Hypertriglyceridemia and omega-3 fatty acids: Their often overlooked role in cardiovascular disease prevention.

AIMS: This review aims to describe the pathogenic role of triglycerides in cardiometabolic risk, and the potential role of omega-3 fatty acids in the management of hypertriglyceridemia and cardiovascular disease. DATA SYNTHESIS: In epidemiological studies, hypertriglyceridemia correlates with an increased risk of cardiovascular disease, even after adjustment for low density lipoprotein cholesterol (LDL-C) levels. This has been further supported by Mendelian randomization studies where triglyceride-raising common single nucleotide polymorphisms confer an increased risk of developing cardiovascular disease. Although guidelines vary in their definition of hypertriglyceridemia, they consistently define a normal triglyceride level as <150 mg/dL (or <1.7 mmol/L). For patients with moderately elevated triglyceride levels, LDL-C remains the primary target for treatment in both European and US guidelines. However, since any triglyceride level in excess of normal increases the risk of cardiovascular disease, even in patients with optimally managed LDL-C levels, triglycerides are an important secondary target in both assessment and treatment. Dietary changes are a key element of first-line lifestyle intervention, but pharmacological treatment including omega-3 fatty acids may be indicated in people with persistently high triglyceride levels. Moreover, in patients with pre-existing cardiovascular disease, omega-3 supplements significantly reduce the risk of sudden death, cardiac death and myocardial infarction and are generally well tolerated. CONCLUSIONS: Targeting resistant hypertriglyceridemia should be considered as a part of clinical management of cardiovascular risk. Omega-3 fatty acids may represent a valuable resource to this aim.

Tricuspid annular plane systolic excursion and pulmonary arterial systolic pressure relationship in heart failure: an index of right ventricular contractile function and prognosis.

Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP

Effects on survival of loop diuretic dosing in ambulatory patients with chronic heart failure using a propensity score analysis.

OBJECTIVE: To ascertain whether increasing doses of orally administered furosemide are associated with impaired survival in outpatients with chronic heart failure (CHF) and left ventricular (LV) systolic dysfunction. METHODS: Transthoracic echo-Doppler examination was carried out at baseline in 813 consecutive CHF outpatients with LV ejection fraction ≤ 45%. The total daily dose of furosemide was assessed for each patient. Chronic kidney disease (CKD) was defined by a glomerular filtration rate < 60 ml/min/1.73 m(2). The end-point was all-cause mortality. To control the prognostic effect of furosemide for the propensity of using high doses of the drug, the Cox model was stratified by the propensity score, itself computed from a multivariable logistic model. Mean follow up was 44 months. RESULTS: After stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide dose (HR 1.38, 95% CI 1.14-1.68, p < 0.001). A daily dose of 50 mg was identified as the best threshold value to predict a high risk of death within 3 years with an area under the ROC curve of 0.68 (95% CI 0.64-0.72). Increasing doses of furosemide were associated with an increased risk of death regardless of LV filling pattern, CKD and background therapy with ACE-inhibitors or beta-blockers. CONCLUSIONS: In outpatients with CHF, after stratification for the propensity score, the risk of death increased linearly across quartiles of furosemide daily dose. A threshold furosemide dose of 50 mg was related with the worse outcome.

Association between decreasing estimated glomerular filtration rate and risk of cardiac conduction defects in patients with type 2 diabetes.

