Usefulness of speckle tracking echocardiography and biomarkers for detecting acute cellular rejection after heart transplantation.

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.

Cardiac shock wave therapy improves myocardial perfusion and preserves left ventricular mechanics in patients with refractory angina: A study with speckle tracking echocardiography.

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.

Comprehensive left ventricular mechanics analysis by speckle tracking echocardiography in Chagas disease.

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.

The impact of ligation of proximal side branches on blood flow and functional status of the internal thoracic artery in coronary anastomosis.

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.

Evaluation of cardiac masses by real-time perfusion imaging echocardiography.

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 (ß), and microvascular blood flow (A x ß) 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 ß 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 [Axß = 2.46 dB/s(-1) (1.42-4.59) versus Axß = 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.

Atorvastatin treatment improves myocardial and peripheral blood flow in familial hypercholesterolemia subjects without evidence of coronary atherosclerosis.

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.

Incremental value of perfusion over wall-motion abnormalities with the use of dobutamine-atropine stress myocardial contrast echocardiography and magnetic resonance imaging for detecting coronary artery disease.

BACKGROUND: Recently, multimodality imaging has been demonstrated to improve the sensitivity of dobutamine stress for the diagnosis of coronary artery disease (CAD). OBJECTIVE: We sought to determine the additional value of myocardial perfusion (MP) over wall-motion (WM) analysis for detecting CAD, using real time myocardial contrast echocardiography (RTMCE) and cardiovascular magnetic resonance (CMR), in the same group of patients. METHODS: We studied 42 patients who underwent RTMCE and CMR during high-dose dobutamine stress with early injection of atropine. RESULTS: No difference was observed in the diagnostic accuracy of RTMCE and CMR for detecting angiographically significant CAD when considering WM analysis alone (73% [95% CI, 65-81] and 78% [95% CI, 70-84], respectively; P = NS) or combined analysis of WM and MP (80% [95% CI, 73-97] and 83% [95% CI, 77-90], respectively; P = NS). Combined analysis of WM and MP had higher sensitivity than the analysis of WM alone by RTMCE (88% [95% CI, 75-100] vs. 72% [95% CI, 54-90]) and by CMR (92% [95% CI, 81-100] vs. 80% [95% CI, 64-96]) with no differences in specificity. The association of abnormal WM and MP abnormalities during high-dose dobutamine-atropine stress had additional value for detecting CAD over the analysis of WM alone, both by RTMCE (χ(2) = 16.16-24.13; P = 0.005) and CMR (χ(2) = 12.73-27.41; P = 0.001). CONCLUSION: RTMCE and CMR using the same dobutamine-atropine stress protocol had comparable diagnostic accuracies for the detection of angiographically significant CAD. MP imaging had additional value over WM analysis for the diagnosis of CAD, both at RTMCE and CMR.

The Impact of Sonothrombolysis on Left Ventricular Diastolic Function and Left Atrial Mechanics Preventing Left Atrial Remodeling in Patients With ST Elevation Acute Myocardial Infarction.

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.

Sonothrombolysis Promotes Improvement in Left Ventricular Wall Motion and Perfusion Scores after Acute Myocardial Infarction. / A Sonotrombólise Promove Melhora dos Índices de Motilidade e Perfusão do Ventrículo Esquerdo após o Infarto Agudo do Miocárdio.

BACKGROUND: It has recently been demonstrated that the application of high-energy ultrasound and microbubbles, in a technique known as sonothrombolysis, dissolves intravascular thrombi and increases the angiographic recanalization rate in patients with ST-segment-elevation myocardial infarction (STEMI). OBJECTIVE: To evaluate the effects of sonothrombolysis on left ventricular wall motion and myocardial perfusion in patients with STEMI, using real-time myocardial perfusion echocardiography (RTMPE). METHODS: One hundred patients with STEMI were randomized into the following 2 groups: therapy (50 patients treated with sonothrombolysis and primary coronary angioplasty) and control (50 patients treated with primary coronary angioplasty). The patients underwent RTMPE for analysis of left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and number of segments with myocardial perfusion defects 72 hours after STEMI and at 6 months of follow-up. P < 0.05 was considered statistically significant. RESULTS: Patients treated with sonothrombolysis had higher LVEF than the control group at 72 hours (50% ± 10% versus 44% ± 10%; p = 0.006), and this difference was maintained at 6 months of follow-up (53% ± 10% versus 48% ± 12%; p = 0.008). The WMSI was similar in the therapy and control groups at 72 hours (1.62 ± 0.39 versus 1.75 ± 0.40; p = 0.09), but it was lower in the therapy group at 6 months (1.46 ± 0.36 versus 1.64 ± 0.44; p = 0.02). The number of segments with perfusion defects on RTMPE was similar in therapy and control group at 72 hours (5.92 ± 3.47 versus 6.94 ± 3.39; p = 0.15), but it was lower in the therapy group at 6 months (4.64 ± 3.31 versus 6.57 ± 4.29; p = 0.01). CONCLUSION: Sonothrombolysis in patients with STEMI resulted in improved wall motion and ventricular perfusion scores over time.

