Doppler-Guided Acoustically Active Injection Catheter: Transendocardial Delivery Assessed by an Efficacy Testing Animal Model.

Percutaneous transendocardial injections of therapeutic agents into the myocardium may not always be effective. We used an animal model for assessing the efficacy of the injections using linoleic acid as a testing agent. Efficacious delivery into the myocardium of a beating heart was indicated by rapidly developed local myocardial necrosis and wall motion abnormalities using echocardiography. We employed this experimental model to test our innovative technology, an acoustically active injection catheter. The Doppler ultrasound-guided acoustically active injection catheter effectively delivers the substance to the myocardium but needs further technical improvements to minimize an unwanted systemic distribution of the agent.

A Real-time Color Doppler Marker for Echocardiographic Guidance of an Acoustically Active Extracorporeal Membrane Oxygenation Cannula.

B-mode ultrasound imaging guidance of cannulas can be compromised by noise, artifacts, and echogenicity that is not distinctive from that of surrounding anatomy. We have modified a venovenous extracorporeal membrane oxygenation cannula by embedding piezoelectric crystals into each of its 3 blood flow ports. Each vibrating crystal acoustically interacts with a Doppler imaging signal and produces an instantaneous color marker. The aim of this study was to compare identification of the extracorporeal membrane oxygenation cannula ports by B-mode imaging versus the color Doppler marker. Unlike B-mode imaging, the color Doppler marker identified the corresponding port even in highly challenging closed-chest scans in anesthetized pigs. The method could improve guidance accuracy of cannulas by ultrasound scans.

An Interposed Pad in Open-Chest Echocardiographic Porcine Scans for Mimicking Ultrasound Signal Attenuation in a Human Chest.

Opening a chest in an experimental echocardiographic animal study eliminates ultrasound signal attenuation by the chest wall. We developed a scanning technique that involves the use of an attenuative pad created from a mixture of urethane and titanium dioxide. The pad was interposed within transmission gel between the transducer face and cardiac surface in open-chest scans in a porcine model. Comparative measurements of left ventricular echogenicity without and with the pad demonstrate that the pad reproducibly causes ultrasound signal attenuation that closely mimics chest attenuation in clinical transthoracic echocardiographic studies.

Left Ventricular Septal Hypertrophy in Elderly Patients With Aortic Stenosis.

OBJECTIVES: Left ventricular (LV) septal hypertrophy in aortic stenosis raises diagnostic and therapeutic questions. However, the etiology and clinical consequences of this finding have not been well studied. The aim of this study was to perform a morphologic evaluation of the LV in aortic stenosis and to investigate the contributing factors and consequences of septal hypertrophy. METHODS: Patients with moderate or severe aortic stenosis were prospectively enrolled. Patients with previous myocardial infarction, wall motion abnormalities, at least moderate valvular regurgitation, known cardiomyopathy, an LV ejection fraction of less than 50%, and age younger than 65 years were excluded. RESULTS: Forty-one patients underwent a final analysis. Septal hypertrophy (LV septal wall thickness ≥15 mm) was confirmed in 21 of 41 patients. The septal hypertrophy group had higher peak aortic valve velocity, a higher diabetes mellitus rate, and a higher rate and longer duration of hypertension than those without septal hypertrophy. The peak aortic valve velocity (odds ratio, 7.1; 95% confidence interval, 1.4-37.1) and diabetes mellitus (odds ratio, 7.4; 95% confidence interval, 1.2-46.2) were the significant factors associated with septal hypertrophy by multivariate analysis. Intraventricular conduction disturbance on electrocardiography was more frequent in the septal hypertrophy group (P = .021). CONCLUSIONS: Left ventricular septal hypertrophy was commonly observed in elderly patients with aortic stenosis, and a higher aortic valve velocity, hypertension, and diabetes mellitus were associated factors. Intraventricular conduction disturbance occurred more often in patients with septal hypertrophy than those without, which implies the pathophysiologic consequence. Further studies are needed to determine the impact of septal hypertrophy and intraventricular conduction disturbance on the prognosis of patients after aortic valve interventions.

Visual Estimation of the Severity of Aortic Stenosis and the Calcium Burden by 2-Dimensional Echocardiography: Is It Reliable?

