Role of Myocardial Strain Imaging in Cancer Therapy-Related Cardiac Dysfunction.

PURPOSE OF REVIEW: This review aims to provide a contemporary perspective on the role of myocardial strain imaging in the management of patients on cardiotoxic therapy. RECENT FINDINGS: Risk/benefit evaluation of cardiotoxic cancer treatment remains challenging, weighing life-saving cancer therapy with fatal cardiac dysfunction potentially caused by cancer therapy. The serial change in left ventricular ejection fraction (LVEF) was conventionally used for the detection of cancer therapy-related cardiac dysfunction (CTRCD). Peak systolic global longitudinal strain (GLS) by speckle-tracking echocardiography has turned into a vital pre- and post-chemotherapy assessment for the early detection of cardiotoxicity. Complexity in cardiotoxic therapy regimen, different definition of CTRCD by LVEF, variations in GLS values, timings, and variable cutoffs make it challenging to standardize the protocol for the detection of CTRCD. GLS > 15% relative reduction from baseline has been widely used. Evidence suggests that GLS could predict early subclinical LV dysfunction, and initiation of cardioprotective therapy led to less decline of LV function. Most of the studies used an echocardiographic endpoint, and the impact of GLS on the long-term clinical outcome is not established. GLS has emerged as a reliable measure to identify early subclinical LV dysfunction by detecting myocardial deformation in patients on cardiotoxic chemotherapy. To date, a significant decline in GLS suggests the initiation of cardioprotective therapy with close monitoring. Interruption of prognostically important cardiotoxic chemotherapies requires a multidisciplinary team approach guided mainly by LVEF and other clinical factors. Further randomized control trials with hard clinical endpoints and longer follow-ups may help to determine the role of GLS in CTRCD.

Low Incidence of Prosthesis-Patient Mismatch Following Extremely Small Transcatheter Aortic Valve Replacement with 20-mm Sapien 3.

Transcatheter aortic valve replacement has been developed as an emerging technique to treat patients with aortic valve disease. However, safety and outcome data on extremely small transcatheter heart valves (THV) is limited. We aimed to assess hemodynamic profiles and clinical outcome of very small balloon expandable THVs with 20-mm Sapien 3 (SP3). We examined data for all patients who received third-generation SP3 THV at a single hospital. Complications and clinical outcomes were defined based on the VARC-2 criteria. Postoperative prosthesis-patient mismatch (PPM) was defined as indexed effective orifice area (EOA) < 0.85 cm 2 /m 2 . We compared clinical characteristics and outcome between patients with 20-mm ( n = 21), 23-mm ( n = 67), and 26- or 29-mm ( n = 113) sized valves. The 20-mm group included significantly higher number of Asian and female populations with lower body surface area. The baseline CT annular area in the 20-mm group was 316.5 ± 24.9 mm 2 . There was no significant difference between groups in procedural mortality or early safety at 30 days. The higher procedural complication was observed in 20-mm group due to significant differences in minor vascular and bleeding complications. Despite higher post-THV gradients and smaller indexed EOA in 20-mm group, no PPM was observed in 20-mm group. The mortality at 30 days and 1 year in 20-mm group was 4.8% and 16.7%, respectively. The patients who received very small THVs with 20-mm SP3 did not result in PPM and experienced favorable early safety and midterm outcome in our cohort.

Management of left ventricular thrombus: a narrative review.

Left ventricular thrombus (LVT) is a serious complication of acute myocardial infarction (MI) and also non-ischemic cardiomyopathies. We performed a narrative literature review, manual-search of reference lists of included articles and relevant reviews. Our literature review indicates that the incidence of LVT following acute MI has decreased, probably due to improvement in patient care as a result of better and earlier reperfusion techniques. Predictors of LVT include anterior MI, involvement of left ventricular (LV) apex (regardless of the coronary territory affected), LV akinesis or dyskinesis, reduced LV ejection fraction (LVEF), severe diastolic dysfunction and large infarct size. LVT is associated with increased risk of systemic embolism, stroke, cardiovascular events and death, and there is evidence that anticoagulant therapy for at least 3 months can reduce the risk of these events. Cardiac magnetic resonance (CMR) has the highest diagnostic accuracy for LVT, followed by echocardiography with the use of echocardiographic contrast agents (ECAs). Although current guidelines suggest use of vitamin K antagonist (VKA) for a minimum of 3 to 6 months, there is growing evidence of the benefits of direct acting oral anticoagulants in treatment of LVT. Embolic events appear to occur even after resolution of LVT suggesting that anticoagulant therapy needs to be considered for a longer period in some cases. Recommendations for the use of triple therapy in the presence of the LVT are mostly based on extrapolation from outcome data in patients with atrial fibrillation (AF) and MI. We conclude that the presence of LVT is more likely in patients with anterior ST-segment elevation MI (STEMI) (involving the apex) and reduced ejection fraction (EF). LVT should be considered a marker of increased long-term thrombotic risk that may persist even after thrombus resolution. Ongoing clinical trials are expected to elucidate the best management strategies for patients with LVT.

