Microvesicles from patients with acute coronary syndrome enhance platelet aggregation.

Microvesicles (MVs) released from leukocytes, platelets and endothelial cells are elevated in patients with acute coronary syndrome (ACS). In the present study, we assessed the potential pro-aggregatory properties of MVs obtained from ACS patients. Thus, we divided the patients into two groups based on clopidogrel-responsiveness, i.e. high on-treatment platelet reactivity (HPR; n = 16), and low or normal on-treatment platelet reactivity (non-HPR; n = 14), respectively. MVs from patients were obtained by high-speed centrifugation, and the pro-aggregatory effect of MVs added to fresh isolated platelets from healthy subjects were analyzed by 96-well microplate aggregometry. MVs from HPR patients significantly enhanced spontaneous platelet aggregation around two times more than MVs from non-HPR patients. The pro-aggregatory effect of three out of four MV phenotypes correlated to MV-concentrations as determined by flow cytometry. Furthermore, MVs from patients with diabetes mellitus (n = 9) had a stronger pro-aggregatory effect compared to MVs from those without diabetes (n = 21; p = .025 between groups). In conclusion, MVs from ACS patients with clopidogrel non-responsiveness enhance platelet aggregation, as do MVs from ACS patients with diabetes. Thus, MVs from patients with hyperreactive platelets boost platelet aggregation. Blocking MV-formation may reduce platelet hyperreactivity.

Myocardial Performance Index Determined by Tissue Doppler Imaging in Patients With Systolic Heart Failure Predicts Poor Long-Term Prognosis: An Observational Cohort Study.

BACKGROUND: Myocardial performance index (MPI) is an echocardiographic parameter that reflects left ventricular (LV) function. MPI determined by means of tissue Doppler imaging (TDI) at different LV sites (global MPI) and its long-term prognostic implications in congestive heart failure (HF) have not been evaluated. METHODS AND RESULTS: A total of 110 patients with HF during acute hospitalization were followed for a mean of 5.0 years for survivors. The myocardial velocities at 4 different LV sites near the mitral annulus from apical views were recorded with the use of pulsed-wave TDI. From myocardial velocity profiles, the MPI at each LV site was calculated: MPI = (isovolumetric contraction time + isovolumetric relaxation time)/ejection time. The global MPI was calculated as the mean from the 4 LV sites. Mean ejection fraction was 25%. A total of 61 patients died during the study period. On multivariate analysis, only MPI emerged as an independent predictor of mortality. With a cutoff value of 0.67, the hazard ratio for cardiovascular mortality during the follow-up period was 13 (95% confidence interval 5.03-34.44; P < .001). A cutoff MPI value of ≥0.67 identified patient mortality during the study period with a sensitivity of 86% and a specificity of 79%. CONCLUSION: Global TDI-derived MPI in patients with HF is a powerful predictor of cardiovascular mortality in patients with systolic HF.

Feasibility of myocardial performance index for evaluation of left ventricular function during dobutamine stress echocardiography before and after coronary artery bypass grafting.

AIMS: Myocardial performance index (MPI) is a measure of combined systolic and diastolic myocardial function. In patients with coronary artery disease (CAD) an increase in MPI is consistent with myocardial dysfunction. The objectives of this study were to characterize the changes in MPI after coronary artery bypass graft (CABG) at rest and at peak dobutamine stress echocardiography (DSE). METHODS AND RESULTS: Thirty-six patients diagnosed with CAD and accepted for CABG were studied by standard echocardiography and DSE 1 month prior and 3 month after CABG. The MPI was calculated using pulsed-wave tissue Doppler imaging (PW-TDI) of the left ventricular (LV) wall-motion velocity. At baseline, ejection fraction (EF; 42.7 ± 8%) and wall-motion score index (WMSI; 1.1 ± 0.2) were impaired at rest as well as at peak DSE (EF; 49.2 ± 9 and WMSI 1.4 ± 0.2). MPI was prolonged both at rest (0.61 ± 0.13) and at peak DSE (0.78 ± 0.16). After CABG, EF and WMSI did not improve at rest (43.7 ± 8% and 1.1 ± 0.2, respectively). On the other hand, MPI improved substantially both at rest (0.45 ± 0.08; P < 0.001) and at peak DSE (0.56 ± 0.1; P < 0.001). At peak DSE an improvement of EF (54.2 ± 9; P < 0.05) and WMSI (1.1 ± 0.16; P < 0.001) was seen as well. CONCLUSION: Myocardial performance index shows significant improvement after CABG in patients with CAD both at rest and peak DSE and appears to be a sensitive measure of myocardial function.

