Constadina Aggeli

Acute Systemic Inflammation Increases Arterial Stiffness and Decreases Wave Reflections in Healthy Individuals

Background— Aortic stiffness is a marker of cardiovascular disease and an independent predictor of cardiovascular risk. Although an association between inflammatory markers and increased arterial stiffness has been suggested, the causative relationship between inflammation and arterial stiffness has not been investigated. Methods and Results— One hundred healthy individuals were studied according to a randomized, double-blind, sham procedure-controlled design. Each substudy consisted of 2 treatment arms, 1 with Salmonella typhi vaccination and 1 with sham vaccination. Vaccination produced a significant (P<0.01) increase in pulse wave velocity (at 8 hours by 0.43 m/s), denoting an increase in aortic stiffness. Wave reflections were reduced significantly (P<0.01) by vaccination (decrease in augmentation index of 5.0% at 8 hours and 2.5% at 32 hours) as a result of peripheral vasodilatation. These effects were associated with significant increases in inflammatory markers such as high-sensitivity C-reactive protein (P<0.001), high-sensitivity interleukin-6 (P<0.001), and matrix metalloproteinase-9 (P<0.01). With aspirin pretreatment (1200 mg PO), neither pulse wave velocity nor augmentation index changed significantly after vaccination (increase of 0.11 m/s and 0.4%, respectively; P=NS for both). Conclusions— This is the first study to show through a cause-and-effect relationship that acute systemic inflammation leads to deterioration of large-artery stiffness and to a decrease in wave reflections. These findings have important implications, given the importance of aortic stiffness for cardiovascular function and risk and the potential of therapeutic interventions with antiinflammatory properties.

Isolated Left Ventricular Noncompaction: An Unclassified Cardiomyopathy with Severe Prognosis in Adults

Noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy, which appears to represent an arrest in intrauterine endomyocardial morphogenesis. It is diagnosed both in children and adults. Its common presentation involves heart failure symptoms, ventricular tachyarrhythmias and thromboembolic events, but the age of onset varies widely. The diagnosis is made by the combined appearance of numerous, excessively prominent trabeculations and multiple deep intertrabecular recesses perfused from the ventricular cavity, commonly involving the apical and midventricular segments of the left ventricle. Although the peculiar echocardiographic picture may possibly lead to the correct diagnosis, this condition may be often misdiagnosed or unrecognized since it is not widely known.

Aortic elastic properties in patients with repaired coarctation of aorta

Patients with successfully repaired coarctation of the aorta have impaired distensibility. Age at surgery as well as left ventricular mass index are factors that are related to the distensibility index.

Safety of myocardial flash-contrast echocardiography in combination with dobutamine stress testing for the detection of ischaemia in 5250 studies

Objective: The purpose of the present study was to provide evidence regarding the safety of real-time flash-contrast echocardiography combined with dobutamine–atropine stress echo (DASE). Background: The combination of perfusion assessment using myocardial contrast echocardiography (MCE) with DASE has shown very promising results for the diagnosis of coronary artery disease. Concerns have, however, been expressed regarding the safety of the use of echo-contrast agents in echocardiography. Design: 5250 individuals (70.8% men, aged 64.6 years (SD 10.6)) were submitted to DASE, with concurrent MCE using a low mechanical index technique with the administration of high-energy impulses in order to assess replenishment time. Results: No deaths or myocardial infarctions were observed. Sustained ventricular tachycardia (VT) or fibrillation requiring resuscitation occurred in two cases (0.04%). The incidence of other arrhythmic events was: sustained VT not requiring resuscitation, 10 (0.18%); non-sustained VT, 18 (0.34%); atrial tachycardia, 4 (0.08%); atrial fibrillation, 25 (0.48%). Other observed adverse events included: intense headache, 52 (1%); intense back pain, 26 (0.5%). Vagal reactions with marked systolic blood pressure falls were observed in 45 cases (0.9%). Hypersensitivity reactions were reported in 23 cases (0.44%), although no serious cases of hypersensitivity requiring hospitalisation were recorded. The sensitivity, specificity and overall accuracy of DASE/MCE were 92%, 61% and 85%, respectively. Conclusions: This report of safety data regarding stress-contrast echocardiography in a large series of subjects suggests that this is an exceptionally safe technique, given that in 5250 studies no study-related deaths or myocardial infarctions were encountered, whereas serious adverse events requiring hospitalisation were extremely rare (one in 2625 studies).