Cardiomyocyte expression of PPARgamma leads to cardiac dysfunction in mice.

Three forms of PPARs are expressed in the heart. In animal models, PPARgamma agonist treatment improves lipotoxic cardiomyopathy; however, PPARgamma agonist treatment of humans is associated with peripheral edema and increased heart failure. To directly assess effects of increased PPARgamma on heart function, we created transgenic mice expressing PPARgamma1 in the heart via the cardiac alpha-myosin heavy chain (alpha-MHC) promoter. PPARgamma1-transgenic mice had increased cardiac expression of fatty acid oxidation genes and increased lipoprotein triglyceride (TG) uptake. Unlike in cardiac PPARalpha-transgenic mice, heart glucose transporter 4 (GLUT4) mRNA expression and glucose uptake were not decreased. PPARgamma1-transgenic mice developed a dilated cardiomyopathy associated with increased lipid and glycogen stores, distorted architecture of the mitochondrial inner matrix, and disrupted cristae. Thus, while PPARgamma agonists appear to have multiple beneficial effects, their direct actions on the myocardium have the potential to lead to deterioration in heart function.

Regulation of plasma fructose and mortality in mice by the aldose reductase inhibitor lidorestat.

Aldose reductase (AR), an enzyme widely believed to be involved in the aberrant metabolism of glucose and development of diabetic complications, is expressed at low levels in the mouse. We studied whether expression of human AR (hAR), its inhibition with lidorestat, which is an AR inhibitor (ARI), and the presence of streptozotocin (STZ)-induced diabetes altered plasma fructose, mortality, and/or vascular lesions in low-density lipoprotein (LDL) receptor-deficient [Ldlr(-/-)] mice. Mice were made diabetic at 12 weeks of age with low-dose STZ treatment. Four weeks later, the diabetic animals (glucose > 20 mM) were blindly assigned to a 0.15% cholesterol diet with or without ARI. After 4 and 6 weeks, there were no significant differences in body weights or plasma cholesterol, triglyceride, and glucose levels between the groups. Diabetic Ldlr(-/-) mice receiving ARI had plasma fructose levels of 5.2 +/- 2.3 microg/ml; placebo-treated mice had plasma fructose levels of 12.08 +/- 7.4 microg/ml, p < 0.01, despite the induction of fructose-metabolizing enzymes, fructose kinase and adolase B. After 6 weeks, hAR/Ldlr(-/-) mice on the placebo-containing diet had greater mortality (31%, n = 9/26 versus 6%, n = 1/21, p < 0.05). The mortality rate in the ARI-treated group was similar to that in non-hAR-expressing mice. Therefore, diabetic hAR-expressing mice had increased fructose and greater mortality that was corrected by inclusion of lidorestat, an ARI, in the diet. If similar effects are found in humans, such treatment could improve clinical outcome in diabetic patients.

Rheumatoid Arthritis and Cardiac Compression Caused by a Large Fibrotic Intrapericardial Mass and Effusion: A Case Report.

BACKGROUND Pericarditis is common in rheumatoid arthritis, mostly occurring as an extra-articular manifestation of the disease. We describe a patient with stable rheumatoid arthritis who presented with a large pericardial effusion and a compressive fibrotic pericardial mass. The patient had recently started treatment with a tumor necrosis factor-alpha (TNF-alpha) antagonist. CASE REPORT The patient was a 58-year-old woman with rheumatoid arthritis who presented with right ventricular compression caused by a pericardial fibrotic mass and a large pericardial effusion. The patient did not have active arthritis at the time of presentation. She had been started on treatment with a tumor necrosis factor-alpha (TNF-alpha) antagonist 4 months prior to this presentation. She was successfully treated with surgical pericardiectomy and resection of the pericardial mass. Pathologic analysis of the pericardial mass demonstrated fibrosis and no evidence of active inflammation, rheumatoid arthritis, opportunistic infection, or malignancy. CONCLUSIONS We describe a patient with stable rheumatoid arthritis who developed subacute right heart compression syndrome secondary to pericardial effusion and fibrous pericardial mass. The exact cause of pericarditis and the pericardial mass remain uncertain. There is a need for increased awareness of the association between use of TNF-alpha antagonists and the possible development of an intrapericardial fibrotic mass and effusion.

