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To characterize Doppler flow patterns of the grafted left internal mammary artery (LIMA) in patients with and without dobutamine stress induced wall motion abnormalities in the graft distribution, we studied 29 patients who underwent coronary artery bypass surgery using LIMA grafts to the left anterior descending coronary artery (LAD). The ungrafted right internal mammary artery (RIMA) was used as a control. RIMA Doppler flow pattern was predominantly systolic in all patients. In patients without ischemia in the LAD distribution, LIMA flow was predominantly diastolic. In patients with ischemia, LIMA flow was predominantly systolic. In the grafted LIMA, a ratio of diastolic to systolic time-velocity integral of > 1.5 best showed absence of ischemia in the graft distribution. In summary, characterization of the Doppler flow pattern in the internal mammary arteries is feasible. In the grafted LIMA, ratios of diastolic to systolic flow are less in patients with an ischemic response in the subtended vascular bed than in those without ischemia. [ABSTRACT FROM AUTHOR]

Background and Aims: Approximately 50% of patients with ST elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) experience microvascular no-reflow. Pre- and post-PCI sonothrombolysis has been shown to decrease infarct size and improve left ventricular (LV) systolic function in STEMI patients receiving urgent PCI. The aim of this study was to investigate whether post-PCI sonothrombolysis alone in STEMI patients with persistent ST elevation could reduce no-reflow and infarct size., Methods: Patients with STEMI with symptoms <12 hours who had persistent ST elevation (≤70% ST resolution) after primary PCI were randomized to sonothrombolysis or control. The primary end point was summed (Σ) ST elevation 60 minutes after study intervention. Secondary end points included infarct size, myocardial perfusion score, LV ejection fraction on cardiovascular magnetic resonance imaging at 2 months follow-up, and clinical outcome at 6-month follow-up., Results: Sixty-seven STEMI patients with persistent ST elevation after PCI were randomized (49 left anterior descending, 18 right coronary/left circumflex artery). No difference was observed in Σ ST elevation 60 minutes after study intervention (mean difference, 0.6 mm; 95% CI, -1.1 to 2.2, P = .50). Complete ST resolution occurred in 14 (40%) of patients treated with sonothrombolysis compared to 6 (19%) of controls (P = .16). Myocardial perfusion score index (1.5 ± 0.3 vs 1.5 ± 0.3, P = .93), infarct size (18.0% ± 10% vs 16.8% ± 11%; P = .29) and LV ejection fraction on cardiovascular magnetic resonance (46% ± 8% vs 47% ± 11% in the control group; P = .86) were comparable. Incidence of all-cause death, acute coronary syndrome, and hospital admission for heart failure at 6-month follow-up was similar between the groups (sonothrombolysis, 2; control, 5)., Conclusions: In STEMI patients with persistent ST elevation after PCI, post-PCI sonothrombolysis did not result in more ST resolution or smaller infarct size compared to control subjects. The incidence of the combined clinical end points was remarkably low in this high-risk patient population., Competing Interests: Conflicts of Interest T.R. Porter receives consultant fees from Lantheus Medical Imaging, and research equipment support from Philips Research North America. The other authors confirm that they have no competing interests., (Copyright © 2024 American Society of Echocardiography. All rights reserved.)

Purpose: Persistent microvascular obstruction (MVO) after successful percutaneous coronary intervention (PCI) in acute ST segment elevation myocardial infarction (STEMI) has been well-described. MVO predicts lack of recovery of left ventricular function and increased mortality. Sonothrombolysis utilizing diagnostic ultrasound induced cavitation of commercially available microbubble contrast has been effective at reducing infarct size and improving left ventricular ejection fraction (LVEF) when performed both pre- and post-PCI. However, the effectiveness of post-PCI sonothrombolysis alone after successful PCI has not been demonstrated., Methods: A prospective randomized controlled trial was performed in 50 consecutive consenting patients with anterior STEMI who underwent a continuous microbubble infusion immediately following successful PCI. Intermittent high mechanical index (MI) impulses were applied only in the sonthrombolysis group. Delayed enhancement magnetic resonance imaging (MRI) was performed at 48 h and again at 6-8 weeks to assess for differences in infarct size, LVEF, and MVO., Results: There were no differences between groups in age, gender, and cardiovascular risk factors. Significant (> 2 segments) MVO following successful PCI was observed in 66% of patients. Although sonothrombolysis reduced the extent of MVO acutely, there were no differences in infarct size, LVEF, or extent of MVO by MRI at 48 h. Twenty-eight patients returned for a follow up MRI at 6-8 weeks. LVEF improved only in the sonothrombolysis group (∆LVEF 7.81 ± 4.57% with sonothrombolysis vs. 1.77 ± 7.02% for low MI only, p = .011)., Conclusion: Post-PCI sonothrombolysis had minimal effect on reducing myocardial infarct size but improved left ventricular systolic function in patients with acute anterior wall STEMI., (© 2024 Wiley Periodicals LLC.)

Background: Acute kidney injury (AKI) is frequently observed after transcatheter aortic valve implantation (TAVI). Of note, it is associated with a threefold increase in all-cause and cardiac death. We propose a new non-contrast strategy for evaluating and performing the TAVI procedure that can be especially valuable for patients with aortic stenosis (AS) and chronic kidney disease (CKD) to prevent AKI., Methods: Patients with severe symptomatic AS and CKD stage ≥3a were evaluated for TAVI using four non-contrast imaging modalities for procedural planning: transesophageal echocardiogram (TEE), cardiac magnetic resonance, multidetector computed tomography (MDCT), and aortoiliac CO 2 angiography. Patients underwent transfemoral (TF) TAVI using the self-expandable Evolut R/Pro, and the procedures were guided by fluoroscopy and TEE. Contrast MDCT and contrast injection at certain checkpoints during the procedure were used in a blinded fashion to guarantee patient safety., Results: A total of 25 patients underwent TF-TAVI with the zero-contrast technique. The mean age was 79.9 ± 6.1 years, 72% in NYHA class III/IV, with a mean STS-PROM of 3.0% ± 1.5%, and creatinine clearance of 49 ± 7 ml/min. The self-expandable Evolut R and Pro were implanted in 80% and 20% of patients, respectively. In 36% of the cases, the transcatheter heart valve (THV) chosen was one size larger than the one by contrast MDCT, but none of these cases presented adverse events. Device success and the combined safety endpoint (at 30 days) both achieved 92%. Pacemaker implantation was needed in 17%., Conclusion: This pilot study demonstrated that the zero-contrast technique for procedural planning and THV implantation was feasible and safe and might become the preferable strategy for a significant population of CKD patients undergoing TAVR. Future studies with a larger number of patients are still needed to confirm such interesting findings., Competing Interests: FB and HR are proctors and consultants for Edwards Lifesciences, Medtronic, and Boston Scientific. AA is a proctor for Boston Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Freire, Nicz, Ribeiro, Filippini, Accorsi, Liberato, Nomura, Cassar, Vieira, Mathias, Pomerantzeff, Tarasoutchi, Abizaid, Kalil Filho and Brito.)

