiving CRT and had significant electrical dyssynchrony. Electrical dyssynchrony was measured at multiple atrioventricular delays and interventricular delays. The QRS area between combinations of 9 anterior and 9 posterior electrograms (QRS area under the curve) was calculated, and cardiac resynchronization index (CRI) was defined as the percent change in QRS area under the curve compared to native conduction. Electrical dyssynchrony maps depicted CRI over the wide range of settings tested. Patients were programmed to an optimal device setting, and echocardiograms were recorded 5.9 ± 3.7 months postoptimization., Results: CRI increased from 49.4% ± 24.0% to 90.8% ± 10.5%. CRT optimization significantly improved LV ejection fraction from 31.8% ± 4.7% to 36.3% ± 5.9% (P < .001) and LV end-systolic volume from 108.5 ± 37.6 to 98.0 ± 37.5 mL (P = .009). Speckle-tracking measures of LV strain significantly improved by 2.4% ± 4.5% (transverse; P = .002) and 1.0% ± 2.6% (longitudinal; P = .017). Aortic to pulmonic valve opening time, a measure of interventricular dyssynchrony, significantly (P = .040) decreased by 14.9 ± 39.4 ms., Conclusion: CRT optimization of electrical dyssynchrony using a novel electrical dyssynchrony mapping technology significantly improves LV systolic function, LV end-systolic volume, and mechanical dyssynchrony. This methodology offers a noninvasive, practical clinical approach to treating nonresponders and incomplete responders to CRT., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: There is no clinical methodology for quantification or display of electrical dyssynchrony over a wide range of atrial-ventricular delays (AVD) and ventricular-ventricular delays (VVD) in patients with cardiac resynchronization therapy (CRT). This study aimed to develop a new methodology, based on wavefront fusion, for mapping electrical synchrony., Methods: A cardiac resynchronization index (CRI) was measured at multiple device settings in 90 patients. Electrical dyssynchrony maps (EDM) were constructed for each patient to display CRI at any combination of AVD and VVD. An optimal synchrony line (OSL) depicted the AVD/VVD combinations producing the highest CRIs. Fusion of right ventricular paced (RVp), left ventricular paced (LVp), and native wavefront offsets were calculated., Results: CRI significantly increased (p < 0.0001) from 58.0 ± 28.1% at baseline to 98.3 ± 1.7% at optimized settings. EDMs in patients with high-grade heart block (n = 20) had an OSL parallel to the simultaneous biventricular pacing (BiVP VV-SIM ) line with leftward shift across all AVDs (RVp-LVp OFFSET  = 50.5 ± 29.8 ms). EDMs in patients with intact AV node conduction (n = 64) had an OSL parallel to the BiVP VV-SIM line with leftward shift at short AVDs (RVp-LVp OFFSET  = 33.4 ± 23.3 ms), curvilinear at intermediate AVDs (triple fusion), and vertical at long AVDs (native-LVp OFFSET  = 85.2 ± 22.8 ms) in all patients except those with poor LV lead position (n = 6)., Conclusion: A new methodology is described for quantifying and graphing electrical dyssynchrony over a physiologic range of AVDs/VVDs. This methodology offers a noninvasive, practical, clinical approach for measuring electrical synchrony that could be applied to optimization of CRT devices., Competing Interests: Declaration of Competing Interest Dr. Alan J. Bank and Dr. Kevin V. Burns own patents related to the methods and technologies used in this manuscript. The technologies are licensed to Medtronic and Dr. Alan Bank and Dr. Kevin Burns may receive royalties if the licensed technologies are commercialized. Dr. Alan Bank has received compensation for consulting with Medtronic., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiac resynchronization therapy (CRT) response is proportional to QRS duration (QRS d ). We hypothesize that this is, in part, due to slower conduction velocity and hence wider range of programmed device settings that produce adequate electrical wavefront fusion and resynchronization in wider QRS d patients., Methods: CRT patients (n = 122) with left ventricular (LV) conduction delay, sinus rhythm and intact atrioventricular node conduction were studied. Patients were categorized by QRS d : narrow (<120 ms; n = 20); moderate (120-150 ms, n = 37); and prolonged (≥150 ms; n = 65). Electrocardiographic