Gender Differences in the Rate of 30-Day Readmissions after Percutaneous Coronary Intervention for Acute Coronary Syndrome.

BACKGROUND: It has been reported that women have higher 30-day readmission rates than men after acute coronary syndrome (ACS). However, readmission after percutaneous coronary intervention (PCI) for ACS is a distinct subset of patients in whom gender differences have not been adequately studied. METHODS: Hawaii statewide hospitalization data from 2010 to 2015 were assessed to compare gender differences in 30-day readmission rates among patients hospitalized with ACS who underwent PCI during the index hospitalization. Readmission diagnoses were categorized using an aggregated version of the Centers for Medicare and Medicaid Services Condition Categories. Multivariable logistic regression was applied to evaluate the effect of gender on the 30-day readmission rate. RESULTS: A total of 5,354 patients (29.4% women) who were hospitalized with a diagnosis of ACS and underwent PCI were studied. Overall, women were older, with more identified as Native Hawaiian, and had a higher prevalence of cardiovascular risk factors compared with men. The 30-day readmission rate was 13.9% in women and 9.6% in men (p < .0001). In the multivariable model, female gender (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.09-1.60), Medicaid (OR, 1.48; 95% CI, 1.07-2.06), Medicare (1.72; 95% CI, 1.35-2.19), heart failure (1.88; 95% CI, 1.53-2.33), atrial fibrillation (OR, 1.54; 95% CI-1.21-1.95), substance use (OR, 1.88; 95% CI, 1.27-2.77), history of gastrointestinal bleeding (OR, 2.43; 95% CI, 1.29-4.58), and chronic kidney disease (OR, 1.78; 95% CI, 1.42-2.22) were independent predictors of 30-day readmissions. Readmission rates were highest during days 1 through 6 (peak, day 3) after discharge. The top three cardiac causes of readmissions were heart failure, recurrent angina, and recurrent ACS. CONCLUSIONS: Female gender is an independent predictor of 30-day readmission after ACS that requires PCI. Our finding suggests women are at a higher risk of post-ACS cardiac events such as heart failure and recurrent ACS, and further gender-specific intervention is needed to reduce 30-day readmission rate in women after ACS.

In vitro mitral chordal cutting by high intensity focused ultrasound.

Mitral regurgitation, when it arises from functional restriction of mitral leaflet closure, can be relieved by surgical cutting of the mitral tendineae chordae. We hypothesized that high intensity focused ultrasound (HIFU) might be useful as a noninvasive extracorporeal technique for cutting mitral chordae. As a pilot study to test this hypothesis, we examined the in vitro feasibility of using HIFU to cut calf mitral chordae with diameters from 0.2 to 1.6 mm. Sixty-seven percent of chordae were completely cut with HIFU, operated at 4.67 MHz and 45 W acoustic power, with up to 120 pulses of 0.3-s duration at 2-s intervals. Forty-five percent were completely cut when the pulse duration was reduced to 0.2 s. The average diameter of those chordae, which were completely cut, was significantly smaller than that of incompletely cut chordae (0.59 +/- 0.30 versus 1.14 +/- 0.30 mm with a pulse duration of 0.2 s, p < 0.0001; 0.68 +/- 0.29 versus 1.32 +/- 0.20 mm with a pulse duration of 0.3 s, p < 0.0001). For each pulse duration, the number of pulses required for complete cutting exhibited a strong positive correlation with the chordae diameter. In conclusion, in vitro feasibility of mitral chordal cutting by HIFU depended on the diameter of chordae but was controllable by HIFU settings. (E-mail: abeyukio@aol.com).

Relationship between body mass and ambulatory blood pressure: comparison with office blood pressure measurement and effect of treatment.