Introduction: Classical low-flow, low-gradient aortic stenosis (LFLG-AS) is an advanced stage of aortic stenosis, which has a poor prognosis with medical treatment and a high operative mortality after surgical aortic valve replacement (SAVR). There is currently a paucity of information regarding the current prognosis of classical LFLG-AS patients undergoing SAVR and the lack of a reliable risk assessment tool for this particular subset of AS patients. The present study aims to assess mortality predictors in a population of classical LFLG-AS patients undergoing SAVR., Methods: This is a prospective study including 41 consecutive classical LFLG-AS patients (aortic valve area ≤1.0 cm 2 , mean transaortic gradient <40 mmHg, left ventricular ejection fraction <50%). All patients underwent dobutamine stress echocardiography (DSE), 3D echocardiography, and T1 mapping cardiac magnetic resonance (CMR). Patients with pseudo-severe aortic stenosis were excluded. Patients were divided into groups according to the median value of the mean transaortic gradient (≤25 and >25 mmHg). All-cause, intraprocedural, 30-day, and 1-year mortality rates were evaluated., Results: All of the patients had degenerative aortic stenosis, with a median age of 66 (60-73) years; most of the patients were men (83%). The median EuroSCORE II was 2.19% (1.5%-4.78%), and the median STS was 2.19% (1.6%-3.99%). On DSE, 73.2% had flow reserve (FR), i.e., an increase in stroke volume ≥20% during DSE, with no significant differences between groups. On CMR, late gadolinium enhancement mass was lower in the group with mean transaortic gradient >25 mmHg [2.0 (0.0-8.9) g vs. 8.5 (2.3-15.0) g; p  = 0.034), and myocardium extracellular volume (ECV) and indexed ECV were similar between groups. The 30-day and 1-year mortality rates were 14.6% and 43.8%, respectively. The median follow-up was 4.1 (0.3-5.1) years. By multivariate analysis adjusted for FR, only the mean transaortic gradient was an independent predictor of mortality (hazard ratio: 0.923, 95% confidence interval: 0.864-0.986, p  = 0.019). A mean transaortic gradient ≤25 mmHg was associated with higher all-cause mortality rates (log-rank p  = 0.038), while there was no difference in mortality regarding FR status (log-rank p  = 0.114)., Conclusions: In patients with classical LFLG-AS undergoing SAVR, the mean transaortic gradient was the only independent mortality predictor in patients with LFLG-AS, especially if ≤25 mmHg. The absence of left ventricular FR had no prognostic impact on long-term outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Tessari, Lopes, Campos, Rosa, Sampaio, Soares, Lopes, Nazzetta, Sândoli de Brito Júnior, Ribeiro, Vieira, Mathias, Fernandes, Lopes, Rochitte, Pomerantzeff, Abizaid and Tarasoutchi.)

Background: The diagnostic ultrasound-guided high mechanical index impulses during an intravenous microbubble infusion (sonothrombolysis) improve myocardial perfusion in acute ST segment elevation myocardial infarction, but its effect on left ventricular diastolic dysfunction (DD), left atrial (LA) mechanics and remodeling is unknown. We assessed the effect of sonothrombolysis on DD grade and LA mechanics., Methods: One hundred patients (59 ± 10 years; 34% women) were randomized to receive either high mechanical index impulses plus percutaneous coronary intervention (PCI) (therapy group) or PCI only (control group) (n = 50 in each group). Diastolic dysfunction grade and LA mechanics were assessed immediately before and after PCI and at 48 to 72 hours, 1 month, and 6 months of follow-up. Diastolic dysfunction grades were classified as grades I, II, and III. The LA mechanics was obtained by two-dimensional speckle-tracking echocardiography-derived global longitudinal strain (GLS)., Results: As follow-up time progressed, increased DD grade was observed more frequently in the control group than in the therapy group at 1 month and 6 months of follow-up (all P < .05). The LA-GLS values were incrementally higher in the therapy group when compared with the control group at 48 to 72 hours, 24.0% ± 7.3% in the therapy group versus 19.6% ± 7.2% in the control group, P = .005; at 1 month, 25.3% ± 6.3% in the therapy group versus 21.5% ± 8.3% in the control group, P = .020; and at 6 months, 26.2% ± 8.7% in the therapy group versus 21.6% ± 8.5% in the control group, P = .015. The therapy group was less likely to experience LA remodeling (odds ratio, 2.91 [1.10-7.73]; P = .03). LA-GLS was the sole predictor of LA remodeling (odds ratio, 0.79 [0.67-0.94]; P = .006)., Conclusion: Sonothrombolysis is associated with better DD grade and LA mechanics, reducing LA remodeling., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of the present study is to assess multimodality imaging findings according to systemic biomarkers, high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, in low-flow, low-gradient aortic stenosis (LFLG-AS)., Background: Elevated levels of BNP and hsTnI have been related with poor prognosis in patients with LFLG-AS., Methods: Prospective study with LFLG-AS patients that underwent hsTnI, BNP, coronary angiography, cardiac magnetic resonance (CMR) with T1 mapping, echocardiogram and dobutamine stress echocardiogram. Patients were divided into 3 groups according to BNP and hsTnI levels: Group 1 ( n  = 17) when BNP and hsTnI levels were below median [BNP < 1.98 fold upper reference limit (URL) and hsTnI < 1.8 fold URL]; Group 2 ( n  = 14) when BNP or hsTnI were higher than median; and Group 3 ( n  = 18) when both hsTnI and BNP were higher than median., Results: 49 patients included in 3 groups. Clinical characteristics (including risk scores) were similar among groups. Group 3 patients had lower valvuloarterial impedance ( P  = 0.03) and lower left ventricular ejection fraction ( P  = 0.02) by echocardiogram. CMR identified a progressive increase of right and left ventricular chamber from Group 1 to Group 3, and worsening of left ventricular ejection fraction (EF) (40 [31-47] vs. 32 [29-41] vs. 26 [19-33]%; p  < 0.01) and right ventricular EF (62 [53-69] vs. 51 [35-63] vs. 30 [24-46]%; p  < 0.01). Besides, there was a marked increase in myocardial fibrosis assessed by extracellular volume fraction (ECV) (28.4 [24.8-30.7] vs. 28.2 [26.9-34.5] vs. 31.8 [28.9-35.5]%; p  = 0.03) and indexed ECV (iECV) (28.7 [21.2-39.1] vs. 28.8 [25.4-39.9] vs. 44.2 [36.4-51.2] ml/m 2 , respectively; p  < 0.01) from Group 1 to Group 3., Conclusions: Higher levels of BNP and hsTnI in LFLG-AS patients are associated with worse multi-modality evidence of cardiac remodeling and fibrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Lopes, Campos, Rosa, Sampaio, Morais, de Brito Júnior, Vieira, Mathias, Fernandes, de Santis, Santos, Rochitte, Capodanno, Tamburino, Abizaid and Tarasoutchi.)