data was acquired during native rhythm and LV-only pacing at varying atrioventricular delays (AVDs). Electrical synchrony was quantified as cardiac resynchronization index (CRI) using multi‑lead electrocardiographic systems and a proprietary algorithm that quantified wavefront fusion. A Gaussian distribution equation was fitted to CRI response., Results: Peak CRI was high (87.6 ± 6.3%) and similar (p = 0.716) across QRS d groups. The standard deviation of the Gaussian distribution significantly correlated with QRS d (R = 0.614, p < 0.001), and progressively and significantly (p < 0.001) increased as QRS d increased from narrow (34.8 ± 10.0 ms), to moderate (50.6 ± 8.4 ms), to prolonged (67.6 ± 18.3 ms). At AVDs 20 and 40 ms from optimal, CRI differed significantly (p < 0.001) between groups, with progressively higher CRI values as native QRS d increased., Conclusion: Electrical resynchronization with optimally programmed LV-only pacing was similar between patients with varying QRS d , including patients with narrow QRS d . The resynchronization window that corresponded with optimal electrical resynchronization decreased as native QRS d decreased. This finding provides one potential explanation for the lack of significant benefit of CRT in narrow QRS d patients in previous studies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) endocardial pacing is a promising method to deliver cardiac resynchronization therapy (CRT). WiSE-CRT is a wireless LV endocardial pacing system, and delivers ultrasonic energy to an LV electrode., Objective: The purpose of this study was to present short-term outcomes with the WiSE-CRT system in centers with no prior implanting experience., Methods: Data were prospectively collected from 19 centers where WiSE-CRT systems were implanted during the roll-in phase of the SOLVE-CRT trial. Patients were followed at 1, 3, and 6 months, including transthoracic echo (TTE) at 6 months., Results: The WiSE-CRT was successfully implanted in all 31 attempted cases, and 30 patients completed the 6-month follow-up. One patient underwent heart transplantation 1 month after implantation, and was excluded. Fourteen (46.7%) patients demonstrated ≥1 NYHA class improvement. TTE data were available in 29 patients. LV ejection fraction, LV end-systolic volume, and LV end-diastolic volume improved from 28.3% ± 6.7% to 33.5% ± 6.9% (P < .001), 134.9 ± 51.3 mL to 111.1 ± 40.3 mL (P = .0004), and 185.4 ± 58.8 mL to 164.9 ± 50.6 mL (P = .0017), respectively. There were 3 (9.7%) device-related type 1 complications: 1 insufficient LV pacing, 1 embolization of an unanchored LV electrode, and 1 skin infection., Conclusions: We demonstrated a high success rate of LV endocardial electrode placement in centers with no prior implanting experience. Favorable clinical responses in heart failure symptoms and significant LV reverse remodeling were noted., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Novel metrics of electrical dyssynchrony based on multi-electrode mapping and ECG-based markers of fusion are better predictors of cardiac resynchronization therapy (CRT) response than QRS duration., Objective: To describe a new methodology for measuring electrical synchrony based on wavefront fusion and electrocardiographic cancellation in patients with CRT and its potential for CRT optimization., Methods: Patients with left bundle branch block (LBBB) type conduction and CRT (n = 84) were studied at multiple device settings using an ECG belt (53 anterior and posterior electrodes). The area between combinations of anterior and posterior curves (AUC) was calculated and cardiac resynchronization index (CRI) defined as percent change in AUC compared to LBBB., Results: In 14 patients with complete heart block or atrial fibrillation, CRI at optimal ventriculo-ventricular delay (VVD) (40 ± 19 ms) was significantly higher than with simultaneous biventricular pacing (BiVp) (90 ± 8.6% vs. 54.2 ± 24.2%, p < 0.001). In all 70 patients paced LV-only, LV-paced wavefront was ahead of native wavefront at short atrio-ventricular delay (AVD) and CRI increased with increase in AVD, peaked, and then decreased. Optimal CRI during LV-only pacing was significantly better than optimal CRI with simultaneous BiVp (89.6 ± 8% vs. 64.4 ± 22%, p < 0.001), and occurred at AVD 68 ± 