AIM: We aimed to assess the association between decreasing estimated glomerular filtration rate (eGFR) or abnormal albuminuria and the risk of certain cardiac conduction defects in patients with type 2 diabetes mellitus (T2DM). METHODS: We examined a hospital-based sample of 923 patients with T2DM discharged from our Division of Endocrinology over the years 2007-2014. Standard electrocardiograms (ECGs) were performed in all patients. eGFR was estimated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, whilst albuminuria was measured by an immuno-nephelometric method on morning spot urine samples. RESULTS: A total of 253 (27.4%) patients had some type of cardiac conduction defects on standard ECGs (defined as at least one heart block among first-degree atrioventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block). Prevalence of patients with eGFRCKD-EPI < 30 mL/min/1.73 m2, eGFRCKD-EPI 59-30 mL/min/1.73 m2 or abnormal albuminuria (i.e. urinary albumin-to-creatinine ratio ≥ 30 mg/g) were 7.0%, 29.4% and 41.3%, respectively. After adjustment for known cardiovascular risk factors, diabetes-related variables and potential confounders, there was a significant, graded association between decreasing eGFR values and risk of any cardiac conduction defects [adjusted-odds ratios of 2.05 (95% CI: 1.2-3.5), 2.85 (95% CI: 1.6-5.1) and 3.62 (95% CI: 1.6-8.1) for eGFRCKD-EPI 89-60, eGFRCKD-EPI 59-30 and eGFRCKD-EPI < 30 mL/min/1.73 m2, respectively]. Conversely, abnormal albuminuria was not independently associated with an increased risk of any conduction defects (adjusted-odds ratio: 1.09, 95% CI: 0.7-1.6). CONCLUSION: Decreasing eGFR is independently associated with an increased risk of cardiac conduction defects in hospitalized patients with T2DM.

Left atrial dilatation in systolic heart failure: a marker of poor prognosis, not just a buffer between the left ventricle and pulmonary circulation.

BACKGROUND: The relation between systolic pulmonary pressure (sPAP) and left atrium in patients with heart failure (HF) is unclear. Diastolic dysfunction, expressed as restrictive mitral filling pattern (RMP), and functional mitral regurgitation (FMR) are associated with both LA enlargement and increased sPAP. We aimed to evaluate whether atrial dilation might modulate the consequences of RMP and FMR on the pulmonary circulation of patients with HF with reduced ejection fraction (HFrEF). METHODS: 1256 HFrEF patients were retrospectively recruited in four Italian centers. Left ventricular (LVD) and atrial (LAD) diameters were measure by m-mode, and EF were measured. RMP was defined as E-wave deceleration time lower than 140 ms. FMR was quantitatively measured. sPAP was evaluated based on maximal tricuspid regurgitant velocity and estimated right atrial pressure. RESULTS: Final study population was formed by 1005 patients because of unavailability of sPAP in 252 patients. Mean EF was 33 ± 3, 35% had RMP, 67% had mild, and 26% moderate-to-severe FMR. 69% of patients had increased sPAP. A significant association was observed between sPAP and EF, RMP, FMR, and LAD (p < 0.0001 for all). At multivariate analysis, LAD was positively associated with sPAP (p < 0.0001) independently of EF, RMP, and FMR. Analogously, LAD (p < 0.05) was associated with more severe symptoms and worse prognosis after adjustment for LV function and FMR. CONCLUSION: LA dilation was positively associated with sPAP independently of EF, RMP, and FMR. This highlights that LA size should be considered a marker of the severity of the disease.

Independent and incremental prognostic value of Doppler-derived mitral deceleration time of early filling in both symptomatic and asymptomatic patients with left ventricular dysfunction.

