Arterial stiffness in hypertensives in relation to expression of angiopoietin-1 and 2 genes in peripheral monocytes.

Angiopoietins (Angs) are important angiogenic and endothelial cell growth factors with many functions, including influence on the vascular wall. Pulse-wave velocity (pwv) is an independent marker of cardiovascular adverse outcome in hypertensives, although all the pathophysiological mechanisms that affect it have not yet been determined. We investigated the relationship between arterial stiffness and Ang-1 and Ang-2 gene expression in the peripheral blood monocytes of hypertensive patients. We studied 53 patients who had untreated grade-1 or grade-2 essential hypertension and no indications of other organic heart disease. Carotid-femoral (c-f) and carotid-radial (c-r) artery waveforms were measured and pwv was determined. The monocytes were isolated using anti-CD14(+) antibodies and mRNAs were estimated by real-time quantitative reverse transcription-PCR. Ang-1 gene expression was strongly correlated with both c-f-pwv (r=0.952, P<0.001) and c-r-pwv (r=0.898, P<0.001). Similarly, Ang-2 gene expression was significantly correlated with both c-f-pwv (r=0.471, P=0.002) and c-r-pwv (r=0.437, P=0.003). Our data provide important evidence that Ang-1 and Ang-2 gene expression levels in peripheral monocytes are closely related with pwv in patients with essential hypertension. This positive correlation may suggest a link between angiogenesis and arterial stiffness in those patients.

Effect of angiotensin-converting enzyme inhibitors on systemic inflammation and myocardial sympathetic innervation in normotensive patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) may cause an increase in the inflammatory status and oxidative stress as well as sympathetic nervous system overactivity, even in the absence of any other organic heart disease. We investigated the effect of perindopril, an angiotensin-converting enzyme inhibitor (ACE-i), on indexes of systemic inflammation and oxidative stress in normotensive patients with type 2 DM. We also examined the effect of the drug on the disturbances of left ventricular myocardial adrenergic innervation that may be seen in these patients. We studied 62 normotensive patients with type 2 DM, who were randomized to receive perindopril (n=32) or placebo (n=30). At the start of the study and after 6 months' therapy blood samples were taken to evaluate total peroxides (TP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), and the patients underwent a (123)I-metaiodobenzylguanidine myocardial scintigraphy study. ACE-i caused a significant reduction in levels of cytokines and TP (P<0.001 for IL-6 and TNF-alpha, P=0.001 for TP). There was also a reduction in total defect score (P<0.001) and the heart to mediastinum ratio at 10 min and 4 h was improved (P<0.001 for both). No significant alterations were observed in the placebo group. Our data indicate that the addition of ACE-i to the medication of normotensive diabetic type 2 patients may improve the disturbed myocardial adrenergic innervation, the systemic inflammatory status and oxidative stress. Our findings indicate the cardioprotective action of ACE-i and suggest that earlier treatment might be appropriate in those patients.

Effect of acute atrial fibrillation on phasic coronary blood flow pattern and flow reserve in humans.

AIMS: To assess the effect of experimentally induced atrial fibrillation on coronary flow in humans. METHODS AND RESULTS: In 16 patients (10 men, mean age 43+/-13 years) with normal coronary vessels, baseline and hyperaemic blood pressure and Doppler phasic coronary flow velocity were measured, using a 0.014 inch intracoronary Doppler flow wire, during sinus rhythm, experimentally induced atrial fibrillation, and right atrial pacing at a similar heart rate to that during atrial fibrillation. Coronary flow velocity integral per minute increased significantly during both right atrial pacing and atrial fibrillation compared to sinus rhythm, but during right atrial pacing the increase was greater (85+/-43% vs 52+/-25%, P<0.001). This difference persisted even after correction for the product of heart rate and blood pressure (1.15+/-0.51 vs 0.97+/-0.46, respectively, P<0.02). In a further 12 paced patients (seven men, mean age 54+/-10 years) with complete atrioventricular block the induction of atrial fibrillation (atrial fibrillation with regular RR interval) caused no significant changes in coronary flow velocity variables. CONCLUSIONS: Acute atrial fibrillation in humans causes an increase in coronary flow that is, however, insufficient to compensate for the augmented myocardial oxygen demand, mainly because of the irregularity in the ventricular rhythm that exists during atrial fibrillation.