Real-time three-dimensional dobutamine stress echocardiography for coronary artery disease diagnosis: validation with coronary angiography

Objective: To compare real-time three-dimensional echocardiography (RT3DE) with two-dimensional dobutamine stress echocardiography (2DE) for the detection of myocardial ischaemia, with angiographic validation of the results. Methods: 56 patients (mean (SD) age 64.5 (6.2) years, 38 males), referred for coronary angiography, were examined by 2DE and RT3DE during the same dobutamine stress protocol. Results: All 56 patients completed the stress protocol uneventfully. The mean (SD) acquisition time for the necessary views to evaluate all segments was 26.3 (2.5) s for RT3DE and 58.8 (3.7) s for 2DE (p<0.001). At peak stress, RT3DE had a higher wall-motion score index (1.25 (0.24) by 2DE, 1.30 (0.27) by RT3DE; p = 0.014). The regional wall-motion score for the four apical segments at peak stress was compared; it was 1.35 (0.55) by 2DE and 1.52 (0.69) by RT3DE (p = 0.003). The diagnostic parameters of 2DE versus RT3DE were: sensitivity 73% vs 78%, specificity 93% vs 89% and overall accuracy 86% vs 85%, respectively. In the left anterior descending artery territory, in particular, where RT3DE had higher regional wall-motion scores, it showed a tendency towards higher sensitivity (85% vs 78%), although this difference did not achieve statistical significance. Conclusion: RT3DE identifies wall-motion abnormalities more readily in the apical region than 2DE, which may explain the tendency towards higher sensitivity in the left anterior descending artery territory. RT3DE results were validated using angiography as reference and findings indicate diagnostic equivalence to 2DE, with the advantage of considerable shorter acquisition times.

Relevance of Adenosine Deaminase and Lysozyme Measurements in the Diagnosis of Tuberculous Pericarditis

Objective: To assess the value of pericardial fluid adenosine deaminase (ADA) and pericardial lysozyme (Lys) as tools in diagnosing tuberculous pericarditis. Methods: Forty-one patients (age range 17–77 years) with significant pericardial effusion were included in the study. Diagnostic pericardiocentesis and pericardial biopsy were performed while serum and pericardial fluid ADA and Lys were measured in all patients. Grouping of patients resulted as follows: group I = 7 patients with tuberculous pericarditis; group II = patients with neoplastic pericarditis; group III = 30 patients with idiopathic pericarditis. Results: Pairwise multiple comparison procedures revealed a significant difference of ADA in group I versus group III (p < 0.05) but not versus group II. Furthermore, pericardial Lys in group I was higher than in groups II and III (p < 0.05). A strong correlation between pericardial ADA and Lys was found (r = 0.733, p = 0.01) for all the patients. Receiver operating curves showed a value of 72 U/l as cutoff point of pericardium ADA, with a sensitivity of 100% and a specificity of 94% in the diagnosis of tuberculous pericarditis. Similarly for pericardial Lys, a value of 6.5 µg/dl had a sensitivity and specificity of 100 and 91.17%, respectively. Conclusions: Both measurements of pericardial ADA and Lys need to be taken into account when attempting the early diagnosis of tuberculous pericarditis.

Estimation of atrial fibrillation recency of onset and safety of cardioversion using NTproBNP levels in patients with unknown time of onset

Objective As shown previously in patients with new-onset atrial fibrillation (AF) without symptoms or signs of heart failure, N-terminal pro-brain natriuretic peptide (NTproBNP) increases rapidly, reaching a maximum within 24–36 h, and then decreases even if AF persists. A study was undertaken to use NTproBNP measurements in patients with AF of unknown time of onset to identify patients with presumed recent onset of the arrhythmia. Design Two-group open cross-sectional study. Setting Hospitalised patients in cardiology departments of four hospitals. Patients Patients presenting with AF of unknown onset and no signs or symptoms of heart failure were separated into two groups: group A with NTproBNP above the cut-off level and group B with a low NTproBNP level. Interventions No therapeutic intervention. All patients underwent transoesophageal echocardiography (TEE). Main outcome measures Presence of left atrial thrombus on TEE. Results In group A (N=43) only two patients (4.7%) were found to have an atrial thrombus on TEE (negative predictive value of raised NTproBNP levels 95.3%) compared with 13 of 43 patients in group B (30.2%; p=0.002). Patients with a higher CHA2DS2VASc score (p=0.002) and a larger left atrium (p<0.001) were more likely to have an atrial thrombus. In the multivariate analysis, NTproBNP below the cut-off level was the most powerful predictor of the presence of thrombus (OR 25.0; p=0.016). Conclusion The reported strong correlation between raised NTproBNP levels and the absence of atrial thrombi on TEE suggests that the short-term increase in NTproBNP levels after AF onset might be used to assess the age of the arrhythmia and thus the safety of cardioversion in patients with AF of unknown onset and no heart failure.