OBJECTIVES: This study sought to investigate the relative and incremental prognostic value of demographic, historical, clinical, echocardiographic and mitral Doppler variables in patients with left ventricular systolic dysfunction. BACKGROUND: The prognostic value of diastolic abnormalities as assessed by mitral Doppler echocardiography has yet to be defined. METHOD: A total of 508 patients with left ventricular ejection fraction < or = 35% were followed up for a mean (+/- SD) period of 29 +/- 11 months. RESULTS: During the follow-up period, 148 patients (29.1%) were admitted to the hospital for congestive heart failure, and 100 patients (19.7%) died. By Cox model analysis, Doppler-derived mitral deceleration time of early filling < or = 125 ms (relative risk [RR] 1.93, 95% confidence interval [CI] 1.4 to 3.7), New York Heart Association functional class III or IV (RR 1.49, 95% CI 1.4 to 2.3), ejection fraction < or = 25% (RR 1.85, 95% CI 1.6 to 2.9), third heart sound (RR 2.06, 95% CI 1.8 to 3.2), age > 60 years (RR 1.95, 95% CI 1.8 to 3.1) and left atrial area > 18 cm2 (RR 1.73, 95% CI 1.6 to 2.7) were all found to be independent and additional predictors of all-cause mortality, and deceleration time was the single best predictor (chi-square 37.80). When all these significant variables were analyzed in hierarchic order, after age, functional class, third sound, ejection fraction and left atrial area, deceleration time still added significant prognostic information (global chi-square from 9.2 to 104.7). Also, deceleration time was the strongest independent predictor of hospital admission for congestive heart failure (RR 4.88, 95% CI 3.7 to 6.9) and cumulative events (congestive heart failure or all-cause mortality, or both; RR 2.44, 95% CI 2.0 to 3.8) in both symptomatic and asymptomatic patients. CONCLUSIONS: Deceleration time of early filling is a powerful independent predictor of poor prognosis in patients with left ventricular systolic dysfunction, whether symptomatic or asymptomatic. A short (< or = 125 ms) deceleration time by mitral Doppler echocardiography adds important prognostic information compared with other clinical, functional and echocardiographic variables.

Reversible restrictive left ventricular diastolic filling with optimized oral therapy predicts a more favorable prognosis in patients with chronic heart failure.

OBJECTIVES: We sought to assess whether in clinically stable patients with chronic heart failure (CHF) the prolongation (i.e., increase) of an initially short (< or = 125 ms) Doppler transmitral deceleration time (DT) of early filling obtained with long-term optimal oral therapy predicts a more favorable prognosis. BACKGROUND: It has been recently demonstrated that transmitral early DT is a powerful independent predictor of poor prognosis in patients with left ventricular dysfunction. However, DT may change over time according to loading conditions and medical treatment. METHOD: One hundred forty-four patients with CHF and a short DT (< or = 125 ms) underwent repeat Doppler echocardiographic study 6 months after the initial examination, while clinically stable with optimal oral therapy, and were then followed up for a mean period of 26 +/- 7 months. RESULTS: After 6 months, DT had not changed in 80 patients (group 1), whereas it was significantly prolonged (> 125 ms) in the remaining 64 patients (group 2). Baseline Doppler echocardiographic features were similar in the two groups. No changes were found after 6 months in group 1, whereas group 2 showed a slight but significant (p < 0.01) reduction in end-systolic volume, an improvement in left ventricular ejection fraction (p < 0.01) and a decrease (p < 0.01) in the degree of tricuspid regurgitation. During follow-up, 37% of patients in group 1 experienced cardiac death versus 11% in group 2 (p < 0.0005). By Cox model analysis, prolongation of a short DT emerged as the single best predictor of survival (chi-square 15.70). CONCLUSIONS: The prolongation of an initially short DT obtained with long-term optimal oral therapy predicts a more favorable outcome in clinically stable patients with CHF.

Doppler-derived mitral deceleration time of early filling as a strong predictor of pulmonary capillary wedge pressure in postinfarction patients with left ventricular systolic dysfunction.