Comparison of venous and arterial blood sampling for the assessment of platelet aggregation with whole blood impedance aggregometry.

Platelet monitoring is presently under evaluation in the clinic as a tool to improve antiplatelet treatment in patients with coronary artery disease (CAD). Measuring platelet function has, however, many inherent problems. It is important not only to evaluate the method used, but also to evaluate and standardize sampling and sample handling. As platelet monitoring is often performed in connection to coronary angiography and percutaneous coronary interventions, arterial sampling may be more convenient. However, in the outpatient follow-up setting venous sampling is, for obvious reasons, more practical and convenient. In the present study we compared platelet aggregation in blood collected from the arterial sheath to blood collected from the antecubital vein using multiple electrode aggregometry in whole blood in 28 patients with CAD. We found that sampling from artery and vein give similar data and that an identical number of patients with insufficient antiplatelet responses ('low responders' to aspirin and clopidogrel, respectively, according to predefined criteria) were detected with respect to adenosine diphosphate induced and arachidonic-acid induced aggregation. Thus both arterial and venous blood samples can be used in the monitoring of platelet function when multiple electrode aggregometry is applied to detect 'low responders'.

Tricuspid annular velocity assessed by doppler tissue imaging as a marker of right ventricular involvement in the acute and late phase after a first ST elevation myocardial infarction.

BACKGROUND: Right ventricular (RV) involvement in patients with ST elevation myocardial infarction (STEMI) is a clinically important problem. The aim of this study was to evaluate the use of tricuspid annular velocity assessed by Doppler tissue imaging (DTI) as a marker of RV involvement in patients with a first STEMI. METHODS: Seventy-one patients with a first STEMI were examined by echocardiography before discharge and after 6 months. The patients were compared to 31 healthy subjects (HS). The diagnosis of RV infarction was based on the presence of >or= 1 mm ST elevation in the right precordial ECG lead V4R. Tricuspid annular systolic and diastolic velocities using pulsed-wave DTI were recorded at the RV free wall. RESULTS: At day 1, tricuspid annular velocities were significantly reduced in patients with, compared to those without, ST elevation in V4R (11.1 vs. 13.7 cm/sec, 9.4 vs. 13.1 cm/sec and 14.1 vs. 15.9 cm/sec for systolic, early, and late diastolic velocities, respectively; P < 0.01). With a cutoff value for a tricuspid annular systolic velocity of 13 cm/sec, sensitivity and specificity for identifying patients with ST elevation in V4R were 89% and 71%, respectively. After 6 months, both tricuspid annular systolic and diastolic velocities in patients with RV infarction had increased significantly, but only tricuspid annular systolic velocity was still reduced compared to HS (12.3 vs. 14.7 cm/sec; P < 0.01). CONCLUSION: Tricuspid annular velocities assessed by DTI may be used as a marker of RV involvement in the acute and the late phase after a first STEMI.

Blood haemoglobin, renal insufficiency, fractional flow reserve and plasma NT-proBNP is associated with index of microcirculatory resistance in chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMVD) is associated with adverse cardiovascular outcome. We aimed to determine the prevalence of CMVD and factors related to index of microcirculatory resistance (IMR) in consecutive patients with chronic coronary syndrome (CCS) undergoing elective coronary angiography. METHODS AND RESULTS: Non-interventional physicians enrolled 274 patients with CCS before angiography, to minimize selection bias by PCI-operators. Fractional flow reserve (FFR) and IMR were measured in the LAD. Subjects with extensively diseased LAD, no measures due to technical reasons or violation of protocol were excluded from the analysis (n = 54). The proportion of patients with IMR corrected for collateral flow (IMRcorr) >25 units was 25% (95% confidence interval [CI] 19%-31%) in all 220 patients. In subjects with FFR ≤0.80 in the LAD the proportion of IMRcorr > 25 units was 21% (95% CI 13%-30%) as compared to subjects with FFR >0.80, 29% (95% CI 21%-36%), p = .268. Haemoglobin (p < .005; r2 = 0.084), FFR in the LAD (p = .001; r2 = 0.049), creatinine clearance (p = .001; r2 = 0.049; inversely), and NT-proBNP (p = .038; r2 = 0.021) were independently associated with IMRcorr in multivariate linear regression analysis. CONCLUSIONS: We report that IMRcorr is associated with renal dysfunction, NT-proBNP, FFR in the LAD and, for the first time, blood haemoglobin. One in four of patients referred for coronary angiography due to CCS have CMVD defined as IMRcorr > 25 in the LAD.

