Miguel Quintana

Independent prognostic importance of a restrictive left ventricular filling pattern after myocardial infarction an individual patient meta-analysis: Meta-analysis research group in echocardiography acute myocardial infarction

Background— Restrictive mitral filling pattern (RFP), the most severe form of diastolic dysfunction, is a predictor of outcome after acute myocardial infarction (AMI). Low power has precluded a definite conclusion on the independent importance of RFP, especially when overall systolic function is preserved. We undertook an individual patient meta-analysis to determine whether RFP is predictive of mortality independently of LV ejection fraction (LVEF), end-systolic volume index, and Killip class in patients after AMI. Methods and Results— Twelve prospective studies (3396 patients) assessing the relationship between prognosis and Doppler echocardiographic LV filling pattern in patients after AMI were included. Individual patient data from each study were extracted and collated into a single database for analysis. RFP was associated with higher all-cause mortality (hazard ratio, 2.67; 95% CI, 2.23 to 3.20; P<0.001) and remained an independent predictor in multivariate analysis with age, gender, and LVEF. The overall prevalence of RFP was 20% but was highest (36%) in the quartile of patients with lowest LVEF (<39%) and lowest (9%) in patients with the highest LVEF (>53%; P<0.0001). RFP remained significant within each quartile of LVEF, and no interaction was found for RFP and LVEF (P=0.42). RFP also predicted mortality in patients with above- and below-median end-systolic volume index (1575 patients) and in different Killip classes (1746 patients). Importantly, when diabetes, current medication, and prior AMI were included in the model, RFP remained an independent predictor of outcome. Conclusions— Restrictive filling is an important independent predictor of mortality after AMI regardless of LVEF, end-systolic volume index, and Killip class.

Independent relationship of left atrial size and mortality in patients with heart failure: an individual patient meta-analysis of longitudinal data (MeRGE Heart Failure)

Left atrial (LA) size is considered a marker of poor prognosis in heart failure (HF) patients. Prior studies have recruited relatively few subjects limiting their power to adequately analyse the interaction between LA size, left ventricular (LV) systolic and diastolic function, and prognosis.

Independence of restrictive filling pattern and LV ejection fraction with mortality in heart failure: an individual patient meta-analysis.

The Doppler echocardiographic restrictive mitral filling pattern (RFP) is an important prognostic indicator in patients with heart failure (HF), but the interaction between RFP, left ventricular ejection fraction (LVEF) and filling pattern remains uncertain.

Prognostic value of predischarge exercise stress echocardiography after acute myocardial infarction

A predischarge exercise test was performed by 70 patients 7 +/- 4 days (mean +/- SD) after acute myocardial infarction (AMI) to determine the short- and long-term prognostic value of predischarge exercise stress echocardiography (Ex-Echo) compared with exercise stress electrocardiography (Ex-ECG). Two-dimensional echocardiograms were obtained at rest and immediately after exercise; a wall motion score index was obtained both at rest and immediately after exercise. Results of the Ex-Echo were positive in 27 patients (39%), whereas those of Ex-ECG were positive in 34 (49%). The wall motion index after exercise was lower in patients who died during follow-up (85 vs 98, p = 0.01) and in those with cardiac events, defined as death, nonfatal reinfarction, or revascularization (88 vs 98, p = 0.005). More patients with a positive Ex-Echo result had short-term cardiac events (within 2 weeks) than patients with a negative Ex-Echo (6 [22%] vs 2 [5%], p = 0.04). The same was true for long-term mortality (12 [44%] vs 3 [7%], p = 0.0002), reinfarctions (10 [37%] vs 4 [9%], p = 0.01), revascularization procedures (11 [41%] vs 7 [16%], p = 0.023), and cardiac events (22 [81%] vs 12 [28%], p < 0.0001). Survival time was shorter in patients with positive compared with negative Ex-Echo results (34% difference between groups, 95% confidence interval [CI] 10% to 58%, p = 0.002). The same applied for cumulative survival free from cardiac events (43%, p = 0.001, 95% CI 9% to 77%.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolated Type 2 Diabetes mellitus Causes Myocardial Dysfunction That Becomes Worse in the Presence of Cardiovascular Diseases: Results of the Myocardial Doppler in Diabetes (MYDID) Study 1