Background: Exercise plays a positive role in the course of the ischemic heart disease, enhancing functional capacity and preventing ventricular remodeling., Objective: To investigate the impact of exercise on left ventricular (LV) contraction mechanics after an uncomplicated acute myocardial infarction (AMI)., Methods: A total of 53 patients was included, 27 of whom were randomized to a supervised training program (TRAINING group), and 26 to a CONTROL group, who received usual recommendations on physical exercise after AMI. All patients underwent cardiopulmonary stress testing and a speckle tracking echocardiography to measure several parameters of LV contraction mechanics at one month and five months after AMI. A p value < 0.05 was considered statistically significant for the comparisons of the variables., Results: No significant difference were found in the analysis of LV longitudinal, radial and circumferential strain parameters between groups after the training period. After the training program, analysis of torsional mechanics demonstrated a reduction in the LV basal rotation in the TRAINING group in comparison to the CONTROL group (5.9±2.3 vs. 7.5±2.9o; p=0.03), and in the basal rotational velocity (53.6±18.4 vs.68.8±22.1 º/s; p=0.01), twist velocity (127.4±32.2 vs. 149.9±35.9 º/s; p=0.02) and torsion (2.4±0.4 vs. 2.8±0.8 º/cm; p=0.02)., Conclusions: Physical activity did not cause a significant improvement in LV longitudinal, radial and circumferential deformation parameters. However, the exercise had a significant impact on the LV torsional mechanics, consisting of a reduction in basal rotation, twist velocity, torsion and torsional velocity which can be interpreted as a ventricular "torsion reserve" in this population.

Aims: Individuals with resistant arterial hypertension are particularly at risk of developing target organ damage and cardiovascular events. The advanced echocardiography technique called myocardial work (MW), through the analysis of the left ventricular pressure-strain loop, is among the possibilities for evaluating these individuals. Our study was designed to describe the behavior of MW indices in individuals with resistant arterial hypertension (RH), controlled hypertension (CH), and normal arterial pressure (N)., Methods and Results: Seventy-one patients underwent Ambulatory Blood Pressure Monitoring (ABPM) and were characterized into three groups after a medical consult: RH (subjects with hypertension on four or more antihypertensive medications despite having controlled blood pressure); CH (subjects with hypertension on up to two antihypertensive medications); and N (individuals with normal ABPM; not using any medications). Echocardiographic analysis was performed using the Vivid E95 ultrasound system and blood pressure was measured at the time of the examination and subsequently used to determine myocardial work indices. RH demonstrated lower global work efficiency (GWE, mean = .95%; p = .005) and higher global wasted work (GWW, mean = 114 mm Hg%; p = .011) compared to other groups. Left ventricular mass measured by three-dimensional echocardiography, systolic wall stress, relative wall thickness and peak systolic dispersion were inversely correlated to GWE. No difference was observed between CH and N groups regarding MW indices. On multivariate analysis, only systolic wall stress remained as an independent predictor of GWE, when controlled by 3D mass index, relative wall thickness, peak systolic dispersion, and the hypertension group., Conclusion: Individuals with resistant hypertension have lower global work efficiency and higher global wasted work, compared to individuals with controlled hypertension and without arterial hypertension., (© 2022 Wiley Periodicals LLC.)

The present CEUS Cardiac Exam Protocols represent the first effort to promulgate a standard set of protocols for optimal administration of ultrasound enhancing agents (UEAs) in echocardiography, based on more than two decades of experience in the use of UEAs for cardiac imaging. The protocols reflect current clinical CEUS practice in many modern echocardiography laboratories throughout the world. Specific attention is given to preparation and dosing of three UEAs that have been approved by the United States Food and Drug Administration (FDA) and additional regulatory bodies in Europe, the Americas and Asia-Pacific. Consistent with professional society guidelines (J Am Soc Echocardiogr 31:241-274, 2018; J Am Soc Echocardiogr 27:797-810, 2014; Eur Heart J Cardiovasc Imaging 18:1205, 2017), these protocols cover unapproved "off-label" uses of UEAs-including stress echocardiography and myocardial perfusion imaging-in addition to approved uses. Accordingly, these protocols may differ from information provided in product labels, which are generally based on studies performed prior to product approval and may not always reflect state of the art clinical practice or guidelines., (© 2022. The Author(s).)

Background: Acute cellular rejection (ACR) is a major complication after heart transplantation. Endomyocardial biopsy (EMB) remains the gold standard for its diagnosis, but it has concerning complications. We evaluated the usefulness of speckle tracking echocardiography (STE) and biomarkers for detecting ACR after heart transplantation., Methods: We prospectively studied 60 transplant patients with normal left and right ventricular systolic function who underwent EMB for surveillance 6 months after transplantation. Sixty age- and sex-matched healthy individuals constituted the control group. Conventional echocardiographic parameters, left ventricular global longitudinal, radial and circumferential strain (LV-GLS, LV-GRS and LV-GCS, respectively), left ventricular systolic twist (LV-twist) and right ventricular free wall longitudinal strain (RV-FWLS) were analyzed just before the procedure. We also measured biomarkers at the same moment., Results: Among the 60 studied patients, 17 (28%) had severe ACR (grade ≥ 2R), and 43 (72%) had no significant ACR (grade 0 - 1R). The absolute values of LV-GLS, LV-twist and RV-FWLS were lower in transplant patients with ACR degree ≥ 2 R than in those without ACR (12.5% ± 2.9% vs 14.8% ± 2.3%, p=0.002; 13.9° ± 4.8° vs 17.1° ± 3.2°, p=0.048; 16.6% ± 2.9% vs 21.4%± 3.2%, p < 0.001; respectively), while no differences were observed between the LV-GRS or LV-GCS. All of these parameters were lower in the transplant group without ACR than in the nontransplant control group, except for the LV-twist. Cardiac troponin I levels were significantly higher in patients with significant ACR than in patients without significant ACR [0.19 ng/mL (0.09-1.31) vs 0.05 ng/mL (0.01-0.18), p=0.007]. The combination of troponin with LV-GLS, RV-FWLS and LV-Twist had an area under curve for the detection of ACR of 0.80 (0.68-0.92), 0.89 (0.81-0.93) and 0.79 (0.66-0.92), respectively., Conclusion: Heart transplant patients have altered left ventricular dynamics compared with control individuals. The combination of troponin with strain parameters had higher accuracy for the detection of ACR than the isolated variables and this association might select patients with a higher risk for ACR who will benefit from an EMB procedure in the first year after heart transplantation.