OBJECTIVES: Guidelines have recommended aortic valve surgery in asymptomatic patients with severe aortic stenosis and a large aortic valve calcium burden. The purpose of this study was to determine whether visual assessment of aortic valve calcium and stenosis severity are reliable based on 2-dimensional echocardiography alone. METHODS: We prospectively enrolled 68 patients with aortic stenosis and compared them with 30 control participants without aortic stenosis. All had aortic valve calcium score assessment by computed tomography. In a random order, 2-dimensional images without hemodynamic data were independently reviewed by 2 level 3-trained echocardiographers, who then classified these patients into categories based on aortic valve calcium and stenosis severity. RESULTS: The 68 patients (mean age ± SD, 74 ± 10 years) were classified as having mild (n = 28), moderate (n = 22), and severe (n = 18) aortic stenosis. When the observers were asked to grade the degree of valve calcification, the agreement between them was poor (κ = 0.33-0.39). The visual ability to determine stenosis severity compared with Doppler echocardiography had high specificity (81% and 88% for observers 1 and 2). However, sensitivity was unacceptably low (56%-67%), and the positive predictive value was poor (44%-50%). Agreement was fair (κ= 0.58-0.69) between the observers for determining severe stenosis. CONCLUSIONS: Our results suggest that visual assessment of aortic valve calcium has high interobserver variability; the visual ability to determine severe aortic stenosis has low sensitivity but high specificity. Our results may have important implications for treatment of patients with aortic stenosis and guiding the use of handheld echocardiography. Further research with larger cohorts is needed to validate the variability, sensitivity, and specificity reported in our study.

A Pilot Study on Novel Use of Color Doppler Imaging for Navigation of Wiring in Coronary Interventions.

OBJECTIVE: To test the Doppler guide wire (DGW) for navigation of the wire positioning by color Doppler ultrasound in the setting of percutaneous coronary intervention (PCI). METHODS: An acoustically active DGW was tested in a water tank before its in vivo use. A waveform generator was connected to the DGW, and a transducer scanned the DGW to visualize a Doppler shift signal between the vibrating piezoelectric crystal located at the DGW tip and Doppler signal from the transducer as a distinct, instantaneous color marker. An intracoronary injection was tested in four male domestic pigs using an open-chest setting. A Judkins left coronary guiding catheter was inserted into the ascending aorta via the right carotid artery under B-mode ultrasound guidance. The DGW with an infusion catheter or over-the-wire (OTW) balloon catheter was inserted into the guiding catheter. The color marker instantaneously defined the DGW tip and navigated the catheter into the left anterior descending artery (LAD). RESULTS: The tip of the DGW was visualized within the guiding catheter by a distinct color marker and helped to engage the guiding catheter to the left main orifice. The DGW with an infusion or OTW balloon catheter was inserted into the LAD. We confirmed that the catheter was positioned in the proximal LAD by the colored territory perfused by an injected indigo carmine solution. CONCLUSION: Ultrasound navigation using acoustically active DGW was feasible. Our pilot study introduces a new concept of color Doppler-navigated wire positioning in the coronary artery in the setting of PCI.

Accurate guidance of a catheter by ultrasound imaging and identification of a catheter tip by pulsed-wave Doppler.

BACKGROUND: With the advent of numerous minimally invasive medical procedures, accurate catheter guidance has become imperative. We introduce and test an approach for catheter guidance by ultrasound imaging and pulsed-wave (PW) Doppler. METHODS: A steerable catheter is fitted with a small piezoelectric crystal at its tip that actively transmits signals driven by a function generator. We call this an active-tip (AT) catheter. In a water tank, we immersed a "target" crystal and a rectangular matrix of four "reference" crystals. Two-dimensional (2D) ultrasound imaging was used for initial guidance and visualization of the catheter shaft, and then PW Doppler mode was used to identify the AT catheter tip and guide it to the simulated target that was also visible in the 2D ultrasound image. Ten guiding trials were performed from random initial positions of the AT catheter, each starting at approximately 8 cm from the target. RESULTS: After the ten navigational trials, the average final distance of the catheter tip from the target was 2.4 ± 1.2 mm, and the range of distances from the trials was from a minimum of 1.0 mm to a maximum of 4.5 mm. CONCLUSIONS: Although early in the development process, these quantitative in vitro results show promise for catheter guidance with ultrasound imaging and tip identification by PW Doppler.

