Bone Marrow Cells Improve Coronary Flow Reserve in Ischemic Nonrevascularized Myocardium: A MiHeart/IHD Quantitative Perfusion CMR Substudy.

OBJECTIVES: This study investigated whether intramyocardial bone marrow-derived hematopoietic progenitor cells (BMCs) increase coronary flow reserve (CFR) in ischemic myocardial regions where direct revascularization was unsuitable. BACKGROUND: Patients with diffuse coronary artery disease frequently undergo incomplete myocardial revascularization, which increases their risk for future adverse cardiovascular outcomes. The residual regional ischemia related to both untreated epicardial lesions and small vessel disease usually contributes to the disease burden. METHODS: The MiHeart/IHD study randomized patients with diffuse coronary artery disease undergoing incomplete coronary artery bypass grafting to receive BMCs or placebo in ischemic myocardial regions. After the procedure, 78 patients underwent cardiovascular magnetic resonance (CMR) at 1, 6, and 12 months and were included in this cardiac magnetic resonance substudy with perfusion quantification. Segments were classified as target (injected), adjacent (surrounding the injection site), and remote from injection site. RESULTS: Of 1,248 segments, 269 were target (22%), 397 (32%) adjacent, and 582 (46%) remote. The target had significantly lower CFR at baseline (1.40 ± 0.79 vs 1.64 ± 0.89 in adjacent and 1.79 ± 0.79 in remote; both P < 0.05). BMCs significantly increased CFR in target and adjacent segments at 6 and 12 months compared with placebo. In target regions, there was a progressive treatment effect (27.1% at 6 months, P = 0.037, 42.2% at 12 months, P = 0.001). In the adjacent segments, CFR increased by 21.8% (P = 0.023) at 6 months, which persisted until 12 months (22.6%; P = 0.022). Remote segments in both the BMC and placebo groups experienced similar improvements in CFR (not significant at 12 months compared with baseline). CONCLUSIONS: BMCs, injected in severely ischemic regions unsuitable for direct revascularization, led to the largest CFR improvements, which progressed up to 12 months, compared with smaller but persistent CFR changes in adjacent and no improvement in remote segments.

Vasodilator Strain Stress Echocardiography in Suspected Coronary Microvascular Angina.

Background: In patients with Ischemia and non-obstructive coronary artery stenosis (INOCA) wall motion is rarely abnormal during stress echocardiography (SE). Our aim was to determine if patients with INOCA and reduced coronary flow velocity reserve (CVFR) have altered cardiac mechanics using two-dimensional speckle-tracking echocardiography (2DSTE) during SE. Methods: In a prospective, multicenter, international study, we recruited 135 patients with INOCA. Overall, we performed high dose (0.84 mg/kg) dipyridamole SE with combined assessment of CVFR and 2DSTE. The population was divided in patients with normal CVFR (>2, group 1, n = 95) and abnormal CVFR (≤2, group 2, n = 35). Clinical and 2DSTE parameters were compared between groups. Results: Feasibility was high for CFVR (98%) and 2DSTE (97%). A total of 130 patients (mean age 63 ± 12 years, 67 women) had complete flow and strain data. The two groups showed similar 2DSTE values at rest. At peak SE, Group 1 patients showed lower global longitudinal strain (p < 0.007), higher mechanical dispersion (p < 0.0005), lower endocardial (p < 0.001), and epicardial (p < 0.0002) layer specific strain. Conclusions: In patients with INOCA, vasodilator SE with simultaneous assessment of CFVR and strain is highly feasible. Coronary microvascular dysfunction is accompanied by an impairment of global and layer-specific deformation indices during stress.

13N-Ammonia myocardial blood flow quantitation in patient with aneurismal coronary artery disease.

Aneurysmal coronary artery disease includes coronary artery aneurysms and ectasia; this condition has been associated with poor long-term outcomes. Few studies have explored myocardial blood flow 13N-ammonia PET/CT MPI added value. We present a 45-year-old man who came to the emergency department with chest pain. After a physical examination and laboratory studies, he was diagnosed with very high-risk unstable angina and referred to the catheterization laboratory. Coronary angiography showed the culprit lesion in the LCx and was treated by angioplasty and stent. LAD was found with coronary artery ectasia (TIMI 2 flow grade) and the RCA with aneurysmal disease in the proximal and middle segments (TIMI 3 flow grade). Medical treatment was decided for these findings and the patient was discharged. Two weeks later, we performed a 13N-ammonia PET/CT MPI founding apical, inferior, and inferoseptal severe ischemia, and reduced hyperemic coronary blood flow and coronary flow reserve in the RCA territory. Flow was normal in the LAD territory. Although coronary angiography remains the gold standard for evaluating these coronary abnormalities, it does not show the physiological compromise. Therefore 13N-ammonia PET/CT MPI should be performed as a complementary noninvasive imaging approach.

Coronary Flow, Left Ventricular Contractile and Heart Rate Reserve in Non-Ischemic Heart Failure.