Background: It has recently been demonstrated that high-energy diagnostic transthoracic ultrasound and intravenous microbubbles dissolve thrombi (sonothrombolysis) and increase angiographic recanalization rates in patients with ST-segment-elevation myocardial infarction. We aimed to study the effect of sonothrombolysis on the myocardial dynamics and infarct size obtained by real-time myocardial perfusion echocardiography and their value in preventing left ventricular remodeling., Methods: One hundred patients with ST-segment-elevation myocardial infarction were randomized to therapy (50 patients treated with sonothrombolysis and percutaneous coronary intervention) or control (50 patients treated with percutaneous coronary intervention only). Left ventricular volumes, ejection fraction, risk area (before treatment), myocardial perfusion defect over time (infarct size), and global longitudinal strain were determined by quantitative real-time myocardial perfusion echocardiography and speckle tracking echocardiography imaging., Results: Risk area was similar in the control and therapy groups (19.2±10.1% versus 20.7±8.9%; P =0.56) before treatment. The therapy group presented a behavior significantly different than control group over time ( P <0.001). The perfusion defect was smaller in the therapy at 48 to 72 hours even in the subgroup of patients with no recanalization at first angiography (12.9±6.5% therapy versus 18.8±9.9% control; P =0.015). The left ventricular global longitudinal strain was higher in the therapy than control immediately after percutaneous coronary intervention (14.1±4.1% versus 12.0±3.3%; P =0.012), and this difference was maintained until 6 months (17.1±3.5% versus 13.6±3.6%; P <0.001). The only predictor of left ventricular remodeling was treatment with sonothrombolysis: the control group was more likely to exhibit left ventricular remodeling with an odds ratio of 2.79 ([95% CI, 0.13-6.86]; P =0.026)., Conclusions: Sonothrombolysis reduces microvascular obstruction and improves myocardial dynamics in patients with ST-segment-elevation myocardial infarction and is an independent predictor of left ventricular remodeling over time.

Background: Cardiac shock-wave therapy (CSWT) has been demonstrated as an option for the treatment of patients with refractory angina (RA), promoting immediate vasodilatory effects and, in the long-term, neoangiogenic effects that would be responsible for reducing the myocardial ischemic load. The aim of this study was to determine the effects of CSWT on myocardial blood flow reserve (MBFR) assessed by quantitative real-time myocardial perfusion echocardiography in patients with RA., Methods: Fifteen patients (mean age 61.5 ± 12.8 years) with RA who underwent CSWT during nine sessions, over 3 months of treatment, were prospectively studied. A total of 32 myocardial segments with ischemia were treated, while another 31 did not receive therapy because of technical limitations. Myocardial perfusion was evaluated at rest and after dipyridamole stress (0.84 mg/kg) before and 6 months after CSWT, using quantitative real-time myocardial perfusion echocardiography. Clinical effects were evaluated using Canadian Cardiovascular Society grading of angina and the Seattle Angina Questionnaire., Results: The ischemic segments treated with CSWT had increased MBFR (from 1.33 ± 0.22 to 1.74 ± 0.29, P < .001), a benefit that was not observed in untreated ischemic segments (1.51 ± 0.29 vs 1.54 ± 0.28, P = .47). Patients demonstrated increased global MBFR (from 1.78 ± 0.54 to 1.89 ± 0.49, P = .017). Semiquantitative single-photon emission computed tomographic analysis of the treated ischemic segments revealed a score reduction from 2.10 ± 0.87 to 1.68 ± 1.19 (P = .024). There was improvement in Canadian Cardiovascular Society score (from 3.20 ± 0.56 to 1.93 ± 0.70, P < .05) and in Seattle Angina Questionnaire score (from 42.3 ± 12.99 to 71.2 ± 14.29, P < .05). No major cardiovascular events were recorded during follow-up., Conclusions: CSWT improved MBFR in ischemic segments, as demonstrated by quantitative real-time myocardial perfusion echocardiography. These results suggest that CSWT has the potential to increase myocardial blood flow, with an impact on symptoms and quality of life in patients with RA., (Copyright © 2019 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This review will provide recent pre-clinical and initial clinical trials exploring the efficacy of sonothrombolysis as an adjunct to current emergent therapies in acute coronary syndromes., Recent Findings: The initial clinical trials examining the efficacy of short pulse duration diagnostic ultrasound (DUS) high mechanical index impulses in patients with ST segment elevation myocardial infarction (STEMI) have demonstrated that there is improved patency of the infarct vessel, and improved microvascular flow following percutaneous coronary intervention. Subsequent randomized prospective trials have confirmed that in patients with acute STEMI receiving an intravenous microbubble infusion, diagnostic high mechanical index impulses applied in the apical windows pre- and post-percutaneous coronary intervention have reduced myocardial infarction size, as assessed by magnetic resonance imaging at 72 h following presentation, and have been associated with better left ventricular systolic function at 6 month follow-up. Sonothrombolysis has potential for improving early epicardial coronary artery patency and reduce left ventricular remodeling when added to current interventional strategies in STEMI.