OBJECTIVES: The aim of this study was to investigate the correlations between Doppler-derived transmitral flow velocity variables and pulmonary capillary wedge pressure in patients with severe left ventricular systolic dysfunction. BACKGROUND: Abnormal relaxation and increased chamber stiffness have opposing effects on the left ventricular filling pattern. When both abnormalities are present at the same time, as often occurs in patients with systolic dysfunction, the ability of Doppler recording to assess diastolic function and predict left ventricular filling pressure may be significantly compromised. METHOD: Pulmonary capillary wedge pressure and Doppler transmitral flow velocity profile were simultaneously recorded in 140 postinfarction patients with ejection fraction < or = 35%. RESULTS: Correlation between the ratio of mitral peak flow velocity in early diastole to peak flow velocity in late diastole (E/A ratio) and pulmonary capillary wedge pressure was weak (r = 0.65). Although the specificity of E/A > or = 2 in predicting > or = 20 mm Hg in pulmonary capillary wedge pressure was high (99%), its sensitivity was low (43%). Conversely, a very close negative correlation was found between mitral deceleration time of early filling and pulmonary capillary wedge pressure (r = -0.90). Sensitivity and specificity of < or = 120 ms in deceleration time in predicting > or = 20 mm Hg in pulmonary capillary wedge pressure were 100% and 99%, respectively. CONCLUSIONS: Doppler-derived mitral deceleration time of early filling provides a simple and accurate means of estimating pulmonary capillary wedge pressure that is particularly useful in patients with a normal or normalized mitral flow velocity pattern.

Accurate noninvasive estimation of pulmonary vascular resistance by Doppler echocardiography in patients with chronic failure heart failure.

OBJECTIVES: This study was undertaken to explore further the relationship between Doppler-derived parameters of pulmonary flow and pulmonary vascular resistance (PVR) and to determine whether PVR could be accurately estimated noninvasively from Doppler flow velocity measurements in patients with chronic heart failure. BACKGROUND: The assessment of PVR is of great importance in the management of patients with heart failure. However, because of the inconclusive and conflicting data available, Doppler estimation of PVR is still considered unreliable. METHODS: Simultaneous Doppler echocardiographic examination and right heart catheterization were performed in 63 consecutive sinus rhythm heart failure patients with severe left ventricular systolic dysfunction. Hemodynamic PVR was calculated with the standard formula. The following Doppler variables on pulmonary flow and tricuspid regurgitation velocity curve were correlated with PVR: maximal systolic flow velocity, pre-ejection period (PEP), acceleration time (AcT), ejection time, total systolic time (TT), velocity time integral, and right atrium-ventricular gradient. RESULTS: At univariate analysis, all variables except maximal systolic flow velocity and velocity time integral showed a significant, although weak, correlation with PVR. The best correlation found was between AcT and PVR (r = -0.68). By regression analysis, only PEP, AcT and TT entered into the final equation, with a cumulative r = 0.87. When the function (PEP/AcT)/TT was correlated with PVR, the correlation coefficient further improved to 0.96. Of note, this function prospectively predicted PVR (r = 0.94) after effective unloading manipulations. CONCLUSIONS: The analysis of Doppler-derived pulmonary systolic flow is a reliable and accurate tool for estimating and monitoring PVR in patients with chronic heart failure due to left ventricular systolic dysfunction.

Technetium-99m sestamibi tomographic evaluation of residual ischemia after anterior myocardial infarction.

OBJECTIVES: This study investigated the value of sestamibi scintigraphy in assessing residual ischemia after anterior myocardial infarction. BACKGROUND: Serial imaging with sestamibi, the uptake and retention of which correlate with regional myocardial blood flow and viability, has been used to estimate salvaged myocardium and risk area after acute infarction. We recently documented that recovery of perfusion and contraction in the infarcted area may continue well after the subacute phase, suggesting myocardial hibernation. Some underestimation of viability in the setting of hibernating myocardium by sestamibi imaging has been reported. METHODS: We studied 58 patients in stable condition after Q wave anterior infarction. Regional perfusion and function were quantitatively assessed by sestamibi tomography and two-dimensional echocardiography at 4 to 6 weeks and at 7 months after infarction. In sestamibi polar maps, abnormal areas with tracer uptake > 2.5 SD below our reference values were computed at rest and after symptom-limited exercise. On two-dimensional echocardiography the ejection fraction and extent of rest wall motion abnormalities were assessed by a computerized system. All patients had coronary angiography between the two studies. RESULTS: At 7 months the extent of rest sestamibi defect was significantly reduced in 40 patients (69%, group 1) and unchanged in 18 (31%, group 2). Rest wall motion abnormalities and ventricular ejection fraction significantly improved in group 1 but not in group 2. Underlying coronary disease, patency of the infarct-related vessel and rest sestamibi defect extent at 5 weeks were comparable between the two groups. At 7 months, an increase in the reversible (stress-rest defect) tracer defect was observed in group 1 (p < 0.05) despite a smaller stress-induced hypoperfusion (p < 0.05). Reversible sestamibi defects and stress hypoperfusion were unchanged in group 2. In 38 (95%) of 40 group 1 patients, the area showing reversible sestamibi defects at 7 months matched the area showing fixed hypoperfusion at 5 weeks. CONCLUSIONS: The reduction in the rest tracer uptake defect that can occur late after infarction may affect the assessment of ischemic burden by sestamibi imaging early after anterior myocardial infarction.