Background: Left ventricular contractile reserve (LVCR), coronary flow velocity reserve (CFVR), and heart rate reserve (HRR) affect outcome in heart failure (HF). They can be simultaneously measured during dipyridamole stress echocardiography (DSE). Aim: To assess the value of comprehensive DSE in patients with non-ischemic HF. Methods: We evaluated 610 patients with HF, no history of coronary artery disease, and no inducible regional wall motion abnormalities: 270 patients with preserved ejection fraction (≥50%), 146 patients with mid-range ejection fraction (40-49%), and 194 patients with reduced ejection fraction (<40%). All underwent DSE (0.84 mg/kg in 6') in 7 accredited laboratories. We measured LVCR (abnormal value ≤ 1.1), CFVR in left anterior descending artery (abnormal value: ≤2.0), and HRR (peak/rest heart rate; abnormal value: ≤1.22). All patients were followed up. Results: Abnormal CFVR, LVCR, and HRR occurred in 29%, 45%, and 47% of patients, respectively (p < 0.001). After a median follow-up time of 20 months (interquartile range: 12-32 months), 113 hard events occurred in 105 patients with 41 deaths, 8 myocardial infarctions, 61 admissions for acute HF, and 3 strokes. The annual mortality rates were 0.8% in 200 patients with none abnormal criteria, 1.8% in 184 patients with 1 abnormal criterion, 7.1% in 130 patients with 2 abnormal criteria, 7.5% in 96 patients with 3 abnormal criteria. Conclusions: Abnormal LVCR, CFVR, and HRR were frequent during DSE in non-ischemic HF patients. They target different pathophysiological vulnerabilities (myocardial function, coronary microcirculation, and cardiac autonomic balance) and are useful for outcome prediction.

Detection of angiographically significant coronary obstruction using resting transthoracic coronary Doppler echocardiography.

BACKGROUND: Transesophageal Doppler echocardiography has shown that significant stenosis can be detected based on the presence of aliasing with color Doppler in the stenotic area. The study aimed to assess the detection of angiographically significant coronary stenosis (ASCS) by analyzing the characteristics and velocities of resting coronary artery flow (RCF) using transthoracic coronary Doppler echocardiography (TCDE). METHODS: TCDE was performed before diagnostic coronary angiography (CA). The following velocities were measured: peak systolic velocity (PSV), peak diastolic velocity (PDV), mean diastolic velocity (MDV), end-diastolic velocity (EDV), and distal to proximal velocity ratios. RESULTS: Twenty-five patients were included, and CA revealed ASCS in 14 patients. With TCDE, the proximal and distal portions of the left anterior descending artery (LAD) could be measured in 84% of cases. Among 12 patients with ASCS in the distal left main coronary artery (LMCA) or proximal or mid LAD, proximal and distal flow could be measured in ten patients. Proximal diastolic velocities were higher in patients with ASCS in the LAD, and a distal MDV/proximal MDV ratio < 0.5 had a 60% sensitivity and a 92% specificity for the detection of ASCS (AUC 0.77, 95% CI 0.56-0.92). For the detection of ASCS limited to the LMCA and/or proximal LAD, the distal MDV/proximal MDV ratio had a sensitivity of 100% and a specificity of 89% (AUC 0.98, 95% CI 0.81-0.99). CONCLUSIONS: Resting TCDE can detect ASCS in the LAD, particularly at the proximal level, analyzing the ratio between distal and proximal flow velocities. These results could not be demonstrated in the RCA and CX arteries.

Marked exercise-induced T-wave heterogeneity in symptomatic diabetic patients with nonflow-limiting coronary artery stenosis.

BACKGROUND: T-wave heterogeneity (TWH) independently predicted cardiovascular mortality in Health Survey 2000 based on 12-lead ECGs recorded at rest. We investigated whether TWH is elevated during exercise tolerance testing (ETT) in symptomatic diabetic patients with nonflow-limiting coronary artery stenosis compared to control subjects without diabetes. METHODS: Cases were all patients (n = 20) with analyzable ECG recordings during both rest and ETT who were enrolled in the Effects of Ranolazine on Coronary Flow Reserve (CFR) in Symptomatic Patients with Diabetes and Suspected or Known Coronary Artery Disease (RAND-CFR) study (NCT01754259); median CFR was 1.44; 80% of cases had CFR <2. Control subjects (n = 9) were nondiabetic patients who had functional flow reserve (FFR) >0.8, a range not associated with inducible ischemia. TWH was analyzed from precordial leads V4 , V5 , and V6 by second central moment analysis, which assesses the interlead splay of T-waves about a mean waveform. RESULTS: During exercise to similar rate-pressure products (p = .31), RAND-CFR patients exhibited a 49% increase in TWH during exercise (rest: 49 ± 5 µV; exercise: 73 ± 8 µV, p = .003). By comparison, in control subjects, TWH was not significantly altered (rest: 52 ± 11 µV; ETT: 38 ± 5 µV, p = .19). ETT-induced ST-segment depression >1 mm (p = .11) and Tpeak -Tend (p = .18) and QTc intervals (p = .80) failed to differentiate cases from controls. CONCLUSIONS: TWH is capable of detecting latent repolarization abnormalities, which are present during ETT in diabetic patients with nonflow-limiting stenosis but not in control subjects. The technique developed in this study permits TWH analysis from archived ECGs and thereby enables mining of extensive databases for retrospective studies and hypothesis testing.

Coronary microvascular dysfunction in women with nonobstructive ischemic heart disease as assessed by positron emission tomography.