Intramuscular transplantation of G-CSF-mobilized CD34(+) cells in patients with critical limb ischemia: a phase I/IIa, multicenter, single-blinded, dose-escalation clinical trial.

A number of preclinical studies have indicated the therapeutic potential of endothelial progenitor cells for vascular regeneration in ischemic diseases. A phase I/IIa clinical trial of transplantation of autologous CD34(+) cells, the endothelial and hematopoietic progenitor-enriched fraction, was performed in no-option patients with atherosclerotic peripheral artery disease or Buerger's disease with critical limb ischemia (CLI). CD34(+) cells were isolated from the G-CSF-mobilized apheresis product using a magnetic cell sorting system. CD34(+) cells (10(5)/kg, n = 6; 5 x 10(5)/kg, n = 8; or 10(6)/kg, n = 3) were injected i.m. into the leg with more severe ischemia. The Efficacy Score, representing changes in the toe brachial pressure index (TBPI), Wong-Baker FACES pain rating scale, and total walking distance 12 weeks after cell transplantation, the primary endpoint, was positive, indicating improvement in limb ischemia in all patients, although no significant dose-response relationship was observed. During the 12-week observation after cell therapy, the Wong-Baker FACES pain rating scale, TBPI, transcutaneous partial oxygen pressure, total or pain-free walking distance, and ulcer size serially improved in all patients. No death or major amputation occurred, and severe adverse events were rare, although mild to moderate events relating to G-CSF and leukapheresis were frequent during the 12-week follow-up. In conclusion, the outcomes of this prospective clinical study indicate the safety and feasibility of CD34(+) cell therapy in patients with CLI. Favorable trends in efficacy parameters encourage a randomized and controlled trial in the future.

Impact of pericardial adhesions on diastolic function as assessed by vortex formation time, a parameter of transmitral flow efficiency.

BACKGROUND: Pericardial adhesions are a pathophysiological marker of constrictive pericarditis (CP), which impairs cardiac filling by limiting the total cardiac volume compliance and diastolic filling function. We studied diastolic transmitral flow efficiency as a new parameter of filling function in a pericardial adhesion animal model. We hypothesized that vortex formation time (VFT), an index of optimal efficient diastolic transmitral flow, is altered by patchy pericardial-epicardial adhesions. METHODS: In 8 open-chest pigs, the heart was exposed while preserving the pericardium. We experimentally simulated early pericardial constriction and patchy adhesions by instilling instant glue into the pericardial space and using pericardial-epicardial stitches. We studied left ventricular (LV) function and characterized intraventricular blood flow with conventional and Doppler echocardiography at baseline and following the experimental intervention. RESULTS: Significant decreases in end-diastolic volume, ejection fraction, stroke volume, and late diastolic filling velocity reflected the effects of the pericardial adhesions. The mean VFT value decreased from 3.61 ± 0.47 to 2.26 ± 0.45 (P = 0.0002). Hemodynamic variables indicated the inhibiting effect of pericardial adhesion on both contraction (decrease in systolic blood pressure and +dP/dt decreased) and relaxation (decrease in the magnitude of -dP/dt and prolongation of Tau) function. CONCLUSION: Patchy pericardial adhesions not only negatively impact LV mechanical functioning but the decrease of VFT from normal to suboptimal value suggests impairment of transmitral flow efficiency.

A Case of Severe Mitral Valve Regurgitation in a Patient with Leadless Pacemaker.

An 85-year-old man with cardiac history notable for atrial fibrillation diagnosed 10 years ago which was being treated with atenolol and warfarin presented to our institution with persistent atrial fibrillation. His echocardiogram showed ejection fraction (EF) of 56%, no regional wall motion abnormalities, mild mitral and pulmonary regurgitation, and trivial tricuspid regurgitation. Despite this treatment, he had recurrent episodes of paroxysmal symptomatic atrial fibrillation with a rapid rate requiring multiple emergency department visits and hospital admissions. Given difficulty to control the rate, he underwent atrioventricular (AV) nodal ablation and leadless pacemaker insertion. Fifteen days after the procedure, he was found to have a severe mitral regurgitation murmur.

Detection of severe stenosis and total occlusion in the left anterior descending coronary artery with transthoracic Doppler echocardiography in the emergency room.