Residual exertional ischemia and unfavorable left ventricular remodeling in patients with systolic dysfunction after anterior myocardial infarction.

OBJECTIVES: This study investigated whether exercise-induced myocardial ischemia influences left ventricular remodeling after anterior myocardial infarction. BACKGROUND: The effects of acute and recurrent ischemia on ventricular function are well established. However, to our knowledge the role of exertional ischemia in the remodeling response after infarction has not been investigated. METHODS: Ninety-one patients with a first anterior Q wave myocardial infarction were studied at 5 weeks by rest echocardiography and exercise scintigraphy. The echocardiographic examination was repeated 6 months later. On the basis of the presence and extent of reversible perfusion defects on exercise scintigraphy, patients were assigned to groups with no exertional ischemia (group 1, n = 20 [22%], mild to moderate ischemia (group 2, n = 45 [49%]) and severe exertional ischemia (group 3, n = 26 [29%]). RESULTS: Initial left ventricular volumes were similar, and no differences were found among the three groups in the remodeling response over the 6-month period of the study. However, patients in groups 2 and 3 with an ejection fraction < or = 40% showed significant (p < 0.01) ventricular enlargement over time, which was similar between the two groups (end-diastolic volume [mean +/- SD] from 74 +/- 13 to 80 +/- 17 ml/m2 in group 2 and from 72 +/- 11 to 81 +/- 19 ml/m2 in group 3; regional dilation from 42 +/- 16% to 52 +/- 22% in group 2 and from 38 +/- 18% to 46 +/- 27% in group 3). In contrast, ventricular dimensions did not change in group 1 patients with an ejection fraction < or = 40% as well as in patients in all three groups with an ejection fraction > 40%. CONCLUSIONS: Exercise-induced myocardial ischemia may contribute to progressive ventricular enlargement in patients with poor left ventricular function after a large anterior myocardial infarction.

Long-term physical training and left ventricular remodeling after anterior myocardial infarction: results of the Exercise in Anterior Myocardial Infarction (EAMI) trial. EAMI Study Group.

OBJECTIVES: The aim of this multicenter randomized study was to investigate whether long-term physical training would influence left ventricular remodeling after anterior myocardial infarction. BACKGROUND: Exercise is currently recommended for patients after myocardial infarction; however, the effects of long-term physical training on ventricular size and remodeling still have to be defined. METHODS: Patients with no contraindications to exercise were studied 4 to 8 weeks after anterior Q wave myocardial infarction and 6 months later by echocardiography at rest and bicycle ergometric testing. After the initial study, patients were randomly allocated to a 6-month exercise training program (n = 49) or a control group (n = 46). A computerized system was used to derive echocardiographic variables of ventricular size, function and topography. RESULTS: After 6 months, a significant (p < 0.01) increase in work capacity (from 4,596 +/- 1,246 to 5,508 +/- 1,335 kp-m) was observed only in the training group, whereas global ventricular size, regional dilation and shape distortion did not change in either the control or the training group. However, compared with patients with an ejection fraction > 40%, patients with an ejection fraction < or = 40% had more significant (p < 0.001) ventricular enlargement at entry and demonstrated further (p < 0.01) global and regional dilation after 6 months, in both the control and the training group (end-diastolic volume from 77 +/- 14 to 85 +/- 17 ml/m2 in the control group and from 74 +/- 11 to 77 +/- 15 ml/m2 in the training group; regional dilation from 46 +/- 18% to 57 +/- 21% in the control group and from 42 +/- 18% to 44 +/- 26% in the training group). Ventricular size and topography did not change in patients with an ejection fraction > 40%. CONCLUSIONS: Patients with poor left ventricular function 1 to 2 months after anterior myocardial infarction are prone to further global and regional dilation. Exercise training does not appear to influence this spontaneous deterioration. Thus, postinfarction patients without clinical complications, even those with a large anterior infarction, may benefit from long-term physical training without any additional negative effect on ventricular size and topography.