22 ms less than the atrial-RV sensed interval. With sequential BiVp, best CRI was 83.9 ± 13% (with LV preactivation of 40 ± 20 ms). Best CRI at any setting was markedly better than CRI at standard setting (91.6 ± 7.7% vs. 52.7 ± 23.3, p < 0.001)., Conclusion: We describe a novel non-invasive investigational tool that quantifies wavefront fusion and electrical dyssynchrony, and may allow for individualized CRT optimization., Competing Interests: Declaration of competing interest Authors have received funding and support from Medtronic, PLC, USA through an External Research Program grant for this study. Medtronic, PLC, USA loaned the ECG belt equipment used to collect the data in this study. Dr. Bank, Mr. Gage, Dr. Schaefer and Dr. Burns applied for and own patents related to the methods used in this study., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Electrical synchronization is likely improved by cardiac resynchronization therapy (CRT), but is difficult to quantify with 12-lead ECG. We aimed to quantify changes in electrical synchrony and potential for optimization with CRT using a body-surface activation mapping (BSAM) system., Methods: Standard deviation of activation times (SDAT) was calculated in 94 patients using BSAM at baseline CRT (CRT bl ), native, and different CRT configurations., Results: SDAT decreased 20% from native to CRT bl (p<0.01) and an additional 26% (p<0.01) at optimal CRT (CRT opt ), the minimal SDAT setting. Patients with LBBB and patients with QRS duration ≥150ms had higher native SDAT and greater decrease with CRT bl (p<0.01); however, the improvement from CRT bl to CRT opt was similar in all four groups (range: 24-28%). CRT opt was achieved with biventricular pacing in 52% and LV-only pacing in 44%. We propose that improved wavefront fusion demonstrated by BSAMs contributed substantially to the improved electrical synchrony., Conclusion: Optimization potential is similar regardless of pre-CRT QRS morphology or duration. BSAM could possibly improve CRT response by individualizing device programming to minimize electrical dyssynchrony., (Copyright © 2017. Published by Elsevier Inc.)

Background: Electrical heterogeneity (EH) during cardiac resynchronization therapy may vary with different left ventricular (LV) pacing sites., Objective: The purpose of this study was to evaluate the relationship between such changes and acute hemodynamic response (AHR)., Methods: Two EH metrics-standard deviation of activation times and mean left thorax activation times-were computed from isochronal maps based on 53-electrode body surface mapping during baseline AAI pacing and biventricular (BiV) pacing from different pacing sites in coronary veins in 40 cardiac resynchronization therapy-indicated patients. AHR at different sites was evaluated by invasive measurement of LV-dp/dt max at baseline and BiV pacing, along with right ventricular (RV)-LV sensing delays and QRS duration., Results: The site with the greatest combined reduction in standard deviation of activation times and left thorax activation times from baseline to BiV pacing was hemodynamically optimal (defined by AHR equal to, or within 5% of, the largest dp/dt response) in 35 of 40 patients (88%). Sites with the longest RV-LV and narrowest paced QRS were hemodynamically optimal in 26 of 40 patients (65%) and 28 of 40 patients (70%), respectively. EH metrics from isochronal maps had much better accuracy (sensitivity 90%, specificity 80%) for identifying hemodynamically responsive sites (∆LV dp/dt max ≥10%) compared with RV-LV delay (69%, 85%) or paced QRS reduction (52%, 76%). Multivariate prediction model based on EH metrics showed significant correlation (R 2 = 0.53, P <.001) between predicted and measured AHR., Conclusion: Changes in EH from baseline to BiV pacing more accurately identified hemodynamically optimal sites than RV-LV delays or paced QRS shortening. Optimization of LV lead location by minimizing EH during BiV pacing, based on body surface mapping, may improve CRT response., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Electrical activation is important in cardiac resynchronization therapy (CRT) response. Standard electrocardiographic analysis may not accurately reflect the heterogeneity of electrical activation., Objective: We compared changes in left