Epidemiologic studies assessing the relationship between blood pressure (BP), body mass, and cardiovascular events have primarily been based on office BP measurements, and few data are available in the elderly. The aim of the present study was to evaluate the relationship between body mass index (BMI) and BP values obtained by ambulatory blood pressure monitoring (ABPM) as compared to office BP measurements, and the effect of anti-hypertensive treatment on the relationship. The study population consisted of 813 subjects participating in the cardiovascular abnormalities and brain lesions (CABL) study who underwent 24-h ABPM. Office BP (mean of two measurements) was found to be associated with increasing BMI, for both SBP (p ≤ 0.05) and DBP (p ≤ 0.001). In contrast, there was no association seen of increasing BMI with ABPM parameters in the overall cohort, even after adjusting for age and gender. However, among subjects not on anti-hypertensive treatment, office SBP and DBP measurements were significantly correlated with increasing BMI (p ≤ 0.01) as were daytime SBP and 24-h SBP, although with a smaller spread across BMI subgroups compared with office readings. In treated hypertensives, there was only a trend toward increasing office DBP and increasing DBP variability with higher BMI. Our results suggest that body mass may have a less significant influence on BP values in the elderly when ABPM rather than office measurements are considered, particularly in patients receiving anti-hypertensive treatment.

Current status and its epidemiological consideration of Fasciola and Eurytrema infections in beef cattle of Japan.

To elucidate current status of fasciolosis and eurytremosis in beef cattle of Japan, inspection data of Tokyo Metropolitan Shibaura Slaughterhouse where beef cattle were shipped from all over Japan were analyzed, and questionnaire to farmers was conducted to assess the relationship between recognition of the disease occurrence in one's own farm and attention to the diseases. The occurrence of fasciolosis and eurytremosis in beef cattle gradually decreased from 18.6% to 0.06% and from 0.58% to 0.02% during the period of 1964 to 2010, respectively. When the current data from 2009 to 2012 were analyzed, the occurrence of fasciolosis was recognized in cattle produced and fattened all over Japan, indicating the disease was prevalent nationwide. While, 97.5% of Eurytrema infection were detected in cattle produced in Okinawa, Shimane and Kagoshima, indicating the disease was endemic in these regions. Higher occurrence (>0.7%) of fasciolosis was observed in minor breeds, such as Japanese Shorthorn. Japanese Black showed 0.09% and 0.05% of occurrence for fasciolosis and eurytremosis, respectively, but F1 crossbred with Japanese Black showed lower occurrence (0.007% and 0.002%, respectively). No tendency of occurrence in the age of cattle at slaughter was recognized, indicating the infections may have occurred at the growing and early fattening stage of cattle. The questionnaire survey revealed that farmers experiencing fasciolosis had more knowledge about the disease, however, factors, such as testing parasite infections and use of anti-Fasciola dewormers, were not affected by the recognition of occurrence.

Assessment of coronary artery disease with nicorandil stress magnetic resonance imaging.

BACKGROUND: Although dipyridamole and adenosine have been used as vasodilator agents, we believe they are inadequate for vasodilator perfusion magnetic resonance imaging, due to adverse effects (flushing, warmth, headaches, and arrhythmia). Nicorandil, a potassium channel opener, has been reported to increase coronary blood flow and it was associated with fewer adverse effects than adenosine or dipiridamole. We set out to investigate whether the coronary artery stenosis could be assessed by nicorandil stress perfusion magnetic resonance imaging. METHODS: First-pass contrast-enhanced magnetic resonance images of the left ventricle acquired from 50 patients at rest and during intravenous administration of nicorandil using multi-slice turbo field echo with multi shot echo-planar-imaging. Coronary angiography was performed within 1 week. RESULTS: There was no adverse effects during nicorandil stress in any patients. The overall sensitivity and specificity of magnetic resonance imaging in identifying patients with significant stenosis of at least one coronary artery were 93.9% (31 of 33 patients) and 94.1% (16 of 17 patients), respectively. The sensitivity of magnetic resonance imaging for detecting significant stenosis in the left anterior descending artery was 87.5%; the sensitivity in the left circumflex artery was 80%; the sensitivity in the right coronary artery was 92.3%. Similar sensitivities were observed for all 3 vascular regions, indicating that all myocardial segments were visualized with similar image quality. CONCLUSIONS: The present study shows that nicorandil stress perfusion magnetic resonance imaging is a safe, feasible technique for assessing coronary artery stenosis severity in a totally-noninvasive manner.