Prediction of Functional Recovery of Hibernating Myocardium Using Harmonic Power Doppler Imaging and Dobutamine Stress Echocardiography in Patients With Coronary Artery Disease

The aim of this study was to compare the accuracy of harmonic power Doppler imaging (HPDI) and dobutamine stress echocardiography (DSE) in predicting recovery of myocardial function after bypass surgery. HPDI using triggering imaging with the administration of Levovist (Shering AG, Berlin, Germany) and DSE were performed in 34 patients (mean age 64 +/- 5 years) with left ventricular dysfunction. A repeat echocardiogram at rest was performed 3 months after revascularization. Of the 408 revascularized dysfunctional segments, 188 (45%) improved on the repeat echocardiogram. HPDI exhibited overall similar sensitivity (88% vs 87%) and accuracy (74% vs 79%) but lower specificity (61% vs 72%, p<0.05) compared with DSE for predicting recovery of myocardial function. Only delayed opacification at the 1:8 triggering point, demonstrated in 62% of viable segments, exhibited higher sensitivity (63%) and positive (58%) and negative (66%) predictive values than early opacification at 1:4 (25%, p<0.001; 35%, p<0.001; and 49%, p<0.001, respectively) in predicting functional recovery. The presence of contrast enhancement within the revascularized area resulted in a significant improvement after revascularization in wall motion score index and ejection fraction compared with areas with residual contrast defect (1.9 +/- 0.3 vs 2.3 +/- 0.3, p<0.01; 36 +/- 6% vs 29 +/- 5%, p<0.01, respectively). Significant correlations were observed between the contrast score index and the follow-up wall motion score index (r = -0.67) and between the contrast score index and the follow-up ejection fraction change (r = 0.65). Triggered HPDI has high sensitivity in detecting hibernating myocardium and can accurately predict the potential for recovery of ischemic left ventricular dysfunction 3 months after revascularization.

Comparison of Muscle Functional Electrical Stimulation to Conventional Bicycle Exercise on Endothelium and Functional Status Indices in Patients With Heart Failure

The aim of this prospective, open-label, cohort study was to compare the effect of muscle functional electrical stimulation (FES) on endothelial function to that of conventional bicycle training. Eligible patients were those with New York Heart Association class II or III heart failure symptoms and ejection fractions ≤ 0.35. Two physical conditioning programs were delivered: FES of the muscles of the lower limbs and bicycle training, each lasting for 6 weeks, with a 6-week washout period between them. Brachial artery flow-mediated dilation (FMD) and other parameters were assessed before and after FES and the bicycle training program. FES resulted in a significant improvement in FMD, which increased from 5.9 ± 0.5% to 7.7 ± 0.5% (95% confidence interval for the difference 1.5% to 2.3%, p < 0.001). Bicycle training also resulted in a substantial improvement of endothelial function. FMD increased from 6.2 ± 0.4% to 9.2 ± 0.4% (95% confidence interval for the difference 2.5% to 3.5%, p < 0.001). FES was associated with a 41% relative increase in FMD, compared to 57% with bicycle exercise (95% confidence interval for the difference between the relative changes 1.2% to 30.5%, p = 0.034). This resulted in attaining a significantly higher FMD value after bicycle training compared to FES (9.2 ± 0.4% vs 7.7 ± 0.5%, p < 0.001). In conclusion, the effect of muscle FES in patients with heart failure on endothelial function, although not equivalent to that of conventional exercise, is substantial. Muscle FES protocols may prove very useful in the treatment of patients with heart failure who cannot or will not adhere to conventional exercise programs.

Effect of biventricular pacing on ventricular repolarization and functional indices in patients with heart failure: lack of association with arrhythmic events

AIMS We prospectively assessed the effects of biventricular (BiV) pacing on electrocardiographic (ECG) and vectorcardiographic (VCG) descriptors of ventricular depolarization and repolarization and their association with appropriate implantable cardioverter defibrillator (ICD) activation. METHODS AND RESULTS We studied 70 consecutive heart failure (HF) (37 ischaemic) patients (64 males, age 66.3 years) with a history of syncope or sustained ventricular tachycardia (VT) who underwent implantation of a BiV-ICD. An invasive electrophysiological study (EPS) was performed before the implantation and 12-lead digital ECGs before and 30 days after implantation. Serial echocardiographic studies were performed. Follow-up duration was 1 year. Maximum (P < 0.001) and minimum (P = 0.004) QT intervals were significantly decreased, whereas QT dispersion was not altered (P = 0.086). QRS duration was shortened (P < 0.001), whereas QRS dispersion was significantly decreased (P = 0.034). Spatial T and QRS vector amplitudes decreased (P < 0.001, for both), whereas the spatial QRS-T angle was not affected (P = 0.671). Twenty-seven (38.6%) patients, experienced appropriate ICD therapies during follow-up. None of the ECG or VCG parameters (pre- or post-implant) were able to identify patients with appropriate ICD therapies during follow-up. Only the presence of a previous episode of sustained VT (spontaneous or inducible on EPS) was strongly associated with appropriate ICD therapies (multivariate P = 0.00 014; odds ratio 24.5). CONCLUSION Improvement or no alteration of ECG and VCG descriptors of ventricular depolarization and repolarization was demonstrated after implantation of a BiV-ICD in HF patients. None of these parameters were associated with appropriate ICD therapies, whereas a previous episode of VT or induction of sustained VT on EPS predicted appropriate ICD treatments.