ventricular size and function after CRT to native electrical dyssynchrony and its change during pacing., Methods: Body surface isochronal maps using 53 anterior and posterior electrodes as well as 12-lead electrocardiograms were acquired after CRT in 66 consecutive patients. Electrical dyssynchrony was quantified using standard deviation of activation times (SDAT). Ejection fraction (EF) and left ventricular end-systolic volume (LVESV) were measured before CRT and at 6 months. Multiple regression evaluated predictors of response., Results: ∆LVESV correlated with ∆SDAT (P = .007), but not with ∆QRS duration (P = .092). Patients with SDAT ≥35 ms had greater increase in EF (13 ± 8 units vs 4 ± 9 units; P < .001) and LVESV (-34% ± 28% vs -13% ± 29%; P = .005). Patients with ≥10% improvement in SDAT had greater ∆EF (11 ± 9 units vs 4 ± 9 units; P = .010) and ∆LVESV (-33% ± 26% vs -6% ± 34%; P = .001). SDAT ≥35 ms predicted ∆EF, while ∆SDAT, sex, and left bundle branch block predicted ∆LVESV. In 34 patients without class I indication for CRT, SDAT ≥35 ms (P = .015) and ∆SDAT ≥10% (P = .032) were the only predictors of ∆EF., Conclusion: Body surface mapping of SDAT and its changes predicted CRT response better than did QRS duration. Body surface mapping may potentially improve selection or optimization of CRT patients., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the frequency and clinical implications of a delayed echocardiographic response to cardiac resynchronization therapy (CRT)., Background: Long-term prognosis for CRT patients is routinely based on the assessment of echocardiograms after 6 to 12 months of therapy. Some patients, however, may require a longer period of therapy before echocardiographic improvements are detectable., Methods: This observational study included all patients with heart failure (HF) receiving a CRT device at a single center from 2003 to 2011. Eligible patients met current indications and had technically adequate echocardiograms from before implantation, approximately 1 year after implantation (mid-term), and ≥3 years after implantation (long-term). A positive echocardiographic response to CRT was defined as a reduction in left ventricular end-systolic volume ≥15%. All-cause mortality was compared for patients in 3 response groups: mid-term responders, long-term responders, and nonresponders., Results: During this study, 294 patients met the study criteria. Of the 120 patients who were nonresponders after 1 year, 52 (43%) experienced a delayed positive response. Delayed, long-term responders had mortality and hospitalization rates similar to mid-term responders and significantly lower than nonresponders., Conclusions: Among patients surviving at least 3 years after implantation of a CRT device and with echocardiographic follow-up, a significant portion of nonresponders after 1 year of CRT experience a delayed echocardiographic response after a longer period of time. Survival and hospitalization rates were similar for all echocardiographic responders, regardless of the time at which the response occurred., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy (CRT) is an exciting therapy that can treat patients with systolic heart failure and left ventricular dysfunction who have a wide QRS complex. Indications for its use have been refined and expanded based on recent clinical data and guidelines, yet the rate of new CRT implants in the United States has not changed much over the past 8 years. Many patients receiving implantable cardioverter-defibrillators can benefit from, but are not receiving, appropriately-indicated CRT devices. We summarize data on CRT use, discuss reasons for probable underutilization, and provide recommendations for augmenting proper and effective use of this highly beneficial therapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) remodeling predicts poor outcomes in heart failure (HF) patients. The HeartNet(®) cardiac restraint device (Paracor Medical Inc., Sunnyvale, CA) may reduce LV remodeling and improve functional capacity, quality of life, and outcomes in HF patients. To evaluate the safety and efficacy of the HeartNet Ventricular Support System in HF patients receiving optimal medical therapy., Methods and Results: Prospective, randomized, controlled, multicenter trial in patients with