Alterations in diastolic function in masked hypertension: findings from the masked hypertension study.

BACKGROUND: In a prior study of patients with diabetes, diastolic function was similarly impaired in masked hypertension (MHT) and sustained hypertension (SHT). We evaluated whether MHT is associated with impaired diastolic function compared with SHT and sustained normotension (NT) in the general population. METHODS: From February 2005 to December 2010, 798 participants without a history of cardiovascular disease or treated hypertension, were enrolled in the Masked Hypertension Study. Participants underwent clinic blood pressure (CBP) and 24-hour ambulatory blood pressure (ABP) measurements. A 2-dimensional Doppler echocardiogram was performed to evaluate diastolic function,s cardiac structure, volume, and systolic function. The 9 CBPs obtained across 3 clinic visits and awake ABP measurements were averaged. Clinic hypertension was defined as systolic/diastolic blood pressure (SBP/DBP) ≥ 140/90 mmHg. Ambulatory hypertension was defined as awake SBP/DBP ≥ 135/85mm Hg. MHT was defined as having ambulatory but not clinic hypertension. White-coat hypertensives (n = 8) were excluded from the analysis. RESULTS: Of the 790 participants, 116 (14.7%) participants had MHT, 37 (4.7%) participants had SHT, and 637 (80.6%) participants had NT. After age, sex, race/ethnicity, and body mass index adjustment, compared with NT, E'-velocities were significantly lower in MHT (P < 0.01) and SHT (P < 0.05), and E/E' ratios were significantly higher MHT (P < 0.05) and SHT (P < 0.05). These associations were independent of left ventricular mass. Diastolic function parameters did not significantly differ between MHT and SHT. CONCLUSIONS: Diastolic function was impaired in MHT compared with NT independent of changes in left ventricular mass.

In vitro atrial septal ablation using high-intensity focused ultrasound.

BACKGROUND: High-intensity focused ultrasound (HIFU) has been applied clinically as a noninvasive therapeutic tool. Atrial septostomy is a palliative treatment for pulmonary artery hypertension. The purpose of this study was to assess the feasibility of atrial septal ablation in vitro using HIFU. METHODS: Fourteen sections of atrial septum from pig hearts were treated. Focused ultrasound energy was applied with an operating frequency of 5.25 MHz at the nominal focal point intensity of 4.0 kW/cm(2) for 0.4 sec in 1-sec intervals. RESULTS: Lesions were created with ultrasonic exposures ranging from 40 to 120 pulses. There were significant relationships between HIFU exposure time and lesion area on the exposed site (R(2) = 0.3389, P < .0001) and lesion volume (R(2) = 0.6161, P < .0001). CONCLUSIONS: HIFU has the potential to create focal perforations without direct tissue contact. This method may prove useful for noninvasive atrial septostomy.

AORTIC PULSE WAVE VELOCITY MEASURED BY PULSE WAVE IMAGING (PWI): A COMPARISON WITH APPLANATION TONOMETRY.

BACKGROUND: Arterial stiffness is a well-established indicator of cardiovascular disease outcome. Pulse Wave Velocity (PWV) is a surrogate for arterial stiffness that is measured either globally using carotid to femoral applanation tonometry or locally using biomedical imaging methods. Pulse Wave Imaging (PWI) is an ultrasound-based method for both qualitative visualisation of pulse wave propagation and quantitative estimation of arterial stiffness. The objective of this study is to assess the PWI performance in PWV estimation by comparing local abdominal aortic PWV values obtained by PWI to the carotid-femoral PWV measured by applanation tonometry. METHODS: A total of 18 subjects (age 18-66, 32.5±14.5) with no history of cardiovascular disease were consecutively tested by both PWI and tonometry. RESULTS: The correlation coefficient r between values found by the two methods was found to be equal to 0.68. A linear regression yielded PWVPWI = 1.02* PWVtonometry +0.15. Tukey mean-difference plots indicated that PWVPWI was significantly lower than PWVtonometry (-0.3 m/s) at lower PWV values (PWV≤7 m/s), whereas PWVPWI was significantly higher (+1.4 m/s) than PWVtonometry at higher PWV values (PWV>7 m/s). CONCLUSIONS: Despite the regional nature of the PWVPWI measurements, as opposed to the global PWVtonometry measurements, abdominal PWVPWI and carotid-femoral PWVtonometry values were found to be similar, with an average bias equal to 0.25 m/s. Such a bias and its variation with PWV may be partially explained by both physiological variations of PWV along the arterial tree and by the increasing uncertainty of the PWV estimate by PWI as PWV increases.