FUNDAMENTO: Demonstrou-se recentemente que a aplicação de ultrassom de alta energia com microbolhas, técnica conhecida como sonotrombólise, causa a dissolução de trombos intravasculares e aumenta a taxa de recanalização angiográfica no infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAM-CSST). OBJETIVO: Avaliar o efeito da sonotrombólise nos índices de motilidade e perfusão miocárdicas em pacientes com IAM-CSST, utilizando a ecocardiografia com perfusão miocárdica em tempo real (EPMTR). MÉTODO: Uma centena de pacientes com IAM-CSST foram randomizados em dois grupos: Terapia (50 pacientes tratados com sonotrombólise e angioplastia coronária primária) e Controle (50 pacientes tratados com angioplastia coronária primária). Os pacientes realizaram EPMTR para analisar a fração de ejeção do ventrículo esquerdo (FEVE), o índice de escore de motilidade segmentar (IEMS) e o número de segmentos com defeito de perfusão miocárdica, 72 horas após o IAM-CSST e com 6 meses de acompanhamento. Foi considerado significativo p < 0,05. RESULTADOS: Pacientes tratados com sonotrombólise apresentaram FEVE mais alta que o grupo Controle em 72 horas (50 ± 10% vs. 44 ± 10%; p = 0,006), e essa melhora foi mantida em seis meses (53 ± 10% vs. 48 ± 12%; p = 0,008). O IEMS foi similar nos grupos Terapia e Controle em 72 horas (1,62 ± 0,39 vs. 1,75 ± 0,40; p = 0,09), mas tornou-se menor no grupo Terapia em 6 meses (1,46 ± 0,36 vs. 1,64 ± 0,44; p = 0,02). O número de segmentos com defeito de perfusão não foi diferente entre os grupos em 72 horas (5,92 ± 3,47 vs. 6,94 ± 3,39; p = 0,15), mas ficou menor no grupo Terapia em 6 meses (4,64 ± 3,31 vs. 6,57 ± 4,29; p = 0,01). CONCLUSÃO: A sonotrombólise em pacientes com IAM-CSST resulta na melhora dos índices de motilidade e perfusão ventricular ao longo do tempo.

Dynamic changes in microcirculatory blood flow during dobutamine stress assessed by quantitative myocardial contrast echocardiography.

BACKGROUND: Although dobutamine-atropine stress echocardiography (DASE) has been widely used for evaluating patients with coronary artery disease (CAD), dynamic changes that occur at microcirculatory level during each stage of stress have not been demonstrated in humans. AIM: We sought to determine variations in myocardial blood flow (MBF) during DASE using quantitative real time myocardial contrast echocardiography (RTMCE). METHODS: We studied 45 patients who underwent coronary angiography and RTMCE. Replenishment velocity of microbubbles in the myocardium (ß) and MBF reserves were obtained at baseline, intermediate stage (70% of maximal predicted heart rate), peak stress, and recovery phase. RESULTS: ß and MBF reserves were lower in patients with than without CAD at intermediate (1.65 vs. 2.10; P=0.001 and 2.44 vs. 3.23; P=0.004) and peak (1.63 vs. 3.00; P<0.001 and 2.14 vs. 3.98; P<0.001, respectively). In patients without CAD, ß, and MBF reserves increased from intermediate to peak and decreased at recovery, while in those without CAD reserves did not change significantly. Optimal cutoff values of ß reserve at intermediate, peak, and recovery were 1.78, 2.09, and 1.70, with areas under the curves of 0.80 (95%CI=0.67-0.94), 0.89 (95%CI=0.79-0.99), and 0.69 (95%CI=0.53-0.85). Sensitivity, specificity and accuracy for detecting CAD at intermediate stage were 68% (95%CI=48-89), 85% (95%CI=71-98), and 78% (95%CI=66-90), at peak stress were 79% (95%CI=61-97), 96% (95%CI=89-100), and 89% (95%CI=80-98), and at recovery were 74% (95%CI=54-93), 65% (95%CI=47-84), and 69% (95%CI=55-82), respectively. CONCLUSION: RTMCE allows for quantification of dynamic changes in microcirculatory blood flow at each stage of DASE. The best parameter for detecting CAD in all stages was ß reserve.