Background: Preclinical studies have demonstrated that high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion (sonothrombolysis) can restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI)., Objectives: This study tested the clinical effectiveness of sonothrombolysis in patients with STEMI., Methods: Patients with their first STEMI were prospectively randomized to either diagnostic ultrasound-guided high MI impulses during an intravenous Definity (Lantheus Medical Imaging, North Billerica, Massachusetts) infusion before, and following, emergent percutaneous coronary intervention (PCI), or to a control group that received PCI only (n = 50 in each group). A reference first STEMI group (n = 203) who arrived outside the randomization window was also analyzed. Angiographic recanalization before PCI, ST-segment resolution, infarct size by magnetic resonance imaging, and systolic function (LVEF) at 6 months were compared., Results: ST-segment resolution occurred in 16 (32%) high MI PCI versus 2 (4%) PCI-only patients before PCI, and angiographic recanalization was 48% in high MI/PCI versus 20% in PCI only and 21% in the reference group (p < 0.001). Infarct size was reduced (29 ± 22 g high MI/PCI vs. 40 ± 20 g PCI only; p = 0.026). LVEF was not different between groups before treatment (44 ± 11% vs. 43 ± 10%), but increased immediately after PCI in the high MI/PCI group (p = 0.03), and remained higher at 6 months (p = 0.015). Need for implantable defibrillator (LVEF ≤30%) was reduced in the high MI/PCI group (5% vs. 18% PCI only; p = 0.045)., Conclusions: Sonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in systolic function after STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Few data exist on the degree of interstitial myocardial fibrosis in patients with classical low-flow, low-gradient aortic stenosis (LFLG-AS) and its association with left ventricular flow reserve (FR) on dobutamine stress echocardiography. This study sought to evaluate the diffuse interstitial fibrosis measured by T1 mapping cardiac magnetic resonance technique in LFLG-AS patients with and without FR. Methods Prospective study including 65 consecutive patients (41 LFLG-AS [mean age, 67.1±8.4 years; 83% men] and 24 high-gradient aortic stenosis used as controls) undergoing dobutamine stress echocardiography to assess FR and cardiac magnetic resonance to determine the extracellular volume (ECV) fraction of the myocardium, indexed ECV (iECV) to body surface area and late gadolinium enhancement. Results Interstitial myocardial fibrosis measured by iECV was higher in patients with LFLG-AS with and without FR as compared with high-gradient aortic stenosis (35.25±9.75 versus 32.93±11.00 versus 21.19±6.47 mL/m 2 , respectively; P<0.001). However, both ECV and iECV levels were similar between LFLG-AS patients with and without FR ( P=0.950 and P=0.701, respectively). Also, FR did not correlate significantly with ECV (r=-0.16, P=0.31) or iECV (r=0.11, P=0.51). Late gadolinium enhancement mass was also similar in patients with versus without FR but lower in high-gradient aortic stenosis (13.3±10.2 versus 10.5±7.5 versus 4.8±5.9 g, respectively; P=0.018). Conclusions Patients with LFLG-AS have higher ECV, iECV, and late gadolinium enhancement mass compared with high-gradient aortic stenosis. Moreover, among patients with LFLG-AS, the degree of myocardial fibrosis was similar in patients with versus those without FR. These findings suggest that diffuse myocardial fibrosis may not be the main factor responsible for the absence of FR in LFLG-AS patients.

Background: Cardiac shockwave therapy (CSWT) is a new potential option for the treatment of patients with chronic coronary disease and refractory angina (RA). We aimed to study the effects of CSWT on left ventricular myocardial perfusion and mechanics in patients with RA., Method: We prospectively studied 19 patients who underwent CSWT. Left ventricular mechanics were evaluated by speckle tracking echocardiography (STE), and myocardial perfusion by single-photon emission computed tomography, using stress/rest-Technetium-99 m Sestamibi, for determination of summed stress score (SSS). Canadian Cardiac Society (CCS), New York Heart Association (NYHA), and quality of life by Seattle Angina Questionnaire (SAQ) were assessed at baseline and 6 months after therapy., Results: CSWT therapy was applied without major side effects. At baseline, 18 patients (94.7%) had CCS class III or IV, and after CSWT there was reduction to 3 (15.8%), P = .0001, associated with improvement in SAQ (38.5%; P < .001). Thirteen (68.4%) had class NYHA III or IV before treatment, with significant reduction to 7 (36.8%); P = .014. No change was observed in the global SSS from baseline to 6-month follow-up (15.33 ± 8.60 vs 16.60 ± 8.06; P = .157). However, there was a significant reduction in the average SSS of the treated ischemic segments (2.1 ± 0.87 pre vs 1.6 ± 1.19 post CSWT; P = .024). Global longitudinal strain by STE remained unaltered (-13.03 ± 8.96 pre vs -15.88 ± 3.43 6-month post CSWT; P = .256)., Conclusion: CSWT is a safe procedure for the treatment of patients with RA that results in better quality of life, improvement in myocardial perfusion of the treated segments with preservation of left ventricular mechanics., (© 2018 Wiley Periodicals, Inc.)

Background: The identification of predictors of mitral valve (MV) repair results is important for quality improvement in cardiac surgery. The aim of this study was to evaluate the relationship between MV morphological quantification by three-dimensional (3D) transesophageal echocardiography and mitral repair results., Methods: Fifty-four patients with MV prolapse who were submitted to surgical repair were divided into 2 groups according to their postoperative mitral regurgitation (MR) degree (group 1, grade 0-I MR; group 2, ≥grade II MR). Morphological parameters related to the mitral ring, dimension of leaflets and prolapse, coaptation line, distance from papillary muscles to the leaflet border and valve angles were analyzed by 3D MV quantification. Cardiac remodeling and MR quantitative parameters were also evaluated., Results: There was no correlation between 3D MV quantification and surgical results; a multivariate analysis did not show an association between morphological parameters and surgical outcome. The distance from the posteromedial papillary muscle to the leaflet border was higher (P = .038) in patients with ≥grade II postoperative MR. The left atrial diameter, left ventricular end-systolic diameter, left ventricular end-diastolic and end-systolic volumes were larger in patients with a significant residual MR (P < .05)., Conclusion: Three-dimensional MV quantification did not predict the postoperative MR grade; however, the distance from the posteromedial papillary muscles to the leaflet border may be related to suboptimal repair results. Furthermore, excessive cardiac remodeling was related to postoperative MR ≥ grade II, what could suggest a potential benefit of early surgical treatment., (© 2018 Wiley Periodicals, Inc.)

Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact. We assessed tissue perfusion by real time myocardial perfusion echocardiography (RTMPE) using commercial microbubbles before and following pASCs treatment. Four weeks after the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1, 2 and 4x106 cells/Kg BW) into the myocardium. The highest dose of pASCs increased myocardial vessel number and blood flow in the border (56% and 3.7-fold, respectively) and in the remote area (54% and 3.9-fold, respectively) while the non-perfused scar area decreased (up to 38%). We also found an increase of immature collagen fibers, although the increase in total tissue collagen and types I and III was similar in all groups. Our results provide evidence that pASCs-induced stimulation of tissue perfusion and accumulation of immature collagen fibers attenuates adverse remodeling post-MI beyond the normal beneficial effects associated with ACE inhibition and beta-blockade.