symptomatic HF and LV ejection fraction ≤35% on optimal medical and device therapy. The primary efficacy end points were changes in peak VO(2), 6-minute walk (6MW) distance, and Minnesota Living with Heart Failure (MLWHF) quality of life score at 6 months. The primary safety end point was all-cause mortality at 12 months. Because the planned adaptive interim analysis of the first 122 subjects with a completed 6-month follow-up indicated futility to reach the peak VO(2) end point, trial enrollment was suspended. Hence, the results on the 96 treatment and 114 control subjects are reported. Groups were similar at baseline. At 6 months, responder frequency for a prespecified improvement was similar between groups for peak VO(2) (P = .502) and MLWHF score (P = .184) but borderline higher for improvement in 6MW distance in the treatment compared with the control group (33 [38%] vs. 25 [25%]; P = .044). At 6 months, the treatment group had a significantly greater improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) (P < .001) and decrease in LV mass (P = .032), LV end-diastolic diameter (P = .015), LV end-systolic diameter (P = .032), and LV end-diastolic volume (P = .031) as compared with controls. At 12 months, all-cause mortality and responder rates were similar in the 2 groups. Success rate for the HeartNet implantation was 99%., Conclusion: Enrollment in the trial was stopped because an interim analysis showed futility of reaching the peak VO(2) end point. However, because of the device safety and favorable signals for LV remodeling and quality of life, further investigation of this device is warranted., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Several randomized trials have shown that cardiac resynchronization therapy (CRT) benefits New York Heart Association (NYHA) functional class I/II heart failure (HF) patients, but it is unknown if similar outcomes occur in the real-world., Methods and Results: All patients receiving CRT between 2003 and 2008 with ejection fraction (EF) ≤35% and QRS duration ≥120 ms were included. Outcomes assessed were subjective clinical response, echocardiographic response, and survival free of cardiovascular (CV) hospitalization. Baseline demographics in functional class I/II (n = 155) and functional class III/IV (n = 512) were similar, except for differences in age and several comorbidities. Clinical response was similar in both groups. The functional class I/II group had a greater decrease in left ventricular (LV) end-diastolic dimension (P = .031), and trended toward greater improvements in LV end-systolic dimension (P = .056) and EF (P = .059). The functional class I/II group had a better 5-year survival rate (79 vs 54%; P < .0001) and survival free of CV hospitalization (45% vs 26%; P < .0001)., Conclusions: In this real-world clinical scenario, NYHA functional class I/II CRT patients improved clinical status, and LV function and size as good as or better than those in NYHA functional class III/IV patients. These observations provide further support for the use of CRT in patients with mild symptoms of HF., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cardiac pacing is a common treatment option for patients with sick sinus syndrome or atrioventricular block, with the ventricular pacing lead often secured in the convenient right ventricular (RV) apical location. While RV pacing reduces symptoms and limitations associated with heart block, it may have detrimental effects on cardiac structure and function, leading to heart failure (HF) in some patients. RV pacing creates electrical dyssynchrony similar to a left-bundle branch block, with conduction occurring cell-by-cell rather than through the His-Purkinje network. Studies have shown that impairment of myocardial metabolism, structure, and function related to RV pacing occurs regionally (most prominently near the pacing site) and globally, within the left ventricle. Strategies being studied to prevent or treat pacing-induced intraventricular mechanical dyssynchrony and HF include: initial biventricular rather than RV pacing in selected patients, programming to avoid or minimize RV pacing, use of alternate (non-apical) RV pacing sites, echocardiographic screening for development of pacing-induced dyssynchrony and HF, and upgrade to biventricular pacing.