Qualitative and quantitative real time myocardial contrast echocardiography for detecting hibernating myocardium.

BACKGROUND: Real time myocardial contrast echocardiography (RTMCE) is an emerging imaging modality for assessing myocardial perfusion that allows for noninvasive quantification of regional myocardial blood flow (MBF). AIM: We sought to assess the value of qualitative analysis of myocardial perfusion and quantitative assessment of myocardial blood flow (MBF) by RTMCE for predicting regional function recovery in patients with ischemic heart disease who underwent coronary artery bypass grafting (CABG). METHODS: Twenty-four patients with coronary disease and left ventricular systolic dysfunction (ejection fraction <45%) underwent RTMCE before and 3 months after CABG. RTMCE was performed using continuous intravenous infusion of commercially available contrast agent with low mechanical index power modulation imaging. Viability was defined by qualitative assessment of myocardial perfusion as homogenous opacification at rest in ≥2 segments of anterior or ≥1 segment of posterior territory. Viability by quantitative assessment of MBF was determined by receiver-operating characteristics curve analysis. RESULTS: Regional function recovery was observed in 74% of territories considered viable by qualitative analysis of myocardial perfusion and 40% of nonviable (P = 0.03). Sensitivity, specificity, positive and negative predictive values of qualitative RTMCE for detecting regional function recovery were 74%, 60%, 77%, and 56%, respectively. Cutoff value of MBF for predicting regional function recovery was 1.76 (AUC = 0.77; 95% CI = 0.62-0.92). MBF obtained by RTMCE had sensitivity of 91%, specificity of 50%, positive predictive value of 75%, and negative predictive value of 78%. CONCLUSION: Qualitative and quantitative RTMCE provide good accuracy for predicting regional function recovery after CABG. Determination of MBF increases the sensitivity for detecting hibernating myocardium.

Sonothrombolysis Improves Myocardial Dynamics and Microvascular Obstruction Preventing Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction.

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.

Shock-Wave Therapy Improves Myocardial Blood Flow Reserve in Patients with Refractory Angina: Evaluation by Real-Time Myocardial Perfusion Echocardiography.

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.

Sonothrombolysis in ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention.

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).

Prognostic value of dobutamine stress myocardial perfusion echocardiography in patients with known or suspected coronary artery disease and normal left ventricular function.

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 (ß) 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 ß 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 ß 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, ß 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.

Global Longitudinal Strain or Left Ventricular Twist and Torsion? Which Correlates Best with Ejection Fraction?

Background: Estimative of left ventricular ejection fraction (LVEF) is a major indication for echocardiography. Speckle tracking echocardiography (STE) allows analysis of LV contraction mechanics which includes global longitudinal strain (GLS) and twist/torsion, both the most widely used. Direct comparison of correlations between these novel parameters and LVEF has never been done before. Objective: This study aims to check which one has the highest correlation with LVEF. Methods: Patients with normal LVEF (> 0,55) and systolic dysfunction (LVEF <0,55) were prospectively enrolled, and underwent echocardiogram with STE analysis. Correlation of variables was performed by linear regression analysis. In addition, correlation among levels of LV systolic impairment was also tested. Results: A total of 131 patients were included (mean age, 46 ± 14y; 43%, men). LVEF and GLS showed a strong correlation (r = 0.95; r2 = 0.89; p < 0.001), more evident in groups with LV systolic dysfunction than those with preserved LVEF. Good correlation was also found with global longitudinal strain rate (r = 0.85; r2 = 0.73; p < 0.001). Comparing to GLS, correlation of LVEF and torsional mechanics was weaker: twist (r = 0.78; r2 = 0.60; p < 0.001); torsion (r = 0.75; r2 = 0.56; p < 0.001). Conclusion: GLS of the left ventricle have highly strong positive correlation with the classical parameter of ejection fraction, especially in cases with LV systolic impairment. Longitudinal strain rate also demonstrated a good correlation. GLS increments analysis of LV systolic function. On the other hand, although being a cornerstone of LV mechanics, twist and torsion have a weaker correlation with LV ejection, comparing to GLS.