Aims: Patients with type 2 diabetes mellitus (DM) often suffer disproportionately and have a worse outcome when burdened with cardiovascular complications compared with those without DM. A specific heart muscle disease reportedly caused by DM per se may explain this. We sought to investigate whether an echo Doppler diagnosis of such a myocardial disease is clinically relevant in DM with or without coexistent coronary artery disease (CAD) and/or hypertension (HTN). Subjects andMethods: Two hundred subjects (127 males, 73 females, 56 ± 10 years) including controls (n = 23), patients with HTN (n = 20), CAD (n = 35), uncomplicated DM (n = 59), DM+HTN (n = 27), DM+CAD (n = 16) and DM+CAD+HTN (n = 20) underwent tissue Doppler-enhanced dobutamine stress echocardiography. Myocardial function was assessed by measuring left ventricular myocardial peak systolic velocity (PSV) and early diastolic velocity at rest and during peak stress, besides measurements of standard Doppler variables. Results: Average left ventricular PSV at rest was significantly lower in CAD (4.7 ± 1.5) compared with controls (5.7 ± 1.2) and in DM+CAD+HTN (4.6 ± 1.4) compared with DM (5.6 ± 1.3; all p < 0.05). During peak stress, lower PSV persisted in CAD (9.5 ± 3.1) and DM+CAD+HTN (8.1 ± 2.7), while appearing de novo in DM (11.3 ± 2.6) and HTN (11.0 ± 2.3) unlike in the controls (12.5 ± 2.5; all p < 0.001). When pooled together, DM subjects with CAD and/or HTN or both had significantly lower PSV (9.1 ± 2.7) than those without (10.0 ± 2.8; p < 0.001). Early diastolic velocity response was equally lower in both groups compared with the controls. Conclusion: The results suggest that dobutamine stress unmasks myocardial functional disturbances caused by uncomplicated DM. The discrete disturbances become quantitatively more pronounced in the presence of coexistent cardiovascular diseases.

Electromechanical coupling, uncoupling, and ventricular function in patients with bundle branch block : A tissue-doppler echocardiographic study

Background: Left bundle branch block (LBBB) is associated with impaired left ventricular (LV) function and increased morbidity and mortality, especially in patients with structural heart diseases. The mechanisms are poorly understood. Subjects and Methods: Subjects with isolated LBBB (n = 20), right bundle branch block (RBBB, n = 20), and controls (C, n = 20) were studied with standard two‐dimentional (2D), and color‐encoded tissue‐Doppler echocardiography (TDE). Inter‐ and intraventricular systolic and diastolic coordination were assessed from the TDE velocity profiles. LV function was assessed by 2D echocardiography, by TDE‐derived peak systolic velocities, and the atrioventricular (AV) plane displacement. Results: Subjects with LBBB had longer electromechanical delays and longer isovolumic relaxation times than did the C and RBBB groups (P < 0.001). For the LBBB subjects compared with the RBBB and C groups, ejection times were shorter, peak systolic velocities and AV plane displacements were lower, they had larger LV end‐systolic volumes and lower LV ejection fraction (all P < 0.001), and the atrial contribution to A‐V plane displacement was higher (P < 0.01). There were no differences in diastolic or filling times among the groups. Conclusions: In patients with LBBB, delayed regional electromechanical coupling and uncoupling leads to generalized intra‐ and interventricular asynchrony, thereby explaining the depressed regional and global LV functions. Assessment of the electromechanical coupling and uncoupling processes and their consequences on cardiac function in patients with BBB and structural heart diseases may be possible using TDE.

Study of left ventricular rotation and torsion in the acute phase of ST-elevation myocardial infarction by speckle tracking echocardiography.

Background: The mechanics of the complex left ventricular (LV) myocardial fiber architecture may accurately be assessed by speckle tracking echocardiography (STE). The role of STE to assess LV mechanical dysfunction in the setting of ST segment elevation myocardial infarction (AMI) is still poorly studied. Patients and Methods: 29 consecutive patients (55 ± 13 years) presenting with AMI underwent STE within 72 hours of admission. Reperfusion was achieved with thrombolysis in 15 patients and with primary percutaneous coronary intervention in 14. LV rotational and torsion data were registered during peak systole. Standard Doppler data included LV ejection fraction (EF), mitral inflow deceleration time (DT), and conventional E/A ratio. E/E′ ratio (mitral inflow E velocity/tissue Doppler E velocity) was calculated as a marker of LV filling pressure. Twelve subjects with clinically indicated but negative dobutamine stress echocardiogram served as Controls. Results: Peak systolic torsion was not only significantly lower in AMI compared with Controls (13.3 ± 7.6 vs. 21.8 ± 6.1; P < 0.01), it was also lower in subjects with LVEF <40% (5.0 ± 2.9) compared with those who had LVEF >40% (10.6 ± 6.6; P < 0.02). Torsion had a modest but significantly positive linear relation (R = 0.6; P < 0.05) with DT, not with E/E′ or LVEF. Conclusion: LV systolic torsion is decreased in AMI and more markedly decreased in patients with LVEF <40%. The most significant linear relationship between DT and torsion may possibly indicate that the LV mechanical dysfunction is also associated with altered filling dynamics. (Echocardiography 2010;27:45‐49)

The ischemic preconditioning effect of adenosine in patients with ischemic heart disease