Electrocardiographic evolutionary changes and left ventricular remodeling after acute myocardial infarction: results of the GISSI-3 Echo substudy.

OBJECTIVES: The aim of this study was to describe the electrocardiographic (ECG) evolutionary changes after an acute myocardial infarction (AMI) and to evaluate their correlation with left ventricular function and remodeling. BACKGROUND: The QRS complex changes after AMI have been correlated with infarct size and left ventricular function. By contrast, the significance of T wave changes is controversial. METHODS: We studied 536 patients enrolled in the GISSI-3-Echo substudy who underwent ECG and echocardiographic studies at 24 to 48 h (S1), at hospital discharge (S2), at six weeks (S3) and six months (S4) after AMI. RESULTS: The number of Qwaves (nQ) and QRS quantitative score (QRSs) did not change over time. From S2 to S4, the number of negative T waves (nT NEG) decreased (p < 0.0001), wall motion abnormalities (%WMA) improved (p < 0.001), ventricular volumes increased (p < 0.0001) while ejection fraction remained stable. According to the T wave changes after hospital discharge, patients were divided into four groups: stable positive T waves (group 1, n = 35), patients who showed a decrease > or =1 in nT NEG (group 2, n = 361), patients with no change in nT NEG (group 3, n = 64) and those with an increase > or =1 in nT NEG (group 4, n = 76). The QRSs and nQ remained stable in all groups. Groups 3 and 4 showed less recovery in %WMA, more pronounced ventricular enlargement and progressive decline in ejection fraction than groups 1 and 2 (interaction time x groups p < 0.0001). CONCLUSIONS: The analysis of serial ECG can predict postinfarct left ventricular remodeling. Normalization of negative T waves during the follow-up appears more strictly related to recovery of regional dysfunction than QRS changes. Lack of resolution and late appearance of new negative T predict unfavorable remodeling with progressive deterioration of ventricular function.

Doppler-derived acceleration rate of right ventricular early filling as a measurement of right atrial pressure in chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

This study demonstrates that a Doppler-derived tricuspid flow velocity pattern provides an accurate, feasible, and noninvasive method of estimating and monitoring mean right atrial pressure in patients with heart failure due to left ventricular systolic dysfunction, and who are both in sinus rhythm and atrial fibrillation. In particular, the acceleration rate of early right ventricular filling is a powerful and independent predictor of mean right atrial pressure.

Heterogeneous fate of perfusion and contraction after anterior wall acute myocardial infarction and effects on left ventricular remodeling.