Fundamento: A estimativa da fração de ejeção do ventrículo esquerdo (FEVE) é uma das pincipais indicações para a ecocardiografia. Speckle tracking (ST) permite a análise da mecânica de contração do VE que inclui a deformação (strain) longitudinal global (SLG) e o twist / torção, sendo ambos os mais utilizados. A comparação direta de correlações entre esses novos parâmetros e a FEVE nunca foi feita antes. Objetivo: Verificar qual delas tem a maior correlação com a FEVE. Métodos: Pacientes com FEVE normal (> 0,55) e disfunção sistólica (FEVE < 0,55) foram prospectivamente inscritos e submetidos a ecocardiograma com análise do ST. A correlação das variáveis foi realizada por análise de regressão linear. Além disso, também foi testada a correlação entre os níveis de comprometimento sistólico do VE. Resultados: Foram incluídos 131 pacientes (média de idade de 46 ± 14 anos e 43% de homens). A FEVE e SLG apresentaram forte correlação (r = 0,95; r2 = 0,89; p < 0,001), mais evidente em grupos com disfunção sistólica do VE do que naqueles com FEVE preservada. Também foi encontrada boa correlação com a taxa de deformação (strain rate) longitudinal (SRL) global (r = 0,85; r2 = 0,73; p < 0,001). Comparando-a à SLG, a correlação entre FEVE e mecânica de torção foi mais fraca: twist (r = 0,78; r2 = 0,60; p < 0,001); Torção (r = 0,75, r2 = 0,56, p < 0,001). Conclusão: A SLG do ventrículo esquerdo apresenta alta correlação positiva com o parâmetro clássico de fração de ejeção, principalmente nos casos de comprometimento sistólico do VE. O SRL também demonstrou uma boa correlação. A SLG incrementa a análise da função sistólica do VE. Por outro lado, apesar de ser a pedra angular da mecânica do VE, o twist e a torção têm uma correlação mais fraca com a ejeção do VE, quando comparados ao SLG.

A Sonotrombólise Promove Melhora dos Índices de Motilidade e Perfusão do Ventrículo Esquerdo após o Infarto Agudo do Miocárdio / Sonothrombolysis Promotes Improvement in Left Ventricular Wall Motion and Perfusion Scores after Acute Myocardial Infarction

Resumo Fundamento Demonstrou-se recentemente que a aplicação de ultrassom de alta energia com microbolhas, técnica conhecida como sonotrombólise, causa a dissolução de trombos intravasculares e aumenta a taxa de recanalização angiográfica no infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAM-CSST). Objetivo Avaliar o efeito da sonotrombólise nos índices de motilidade e perfusão miocárdicas em pacientes com IAM-CSST, utilizando a ecocardiografia com perfusão miocárdica em tempo real (EPMTR). Método Uma centena de pacientes com IAM-CSST foram randomizados em dois grupos: Terapia (50 pacientes tratados com sonotrombólise e angioplastia coronária primária) e Controle (50 pacientes tratados com angioplastia coronária primária). Os pacientes realizaram EPMTR para analisar a fração de ejeção do ventrículo esquerdo (FEVE), o índice de escore de motilidade segmentar (IEMS) e o número de segmentos com defeito de perfusão miocárdica, 72 horas após o IAM-CSST e com 6 meses de acompanhamento. Foi considerado significativo p < 0,05. Resultados Pacientes tratados com sonotrombólise apresentaram FEVE mais alta que o grupo Controle em 72 horas (50 ± 10% vs. 44 ± 10%; p = 0,006), e essa melhora foi mantida em seis meses (53 ± 10% vs. 48 ± 12%; p = 0,008). O IEMS foi similar nos grupos Terapia e Controle em 72 horas (1,62 ± 0,39 vs. 1,75 ± 0,40; p = 0,09), mas tornou-se menor no grupo Terapia em 6 meses (1,46 ± 0,36 vs. 1,64 ± 0,44; p = 0,02). O número de segmentos com defeito de perfusão não foi diferente entre os grupos em 72 horas (5,92 ± 3,47 vs. 6,94 ± 3,39; p = 0,15), mas ficou menor no grupo Terapia em 6 meses (4,64 ± 3,31 vs. 6,57 ± 4,29; p = 0,01). Conclusão A sonotrombólise em pacientes com IAM-CSST resulta na melhora dos índices de motilidade e perfusão ventricular ao longo do tempo.