BACKGROUND: The noninvasive measurement of coronary flow velocity in the left anterior descending artery (LAD) has recently been realized by using the transthoracic Doppler echocardiography (TTDE). A couple of investigations demonstrated that the diastolic-to-systolic peak velocity ratio (DSVR) by TTDE is a simple and noninvasive method for the detection of severe stenosis in the elective settings. However, the usefulness of DSVR by TTDE in the emergency settings has not been evaluated. OBJECTIVE: The purpose of this study was to assess the clinical feasibility to document the LAD flow by TTDE in emergency patients who complained of chest pain. METHODS: We studied 49 consecutive patients with acute coronary syndrome who were going to undergo emergency coronary angiography (CAG) for the anatomical diagnosis and the facilitated percutaneous coronary intervention (PCI). Prior to CAG, we recorded the LAD flow by TTDE and measured the diastolic peak velocity (DVp), systolic peak velocity (SVp), and their ratio, DSVR (DVp/SVp) of LAD flow. RESULTS: By CAG, the culprit lesions actually resided in the proximal LAD in 36 patients. Among the 36 patients, we detected the Doppler LAD flow in 29. Five out of 7 patients who were unable to detect the LAD flow revealed total occlusions by CAG. DSVR of the LAD is significantly lower in 17 patients who showed severe stenoses (>90%) than those in the rest of 12 patients who did not show such critical stenoses (1.44 +/- 0.16 vs 2.10 +/- 0.26, P < 0.0001). CONCLUSION: In the emergency settings, a noninvasive assessment of the LAD flow by TTDE accurately estimates the critical stenotic lesions of the LAD.

Real-Time Visualization of an Acoustically Active Injection Catheter With Ultrasound Imaging: Algorithm and In Vivo Validation in a Swine Model.

OBJECTIVE: To independently visualize a catheter and needle during minimally invasive surgery in order to aid in precisely guiding them to their intended location. METHODS: Symmetric frequency detection allows for the visualization of the acoustically active catheter tip as a unique color in live imaging. This study extends the algorithm to identify two different crystals by unique colors, validating the algorithm with in vivo pig experiments while simulating the human condition using different attenuation pads. RESULTS: The catheter and needle tip were identified with unique colors, differentiable from common Doppler colors, with a frame rate varying between 8 and 10 Hz. Both were visible at graded levels of attenuation induced by interposed polymer pads. Reducing ensemble length increased the frame rate and decreased the signal-to-noise ratio (SNR), though not significantly. At the highest in-path attenuation of 12 dB at 5 MHz, the catheter spot marker was visible whereas the needle was not. The SNR of the catheter signal varied between 12.50 and 18.24 dB and the size of the spot marker varied between 149 and 1015 mm2. The SNR of the needle signal varied between 6.37 and 16.3 dB and the size of the spot marker between 59 and 169 mm2. A reliability index greater than 50% was achieved for all cases except for the needle crystal at the highest attenuation setting. CONCLUSION: Modified symmetric frequency detection algorithm can uniquely visualize both catheter and needle in real time with in-path attenuation. SIGNIFICANCE: Unambiguous and distinct visualization of separate locations on the catheter facilitates real-time tracking of minimally invasive procedures.

Left atrial volume: predictor of atrial fibrillation in patients with degenerative mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: In patients with mitral regurgitation (MR) due to degenerative mitral valve prolapse (MVP), preoperative atrial fibrillation (AF) has been identified as an independent predictor of survival after surgery for MR. Thus, the determinants of preoperative AF may have critical implications to evaluate the timing of mitral valve repair. The study aim was to investigate the role of left atrial (LA) volume in predicting preoperative AF in patients with severe MR due to degenerative MVP. METHODS: Sixty-six patients with severe degenerative MR (regurgitant volume > or =60 ml, regurgitant fraction > or =50%, effective regurgitant orifice area > or =0.4 cm(2)) in sinus rhythm (SR) at diagnosis and conservatively managed were eligible for the study. Complete two-dimensional (2-D) echocardiographic and Doppler measurements, including the measurement of maximum LA volume, were performed in all patients. RESULTS: During follow up under conservative management (18.1+/-4.8 months), eight patients (12%) experienced conversion to AF, and 58 remained in SR. The mean LA dimension was 4.0+/-0.5 cm in patients with SR, and 5.1+/-0.8 cm in those who developed AF (p <0.0001). The mean LA volume and LA volume index (indexed to body surface area) were 95 +/-23 ml and 60+/-14 ml/m(2) respectively in patients with SR, and 166+/-66 ml and 104+/-42 ml/m(2) respectively in those who developed AF (both p <0.0001). The optimal cut-off value for LA volume to predict AF conversion was 117.5 ml (sensitivity 88%, specificity 83%), and for LA volume index was 75 ml/m(2) (sensitivity 88%, specificity 88%). CONCLUSION: LA volume measurement should be considered in patients with degenerative severe MR diagnosed in SR. A LA volume index > or =75 ml/m(2) reflects the risk of subsequent AF, and patients should be closely monitored.