IntroductionIn vivo and in vitro evidence suggests that adenosine and its agonists play key roles in the process of ischemic preconditioning. The effects of low-dose adenosine infusion on ischemic preconditioning have not been thoroughly studied in humans.AimsWe hypothesised that a low-dose adenosine infusion could reduce the ischemic burden evoked by physical exercise and improve the regional left ventricular (LV) systolic function.Materials and methodsWe studied nine severely symptomatic male patients with severe coronary artery disease. Myocardial ischemia was induced by exercise on two separate occasions and quantified by Tissue Doppler Echocardiography. Prior to the exercise test, intravenous low-dose adenosine or placebo was infused over ten minutes according to a randomized, double blind, cross-over protocol. The LV walls were defined as ischemic if a reduction, no increment, or an increment of < 15% in peak systolic velocity (PSV) was observed during maximal exercise compared to the baseline values observed prior to placebo-infusion. Otherwise, the LV walls were defined as non-ischemic.ResultsPSV increased from baseline to maximal exercise in non-ischemic walls both during placebo (P = 0.0001) and low-dose adenosine infusion (P = 0.0009). However, in the ischemic walls, PSV increased only during low-dose adenosine infusion (P = 0.001), while no changes in PSV occurred during placebo infusion (P = NS).ConclusionLow-dose adenosine infusion reduced the ischemic burden and improved LV regional systolic function in the ischemic walls of patients with exercise-induced myocardial ischemia, confirming that adenosine is a potential preconditioning agent in humans.

Markers of risk after acute myocardial infarction. A comparison of clinical variables, ambulatory and exercise electrocardiography, echocardiography, and stress echocardiography

BackgroundShort-term mortality after myocardial infarction has decreased continuously among members of selected populations. Nonetheless, the long-term prognosis among members of unselected populations remains bad. Further research in risk stratification is therefore needed. In the present study we tested the additive value of clinical variables, echocardiography, ambulatory electrocardiography, exercise testing, and stress echocardiography in assessing the long-term prognosis after acute myocardial infarction. MethodsTwo-dimensional echocardiography and ambulatory electrocardiography (analysis of ST-segment changes and of heart rate variability) were performed for 74 patients aged < 75 years who had had an acute myocardial infarction. Before their discharge from hospital, 70 patients were subjected to a combined exercise test and stress echocardiography. The time of follow-up was ≥ 3 years. ResultsDuring follow-up 18 patients died, and 38 suffered cardiac events defined as death, nonfatal reinfarction and the need for revascularization. We first tested 31 covariates in a univariate regression analysis. A subsequent multivariate analysis was performed in two stages. During the first of these, clinical variables (a history of systemic hypertension, infarct localization, and diabetes mellitus) and variables derived from noninvasive tests (new-onset wall-motion abnormality during stress echocardiography, ST-segment depression and heart-rate variability during ambulatory electrocardiography, the ejection fraction by echocardiography at rest, and the double product during exercise tests) predicted mortality. After the second stage, however, the only remaining independent predictors of mortality were the presence of a new-onset wall-motion abnormality (P < 0.0001, relative risk 13.5, 95% confidence interval 3.6–51.3), ST-segment depression during ambulatory electrocardiography (P= 0.003, relative risk 5.0, 95% confidence interval 1.7–15.7) and a decreased heart rate variability (P= 0.007). ConclusionsThe only variables that were of independent value in assessing the long-term mortality were those expressing residual myocardial ischemia and the cardiovascular sympatho-vagal balance. It is, therefore, recommended that one should monitor these variables for patients recovering from an acute myocardial infarction.

Understanding differences in results from literature-based and individual patient meta-analyses: an example from meta-analyses of observational data.

BACKGROUND Meta-analyses are increasingly used to summarise observational data however a literature meta-analysis (LMA) may give different results to the corresponding individual patient meta-analysis (IPMA). This study compares the published results of equivalent LMAs and IPMAs, highlighting factors that can affect the results and therefore impact on clinical interpretation of meta-analyses. METHOD Univariate results from published meta-analyses of prospective observational outcome data were compared, as were the number of studies, patients and length of follow-up. The absolute difference in survival was calculated. The association between severe diastolic dysfunction (RFP) and death post acute myocardial infarction (AMI) and in chronic heart failure (HF) were used as clinical examples. RESULTS The IPMA hazard ratio was lower that the LMA odds ratio: AMI hazard ratio 2.67 (95% confidence interval 2.23 to 3.20), odds ratio 4.10 (3.38 to 4.99); HF hazard ratio 2.42 (2.06 to 2.83), odds ratio 4.36 (3.60 to 5.04). The IPMAs contained most of the studies from the LMAs as well as additional unpublished data, and a longer length of follow-up was available in the IPMAs (AMI 3.7 vs 2.6 yr, HF 4.0 vs 1.5 yr). Restricting analysis to the same studies in both the LMA and IPMA resulted in a similar difference in effect sizes between methods to those found in the published analyses. CONCLUSIONS The result of a meta-analysis is affected by whether study level or individual patient data have been used, and the variant of analysis that is required. Awareness and consideration of these factors is important for clinical interpretation of meta-analyses.