After acute myocardial infarction, patency of infarct vessel and extent of left venticular (LV) dysfunction are major determinants of ventricular remodeling. Spontaneous, delayed reperfusion in the infarct zone occurs in a sizeable number of patients well after the subacute phase. The aim of this study was to determine the relation between the occurrence of this spontaneous, delayed reperfusion and LV remodeling. In 84 patients, resting LV volumes, topography, regional function, and perfusion were quantitatively evaluated by 2-dimensional echocardiography and sestamibi tomography 5 weeks (study 1) and 7 months (study 2) after anterior Q-wave infarction. At study 2, LV end-diastolic volume increased by > 15% in 17 patients (20%, LV remodeling); they had already had at study 1 significantly larger LV volumes, more severe hypoperfusion and wall motion abnormalities, and greater regional dilation than patients with stable LV volumes. Delayed reperfusion occurred in 8 of 17 patients with and in 42 of 67 patients without LV remodeling (47% vs 63%; p=NS). At study 2, LV regional dilation and end-diastolic volumes were stable in patients with, but increased in patients without, spontaneous reperfusion (from 25+/-24% to 29+/-26% at study 2 [p<0.05] and from 65+/-14 to 68+/-18 ml/m2 [p <0.05]). At multivariate analysis, however, regional ventricular dilation at study 1 was the sole predictor of further LV remodeling. Thus, after acute myocardial infarction, spontaneous reperfusion occurring after 5 weeks plays only a minor role in influencing LV remodeling. Benefits from delayed reperfusion seem limited to patients with preserved LV volumes; patients with an enlarged left ventricle 5 weeks after acute infarction are prone to further LV remodeling, irrespective of delayed reperfusion.

Estimation of pulmonary wedge pressure by transmitral Doppler in patients with chronic heart failure and atrial fibrillation.

Previous studies have demonstrated that left ventricular (LV) filling pressures can be estimated from transmitral Doppler recording in patients in sinus rhythm who have a broad spectrum of cardiac diseases. However, the correlation between pulmonary wedge pressure (PWP) and mitral Doppler profile has not yet been clearly defined in patients with atrial fibrillation, particularly in the presence of severe LV systolic dysfunction. The aim of this study was to evaluate the correlations between PWP and transmitral Doppler variables in patients with atrial fibrillation and chronic heart failure due to dilated cardiomyopathy. PWP and the mitral Doppler profile were simultaneously recorded in 35 consecutive heart failure patients (28 men, 7 women; mean age, 69 +/- 9 years) with severe LV dysfunction (mean ejection fraction 22% +/- 5%). Doppler measurements were averaged over 10 cardiac cycles. In addition, left atrial areas were derived from the apical 4-chamber view. Significant relations were observed between PWP and several parameters derived from the mitral flow: isovolumic relaxation time (r = -70), acceleration rate (r = 0.78), deceleration rate (r = 0.82), and deceleration time (r = -0.95). However, by stepwise multivariate analysis, deceleration time emerged as the sole independent predictor of PWP (r2 = 0.95, F = 590). The analysis led to the following equation: PWP = 51 - 0.26 (deceleration time). Our data suggest that mitral Doppler echocardiography is a useful tool for predicting PWP in heart failure patients with severe LV dysfunction even in the presence of atrial fibrillation.

EAMI--exercise training in anterior myocardial infarction: an ongoing multicenter randomized study. Preliminary results on left ventricular function and remodeling. The EAMI Study Group.

To determine the effects of a 6-month exercise training program on left ventricular (LV) function and remodeling, 49 consecutive patients (pts) with first Q anterior myocardial infarction (51 +/- 8 years), in I-II NYHA class, were studied 4 to 8 weeks after the acute episode and 6 months later by 2D-ECHO and upright bicycle ergometric test. At entry, pts were randomly allocated to physical training (T = 25pts) or control (C = 24pts). Global endocardial surface area (ESA), LV volumes and EF, extent of abnormal wall motion (%WMA), of regional dilatation (%REG DIL), and the shape distortion (DIST) index were analyzed. After 6 months, a significant increase in work capacity (4,589 +/- 1,417 to 5,379 +/- 1,485 KPM/min, p less than 0.03) and in lactic anaerobic threshold (45 +/- 13 to 63 +/- 15 W, p less than 0.01) was observed only in T. Initial ESA, EDV, EF, %WMA, %REG DIL, and DIST index were similar and they did not change after 6 months in both groups. However, pts with less than 40%EF had greater (p less than 0.0001) EDV and %WMA with marked DIST index at entry and showed further (p less than 0.01) deterioration after 6 months both in C and in T (EDV, ml/m2: 68 +/- 12 to 77 +/- 18 in C, 71 +/- 12 to 74 +/- 18 in T; %REG DIL: 39 +/- 20 to 49 +/- 24 in C, 32 +/- 12 to 35 +/- 23 in T; DIST index: 0.16 +/- 0.07 to 0.21 +/- 0.09 in C, 0.2 +/- 0.07 to 0.22 +/- 0.1 in T). These variables did not change in pts with greater than 40%EF. Thus, from these preliminary data, pts with less than 40%EF at entry are prone to further global and regional LV deterioration. Physical training does not seem to increase this spontaneous deterioration.