Background: Several clinical trials have confirmed that cardiac resynchronization therapy (CRT) improves outcomes in well defined patient populations. It is uncertain, however, whether outcomes are similar in real-world clinical settings. This study compared outcomes after CRT with defibrillator (CRT-D) in a large real-world private-practice cardiology setting with those in the COMPANION multicenter trial., Methods and Results: A total of 429 consecutive patients who received CRT-D for standard indications (group 1) were retrospectively compared with the 595 patients (group 3) in the COMPANION CRT-D cohort regarding survival and survival free of cardiovascular (CV) hospitalization. A subgroup of the group 1 patients who met the COMPANION entrance criteria (group 2) was also compared with the COMPANION cohort (group 3) both with and without propensity-matching statistical analysis. Survival and survival free of CV hospitalization was better in group 1 than in group 3. Survival in group 2 with and without propensity matching was similar to group 3. However, survival free of CV hospitalization was better in the real-world patients (group 2) even after adjustment for differences in baseline characteristics., Conclusions: Survival and CV hospitalization outcomes in a real-world clinical setting are as good as, or better than, those demonstrated in the COMPANION research trial., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Chronic right ventricular pacing may lead to left ventricular dyssynchrony, systolic dysfunction, remodeling, and heart failure. Cardiac mechanics may differ between paced and nonpaced heart failure patients, and their optimal treatment may also differ., Methods and Results: Echocardiograms were analyzed using tissue Doppler imaging and speckle tracking echocardiography in 20 patients with chronic right ventricular pacing for complete heart block (RVP group), 29 nonpaced patients with different heart failure etiologies but ejection fractions similar to the RVP group (HF group), and 25 control subjects without pacemakers or heart failure (control group). Left ventricle volumes were smaller in RVP than HF (end-diastolic volume = 93.6 ± 25.1 mL vs. 112.1 ± 22.8 mL), but intraventricular longitudinal and radial dyssynchrony were similar. Dyssynchrony within the septum was greater (number of segments lengthening during systole = 1.9 ± 1.7 vs. 0.9 ± 1.8), systolic torsion was lower (6.2 ± 7.3° vs. 10.6 ± 4.2°), untwisting was delayed (time from peak torsion to peak untwist rate = 188 ± 141 ms vs. 102 ± 73 ms), and apical rotation was reversed in more subjects (35% vs 0%) in RVP than HF groups (P < .05 for all)., Conclusions: Intraventricular dyssynchrony was similar between RVP and HF groups with similar ejection fraction. However, RVP subjects had smaller ventricles, greater dyssynchrony within the septum, lower torsion, altered apical rotation, and delayed untwisting., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Biomarkers of inflammation and hemostasis have been associated with left ventricular (LV) mass. We studied relationships of C-reactive protein (CRP), interleukin-6 (IL6), D-dimer, soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor 1 (PAI-1), soluble thrombomodulin (sTM), soluble tumor necrosis factor type 1 receptor (sTNFR1), von Willebrand factor (vWF), soluble E-selectin (sE-selectin), factor VIII, fibrinogen, matrix metalloproteinase 3 (MMP3), and matrix metalloproteinase 9 (MMP9) with LV mass in an asymptomatic population. Multi-Ethnic Study of Atherosclerosis participants underwent magnetic resonance imaging to characterize LV mass; biomarkers were measured using standardized protocols (N = 763 to 4979). Adjusted models were used to associate each biomarker with LV mass while correcting for potential confounding., Findings: LV mass was associated with many biomarkers after adjustment for demographic characteristics and traditional cardiovascular risk factors. Although the demographic and risk factor adjustments attenuated the association of CRP and IL6 with LV mass, further adjustment for weight changed regression coefficients from positive to negative for CRP and IL6 for LV mass. sTM, Factor VIII, and vWF were directly associated with LV mass in fully-adjusted models. For sTNFR1, sICAM-1, D-dimer, fibrinogen, and PAI-1, adjustment for risk factors and weight rendered associations with LV mass nonsignificant., Conclusions: In this large cohort free of clinical cardiovascular disease, several hemostasis and inflammation markers were associated with LV mass. The unusual finding of a negative relationship of CRP and IL6 with LV mass only after adjustment for weight suggests that the effects of inflammation on LV mass are strongly influenced by obesity.