Traditional approaches for risk assessment of ischemic heart disease (IHD) are based on the physiological consequences of an epicardial coronary stenosis. Of note, normal coronary arteries or nonobstructive coronary artery disease (CAD) is a common finding in women with signs and symptoms of ischemia. Therefore, assessment of risk based on a coronary stenosis approach may fail in women. Positron emission tomography (PET) quantifies absolute myocardial blood flow (MBF) which may help to elucidate other mechanisms involved such as endothelial dysfunction and alterations in the smooth muscle cell relaxation responsible for IHD in women. The objective of the present review is to describe the current state of the art of PET imaging in assessing IHD in women with nonobstructive CAD.

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.

Myocardial blood flow assessment with 82rubidium-PET imaging in patients with left bundle branch block

OBJECTIVES: Perfusion abnormalities are frequently seen in Single Photon Emission Computed Tomography (SPECT) when a left bundle branch block is present. A few studies have shown decreased coronary flow reserve in the left anterior descending territory, regardless of the presence of coronary artery disease. OBJECTIVE: We sought to investigate rubidium-82 (82Rb) positron emission tomography imaging in the assessment of myocardial blood flow and coronary flow reserve in patients with left bundle branch block. METHODS: Thirty-eight patients with left bundle branch block (GI), median age 63.5 years, 22 (58%) female, 12 with coronary artery disease (≥70%; GI-A) and 26 with no evidence of significant coronary artery disease (GI-B), underwent rest-dipyridamole stress 82Rb-positron emission tomography with absolute quantitative flow measurements using Cedars-Sinai software (mL/min/g). The relative myocardial perfusion and left ventricular ejection fraction were assessed in 17 segments. These parameters were compared with those obtained from 30 patients with normal 82Rb-positron emission tomography studies and without left bundle branch block (GII). RESULTS: Stress myocardial blood flow and coronary flow reserve were significantly lower in GI than in GII (p<0.05). The comparison of coronary flow reserve between GI-A and GI-B showed that it was different from the global coronary flow reserve (p<0.05) and the stress flow was significantly lower in the anterior than in the septal wall for both groups. Perfusion abnormalities were more prevalent in GI-A (p=0.06) and the left ventricular ejection fraction was not different between GI-A and GI-B, whereas it was lower in GI than in GII (p<0.001). CONCLUSION: The data confirm that patients with left bundle branch block had decreased myocardial blood flow and coronary flow reserve and coronary flow reserve assessed by 82Rb-positron emission tomography imaging may be useful in identifying coronary artery disease in patients with left bundle branch block.

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent echocardiographic studies should be interpreted in comparison with the data obtained from the 6-month study. An echocardiographic study, which shows no change from the baseline study, has a high negative predictive value for GR. There is no single systolic or diastolic parameter that can be reliably used to diagnose GR. However, in case several parameters are abnormal, the likelihood of GR increases. When an abnormality is detected, careful revision of images of the present and baseline study (side-by-side) is highly recommended. Global longitudinal strain (GLS) is a suitable parameter to diagnose subclinical allograft dysfunction, regardless of aetiology, by comparing the changes occurring during serial evaluations. Evaluation of GLS could be used in association with endomyocardial biopsy (EMB) to characterize and monitor an acute GR or global dysfunction episode. RV size and function at baseline should be assessed using several parameters, which do not exclusively evaluate longitudinal function. At follow-up echocardiogram, all these parameters should be compared with the baseline values. 3DE may provide a more accurate and comprehensive assessment of RV size and function. Moreover, due to the unpredictable shape of the atria in transplanted patients, atrial volume should be measured using the discs' summation algorithm (biplane algorithm for the left atrium) or 3DE. Tricuspid regurgitation should be looked for and properly assessed in all echocardiographic studies. In case of significant changes in severity of tricuspid regurgitation during follow-up, a 2D/3D and colour Doppler assessment of its severity and mechanisms should be performed. Aortic and mitral valves should be evaluated according to current recommendations. Pericardial effusion should be serially evaluated regarding extent, location, and haemodynamic impact. In case of newly detected pericardial effusion, GR should be considered taking into account the overall echocardiographic assessment and patient evaluation. Dobutamine stress echocardiography might be a suitable alternative to routine coronary angiography to assess cardiac allograft vasculopathy (CAV) at centres with adequate experience with the methodology. Coronary flow reserve and/or contrast infusion to assess myocardial perfusion might be combined with stress echocardiography to improve the accuracy of the test. In addition to its role in monitoring cardiac chamber function and in diagnosis the occurrence of GR and/or CAV, in experienced centres, echocardiography might be an alternative to fluoroscopy to guide EMB, particularly in children and young women, since echocardiography avoids repeated X-ray exposure, permits visualization of soft tissues and safer performance of biopsies of different RV regions. Finally, in addition to the indications about when and how to use echocardiography, the document also addresses the role of the other cardiovascular imaging modalities during follow-up of heart transplant patients. In patients with inadequate acoustic window and contraindication to contrast agents, pharmacological SPECT is an alternative imaging modality to detect CAV in heart transplant patients. However, in centres with adequate expertise, intravascular ultrasound (IVUS) in conjunction with coronary angiography with a baseline study at 4-6 weeks and at 1 year after heart transplant should be performed to exclude donor coronary artery disease, to detect rapidly progressive CAV, and to provide prognostic information. Despite the fact that coronary angiography is the current gold-standard method for the detection of CAV, the use of IVUS should also be considered when there is a discrepancy between non-invasive imaging tests and coronary angiography concerning the presence of CAV. In experienced centres, computerized tomography coronary angiography is a good alternative to coronary angiography to detect CAV. In patients with a persistently high heart rate, scanners that provide high temporal resolution, such as dual-source systems, provide better image quality. Finally, in patients with insufficient acoustic window, cardiac magnetic resonance is an alternative to echocardiography to assess cardiac chamber volumes and function and to exclude acute GR and CAV in a surveillance protocol.