Acoustically Active Catheter for Intracardiac Navigation by Color Doppler Ultrasonography.

Navigation of intracardiac catheters by echocardiography is challenging because of the fundamental limitations of B-mode ultrasonography. We describe a catheter fitted with a piezoelectric crystal, which vibrates and produces an instantaneous marker in color flow Doppler scans. The navigation learning curve was explored first in six pigs. Accuracy and precision of targeting with the navigation marker "off" (i.e., B-mode imaging) and "on" were assessed in another six pigs. Paired comparisons confirmed significantly (p = 0.04) shorter mean distances achieved in each pig with the color Doppler marker. Pooled (mean ± standard deviation) distance of the catheter tip from the target crystal was 5.27 ± 1.62 mm by B-mode guidance and 3.66 ± 1.45 mm by color Doppler marker navigation. Dye injection targeted into the ischemic border zone was successful in 8 of 10 pigs. Intracardiac catheter navigation with color Doppler ultrasonography is more accurate compared with conventional guidance by B-mode imaging.

Diagnosis and management of patients with asymptomatic severe aortic stenosis.

Aortic stenosis (AS) is a disease that progresses slowly for years without symptoms, so patients need to be carefully managed with appropriate follow up and referred for aortic valve replacement in a timely manner. Development of symptoms is a clear indication for aortic valve intervention in patients with severe AS. The decision for early surgery in patients with asymptomatic severe AS is more complex. In this review, we discuss how to identify high-risk patients with asymptomatic severe AS who may benefit from early surgery.

Predictors of Elevated Cardiac Enzyme Levels in Hospitalized Patients with Atrial Fibrillation and No Known Coronary Artery Disease.

We retrospectively studied the predictive capabilities of elevated cardiac enzyme levels in terms of the prognosis of patients who were hospitalized with atrial fibrillation and who had no known coronary artery disease. Among 321 patients with atrial fibrillation, 60 without known coronary artery disease had their cardiac enzyme concentrations measured during hospitalization and underwent stress testing or cardiac catheterization within 12 months before or after hospitalization. We then compared the clinical and electrocardiographic characteristics of the 20 patients who had elevated cardiac enzyme levels and the 40 patients who had normal levels. Age, sex, and comorbidities did not differ between the groups. In the patients with elevated cardiac enzyme levels, the mean concentrations of troponin T and creatine kinase-MB isoenzymes were 0.08 ± 0.08 ng/mL and 6.49 ± 4.94 ng/mL, respectively. In univariate analyses, only peak heart rate during atrial tachyarrhythmia was predictive of elevated enzyme levels (P <0.0001). Mean heart rate was higher in the elevated-level patients (146 ± 22 vs 117 ± 29 beats/min; P=0.0007). Upon multivariate analysis, heart rate was the only independent predictor of elevated levels. Coronary artery disease was found in only 2 patients who had elevated levels and in one patient who had normal levels (P=0.26). Increased myocardial demand is probably why the presenting heart rate was predictive of elevated cardiac enzyme levels. Most patients with elevated enzyme levels did not have coronary artery disease, and none died of cardiac causes during the 6-month follow-up period. To validate our findings, larger studies are warranted.

Coronary flow velocity pattern immediately after percutaneous coronary intervention as a predictor of complications and in-hospital survival after acute myocardial infarction.

