Paolo Rizzon

Cardiac resynchronization therapy tailored by echocardiographic evaluation of ventricular asynchrony

OBJECTIVES The value of interventricular and intraventricular echocardiographic asynchrony parameters in predicting reverse remodeling after cardiac resynchronization therapy (CRT) was investigated. BACKGROUND Cardiac resynchronization therapy has been suggested as a promising strategy in patients with severe heart failure and left bundle branch block (LBBB), but the entity of benefit is variable and no criteria are yet available to predict which patients will gain. METHODS Interventricular and intraventricular mechanical asynchrony was evaluated in 20 patients (8 men and 12 women, 63 +/- 10 years) with advanced heart failure caused by ischemic (n = 4) or nonischemic dilated cardiomyopathy (n = 16) and LBBB (QRS duration of at least 140 ms) using echocardiographic Doppler measurements. Left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-systolic volume index (LVESVI) were calculated before and one month after CRT. Patients with a LVESVI reduction of at least 15% were considered as responders. RESULTS Cardiac resynchronization therapy significantly improved ventricular volumes (LVEDVI from 150 +/- 53 ml/m(2) to 119 +/- 37 ml/m(2), p < 0.001; LVESVI from 116 +/- 43 ml/m(2) to 85 +/- 29 ml/m(2), p < 0.0001). At baseline, the responders had a significantly longer septal-to-posterior wall motion delay (SPWMD), a left intraventricular asynchrony parameter; only QRS duration and SPWMD significantly correlated with a reduction in LVESVI (r = -0.54, p < 0.05 and r = -0.70, p < 0.001, respectively), but the accuracy of SPWMD in predicting reverse remodeling was greater than that of the QRS duration (85% vs. 65%). CONCLUSIONS In patients with advanced heart failure and LBBB, baseline SPWMD is a strong predictor of the occurrence of reverse remodeling after CRT, thus suggesting its usefulness in identifying patients likely to benefit from biventricular pacing.

Transesophageal Doppler echocardiography evaluation of coronary blood flow velocity in baseline conditions and during dipyridamole-induced coronary vasodilation.

Transesophageal echocardiography allows the evaluation of proximal coronary artery anatomy and coronary blood flow velocity (CBFV). To assess the potential of transesophageal echocardiography in evaluating CBFV and its variations induced by coronary-active drugs, we studied 15 patients by high-quality pulsed wave Doppler recordings of CBFV. In these patients, transesophageal Doppler evaluation of CBFV was performed before, 2 minutes after cessation of dipyridamole infusion (0.56 mg/kg in 4 minutes), and 2 minutes after aminophylline infusion (240 mg injected 4 minutes after cessation of dipyridamole infusion). The following CBFV parameters were evaluated at each of the three steps of the study protocol: maximal and mean diastolic velocities and maximal and mean systolic velocities. Furthermore, the following indexes of coronary flow reserve were evaluated: the ratio between maximal diastolic velocity recorded after and before dipyridamole administration and the ratio between mean diastolic velocity recorded after and before dipyridamole administration. Nine of the 15 patients had a normal left anterior descending coronary artery (group A), whereas the remaining six had significant (less than or equal to 75%) stenosis (group B). In group A patients, all CBFV parameters increased significantly during dipyridamole infusion and returned to near baseline values after aminophylline infusion. In group B patients, on the other hand, none of the CBFV parameters increased after dipyridamole infusion. Dipyridamole/baseline maximal diastolic velocity and mean diastolic velocity ratios were, respectively, 3.22 +/- 0.96 and 3.04 +/- 0.88 in group A and 1.46 +/- 0.45 (p less than 0.01 versus group A) and 1.48 +/- 0.49 (p less than 0.01 versus group A) in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison Between Noninvasive Indices of Baroreceptor Sensitivity and the Phenylephrine Method in Post–Myocardial Infarction Patients

BACKGROUND Depressed baroreflex sensitivity obtained by means of a phenylephrine test plays a prognostic role in patients with a previous myocardial infarction. Our purpose was to evaluate the correlation and agreement between the baroreflex sensitivity obtained with phenylephrine and that obtained by two noninvasive methods: the alpha-index and sequence analysis. METHODS AND RESULTS The alpha-index was measured by means of the spectral analysis of RR and systolic blood pressure variabilities in both the high- and low-frequency bands; sequences were identified from simultaneously recorded time series in which the RR and systolic blood pressure concurrently increased or decreased. Noninvasive baroreflex sensitivity tests were performed during both spontaneous and controlled respiration. Fifty-two consecutive patients with recent myocardial infarction underwent the analyses. Although the correlations between phenylephrine and either of the noninvasive methods were always significant, those found during controlled respiration had the highest r values (r=.70). However, the limits of agreement calculated by means of the Bland and Altman method were wide for both noninvasive methods. CONCLUSIONS The results obtained by means of noninvasive baroreflex sensitivity assessments should not be used in clinical practice as an alternative to those obtained by the phenylephrine method.