Background: Chagas disease (CD) is highly endemic in Latin America, and has been emerging in developed countries. Early diagnosis of left ventricular (LV) systolic dysfunction, routinely done by echocardiography, is crucial for therapy. Speckle tracking echocardiography allows determination of LV segmental rotations, twist/torsion, and this analysis may disclose an unapparent myocardial contractile deficit in initial stages of CD. Therefore, this study aimed to highlight a possible unapparent myocardial contractile deficit in CD indeterminate form (IF) by a comprehensive torsional mechanics analysis., Methods: Patients with CDIF diagnosis, initial chagasic cardiomyopathy (CCMP characterized by ECG abnormalities and LVEF > 0.55), and normal controls were prospectively enrolled, and underwent conventional echocardiogram with images acquisition for STE offline analysis. Target parameters were basal and apical rotations, and calculation of twist and torsion., Results: A total of 42 patients were included (CDIF, eight; CCMP, 13; and 21 controls). Chagasic patients had a mean age of 55 years, five (24 %) men, and controls, 50 years, seven (33 %) men. Torsional mechanics analyzes resulted in no significant difference in all parameters studied between groups. Twist in CDIF was 20.8° ± 6.5°; CCMP, 19.0° ± 3.5° and controls, 19.7° ± 3.7° (p = 0.67). Torsion in CDIF was 2.6° ± 0.8°; CCMP, 2.4° ± 0.6° and controls, 2.4° ± 0.5° (p = 0.63)., Conclusions: Patients with Chagas disease have no abnormalities in torsional mechanics during its indeterminate and initial cardiomyopathy stages.

Objective: We sought to determine the prognostic value of qualitative and quantitative analysis obtained by real-time myocardial perfusion echocardiography (RTMPE) in patients with known or suspected coronary artery disease (CAD)., Background: Quantification of myocardial blood flow reserve (MBFR) in patients with CAD using RTMPE has been demonstrated to further improve accuracy over the analysis of wall motion (WM) and qualitative analysis of myocardial perfusion (QMP)., Methods: From March 2003 to December 2008, we prospectively studied 168 patients with normal left ventricular function (LVF) who underwent dobutamine stress RTMPE. The replenishment velocity reserve (β) and MBFR were derived from RTMPE. Acute coronary events were: cardiac death, myocardial infarction and unstable angina with need for urgent coronary revascularization., Results: During a median follow-up of 34 months (5 days to 6.9 years), 17 acute coronary events occurred. Abnormal β reserve in ≥2 coronary territories was the only independent predictor of events hazard ratio (HR) = 21, 95% CI = 4.5-99; p<0.001). Both, abnormal β reserve and MBFR added significant incremental value in predicting events over qualitative analysis of WM and MP (χ2 = 6.6 and χ2 = 24.6, respectively; p = 0.001 and χ2 = 6.6 and χ2 = 15.5, respectively; p = 0.012, respectively). When coronary angiographic data was added to the multivariate analysis model, β reserve remained the only predictor of events with HR of 21.0 (95% CI = 4.5-99); p<0.001., Conclusion: Quantitative dobutamine stress RTMPE provides incremental prognostic information over clinical variables, qualitative analysis of WM and MP, and coronary angiography in predicting acute coronary events.

Background: The effect of proximal side branches on the patency of the internal thoracic artery (ITA) is controversial. We used echocardiography and Doppler to verify the effect of ligation of branches on the flow and coronary flow reserve (CFR) of the grafted ITA in patients after coronary artery bypass grafting (CABG)., Methods: We prospectively investigated 53 patients with preserved left ventricular ejection fraction (LVEF >50%) who underwent CABG of the ITA. In Group I (25 patients), major branches were ligated during ITA anastomosis to the left anterior descending (LAD) coronary artery, whereas no ligation was performed in Group II (28 patients). Systolic flow (SF), diastolic flow (DF), and total flow (TF = SF + DF) were measured by Doppler echocardiography at the proximal level of the ITA preoperatively, at early postoperative stage, and 6 months after surgery. Dobutamine stress echocardiography (DSE) was performed at 6 months to determine CFR., Results: The ITA flow was predominantly systolic before surgery and diastolic in the postoperative period. We found no differences between the groups in DF. On DSE, SF (19.5±9 mL/min vs 32.7±19 mL/min; P=.003) and TF (79±21 mL/min vs 101±47 mL/min; P=.037) were higher in Group II. There were no differences in CFR (1.9±0.46 vs 2.11±0.56; P=.143)., Conclusion: In patients with preserved LVEF, ligation of major side branches during anastomosis to the LAD does not alter ITA flow or CFR., (© 2016, Wiley Periodicals, Inc.)

Background: Pre-clinical trials have demonstrated that, during intravenous microbubble infusion, high mechanical index (HMI) impulses from a diagnostic ultrasound (DUS) transducer might restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI)., Objectives: The purpose of this study was to test the safety and efficacy of this adjunctive approach in humans., Methods: From May 2014 through September 2015, patients arriving with their first STEMI were randomized to either DUS intermittent HMI impulses (n = 20) just prior to emergent percutaneous coronary intervention (PCI) and for an additional 30 min post-PCI (HMI + PCI), or low mechanical index (LMI) imaging only (n = 10) for perfusion assessments before and after PCI (LMI + PCI). All studies were conducted during an intravenous perflutren lipid microsphere infusion. A control reference group (n = 70) arrived outside of the time window of ultrasound availability and received emergent PCI alone (PCI only). Initial epicardial recanalization rates prior to emergent PCI and improvements in microvascular flow were compared between ultrasound-treated groups., Results: Median door-to-dilation times were 82 ± 26 min in the LMI + PCI group, 72 ± 15 min in the HMI + PCI group, and 103 ± 42 min in the PCI-only group (p = NS). Angiographic recanalization prior to PCI was seen in 12 of 20 HMI + PCI patients (60%) compared with 10% of LMI + PCI and 23% of PCI-only patients (p = 0.002). There were no differences in microvascular obstructed segments prior to treatment, but there were significantly smaller proportions of obstructed segments in the HMI + PCI group at 1 month (p = 0.001) and significant improvements in left ventricular ejection fraction (p < 0.005)., Conclusions: HMI impulses from a diagnostic transducer, combined with a commercial microbubble infusion, can prevent microvascular obstruction and improve functional outcome when added to the contemporary PCI management of acute STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Chagas disease (CD) is a frequent cause of dilated cardiomyopathy (CMP) in developing countries, leading to clinical heart failure and worse prognosis. Therefore, the development and evolution of this CMP has always been a major topic in numbers of previous studies. A comprehensive echocardiographic study of left ventricular (LV) mechanics, fully assessing myocardial contraction, has never been done before. This could help characterize and improve the understanding of the evolution of this prevalent CMP., Methods: A total of 47 chagasic and 84 control patients were included in this study and allocated in groups according to LV ejection fraction. 2D-Echocardiogram was acquired for LV mechanics analysis by speckle tracking echocardiography., Results: Mean age of chagasic individuals was 55y and 16 (34 %) were men. Significant difference was found in global longitudinal velocity analysis, with lower values in indeterminate form. In the group with severe systolic dysfunction, a paradoxical increase in longitudinal and apical radial displacements were demonstrated. In parallel, segmental analyzes highlighted lower values of radial displacement, strain and strain rate into inferior and inferolateral walls, with increase of these values in septal and anterior walls., Conclusion: Chagasic CMP has a vicarious pattern of contraction in the course of its evolution, defined by reduced displacement and strain into inferior and posterior walls with paradoxical increase in septal and anterior segments. Also, lower longitudinal velocities were demonstrated in CD indeterminate form, which may indicate an incipient myocardial injury.