Septal pouch in the left atrium and risk of ischemic stroke.

OBJECTIVES: We sought to assess the association between the presence of a septal pouch in the left atrium and ischemic stroke. BACKGROUND: It has been suggested that the presence of a left septal pouch (LSP) may favor the stasis of blood and possibly result in thromboembolic complications. However, the embolic potential of an LSP is not known. METHODS: The association between an LSP and risk of stroke was assessed using a population-based case-control study design. The presence of an LSP was assessed by transesophageal echocardiography in 187 patients >50 years of age with a first-ever ischemic stroke (96 men, mean age 70.6 ± 9.0 years) and in 157 control subjects matched to patients by age, sex, and race/ethnicity. The association between an LSP and risk of stroke was assessed after adjustment for other stroke risk factors. RESULTS: Patients with LSPs were younger than control subjects (67.5 ± 9.1 years vs. 69.6 ± 8.8 years; p = 0.046), with a lower prevalence of hypertension (68.0% vs. 80.3%; p = 0.01). There were no differences in the prevalence of LSPs between stroke patients and control subjects (28.9% vs. 29.3%, respectively; p = 0.93). The subgroup of 69 patients (36.9%) with cryptogenic stroke showed a similar prevalence of LSPs (31.9% vs. 29.3%; p = 0.70). Multivariable analysis showed that the presence of an LSP was not associated with ischemic stroke (odds ratio: 1.09; 95% confidence interval: 0.64 to 1.85) or cryptogenic stroke (odds ratio: 1.41; 95% confidence interval: 0.71 to 2.78). CONCLUSIONS: This study does not demonstrate evidence of the association of the presence of an LSP with ischemic stroke or cryptogenic stroke. The stroke risk associated with LSPs requires further evaluation in the younger stroke populations. The cofactors that may turn an LSP from an innocent bystander to a causative mechanism for stroke remains to be elucidated.

Ceramide is a cardiotoxin in lipotoxic cardiomyopathy.

Ceramide is among a number of potential lipotoxic molecules that are thought to modulate cellular energy metabolism. The heart is one of the tissues thought to become dysfunctional due to excess lipid accumulation. Dilated lipotoxic cardiomyopathy, thought to be the result of diabetes and severe obesity, has been modeled in several genetically altered mice, including animals with cardiac-specific overexpression of glycosylphosphatidylinositol (GPI)-anchored human lipoprotein lipase (LpL(GPI)). To test whether excess ceramide was implicated in cardiac lipotoxicity, de novo ceramide biosynthesis was inhibited pharmacologically by myriocin and genetically by heterozygous deletion of LCB1, a subunit of serine palmitoyltransferase (SPT). Inhibition of SPT, a rate-limiting enzyme in ceramide biosynthesis, reduced fatty acid and increased glucose oxidation in isolated perfused LpL(GPI) hearts, improved systolic function, and prolonged survival rates. Our results suggest a critical role for ceramide accumulation in the pathogenesis of lipotoxic cardiomyopathy.

Extracardiac ablation of the left ventricular septum in beating canine hearts using high-intensity focused ultrasound.

BACKGROUND: High-intensity focused ultrasound (HIFU) produces immediate focal lesions without direct tissue contact. Previously, we reported the HIFU potential for cardiac ablation. The purpose of this study was to evaluate the possibility of myocardial ablation in the left ventricle of beating dog hearts with monitoring by 2-dimensional echocardiography. METHODS: The operating frequency and the acoustic intensity were 5.25 MHz and 23 kW/cm(2), and the focal length and diameter were 3.3 mm axial and 0.37 mm wide at a distance of 35 mm from the transducer. Three dogs underwent a left-sided thoracotomy. The right ventricular surface was coupled with the transducer. The timing of the HIFU exposure was set during the early systolic phase using an electrocardiographic triggering system. The focal point was set in the left ventricular septum using 2-dimensional echocardiography mounted in the HIFU transducer. Ultrasound energy was delivered for 0.2 seconds. For each dog, we created 18 lesions. Exposures were performed 20, 30, or 40 times. Lesion size was assessed by manually measuring its length and width. RESULTS: All lesions except one were clearly visible. The histologic lesion area was 18.7 +/- 8.3, 26.3 +/- 8.7, and 35.5 +/- 15.7 mm(2) (20, 30, and 40 times, respectively). The intraclass correlation coefficients were found to be 0.72, 0.63, 0.75, and 0.73 for lesion length, width, area, and depth, respectively. CONCLUSION: HIFU can be used to create targeted, well-demarcated thermal lesions in the ventricular septum myocardium during cardiac contraction.