Plasma leptin is independently associated with the intima-media thickness of the common carotid artery

OBJECTIVE: To investigate whether intima-media thickness (IMT) of the common carotid artery (CCA), an early marker of asymptomatic atherosclerosis, is significantly and independently associated with plasma concentrations of leptin, an adipose tissue hormone that has recently been proposed as a cardiovascular risk factor in obese patients.DESIGN: Cross-sectional sample of normal-weight and obese men and women.SUBJECTS: One-hundred and twenty healthy subjects (52 men and 68 women), aged 18–45 y and with a wide range of BMI, were recruited for the study.MEASUREMENTS: Fasting plasma leptin concentrations and the IMT of the CCA were measured in all subjects. Leptin concentrations were measured by radioimmunoassay and the IMT of the CCA was quantified by high resolution B-mode ultrasound imaging. Central fat (measured by waist circumference), smoking habits, blood pressure, insulin sensitivity (measured by the insulin tolerance test), and fasting plasma glucose, insulin and lipid pattern (cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol) were also measured.RESULTS: IMT of the CCA was positively correlated with log leptin concentrations (P<0.005 in men and P<0.001 in women), body mass index (P<0.001 in men and women), waist circumference (P<0.001 in men and women), age (P<0.001 in men and P<0.05 in women), and negatively associated with insulin sensitivity in both sexes (P<0.05). IMT was also directly correlated with cholesterol (P<0.05), LDL-cholesterol (P<0.01) and systolic blood pressure in men (P<0.05), and with diastolic blood pressure levels in women (P<0.05). When a multiple linear regression model was used without body mass index (BMI), the correlation between leptin and IMT was maintained in both men (P<0.01) and women (P<0.005), independent of age, insulin sensitivity, smoking habits, systolic blood pressure, fasting glucose, triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol. By contrast, BMI-adjusted leptin concentrations were not significantly associated with IMT (Pc (partial correlation): 0.41 in men and 0.15 in women). Moreover, when BMI was entered into a multiple linear regression model without leptin, the correlation between BMI and IMT was maintained in both men (P<0.005) and women (P<0.01), independent of the same parameters.CONCLUSION: Plasma leptin concentrations are independently associated with the IMT of the CCA, suggesting that the increase of adipose tissue mass (or leptin per se) may have an unfavourable influence on the development of atherosclerosis. However, the association between IMT and leptin seems to be dependent and/or confounded by the relationship between IMT and obesity.

Short- and long-term reproducibility of time and frequency domain heart rate variability measurements in normal subjects

OBJECTIVE To obtain data relating to the reproducibility of the time and frequency domain measurements obtained from 10-min ECG recordings. METHODS Eighteen normal volunteers underwent evaluations of time and frequency domain heart rate variability 2 weeks and 7 months after baseline analysis. The time domain parameters were mean NN, the standard deviation of NN intervals, the percentage of successive NN intervals > 50 ms and the root mean square successive difference of NN intervals. The frequency domain evaluations (total power, low frequency, and high frequency) were made by means of both the Fast Fourier Transform algorithm (FFT) and the autoregressive method (AR) from 10-min ECG recordings made under three different conditions: rest, controlled respiration, and after a passive head-up tilt test. Reproducibility was evaluated by means of the interclass correlation coefficient (ICC), comparing baseline values with the results obtained at the second week and the seventh month. Time domain evaluation were also made from 10-min ECG. RESULTS All of the time domain measurements had an ICC > or = 0.75, except for the standard deviation of NN intervals, which had an ICC of 0.57. The frequency domain parameters obtained by means of either FFT or AR showed similar reproducibility. Low frequency was reproducible under all three conditions, total power only at rest, and high frequency only during controlled respiration. CONCLUSION The reproducibility of frequency domain parameters depends on the analysed condition. These results are of primary importance when the effects of drugs or other interventions on heart rate variability are under investigation.