Background: Left ventricular (LV) dysfunction is the major reason for poor outcomes in patients with congenital complete atrioventricular block (CCAVB) and pacemaker. Long-term pacing has been associated with LV mechanical dyssynchrony. However, the relationship of dyssynchrony and LV dysfunction is not clear., Objective: We sought to evaluate the prevalence of LV dyssynchrony by real time three-dimensional echocardiography (RT3DE) in patients with CCAVB and its association with LV dysfunction. In addition, we evaluated the agreement between RT3DE and tissue Doppler imaging (TDI) for detecting LV dyssynchrony., Method: We studied 50 patients [median age 20 years old (5 months to 62 years), 68% women] with CCAVB and pacemaker who underwent complete two-dimensional echocardiography and RT3DE. LV dyssynchrony was considered if the systolic dyssynchrony index (SDI) was ≥ 5%. Intraventricular mechanical delay was defined by TDI when differences in electromechanical activation between LV walls were > 65 msec., Results: LV systolic dysfunction was present in 16 patients (32%) by two-dimensional and in 20 patients (40%) by RT3DE. There was a good correlation between LV ejection fraction by two-dimensional and RT3DE (r = 0.75; P < 0.001). Fourteen (28%) patients had intraventricular dyssynchrony by TDI, while 12 (24%) had intraventricular dyssynchrony by RT3DE. There was a good agreement between LV dyssynchrony by TDI and RT3DE (Kappa = 0.735; P < 0.001). There was a negative correlation between LV ejection fraction and SDI obtained by RT3DE (r = -0.58; P < 0.001) CONCLUSIONS: In patients with CCAVB and long-term pacing, LV dyssynchrony occurred in one-third of patients and was related to LV dysfunction. There was a good correlation between dyssynchrony obtained by RT3DE and TDI., (© 2015, Wiley Periodicals, Inc.)

Objective: Polycystic ovary syndrome (PCOS) is associated with increased risk for cardiovascular disease. We sought to evaluate the effects of insulin resistance (IR) on myocardial microcirculation and peripheral artery function in patients with PCOS., Methods: We studied 55 women (28 with PCOS without IR, 18 with PCOS and IR and 11 normal controls) who underwent laboratorial analysis, high-resolution vascular ultrasound and real time myocardial contrast echocardiography (RTMCE). Intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) were evaluated by vascular ultrasound. The replenishment velocity (β), plateau of acoustic intensity (A) and myocardial blood flow reserve (MBFR) were determined by quantitative dipyridamole stress RTMCE., Results: β reserve in group PCOS + IR was lower than control (2.34 ± 0.55 vs. 3.60 ± 0.6; P < 0.001) and than PCOS without IR (2.34 ± 0.55 vs. 3.17 ± 0.65; P < 0.001). MBFR in patients with PCOS without IR did not differ from those of control (4.59 ± 1.59 vs. 5.30 ± 1.64; P = 0.22) or from patients with PCOS + IR (4.59 ± 1.59 vs. 3.70 ± 1.47; P = 0.07). When comparing with control group, patients with PCOS + IR had lower MBFR (5.30 ± 1.64 vs. 3.70 ± 1.47; P = 0.01). No significant differences were found between control, PCOS without IR and PCOS + IR for FMD (0.18 ± 0.05, 0.15 ± 0.04 and 0.13 ± 0.07; P =NS) or IMT (0.48 ± 0.05, 0.47 ± 0.05 and 0.49 ± 0.07; P = NS)., Conclusion: Women with PCOS and IR had depressed β and MBFR as demonstrated by quantitative RTMCE, but no alteration in endothelial dysfunction or IMT. PCOS without IR showed isolated depression in β reserve, probably an earlier marker of myocardial flow abnormality., (© 2014, Wiley Periodicals, Inc.)

Background: Diagnosis of cardiac masses is still challenging by echocardiography and distinguishing tumors from thrombi has important therapeutical implications. We sought to determine the diagnostic value of real-time perfusion echocardiography (RTPE) for cardiac masses characterization., Methods: We prospectively studied 86 patients, 23 with malignant tumors (MT), 26 with benign tumors (BT), 33 with thrombi and 6 with pseudotumors who underwent RTPE. Mass perfusion was analyzed qualitatively and blood flow volume (A), blood flow velocity (β), and microvascular blood flow (A x β) were determined by quantitative RTPE., Results: Logistic regression models showed that the probability of having a tumor increased by 15.8 times with a peripheral qualitative perfusion pattern, and 34.5 times with a central perfusion pattern, in comparison with the absence of perfusion. Using quantitative RTPE analysis, thrombi group had parameters of blood flow lower than tumor group. A values for thrombi, MT, and BT were 0.1 dB (0.01-0.22), 2.78 dB (1-7) and 2.58 dB (1.44-5), respectively; p < 0.05, while A x β values were 0.0 dB/s(-1) (0.01-0.14), 2.00 dB/s(-1) (1-6), and 1.18 dB/s(-1) (0.52-3), respectively; p < 0.05. At peak dipyridamole stress, MT had greater microvascular blood volume than BT [A = 4.18 dB (2.14-7.93) versus A = 2.04 dB (1.09-3.55); p < 0.05], but no difference in blood flow [Axβ = 2.46 dB/s(-1) (1.42-4.59) versus Axβ = 1.55 dB/s [1] (0.51-4.08); p = NS]. An A value >3.28 dB at peak dipyridamole stress predicted MT (AUC = 0.75) and conferred 5.8-times higher chance of being MT rather than BT., Conclusion: RTPE demonstrated that cardiac tumors have greater microvascular blood volume and regional blood flow when compared with thrombi. Dipyridamole stress was useful in differentiating MT from BT.

Natural myocardial markers, or speckles, originated from constructive and destructive interference of ultrasound in the tissues may provide early diagnosis of myocardial changes and be used in the prediction of some cardiac events. Due to its relatively temporal stability, speckles can be tracked by dedicated software along the cardiac cycle, enabling the analysis of the systolic and diastolic function. They are identified by either conventional 2D grey scale and by 3D echo, conferring independence of the insonation angle, thus allowing assessment of cardiac mechanics in the three spatial planes: longitudinal, circumferential, and radial. The purposes of the present paper are: to discuss the role and the meaning of cardiac strain obtained by speckle tracking during the evaluation of cardiac physiology and to discuss clinical applications of this novel echocardiographic technology.

