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.

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).

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.

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.

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.

Prognostic value of qualitative and quantitative vasodilator stress myocardial perfusion echocardiography in patients with known or suspected coronary artery disease.

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 (ß) 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 ß 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 ß 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 ß 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.

Prognostic value of coronary and microvascular flow reserve in patients with nonischemic dilated cardiomyopathy.

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 (ß), 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 ß reserve was 2.05 ± 0.39, and mean myocardial blood flow reserve (A(N) × ß) 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 ß reserve ≤ 2.0 (relative risk, 3.22; 95% confidence interval, 1.18-8.79; P < .001). After adjustment for ß 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 ß 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.

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.