Effects of Insulin Resistance on Myocardial Blood Flow and Arterial Peripheral Circulation in Patients with Polycystic Ovary Syndrome.

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 (ß), plateau of acoustic intensity (A) and myocardial blood flow reserve (MBFR) were determined by quantitative dipyridamole stress RTMCE. RESULTS: ß 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 ß and MBFR as demonstrated by quantitative RTMCE, but no alteration in endothelial dysfunction or IMT. PCOS without IR showed isolated depression in ß reserve, probably an earlier marker of myocardial flow abnormality.

Adenosina intracoronaria durante la angioplastía primaria para la preservación del flujo coronario / Intracoronary adenosine during primary angioplasty and coronary flow preservation

Introducción: El uso de adenosina intracoronario durante la angioplastía coronaria ha sido controversial en los últimos años. El beneficio teórico en el flujo epi-cárdico y microcirculatorio (MC) no se ha demostrado categóricamente en estudios clínicos. Objetivo: Evaluar el efecto de protección de la MC y del flujo epicárdico al utilizar adenosina intracoronaria durante la AP. Métodos: Estudio clínico randomizado multicéntrico, caso-control con análisis post hoc ciego, en pacientes portadores de SCA con SDST. Un total de 122 pacientes aleatorizados 1:1, se consideró caso (A(+)) aquel que se administró adenosina en dosis de 120 microgramos intracoronario en bolo y luego infusión periférica de 6mg en 33ml de suero fisiológico a pasar en 2-3 minutos Se evaluaron criterios clínicos, angiográficos y electrocar-diográficos de reperfusión epicárdica y microvascular. Observadores ciegos evaluaron el conteo de cuadros TIMI (cTFC) y "blush" miocárdico (BM). Se compararon las características clínicas, angiográficas basales y los resultados angiográficos finales entre ambos grupos, usando t-Student, prueba de Mann-Whitney, Chi cuadrado y test exacto de Fisher según correspondiera. En todos los pacientes se evaluó la resolución del SDST con el score de ST. Además, se evaluó las posibles complicaciones por uso de adenosina intracoronaria. Resultados: Entre 2012-2014 se reclutaron 122 pacientes. Al comparar las características basales entre el grupo A(+) vs los A(-) no hubo diferencias significativas en la edad (59+/-10 años para A(+) vs 58+/-10 años para A(-), p:0,97), ni en las comorbilidades. Al comparar las características angiográficas basales, no se encontró diferencias en los vasos culpables (ADA 44% en A(+) vs 43% en A(-), p:0.57), en las cargas trombóticas (Alta carga: 69% para A(+) vs 74% para A(-), p:0.53), en el flujo TIMI pre (TIMI 0-1 86% para ambos grupos, p:0,69), cTFC pre (87+/-23 cuadros en A(+) vs 88+/-25 cuadros en A(-), p:0.99), Killip de ingreso (Killip I, 86% para A(+) vs 76% para A(-), p:0,11) y fracción de eyección (51+/-8% para A(+) vs 48+/-9% para (-), p:0,61). Al evaluar los resultados angiográficos finales encontramos diferencias significativas en el flujo TIMI (TIMI 3 96% para grupo A(+) vs 74% para grupo A(-), p:0,002). No encontramos diferencias significativas en el BM (Blush 3 73% para ambos grupos, p:0.74), el cTFC final (24+/-11 cuadros en A(+) vs 26+/-12 cuadros en A(-), p:0,85). Si consideramos cTFC <23cuadros como éxito angiográficos, tampoco encontramos diferencias significativas (56% para A(+) vs 53% para A(-), p:0,45). Por último tampoco hubo diferencias significativas con la resolución del segmento ST (44% para A(+) vs 58% para A(-), p:0,126). Conclusión: De acuerdo a los resultados obtenidos podemos inferir que la adenosina intracoronaria cumple un rol en la conservación óptima del flujo epicárdico coronario, pero sin influir en la microcirculación. Mayores estudios se requieren para determinar si se traduce en algún beneficio clínico.