BACKGROUND: Recently, it was reported that the degree of microvascular injury and left ventricular functional recovery during the chronic period can be predicted after treatment of the infarct-related artery based on the coronary flow velocity (CFV) pattern assessed using a Doppler guidewire. The aim of this prospective study was to examine whether the CFV pattern may predict complications and in-hospital survival after acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 169 consecutive patients with a first anterior AMI successfully treated with percutaneous coronary intervention (PCI). We examined the CFV pattern immediately after PCI using a Doppler guidewire. In accordance with previous findings, we defined severe microvascular injury as a diastolic deceleration time < or =600 ms and the presence of systolic flow reversal. Patients were divided into two groups: those without severe microvascular injury (n=118; group 1) and those with severe microvascular injury (n=51; group 2). All of the patients who had cardiac rupture were in group 2. Congestive heart failure (CHF) was observed more frequently in group 2 than in group 1 (53% versus 8%, P<0.001). The in-hospital cardiac mortality rate was significantly higher in group 2 than in group 1 (18% versus 0%, P<0.001). Nine patients in group 2 died, 5 patients because of CHF and 4 patients because of cardiac rupture. CONCLUSIONS: These findings suggest that the CFV pattern is an accurate predictor of the presence or absence of complications and of in-hospital survival after AMI.

Prognosis of retrograde dissection from the descending to the ascending aorta.

BACKGROUND: Natural history of aortic dissection (AD) with intimal tear in the descending or abdominal aorta and retrograde extension into the ascending aorta (retrograde AD) remains unknown. The purpose of this study was to elucidate medium-term prognosis of patients with retrograde AD. METHODS AND RESULTS: Study population consisted of 109 patients with acute type A AD. There were 27 patients (25%) with retrograde AD and 82 patients (75%) with intimal tear in the ascending aorta (antegrade AD). In antegrade AD patients, 60 patients underwent surgery and 22 patients were treated medically. In retrograde AD patients, 14 patients showed localized crescentic high attenuation area along the ascending aortic wall without enhancement in computed tomography. Transesophageal echocardiography revealed complete thrombosis of false lumen (FL) in the ascending aorta (retrograde thrombosed). The remaining 13 patients showed incomplete or no thrombosis (retrograde nonthrombosed). All retrograde nonthrombosed AD patients underwent surgery except for 1 patient with stroke, whereas all retrograde thrombosed AD patients were treated medically. In-hospital mortality rate of retrograde AD patients was significantly lower than that of antegrade AD patients (15% versus 38%, P=0.027). The survival rates in retrograde AD patients were all 85% at 1, 2, and 5 years, which were significantly higher than those of antegrade AD patients (63%, 62%, and 57%, respectively)(P=0.009). CONCLUSIONS: Patients with type A retrograde AD have better medium-term prognosis than patients with antegrade AD. Retrograde AD patients with thrombosed FL in the ascending aorta could be treated medically with timed surgical repair.

Long-term prognosis of patients with type B aortic intramural hematoma.

BACKGROUND: The long-term clinical course of patients with type B aortic intramural hematoma (IMH) and predictors for progression remains unknown. The difference of aortic pathology may have a different impact on clinical course compared with classic aortic dissection (AD). The purpose of this study was to investigate long-term clinical course and predictors of progression in patients with type B IMH. METHODS AND RESULTS: Clinical data were compared retrospectively between 53 patients with acute type B IMH (IMH group) and 57 patients with acute type B AD (AD group). All patients were treated initially with medical therapy. Two patients in IMH group and 14 patients in AD group underwent surgical repair because of aortic enlargement. The in-hospital mortality rate in IMH group was significantly lower than that in AD group (0% and 14%, P=0.006). Mean follow-up periods were 53+/-43 months, which revealed 3 and 5 late deaths, respectively. Eleven patients with IMH showed progression (development of aortic dissection or aortic enlargement) in follow-up imaging study. The actuarial survival rates in IMH group were 100%, 97%, and 97% at 1, 2, and 5 years, which were significantly higher than those in AD group (83%, 79%, and 79%) (P=0.009). Multivariate analysis identified age >70 years and new appearance of an ulcerlike projection as the strongest predictors of progression in patients with IMH. CONCLUSIONS: Patients with type B IMH have better long-term prognosis than patients with AD. Older age and appearance of an ulcerlike projection are predictive for progression in patients with type B IMH.