Abstract Background It has recently been demonstrated that the application of high-energy ultrasound and microbubbles, in a technique known as sonothrombolysis, dissolves intravascular thrombi and increases the angiographic recanalization rate in patients with ST-segment-elevation myocardial infarction (STEMI). Objective To evaluate the effects of sonothrombolysis on left ventricular wall motion and myocardial perfusion in patients with STEMI, using real-time myocardial perfusion echocardiography (RTMPE). Methods One hundred patients with STEMI were randomized into the following 2 groups: therapy (50 patients treated with sonothrombolysis and primary coronary angioplasty) and control (50 patients treated with primary coronary angioplasty). The patients underwent RTMPE for analysis of left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and number of segments with myocardial perfusion defects 72 hours after STEMI and at 6 months of follow-up. P < 0.05 was considered statistically significant. Results Patients treated with sonothrombolysis had higher LVEF than the control group at 72 hours (50% ± 10% versus 44% ± 10%; p = 0.006), and this difference was maintained at 6 months of follow-up (53% ± 10% versus 48% ± 12%; p = 0.008). The WMSI was similar in the therapy and control groups at 72 hours (1.62 ± 0.39 versus 1.75 ± 0.40; p = 0.09), but it was lower in the therapy group at 6 months (1.46 ± 0.36 versus 1.64 ± 0.44; p = 0.02). The number of segments with perfusion defects on RTMPE was similar in therapy and control group at 72 hours (5.92 ± 3.47 versus 6.94 ± 3.39; p = 0.15), but it was lower in the therapy group at 6 months (4.64 ± 3.31 versus 6.57 ± 4.29; p = 0.01). Conclusion Sonothrombolysis in patients with STEMI resulted in improved wall motion and ventricular perfusion scores over time.

Value of adenosine infusion for infarct size determination using real-time myocardial contrast echocardiography.

BACKGROUND: Myocardial contrast echocardiography has been used for determination of infarct size (IS) in experimental models. However, with intermittent harmonic imaging, IS seems to be underestimated immediately after reperfusion due to areas with preserved, yet dysfunctional, microvasculature. The use of exogenous vasodilators showed to be useful to unmask these infarcted areas with depressed coronary flow reserve. This study was undertaken to assess the value of adenosine for IS determination in an open-chest canine model of coronary occlusion and reperfusion, using real-time myocardial contrast echocardiography (RTMCE). METHODS: Nine dogs underwent 180 minutes of coronary occlusion followed by reperfusion. PESDA (Perfluorocarbon-Exposed Sonicated Dextrose Albumin) was used as contrast agent. IS was determined by RTMCE before and during adenosine infusion at a rate of 140 mcg.Kg(-1).min(-1). Post-mortem necrotic area was determined by triphenyl-tetrazolium chloride (TTC) staining. RESULTS: IS determined by RTMCE was 1.98 +/- 1.30 cm2 and increased to 2.58 +/- 1.53 cm2 during adenosine infusion (p = 0.004), with good correlation between measurements (r = 0.91; p < 0.01). The necrotic area determined by TTC was 2.29 +/- 1.36 cm2 and showed no significant difference with IS determined by RTMCE before or during hyperemia. A slight better correlation between RTMCE and TTC measurements was observed during adenosine (r = 0.99; p < 0.001) then before it (r = 0.92; p = 0.0013). CONCLUSION: RTMCE can accurately determine IS in immediate period after acute myocardial infarction. Adenosine infusion results in a slight better detection of actual size of myocardial damage.

Noninvasive detection of coronary allograft vasculopathy by myocardial contrast echocardiography.

BACKGROUND: Noninvasive detection of coronary allograft vasculopathy is still challenging. To determine the accuracy of myocardial contrast echocardiography (MCE) in detecting coronary allograft vasculopathy after heart transplantation, we studied 35 asymptomatic patients (30 men, aged 46 +/- 12.7 years) with normal left ventricular function. METHODS: Patients underwent MCE with continuous contrast (perfluorocarbon-exposed sonicated dextrose albumin) administration. Images were obtained at baseline and during peak dobutamine (up to 40 mg/kg/min) with intermittent harmonic imaging. Areas failing to increase contrast enhancement during peak stress were regarded as abnormal. Coronary artery obstructions greater than 50% at angiography were considered significant. RESULTS: Seven out of 10 patients with coronary artery disease had a positive MCE and one patient with a positive MCE had no angiographically detected disease (sensitivity = 70%, specificity = 96%, accuracy = 88.6%). Agreement between the vascular territory and perfusion defects was good for the left anterior descending coronary artery (kappa = 0.56), but not for other arteries. Although 5 patients had multivessel disease, multiple perfusion defects were detected in only one patient. CONCLUSION: MCE showed good accuracy in detecting the presence of coronary allograft vasculopathy after heart transplantation; however, it failed to identify the extent of the disease.