Comparative study of high-resolution microimaging with 30-MHz scanner for evaluating cardiac function in mice.

BACKGROUND: The accurate assessment of cardiac function in mice is challenging because of their small heart size and rapid heart rate. METHODS: We examined the usefulness of novel high-resolution echocardiography (HRE) with a 30-MHz transducer in evaluating cardiac function in 20 mice compared with conventional echocardiography (CE) with a 13-MHz transducer. The left ventricular (LV) regional wall motion (RWM), LV end-diastolic dimension, fractional shortening, anterior LV wall thickness, E/A, and myocardial performance index were assessed. RESULTS: RWM analysis was more feasible by HRE than by CE (P < .05). Interobserver agreement in RWM analysis and correlation in LV end-diastolic dimension, fractional shortening, anterior LV wall thickness, E/A, and myocardial performance index were all better with HRE than CE. CONCLUSIONS: HRE is superior to CE in assessing LV function in mice. HRE is potentially a useful method for accurate assessment of cardiac function in various mice models.

Acute lipoprotein lipase deletion in adult mice leads to dyslipidemia and cardiac dysfunction.

The most energy-requiring organ in the body, the cardiac muscle, relies primarily on lipoprotein-derived fatty acids. Prenatal loss of cardiac lipoprotein lipase (LPL) leads to hypertriglyceridemia, but no cardiac dysfunction, in young mice. Cardiac specific loss of LPL in 8-wk-old mice was produced by a 2-wk tamoxifen treatment of MerCreMer (MCM)/Lpl(flox/flox) mice. LPL gene deletion was confirmed by PCR analysis, and LPL mRNA expression was reduced by approximately 70%. One week after tamoxifen was completed, triglyceride was increased with LPL deletion, 162 +/- 53 vs. 91 +/- 21 mg/dl, P < 0.01. Tamoxifen treatment of Lpl(flox/flox) mice did not cause a significant increase in triglyceride levels. Four weeks after tamoxifen, MCM/Lpl(flox/flox) mice had triglyceride levels of 190 +/- 27 mg/dl, similar to those of mice with prenatal LPL deletion. One week after the tamoxifen, MCM/Lpl(flox/flox), but not Lpl(flox/flox), mice had decreases in carnitine palmitoyl transferase I mRNA (18%) and pyruvate dehydrogenase kinase 4 mRNA (38%). These changes in gene expression became more robust with time. Acute loss of LPL decreased ejection fraction and increased mRNA levels for atrial natriuretic factor. Our studies show that acute loss of LPL can be produced and leads to rapid alteration in gene expression and cardiac dysfunction.

Feasibility of using a real-time 3-dimensional technique for contrast dobutamine stress echocardiography.

This is the first feasibility study using real-time 3-dimensional (3D) (RT3D) transthoracic contrast echocardiography with full-volume acquisition to evaluate left ventricular wall motion in patients undergoing dobutamine stress echocardiography. RT3D contrast and noncontrast 3D images were obtained at rest and peak dose dobutamine infusion and reviewed for image quality. A total of 14 patients underwent complete rest and stress RT3D contrast and noncontrast imaging. Ultrasound contrast significantly increased the proportion of segments adequately visualized during rest and peak dobutamine infusion (91%-98%, P = .001, and 87%-99%, P = .001, respectively). With contrast there was almost complete concordance between observers (96.9% at rest and 98.2% at peak stress with almost no interobserver variability), whereas noncontrast studies had much lower agreement (84.4% at rest and 79.9% at peak stress with kappa values < 0.4). Three-dimensional contrast studies compared favorably with standard 2-dimensional imaging. Time for acquisition of all data sets with and without contrast was less than 90 seconds. RT3D dobutamine contrast stress echocardiography is feasible, greatly improves image quality compared with noncontrast images, and quickly acquires full data sets for subsequent analysis.