Prognostic value of pulse-wave tissue Doppler parameters in patients with systolic heart failure.

The aim was to study the prognostic value of left ventricular (LV) function using pulse-wave tissue Doppler imaging (TDI) in an ordinary population with heart failure (HF). One hundred fifty-six patients hospitalized for HF and LV ejection fraction < or =40% were examined using conventional echocardiography and pulse-wave TDI for the assessment of longitudinal LV function. Mitral annular systolic and early diastolic (e') velocities were recorded from a mean of 4 annular sites from the apical 2- and 4-chamber views. Noninvasive LV filling pressure was calculated from the ratio between transmitral early inflow velocity (E) and e'. All patients were followed up for 2 years, and data from the National Registry of Deaths were collected. Mean LV ejection fraction was 24.7 +/- 7.2%. TDI recordings showed a mean mitral annular systolic velocity of 5.0 +/- 1.0 cm/s and e' velocity of 6.2 +/- 1.9 cm/s. E/e' ratio was 14.1 +/- 4.8. Thirty patients (19%) had atrial fibrillation. During follow-up, 27 patients (17%) died of a cardiovascular cause. Multivariate analysis showed that only E/e' ratio and age were predictors of cardiovascular mortality. A cut-off value for E/e' ratio >13 had sensitivity of 84% and specificity of 45% to identify patients who died within 2 years of cardiac reasons. In conclusion, in the acute stage of HF, E/e' ratio is a strong independent predictor of long-term cardiovascular mortality in an ordinary population with HF and systolic dysfunction. Systolic and diastolic velocities had no independent prognostic value.

Detection of left ventricular dysfunction by Doppler tissue imaging in patients with complete recovery of visual wall motion abnormalities 6 months after a first ST-elevation myocardial infarction.

AIMS: The aim of this study was to assess left ventricular (LV) systolic and diastolic function, using Doppler tissue imaging (DTI), in patients with complete recovery of visual wall motion abnormalities six months after a first ST-elevation myocardial infarction (STEMI). METHODS: Out of 90 patients presenting with a STEMI, 68 patients without a history of heart disease were examined by echocardiography before discharge and after 6 months. The patients were compared to 41 age matched healthy subjects (HS). LV function was assessed by visual wall motion and mitral annular velocities using pulsed wave DTI. RESULTS: Sixty-eight patients had visual wall motion abnormalities at baseline. Of these, 19 patients showed complete recovery of wall motion at 6-months follow-up. Patients with complete recovery of wall motion abnormalities had significantly reduced peak systolic and peak early diastolic mitral annular velocities compared to HS at 6 months (8.3 cm s(-1) versus 9.9 cm s(-1), P<0.001 for systolic velocity and 9.3 cm s(-1) versus 13.1 cm s(-1), P<0.001 for diastolic velocity, respectively). CONCLUSION: In patients presenting with a first STEMI, mitral annular systolic and early diastolic velocities assessed by DTI at 6-months follow-up are significantly reduced compared to HS, despite normal standard echocardiographic parameters of LV function. This probably reflects a residual subendocardial damage not detected by conventional echocardiographic methods.

Acute effects of smoking on diastolic function in healthy participants: studies by conventional doppler echocardiography and doppler tissue imaging.