Effects of l-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the l-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial

OBJECTIVES This study was performed to evaluate the effects of L-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. BACKGROUND Carnitine is a physiologic compound that performs an essential role in myocardial energy production at the mitochondrial level. Myocardial carnitine deprivation occurs during ischemia, acute myocardial infarction and cardiac failure. Experimental studies have suggested that exogenous carnitine administration during these events has a beneficial effect on function. METHODS The L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial was a randomized, double-blind, placebo-controlled, multicenter trial in which 472 patients with a first acute myocardial infarction and high quality two-dimensional echocardiograms received either placebo (239 patients) or L-carnitine (233 patients) within 24 h of onset of chest pain. Placebo or L-carnitine was given at a dose of 9 g/day intravenously for the first 5 days and then 6 g/day orally for the next 12 months. Left ventricular volumes and ejection fraction were evaluated on admission, at discharge from hospital and at 3, 6 and 12 months after acute myocardial infarction. RESULTS A significant attenuation of left ventricular dilation in the first year after acute myocardial infarction was observed in patients treated with L-carnitine compared with those receiving placebo. The percent increase in both end-diastolic and end-systolic volumes from admission to 3-, 6- and 12-month evaluation was significantly reduced in the L-carnitine group. No significant differences were observed in left ventricular ejection fraction changes over time in the two groups. Although not designed to demonstrate differences in clinical end points, the combined incidence of death and congestive heart failure after discharge was 14 (6%) in the L-carnitine treatment group versus 23 (9.6%) in the placebo group (p = NS). Incidence of ischemic events during follow-up was similar in the two groups of patients. CONCLUSIONS L-Carnitine treatment initiated early after acute myocardial infarction and continued for 12 months can attenuate left ventricular dilation during the first year after an acute myocardial infarction, resulting in smaller left ventricular volumes at 3, 6 and 12 months after the emergent event.

Effect of respiratory rate on the relationships between RR interval and systolic blood pressure fluctuations: a frequency-dependent phenomenon

OBJECTIVE The aims of this study were to determine the relationships between oscillations in systolic blood pressure and heart period at different breathing frequencies and to investigate the role of sympathetic contribution to this relationship. METHODS Fourteen healthy volunteers underwent three randomized periods of controlled breathing at 6, 10 and 16 breaths/min. ECG (RR), respiratory signal (RESP) and systolic blood pressure (SBP) were continuously recorded. The component of RR and SBP oscillations related to respiration (RRResp and SBPResp) was defined by means of uni- and bivariate spectral analysis. The squared coherence (K2) and phase between RR and RESP, and RR and SBP (RR-SBP) were also assessed. When the K2 of RR-SBP in the respiratory band was > 0.5, we considered the phase and calculated the closed-loop gain between the two signals. Seven subjects were also studied after chronic metoprolol treatment. RESULTS Although the mean values of RR and SBP did not differ between the three periods of breathing, the higher the respiratory rate, the smaller the RRResp and SBPResp. The phase was always negative (SBPResp changes preceded RRResp changes), thus suggesting a baroreflex link. The higher the respiratory rate, the lower the gain and phase. Pharmacological beta-adrenoceptor blockade increased the gain and shifted the phase, but the relationships found at baseline between the respiratory rate and both the gain and phase remained unchanged. CONCLUSIONS The effect of breath rate on the relationship between heart rate and systolic pressure variabilities is a frequency-dependent phenomenon that is also independent of the sympathetic drive.

Analysis of microvascular integrity, contractile reserve, and myocardial viability after acute myocardial infarction by dobutamine echocardiography and myocardial contrast echocardiography