Ventricular pacing causes early myocardial shortening at the pacing site and pre-stretch at the opposing ventricular wall. This contraction pattern is energetically inefficient and may lead to decreased cardiac function. This study was designed to describe the acute effects of right ventricular apical (RV(a)) pacing on dyssynchrony and systolic function in human subjects with normal left ventricular (LV) function and compare these effects to pacing from alternate ventricular sites. Patients (n = 26) undergoing an electrophysiology evaluation were studied during atrial pacing (AAI) and dual chamber pacing from the RV(a), left ventricular free wall (LV(fw)), and the combination of RV(a) and LV(fw) (BiV). Tissue Doppler imaging was used to measure intramural dyssynchrony by utilizing an integrated cross-correlation synchrony index (CCSI) from the apical 4-chamber view. RV(a) and BiV pacing significantly reduced systolic function as measured by longitudinal systolic contraction amplitude (SCA(long)) (p < 0.05) and LV velocity time integral (VTI) (p < 0.05) compared to AAI and LV(fw) pacing. RV(a) (and to a lesser extent BiV) pacing resulted in septal and lateral intramural dyssynchrony as indicated by significantly (p < 0.05) lower CCSI values as compared to AAI. CCSI was significantly (p < 0.05) worse during RV(a) than LV(fw) pacing. In patients with normal LV function, acute ventricular pacing in the RV(a) alone, or in conjunction with LV(fw) pacing (BiV), results in impaired regional and global LV systolic function and intramural dyssynchrony as compared to LV(fw) pacing alone.

Background: Retrospective single-center studies have shown that measures of mechanical dyssynchrony before cardiac resynchronization therapy (CRT), or acute changes after CRT, predict response better than QRS duration. The Prospective Minnesota Study of Echocardiographic/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) study was a prospective multicenter study designed to determine whether acute (1 week) changes in mechanical dyssynchrony were associated with response to CRT., Methods and Results: Nine Minnesota Heart Failure Consortium centers enrolled 71 patients with standard indications for CRT. Left ventricular (LV) size, function, and mechanical dyssynchrony (echocardiography [ECHO], tissue Doppler imaging [TDI], speckle-tracking echocardiography [STE]) as well as 6-minute walk distance and Minnesota Living with Heart Failure Questionnaire scores were measured at baseline and 3 and 6 months after CRT. Acute change in mechanical dyssynchrony was not associated with clinical response to CRT. Acute change in STE radial dyssynchrony explained 73% of the individual variation in reverse remodeling. Baseline measures of mechanical dyssynchrony were associated with reverse remodeling (but not clinical) response, with 4 measures each explaining 12% to 30% of individual variation., Conclusions: Acute changes in radial mechanical dyssynchrony, as measured by STE, and other baseline mechanical dyssynchrony measures were associated with CRT reverse remodeling. These data support the hypothesis that acute improvement in LV mechanical dyssynchrony is an important mechanism contributing to LV reverse remodeling with CRT.

The AcuNav-catheter is a vector-phased array ultrasound catheter that has shown great utility for both diagnosis and electrophysiological interventions. To test the feasibility of limited catheter reuse and to ensure that reprocessed catheters would produce acceptable clinical images, the present study compared the 2-D and Doppler image quality, as determined by clinical assessment, with the catheter's functional status as determined by the FirstCall 2000 transducer tester. Reprocessed catheters from four functional categories, two acceptable and two unacceptable, were used to collect images, 2-D and Doppler, from a porcine heart. The images were blinded and then rated by clinical evaluation. The study found that catheter images from all functional categories were found to be clinically acceptable except for those from the lowest unacceptable category. In addition, examination of tip deflection characteristics showed no significant difference between new and reprocessed catheters. We conclude that reprocessed AcuNav catheters that pass functional tests are able to produce clinical images, 2-D and Doppler, which are equivalent to their new counterparts.