The acute effects of smoking on left ventricular (LV) function were studied in 36 healthy participants (mean age 38 +/- 10 years). The studies were made before and immediately and 30 minutes after smoking a cigarette. From apical 4- and 2-chamber views, the mitral annular velocities, determined by pulsed wave Doppler tissue imaging, were measured at 4 LV sites corresponding to the septum and the anterior, lateral, and inferior walls. A mean value from the 4 sites was used to assess LV function. The peak systolic, early diastolic, late diastolic, and the ratio of early to late diastolic velocities were recorded. In addition, other conventional Doppler echocardiographic diastolic parameters were also determined. Heart rate was increased immediately after smoking (from 67 +/- 8 to 74 +/- 10 bpm, P <.001). There was no change in systolic mitral annular velocity. Diastolic LV function was changed significantly immediately after smoking. The transmitral A wave increased (0.55 +/- 0.1 vs 0.7 +/- 0.1 m/s, P <.001), the transmitral E/A ratio decreased (1.5 +/- 0.6 vs 1.1 +/- 0.3, P <.001), and the transmitral E-wave deceleration time increased (186 +/- 42 vs 211 +/- 44 ms, P <.05). The diastolic myocardial velocity at the mitral annulus also changed significantly: the early diastolic velocity decreased (16 +/- 3 vs 15 +/- 3 cm/s, P <.001), the late diastolic velocity increased (10.9 +/- 2.2 vs 12 +/- 2.4 cm/s, P <.001), and the ratio of early to late diastolic annular velocities decreased (1.5 +/- 0.5 vs 1.2 +/- 0.4, P <.001). The changes in the transmitral flow velocities remained unaltered even 30 minutes afterward, although the heart rate returned to normal. The results were similar in both smokers and nonsmokers. Acute smoking of a cigarette influences LV diastolic function in healthy participants. The mechanism behind this effect cannot be explained only by changes in the heart rate or loading conditions. The mechanism is probably more complex.

Effects of Low-Dose Dobutamine on Displacement of the Atrioventricular Plane and Assessment of Myocardial Viability in Patients with Acute Myocardial Infarction Treated with Thrombolysis.

Previous echocardiographic studies have highlighted the usefulness of atrioventricular (AV) plane displacement (the mitral annular motion) in assessing left ventricular function at rest. However, the effects of low-dose dobutamine on AV plane displacement in thrombolyzed patients with acute myocardial infarction (AMI) are unknown. Thirty-four patients with AMI treated with a thrombolytic agent and having rest wall motion abnormalities at the infarct site were studied with rest and low-dose dobutamine echocardiography before discharge. Thirty-one patients were followed up 18 months later with rest echocardiography. The systolic descent of the AV plane toward the apex at four different left ventricular sites (i.e., at the septal, anterior, lateral, and inferior walls) was recorded to assess left ventricular function. Compared with age-matched healthy subjects, the AV plane displacement was significantly reduced, especially at the infarct sites, in AMI patients at rest. During low-dose dobutamine, the AV plane displacement was increased at infarct sites (P < 0.001) in patients with signs of viability. A cutoff point of an increase in AV plane displacement of >/= 2 mm at the infarct sites during low-dose dobutamine stress had a sensitivity of 89% and a specificity of 87% in assessing myocardial viability. Using the same cutoff point of a spontaneous increase in the AV plane displacement of >/= 2 mm during the follow-up rest echocardiography, 87% of the patients with initial signs of viability and only 25% without signs of viability showed a spontaneous late recovery of initially stunned myocardium. Thus, the study shows that changes in the amplitude of the AV plane displacement during low-dose dobutamine stress echocardiography can easily be used to detect myocardial viability at an early stage with late potential spontaneous recovery.

Left Ventricular Regional Diastolic Dysfunction in Patients with First Myocardial Infarction Determined by Diastolic Motion of the Atrioventricular Plane.

Motion of the left ventricular [left ventricle (LV)] atrioventricular (AV) plane has been used to assess systolic LV function. The method has not been used properly to assess diastolic function, especially after a first myocardial infarction (MI). The diastolic function was assessed in 47 previously healthy patients with a first MI assessed by echocardiographic diastolic motion of the LV AV plane. The motion of the AV plane was recorded at four different LV sites, that is, at the septal, anterior, lateral, and inferior walls. Two distinct phases of motion were noticed during diastole at all the sites: one at the early diastole caused by rapid filling of the LV and the other at late diastole during the atrial contraction. The contribution of left atrial contraction to LV filling at different LV sites was calculated by relating the magnitude of the motion caused by atrial contraction to the total diastolic AV plane motion at the respective sites. These left atrial contributions were regarded as the regional diastolic function of the respective LV sites. The global LV diastolic function was determined from the left atrial contribution to total AV plane motion from the above four sites. Patients with anterior MI had a significantly lower ejection fraction than those with inferior MI (41% and 49%, respectively; P < 0.01). Compared with age-matched healthy subjects, the regional atrial contribution to diastolic filling was significantly higher at the anterior wall in anterior MI (38% and 52%, respectively; P < 0.001) and at the inferior wall in inferior MI (43% and 53%, respectively; P < 0.01). The atrial contribution to global LV filling was increased in anterior MI (48% compared with 42% in healthy subjects; P < 0.05) but not in inferior MI. These findings suggest that the diastolic AV plane displacement (AVPD) may be used to assess both the regional and the global diastolic function in patients following an MI.