The purpose of this study was to evaluate, in postinfarction dysfunctioning myocardium, the relative potential of myocardial contrast and low-dose dobutamine echocardiography in detecting myocardial viability, and the relation between microvascular integrity, contractile reserve, and functional recovery at follow-up. Twenty-four patients with recent myocardial infarction were studied before hospital discharge with low-dose dobutamine and myocardial contrast echocardiography. In the dysfunctioning infarct area, wall motion score index was calculated at baseline, during low-dose dobutamine, and at 3-month follow-up. Revascularization of the infarct-related artery was performed if clinically indicated. Eighteen patients (group A) had myocardial enhancement of the dysfunctioning infarct area at myocardial contrast echocardiography of >50%, whereas the remaining patients (group B) had an increase of < or = 50%. Wall motion score index was similar at baseline in groups A and B (2.6 +/- 0.4 and 2.8 +/- 0.2; p = NS), but it improved during low-dose dobutamine and at follow-up only in group A (1.9 +/- 0.9 and 1.9 +/- 0.7, respectively; p <0.001 vs baseline). In group B, wall motion score index was 2.7 +/- 0.4 with low-dose dobutamine and 2.8 +/- 0.2 at follow-up (p = NS vs rest). In identifying viable myocardial segments, myocardial contrast echo had 100% sensitivity and 46% specificity, whereas low-dose dobutamine echo had 71% sensitivity and 88% specificity. Thus, microvascular integrity after acute myocardial infarction is a fundamental prerequisite for ensuring myocardial contractile reserve and regional functional recovery. Myocardial contrast and low-dose dobutamine echocardiography have different, but complementary, diagnostic characteristics in detecting myocardial viability.

Detection of coronary artery disease by digital stress echocardiography: Comparison of exercise, transesophageal atrial pacing and dipyridamole echocardiography☆

OBJECTIVES This study assessed and compared the diagnostic potential of exercise, transesophageal atrial pacing and dipyridamole stress echocardiography in a clinical setting. BACKGROUND Although they have been widely studied, no data exist with regard to comparisons of these procedures in a head-to-head study in different clinical settings. METHODS One hundred four consecutive patients with suspected coronary artery disease undergoing coronary angiography and with no previous myocardial infarction or rest left ventricular wall motion abnormalities underwent digital posttreadmill, transesophageal atrial pacing and dipyridamole echocardiography. RESULTS Feasibility of digital exercise echocardiography was 84%; 8 of 88 remaining patients had a nondiagnostic exercise echocardiographic test (inadequate exercise or imaging). In 80 patients with feasible and diagnostic digital exercise echocardiography, sensitivity, specificity and accuracy were, respectively, 89%, 91% and 90%. Eighty of the 104 patients underwent transesophageal atrial pacing and dipyridamole echocardiography. Feasibility of the alternative stress procedures was 77% for transesophageal atrial pacing and 96% for dipyridamole. In 60 patients successfully undergoing both alternative stress procedures, sensitivity and specificity were 83% and 76% for atrial pacing and 43% and 92% for dipyridamole echocardiography, respectively. In the group of 24 patients with nondiagnostic exercise echocardiography and consequent indication to alternative stress procedures, accuracy of transesophageal atrial pacing was higher than that of dipyridamole echocardiography (73% vs. 45%, p = 0.06). CONCLUSIONS Because of its higher diagnostic potential and additional functional information, exercise is the stress of choice when stress echocardiography is used to detect the presence of coronary artery disease. Alternative stresses can be used in patients with nondiagnostic exercise echocardiography. Transesophageal and dipyridamole echocardiography differ in feasibility and diagnostic reliability (higher sensitivity of transesophageal atrial pacing, higher specificity of dipyridamole). These characteristics must be considered when selecting procedures to be used as alternatives to exercise.

Doppler echocardiographic evaluation of the effect of atrial pacing-induced ischemia on left ventricular filling in patients with coronary artery disease

Very little is known about the effects of acute myocardial ischemia on left ventricular filling. Previous studies of these effects have been of limited value because they were performed with 1) imaging techniques that, like cineventriculography or radionuclide ventriculography, do not allow beat to beat monitoring of left ventricular filling throughout the entire ischemic attack; and 2) exercise, which, even if effective in inducing myocardial ischemia in patients with coronary artery disease, also considerably shortens cycle length, thus leading to additional nonischemic filling alterations. To overcome these limitations, left ventricular filling was studied by means of Doppler echocardiographic evaluation of transmitral flow velocities before and immediately after rapid atrial pacing in 17 patients. Eight patients had coronary artery disease but did not develop ischemia (ST depression greater than or equal to 1.5 mm) during atrial pacing (Group 1) whereas nine had coronary artery disease and developed ischemia during atrial pacing (Group 2). No differences were observed from rest to postpacing in any of the filling variables considered in Group 1 patients. In contrast, a significant rearrangement of left ventricular filling occurred during ischemia in Group 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)