Background: The effect of Intracoronary adenosine for coronary flow preservation during primary PTCA is debatable. Clinical studies have not established a benefit of adenosine administration upon epicar-dic or microcirculatory flows. Aim: to evaluate micro circulatory flow preservation after administration of intracoronary adenosine during primary PTCA. Method: From 2012 to 2014, 122 patients with ST elevation myocardial infarction randomized to either adenosine of control (2:1) were included in a controlled clinical trial. Adenosine was administered in a 120 mg bolus followed by 6mg solution during 2 to 3 min. Epicardic and micro vascular flows were evaluated through clinical, angiographic, electrocardiographic and reperfusion variables. TIMI (cTFC) and myocardial "blush" were measured by blind observers. Results: Basal characteristics, namely age and co-morbidities were similar between groups. Also, the distribution of coronary vessels involved in MI was similar with a preponderance of the LAD artery. There was an high proportion of patients with an elevated thrombus load (Adenosine 69%, controls 74%) ; TIMI flow 0-1 was 86% in both groups and TIMI cTFC was not different (adenosine: 87±23 , controls 88±25 ). Over 75% of patients were Killip I, and the ejection fraction was slightly decreased (adenosine 51±8% , controls 48±9% , NS). In contrast, TIMI flow was significantly greater for adenosine (TIMI 3 96% for adenosine and 74% for controls, p=0.002). No difference was observed in myocardial blush (B 3 73% in both groups) nor cTFC (24±11 vs. 26±12, respectively). Finally, regression of ST elevation was similar in both groups. Conclusion: Intracoronary adenosine during PTCA in ST elevation MI was associated to a better epicardial but not microvascular flow. Further study is needed to evaluate the eventual clinical benefit of these effects.

Coronary flow velocity reserve during pharmacologic stress echocardiography with normal contractility adds important prognostic value in diabetic and nondiabetic patients.

BACKGROUND: Coronary flow velocity reserve (CFVR) increases the diagnostic sensitivity of stress echocardiography. The aim of this study was to evaluate the prognostic value of CFVR in patients without new wall motion abnormalities during pharmacologic stress echocardiography. METHODS: The outcomes of 651 patients with normal wall motion response during stress echocardiography with dobutamine up to 50 µg/kg/min (n = 351) or dipyridamole up to 0.84 mg/kg over 4 min (n = 300) were evaluated. CFVR was calculated simultaneously in the distal territory of the left anterior descending coronary artery. CFVR ≥ 2 was defined as normal. Major events considered during follow-up were cardiovascular death, myocardial infarction, and late myocardial revascularization. RESULTS: Normal CFVR was recorded in 523 patients and reduced CFVR in 128. During a mean follow-up period of 34.6 ± 18 months, 48 major events occurred, in 25 patients (4.8%) with normal and 23 patients (18%) with reduced CFVR; event-free survival was significantly different between patients with normal versus abnormal CFVR (P < .0001). Diabetes increased risk only in patients with abnormal CFVR (P = .05). In the multivariate analysis, CFVR and history of smoking were the only independent predictors of combined morbidity and mortality. Abnormal CFVR was associated with a higher event rate, independently of the pharmacologic stress technique used. The event hazard ratio was inversely proportional to CFVR. CONCLUSIONS: CFVR was an independent predictor of mortality after pharmacologic stress echocardiography with normal wall motion, and the degree of decrease was associated with increased risk. Diabetes worsened prognosis only with abnormal CFVR.

Reserva de Velocidade de Fluxo Coronariano durante o Ecocardiograma sob Estresse com Dobutamina / Coronary Flow Velocity Reserve during Dobutamine Stress Echocardiography

Fundamento: A reserva de velocidade de fluxo coronariano (RVFC) ≥ 2 é adequada para inferir bom prognóstico ou ausência de coronariopatia importante. Objetivo: Identificar parâmetros relevantes na obtenção da RVFC (adequada ou inadequada) na descendente anterior (ADA), durante o ecocardiograma sob estresse com dobutamina (EED). Métodos: Avaliação de 100 pacientes encaminhados para pesquisa de isquemia miocárdica através do EED, orientados para suspender o betabloqueador 72 horas antes do exame. Calculou-se a RVFC pela divisão do pico de velocidade (cm/s) diastólica (PVD) verificado no EED (PVD-EED) pelo de repouso (PVD-REP). No grupo I, a RVFC < 2 e no grupo II a RVFC ≥ 2. Foram utilizados o teste t de Student e o exato de Fisher. Significância estatística quando p < 0,05. Resultados: Em repouso, o tempo (segundos) para obter o Doppler na ADA nos grupos I e II não diferiu (53 ± 31 vs. 45 ± 32; p = 0,23). No EED, registrou-se a ADA em 92 pacientes. O grupo I evidenciou pacientes mais velhos (65,9 ± 9,3 vs. 61,2 ± 10,8 anos; p = 0,04), menor fração de ejeção (61 ± 10 vs. 66 ± 6%; p = 0,005), maior PVD-REP (36,81 ± 08 vs. 25,63 ± 06 cm/s; p < 0,0001) e menor RVFC (1,67 ± 0,24 vs. 2,53 ± 0,57; p < 0,0001), entretanto o PVD-EED não diferiu (61,40 ± 16 vs. 64,23 ± 16 cm/s; p = 0,42). A suspensão do betabloqueador associou-se à chance 4 vezes maior de ocorrer RVFC < 2 (OR = 4; 95% IC [1,171 - 13,63], p = 0,027). Conclusão: O PVD-REP foi o principal parâmetro para determinar uma RVFC adequada. A suspensão do betabloqueador associou-se significativamente com RVFC inadequada. A elevada exequibilidade e o tempo para registro da ADA favorecem a utilização dessa metodologia. .