Detection of abnormal left ventricular function by Doppler tissue imaging in patients with a first myocardial infarction and showing normal function assessed by conventional echocardiography.

AIMS: The aim of the study was to characterize left ventricular (LV) function by Doppler tissue imaging (DTI) after a first myocardial infarction (MI) where the conventional echo-Doppler parameters showed no abnormalities. METHODS: Out of 202 patients who were referred for an echocardiogram, 19 patients were previously healthy and had a normal ejection fraction and no wall motion abnormalities at echocardiogram. These 19 patients were compared with 16 age-matched healthy subjects (HS). The longitudinal LV function was assessed using the mitral annular velocities (mean value from four different sites of the LV) determined by DTI. RESULTS: The patients with MI had significantly reduced peak systolic and peak early diastolic mitral annular velocities compared to HS (8.6 v. 9.7 cm/s, P<0.001 for systolic velocity, and 10.9 v. 12.3 cm/s, P<0.01 for diastolic velocity, respectively). The patients had normal diastolic LV function assessed by the conventional Doppler echocardiogram (e.g. transmitral flow, IVRT and pulmonary venous flow patterns). To assess the LV filling pressure, the ratio of the transmitral early wave velocity assessed by conventional echo-Doppler and peak early diastolic mitral annular velocity determined by DTI (E/Edti) was used. The E/Edti was significantly higher in patients than in HS (7.0 v. 5.7, P<0.05). CONCLUSION: Previously healthy subjects who are suffering from a first MI and showing normal systolic and diastolic LV function, determined by conventional echo-Doppler methods, show decreased mitral annular systolic and diastolic velocities determined by DTI compared to healthy subjects. This is probably evidence of mild subendocardial damage due to MI that remains undetected by conventional echo-Doppler methods.

Characteristics of left ventricular diastolic function in patients with systolic heart failure: a Doppler tissue imaging study.

OBJECTIVE: Our aim was to characterize myocardial velocity profiles in different types of diastolic dysfunction for patients with severely decreased left ventricular (LV) systolic function. METHODS: A total of 126 patients with congestive heart failure and an LV ejection fraction of 35% or less were included. Patients underwent an echocardiographic Doppler examination, with measurement of the transmitral inflow pattern, and Doppler tissue imaging of the mitral annulus. RESULTS: Compared with age-matched control subjects, the patients had decreased systolic (9.5 vs 4.9 cm/s, P < .001) and early diastolic (11.6 vs 5.6 cm/s, P < .001) mitral annular velocities. According to the transmitral inflow pattern, 56 patients had signs of a LV restrictive pattern, 36 had a pseudonormalization pattern, and 34 had an abnormal relaxation pattern. The peak systolic and early diastolic mitral annular velocities were quite similarly reduced in different diastolic groups (systolic velocities of 4.6, 5.0, and 5.3 cm/s, and early diastolic velocities of 5.7, 5.8, and 5.1 cm/s at restrictive, pseudonormal, and abnormal relaxation, respectively). The ratio of the transmitral early wave and mitral annular early velocity, an expression of LV filling pressure, was highest in the restrictive group compared with other groups (17.0, 14.6, and 11.7 in the above 3 groups, respectively, P < .001 among groups). The ratio of the transmitral early wave and mitral annular early velocity was also higher in the pseudonormal group than in a control group of patients with ejection fraction of 35% or more with signs of a normal/pseudonormal pattern (14.6 vs 9.0, P < .001). CONCLUSION: Doppler tissue imaging may enhance the estimates of diastolic dysfunction in patients with decreased LV systolic function, and help to disclose abnormal diastolic function especially in a pseudonormal group.