Chronic mitral regurgitation and Doppler estimation of left ventricular filling pressures in patients with heart failure.

Previous studies relating Doppler parameters and pulmonary capillary wedge pressures (PCWP) typically exclude patients with severe mitral regurgitation (MR). We evaluated the effects of varying degrees of chronic MR on the Doppler estimation of PCWP. PCWP and mitral Doppler profiles were obtained in 88 patients (mean age 55 +/- 8 years) with severe left ventricular (LV) dysfunction (mean ejection fraction 23% +/- 5%). Patients were classified by severity of MR. Patients with severe MR had greater left atrial areas, LV end-diastolic volumes, and mean PCWPs and lower ejection fractions (each P <.01). In patients with mild MR, multiple echocardiographic parameters correlated with PCWP; however, with worsening MR, only deceleration time strongly related to PCWP. From stepwise multivariate analysis, deceleration time was the best independent predictor of PCWP overall, and it was the only predictor in patients with moderate or severe MR. Doppler-derived early mitral deceleration time reliably predicts PCWP in patients with severe LV dysfunction irrespective of degree of MR.

Restrictive left ventricular filling pattern as a strong predictor of depressed baroreflex sensitivity in heart failure.

BACKGROUND: The aim of this study was to test the hypothesis that a restrictive left ventricular diastolic filling pattern, as an index of elevated pulmonary wedge pressure, would predict a depressed baroreflex sensitivity (BRS) in patients with chronic heart failure. METHODS: A total of 189 consecutive patients with an ejection fraction < or = 40% at echocardiography, in sinus rhythm and clinically stable for at least 1 month in oral therapy, underwent clinical examination, echo-Doppler study and the phenylephrine test. RESULTS: The correlations between the NYHA functional class, echo-Doppler variables and BRS were weak, although significant (r ranging from -0.15 to 0.40). However, patients with a deceleration time < 140 ms as an expression of restrictive filling, compared to those with a deceleration time > or = 140 ms, had a lower BRS (3 +/- 4 vs 6 +/- 4 ms/mmHg, p < 0.00001), a lower ejection fraction (20 +/- 6 vs 28 +/- 7%, p < 0.00001), greater left ventricular (end-diastolic volume index 137 +/- 43 vs 113 +/- 45 ml/m2, p < 0.00001) and left atrial dimensions (25 +/- 6 vs 20 +/- 5 cm2, p < 0.00001), more severe mitral regurgitation (3 +/- 1 vs 2.3 +/- 1, p < 0.00001) and were in a higher NYHA class (2.3 +/- 0.6 vs 1.8 +/- 0.5, p < 0.00001). Medications at the time of the study were similar in the two groups. At stepwise regression analysis, the deceleration time emerged as the most powerful independent predictor of a depressed BRS (< 3 ms/mmHg), followed by mitral regurgitation, age, and NYHA class (all data p = 0.0001). CONCLUSIONS: In patients with chronic heart failure, the presence of a restrictive left ventricular filling pattern is highly predictive of autonomic derangement as expressed by low values of BRS.