The feasibility and potential for the morphological and hemodynamic investigation of the heart has been increasing the use of the echocardiography in the research setting. Additionally, the development of new technologies, like the real time 3D echocardiography and speckle tracking, demands validation throughout experimental studies before being instituted in the clinical setting. This paper aims to provide information concerning the particularities of the echocardiographic examination in quadruped mammals, targeting the experimental research.

Background: Quantification of myocardial blood flow reserve in patients with coronary artery disease using real-time myocardial perfusion echocardiography (RTMPE) has been demonstrated to further improve accuracy over the analysis of wall motion and qualitative analysis of myocardial perfusion. The aim of this study was to determine the prognostic value of qualitative and quantitative analyses obtained by RTMPE in patients with known or suspected coronary artery disease., Methods: From March 2003 to December 2008, 227 consecutive patients with normal left ventricular function who underwent RTMPE were prospectively studied. Replenishment velocity reserve (β) and myocardial blood flow reserve were derived from RTMPE. Primary outcomes were cardiac death, myocardial infarction and unstable angina with need for urgent coronary revascularization, and secondary outcomes were coronary bypass graft surgery or angioplasty., Results: During a median follow-up period of 32 months (range, 5 days to 6.9 years), 19 major events (two deaths, six myocardial infarctions, and 11 episodes of unstable angina) and 46 total events occurred. Wall motion (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.4-5.6; P = .003) and qualitative myocardial perfusion analysis (HR, 4.3; 95% CI, 2.1-8.5; P < .001) were predictors of total events but not primary events. Abnormal myocardial blood flow reserve and abnormal β reserve were predictors of total events (HR, 8.1; 95% CI, 3-21; P < .001; and HR, 16.5; 95% CI, 5.5-49; P < .001) and primary events (HR, 3.8; 95% CI, 1-15; P = .048; and HR, 8.7; 95% CI, 1.8-40; P = .005). On multivariate analysis, only abnormal β reserve was an independent predictor of total (HR, 10.6; 95% CI, 2.5-43; P = .001) and primary (HR, 10.5; 95% CI, 1.5-6; P = .015) events. Abnormal β reserve added incremental value in predicting primary events (χ(2) = 2.0-13.2; P = .014)., Conclusions: Quantitative adenosine stress RTMPE added independent and additional prognostic information over wall motion and qualitative myocardial perfusion analysis in patients with known or suspected coronary artery disease and normal left ventricular function., (Copyright © 2013. Published by Mosby, Inc.)

Background: Coronary and microvascular blood flow reserve have been established as important predictors of prognosis in patients with cardiovascular disease. The aim of this study was to assess the value of coronary flow velocity reserve (CFVR) and real-time myocardial perfusion echocardiography (RTMPE) for predicting events in patients with nonischemic dilated cardiomyopathy., Methods: One hundred ninety-five patients (mean age 54 ± 12 years; 66% men) with dilated cardiomyopathy (left ventricular ejection fraction < 35% and no obstructive coronary disease on invasive angiography or multidetector computed tomography) who underwent dipyridamole stress (0.84 mg/kg over 10 min) RTMPE were prospectively studied. CFVR was calculated as the ratio of hyperemic to baseline peak diastolic velocities in the distal left anterior coronary artery. The replenishment velocity (β), plateau of acoustic intensity (A(N)), and myocardial blood flow reserve were obtained from RTMPE., Results: Mean CFVR was 2.07 ± 0.52, mean A(N) reserve was 1.05 ± 0.09, mean β reserve was 2.05 ± 0.39, and mean myocardial blood flow reserve (A(N) × β) was 2.15 ± 0.48. During a median follow-up period of 29 months, 45 patients had events (43 deaths and two urgent transplantations). Independent predictors of events were left atrial diameter (relative risk, 1.16; 95% confidence interval, 1.08-1.26; P < .001) and β reserve ≤ 2.0 (relative risk, 3.22; 95% confidence interval, 1.18-8.79; P < .001). After adjustment for β reserve, CFVR and myocardial blood flow reserve no longer had predictive value. Left atrial diameter added prognostic value over clinical factors and left ventricular ejection fraction (χ2 = 36.8-58.5, P < .001). Beta reserve added additional power to the model (χ2 = 70.2, P < .001)., Conclusions: Increased left atrial diameter and depressed β reserve were independent predictors of cardiac death and transplantation in patients with nonischemic dilated cardiomyopathy. Beta reserve by RTMPE provided incremental predictive value beyond that provided by current known prognostic clinical and echocardiographic factors., (Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Background: Hypercholesterolemia induces early microcirculatory functional and structural alterations that are reversible by cholesterol reduction. Real time myocardial contrast echocardiography (RTMCE) and vascular ultrasound evaluate the effects of hyperlipidemia on peripheral and central blood flow reserve. This study investigated the effects of lipid-lowering therapy on coronary and peripheral artery circulation in patients with familial hypercholesterolemia (FH)., Methods: RTMCE and vascular ultrasound were performed in 10 healthy volunteers (validation group) at baseline and after 12-week clinical observation, and in 16 age- and sex-matched FH patients without obstructive coronary artery disease (CAD) by computed tomography angiography at baseline and after 12-week atorvastatin treatment. Indexes of relative myocardial blood flow (MBF) were obtained at rest and during adenosine infusion., Results: In validation group, there was no significant difference between flow-mediated dilation (FMD) at baseline and after 12 weeks (0.15 ± 0.02 vs. 0.14 ± 0.03; P = 0.39). Similarly, no differences were observed in MBF reserve at baseline and after 12 weeks (3.31 ± 0.63 vs. 3.48 ± 0.89; P = 0.89). FMD was blunted in FH patients, at baseline, as compared with validation group (0.08 ± 0.04 vs. 0.15 ± 0.02; P < 0.001) and became similar to that group (0.13 ± 0.05 vs. 0.14 ± 0.03; P = 0.07) after treatment. MBF reserve was blunted at baseline in FH patients in comparison with the validation group (2.78 ± 0.71 vs. 3.31 ± 0.63; P = 0.003). After treatment, MBF reserve values were no longer different (3.43 ± 0.66 and 3.48 ± 0.89; P = 0.84, respectively, for FH and validation groups)., Conclusion: Patients with FH and no obstructive CAD have blunted MBF reserve and lower FMD values as compared with healthy volunteers. Both FMD and MBF reserve were normalized after atorvastatin treatment., (© 2012, Wiley Periodicals, Inc.)