Background: A coronary flow velocity reserve (CFVR) ≥ 2 is adequate to infer a favorable prognosis or the absence of significant coronary artery disease. Objective: To identify parameters which are relevant to obtain CFVR (adequate or inadequate) in the left anterior descending coronary artery (LAD) during dobutamine stress echocardiography (DSE). Methods: 100 patients referred for detection of myocardial ischemia by DSE were evaluated; they were instructed to discontinue the use of β-blockers 72 hours prior to the test. CFVR was calculated as a ratio of the diastolic peak velocity (cm/s) (DPV) on DSE (DPV-DSE) to baseline DPV at rest (DPV-Rest). In group I, CFVR was < 2 and, in group II, CFVR was ≥ 2. The Fisher's exact test and Student's t test were used for the statistical analyses. P values < 0.05 were considered statistically significant. Results: At rest, the time (in seconds) to obtain Doppler in LAD in groups I and II was not different (53±31 vs. 45±32; p=0.23). During DSE, LAD was recorded in 92 patients. Group I patients were older (65.9±9.3 vs. 61.2±10.8 years; p=0.04), had lower ejection fraction (61±10 vs. 66±6%; p=0.005), higher DPV-Rest (36.81±08 vs. 25.63 ± 06cm/s; p<0.0001) and lower CFVR (1.67 ± 0.24 vs. 2.53 ± 0.57; p<0.0001), but no difference was observed regarding DPVDSE (61.40±16 vs. 64.23±16cm/s; p=0.42). β-blocker discontinuation was associated with a 4-fold higher chance of a CFVR < 2 (OR= 4; 95% CI [1.171-13.63], p=0.027). Conclusion: DPV-Rest was the main parameter to determine an adequate CFVR. β-blocker discontinuation was significantly associated with inadequate CFVR. The high feasibility and the time to record the LAD corroborate the use of this methodology. .

Impaired coronary flow reserve in patients with indeterminate form of Chagas' disease.

BACKGROUND: Previous studies suggest that microvascular abnormalities may contribute to the pathogenesis of Chagas' heart disease. Coronary flow reserve (CFR) expressed by the maximum achievable flow relative to baseline flow in the coronary microcirculation, may be useful in identifying patients who may be developing cardiac manifestations of the disease. This study aims to assess the CFR in patients with indeterminate form of Chagas' disease, and also to identify the determinants of CFR. METHODS: Sixty-four asymptomatic patients (37% male; age 49.9 ± 11.5 years) with normal cardiovascular exams classified as in indeterminate form of Chagas' disease underwent transthoracic dipyridamole (0.84 mg/kg in 6 min) stress echocardiography, and were compared with a control group of healthy patients. Coronary flow reserve was assessed on left anterior descending artery using pulsed Doppler as the ratio of maximal peak vasodilation (dipyridamole) to rest diastolic flow velocity. A treadmill exercise test was performed to rule out ischemia. RESULTS: All patients had good functional capacity assessed by exercise testing with peak oxygen consumption (VO2 ) of 28 ± 11 mL/kg per minute, similar to the controls. There were no differences in the echocardiographic parameters of diastolic and systolic left ventricular function and right ventricular function between the patients and controls. Coronary flow reserve was significantly lower in Chagas' disease patients than those in healthy individuals (1.9 ± 0.4 vs. 2.6 ± 0.5; P < 0.001). Several factors were correlated with the CFR, including age, ejection fraction, left ventricular diastolic function, heart rate recovery, and the presence of Chagas' disease. In a multivariate analysis, age and positive serology for Chagas' disease were independent factors associated with the CFR. CONCLUSIONS: Coronary flow reserve was impaired in Chagas' disease patients in the indeterminate form compared with healthy individuals with similar clinical features. Among all variables tested, age and positive serology for Chagas' disease were independent factors associated with the CFR.

Increased red cell distribution width in patients with slow coronary flow syndrome

OBJECTIVE: An elevated red cell distribution width has been recognized as a predictor of various cardiovascular diseases. Slow coronary flow syndrome is an important angiographic clinical entity with an unknown etiology. This study aimed to examine the relationship between red cell distribution width and the presence of slow coronary flow syndrome. METHODS: In total, 185 patients with slow coronary flow syndrome and 183 age- and gender-matched subjects with normal coronary flow (controls) were prospectively enrolled in this study. Red cell distribution width and C-reactive protein were measured upon admission, and the results were compared between the patients with slow coronary flow syndrome and normal controls. RESULTS: Red cell distribution width levels were significantly higher in the patients with slow coronary flow syndrome than the normal controls. Moreover, the data showed that the plasma C-reactive protein levels were also higher in the patients with slow coronary flow syndrome than in the normal controls. In addition, a multivariate analysis indicated that C-reactive protein and red cell distribution width were the independent variables most strongly associated with slow coronary flow syndrome. Finally, the red cell distribution width was positively correlated with C-reactive protein and mean thrombosis in the myocardial infarction frame counts of the patients with slow coronary flow syndrome. CONCLUSION: The data demonstrated that red cell distribution width levels are significantly higher and strongly positively correlated with both C-reactive protein and thrombosis in the myocardial infarction frame counts of patients with slow coronary flow syndrome. These findings suggest that red cell distribution width may be a useful marker for patients with slow coronary flow syndrome. .

Assessment of coronary flow with transthoracic color Doppler echocardiography in patients with hypertrophic cardiomyopathy.

BACKGROUND: Recent advances in echocardiography have allowed assessment of flow velocity in the epicardial coronary arteries of patients with ischemic heart disease, using transthoracic color Doppler echocardiography (TTDE). However, few data are available regarding coronary blood flow in patients with hypertrophic cardiomyopathy (HCM). OBJECTIVE: To assess the epicardial coronary arteries of patients with HCM. MATERIAL AND METHODS: A group of 25 patients with HCM was assessed prospectively (mean age 57 ± 21 years, 11 male) using TTDE; flow velocities in the epicardial coronary arteries were measured and compared with those obtained in 10 age- and gender-matched controls. Analysis of the diastolic spectral waveform included flow velocity integral (VTI), peak velocity, deceleration time, and deceleration slope measurements, while systolic waveform analysis included peak flow measurement and morphology assessment (positive, absent or negative). An analysis of variance (ANOVA) test was used for multiple comparisons for variables with a normal distribution, and a Kruskal-Wallis test was used for variables with non-Gaussian distribution. RESULTS: Patients with HCM exhibited an increase in diastolic flow velocity with a rapid deceleration slope and a systolic slope which was decreased, absent or reversed, compared to normal subjects. On linear regression analysis there was no correlation with the type of hypertrophy or magnitude of the intraventricular pressure gradient in patients with obstructive HCM. CONCLUSION: In patients with HCM, noninvasive assessment with TTDE revealed abnormal findings in the distal flow of the epicardial coronary arteries, very similar to those seen in the no-reflow phenomenon. These findings were independent of the type of hypertrophy and magnitude of the intraventricular pressure gradient in patients with obstructive HCM.

Experiencia con Ecocardiograma de estrés dipiridamol y Reserva coronaria no invasiva: Comunicación preliminar / Dipyridamol Stress Echocardiography and Non-invasive Coronary Reserve: Preliminary report

Antecedentes: El Ecocardiograma de Estrés (EE) es una técnica ampliamente utilizada en el estudio de pacientes con Enfermedad Coronaria conocida o sospechada Recientemente se ha preconizado efectuar el test vasodilatador, método recomendado para evaluar no invasivamente la reserva de flujo coronario (RFC). Objetivos: Mostrar la experiencia preliminar con el EE Dipiridamol, con un seguimiento inicial, así como el estudio de la RFC en la porción distal de la arteria Descendente Anterior (ADA). Métodos: Se analizaron 164 pacientes (101 hombres, edad promedio 65 años) a los que se les efectuó un EE Dipiridamol entre Julio 2011 y Septiembre 2012, con una dosis de 0.84mg/kg en 6 minutos, que incluyó el estudio de RFC. Todos los pacientes completaron la prueba sin efectos secundarios significativos, y en un tiempo menor a 25 minutos. El seguimiento se hizo con miras a la aparición de eventos cardiovasculares mayores (revascularización, infarto al miocardio y muerte cardíaca). Resultados: EE resultó positivo para isquemia en 19 (21 por ciento) pacientes. En 19 (12 por ciento) el EE resultó alterado por motilidad parietal; 29 (15 por ciento) presentaron respuesta anormal en la RFC, con una coincidencia de 12 pacientes (7 por ciento) con ambos tipo de alteración; En 142 (88 por ciento) pacientes se logró medir la RFC en ADA. En 151 pacientes se obtuvo datos confiables del seguimiento, que fue en promedio 10 meses (6 a 18); entre estos, 10 pacientes tuvieron alguna revascularización. No hubo infartos ni fallecidos por causa cardio-vascular. Dado el corto período de seguimiento y baja incidencia de eventos, no se pudo establecer el valor predictivo del resultado de la prueba en esta muestra. Conclusiones: Esta experiencia permitió familiarizarse con la técnica del EE con Dipiridamol y estudiar en un alto porcentaje la RFC en la ADA. La técnica es segura y consume muy poco tiempo. Queda pendiente la determinación del valor predictivo de estos resultados en nuestras manos.

Background: Stress Echocardiography is a common technique in the study of patients with known or suspected Coronary artery disease (CAD). Recently the vasodilation test has been recommended for the non invasive study of Coronary Flow Reserve (CFR). Aim: to report our preliminary experience with Di-pyridamol Stress Echocardiography (DSE), an initial follow-up, and the study of CFR in the distal portion of the left anterior descending coronary artery (LAD). Methods: 164 consecutive patients (101 men, mean age 65) with suspected or known CAD underwent a high-dose DSE (0.84 mg/kg over 6 min) between July 2011 and September 2012. The test included a study of CFR. All patients completed the test within 25 min. Prospective follow-up regarding major adverse cardiovascular events(revascularization, cardiac mortality and infarction) was conducted for a mean of 10 months (range 6-18) Results: DSE was positive for ischemia in 34 (21 percent) patients, showed abnormal wall motion in 19 (12 percent), abnormal CFR in 29 (15 percent) , and both abnormalities in12 (7 percent). 142 patients (88 percent) had a normal CFR in the LAD. 151 patients were followed for a mean of 10 months (6 to 18). Ten of these patients required some type of revascularization. There were no myocardial infarctions or cardiac deaths. Due to the short follow up period and the low incidence of events, it was not possible to estimate the predictive value of abnormal CFR. Conclusion: The dipyridamol echo stress test with a study of coronary flow reserve is safe and brief. The predictive value for cardiac events remains to be determined.

Myocardial Contrast Echocardiography in the Evaluation of Hypertensive Heart Disease.

Myocardial contrast echocardiography (MCE) has an established role in left ventricular assessment by improving the ventricular opacification and endocardial border definition especially in patients with sub-optimal echocardiographic images. With advances in cardiac ultrasound imaging technology and the development of new contrast agents, the clinical utility of this technique has greatly expanded to include assessment of coronary reperfusion in the setting of acute myocardial infarction, determination of myocardial viability within infarct zones as well as assessment of coronary microcirculation and flow reserve in patients with microvascular coronary disease. Improvements in image quality with intravenous contrast agents can facilitate image acquisition and enhance delineation of regional wall motion abnormalities at peak levels of exercise. Numerous studies have confirmed the clinical utility of contrast enhancement during echocardiographic studies, particularly in patients undergoing stress testing. In this paper, we explore the evidence in support of MCE and its potential clinical applications. Our review aims to summarize (1) the basic principles of myocardial contrast echocardiography including recent advances in the ultrasound technology and contrast agents (2) its clinical applications in the diagnosis of cardiovascular diseases and finally, (3) its potential role in risk stratification and assessment of microvascular perfusion in patients with hypertensive heart disease.

Intervenciones coronarias percutáneas guiadas con medición de flujo de reserva coronario / Percutaneous coronary intervention guided by measurement of coronary flow reserve

Introducción: La revascularización de una estenosis coronaria que induce isquemia mejora el estatus funcional del paciente y su pronóstico. Por el contrario, la angioplastía de una lesión que no provoca isquemia puede implicar complicaciones sin beneficios. La medición de flujo de reserva coronario (FFR) es un índice del significado fisiopatológico de las estenosis coronarias. Objetivos: Comparar los eventos cardiovasculares adversos mayores (MACE) en pacientes en quienes la FFR permitió excluir una o más lesiones de angioplastia (Grupo FFR >0,75) con aquellos en que ésta obligó a la revascularización (grupo FFR < 0,75). Métodos: Estudio observacional en 74 pacientes derivados para angioplastía entre agosto de 2006 y julio de 2010. Se realizó medición de FFR con ade-nosina a lesiones de severidad intermedia (60-70 por ciento). Una FFR translesional <0,75 se consideró significativa para isquemia y subsidiaria de angioplastía. Se hizo un seguimiento de los MACE definidos como: muerte, infarto, necesidad de revascularización y/o presencia de angor. Resultados: 35 pacientes (47,3 por ciento) constituyeron el Grupo FFR >0,75, y en ellos disminuyó el porcentaje de lesiones múltiples angiográficamente significativas (dos o más vasos), desde un 51,4 por ciento (previo a la realización de FFR), a un 25,7 por ciento. En este grupo se utilizó un promedio de 0.7 stents por paciente, mientras que en el grupo FFR <0,75 (39 pacientes), este fue de 1.5 stents. Se efectuó un seguimiento promedio de 21,5 meses. Diecinueve pacientes (25,6 por ciento) desarrollaron MACE (28 eventos). No hubo fallecidos ni diferencias significativas en el análisis multifactorial en cuanto a infartos o angor, pero sí en la necesidad de nueva revascularización, siendo ésta significativamente mayor en el grupo FFR <0,75 (12,8 por ciento versus 2,9 por ciento, p=0,047). Conclusiones: La medición del FFR permite, en caso de descartar isquemia, disminuir la necesidad de angioplastías...

The treatment of coronary stenosis causing myocardial ischemia improves functional capacity and prognosis. Treatment of non-ischemia inducing coronary stenosis may lead to complications with no benefit to the patient Measurement of coronary flow reserve (CFR) may be used to assess the significance of coronary artery stenosis. Aim: To compare major adverse cardiovascular events (MACE) in patients with significant stenosis (CFR < 0.75), with those in which one or more stenosis was not significant (CFR > 0.75) and thus were not subjected to PTCA in the corresponding artery. Methods: 74 patients were included from August 2006 to July 2010. CFR was measured in lesions exhibiting 6070 percent stenosis, using adenosine. A value <0.75 was considered significant and led to PTCA. Patients were followed for death, myocardial infarction, revascularization and/or angina. Results: 35 patients (47 percent) constituted the >0.75 CFR group. After evaluation of CFR the number of significant coronary stenosis decreased from 51.4 percent to 25.7 percent. They received a mean of 0.7 stents per patient. On the other hand, in the group with CFR <0.75 (39 patients) the mean number of stents was 1.5. Patients were followed for a mean of 21.5 months. 28 MACE events were observed in 19 patients (25.6 percent). No deaths were observed. Multivariable analysis revealed no significant difference between groups regarding myocardial infarction or angina. The need for myocardial revascularization was greater in the CFR <0.75 group compared to the CFR >0.75 group (12.8 percent vs 2.9 percent, respectively, p=0.047). Conclusion: The exclusion of myocardial ischemia as inferred by a CFR >0.75 allowed a significantly lower number of PTCAs without increase in MACE at a medium term follow up. A greater number of revascularization procedures was required in patients with CFR <0.75, which is expected from the greater number of lesions subjected to PTCA.