Autonomic imbalance during the day in patients with inflammatory bowel disease in remission. Evidence from spectral analysis of heart rate variability over 24 hours.

BACKGROUND: Autonomic function in inflammatory bowel disease has not yet been studied by means of analysis of 24-hour heart rate variability. AIM: To measure heart rate variability in inflammatory bowel disease patients in remission. PATIENTS AND METHODS: Study population comprised 27 patients with inflammatory bowel disease in remission and 28 healthy, sex- and age-matched controls. Two frequency ranges were analysed: low frequency (0.06-0.15 Hz) and high frequency (0.15-0.40 Hz). RESULTS: Mean values of low frequency and low frequency/high frequency ratio were lower in patients than in controls (p < 0.001). High frequency in patients tended to be higher than in controls (p = 0.09). The only factor that had a marginal effect on heart rate variability indexes was age. In high frequency, there was a significant time effect (p = 0.001) for both groups. There was also a significant time effect in low frequency/high frequency ratio in both groups (p < 0.001). During daytime, the mean values in low frequency/high frequency ratio were lower in patients than in controls (p < 0.001). CONCLUSIONS: There is a shift in the autonomic balance in patients with inflammatory bowel disease in remission towards a condition of relative parasympathetic predominance, which, in the first place, reflects a sympathetic pullback. This imbalance has a circadian rhythm and it is more pronounced during the day.

QT dispersion in patients with mitral valve prolapse is related to the echocardiographic degree of the prolapse and mitral leaflet thickness.

BACKGROUND: Ventricular arrhythmias are common in patients with mitral valve prolapse (MVP). Previous studies have provided evidence that a higher degree of systolic mitral valve displacement and the presence of a thickened anterior mitral leaflet are related to an increased incidence of complex ventricular arrhythmias and risk of sudden death in these patients. The aim of our study was to investigate whether QT dispersion in patients with MVP is associated with the echocardiographic degree of the prolapse and mitral leaflet thickness. METHODS: QT and JT intervals and dispersions were measured in 89 patients with primary mitral valve prolapse (26 men and 63 women with mean age 39 +/- 14 years). All patients underwent a full echocardiographic examination and a scoring system was used to determine the degree of MVP. Anterior mitral leaflet thickness was also measured. Twenty-four hour Holter monitoring was used to assess ventricular arrhythmogenesis. RESULTS: According to their echocardiographic score. patients were divided into three groups (Group A. B and C) reflecting the different degrees of the prolapse. QT dispersion in patients with the highest degree of MVP, i.e. Group C was significantly greater (65 +/- 13 ms) than that of the other two groups (Group A: 38 +/- 14 ms, P<0.005 and Group B: 45 +/- 12 ms, P<0.005). Similar differences between groups were also found for JT dispersion. Multiple regression analysis revealed that among the demographic and clinical variables that were tested, only the echocardiographic degree of the prolapse and anterior mitral leaflet thickness were independently associated with QT dispersion. Holter monitoring showed that the incidence of complex ventricular arrhythmias was also higher in patients with more severe MVP. CONCLUSIONS: Our results indicate that QT and JT dispersions are related to the echocardiographic degree of MVP and mitral leaflet thickness. The echocardiographic assessment of the severity of the prolapse may help to identify a subgroup of patients at increased risk of life-threatening arrhythmias.

Electrocardiographic diagnosis of acute myocardial infarction in the presence of ventricular paced rhythm.

ST-segment deviation was recently described as the only ECG finding that was useful in the diagnosis of acute myocardial infarction during right ventricular pacing. This report shows that the same sign may also indicate the amount of myocardium in jeopardy and the coronary artery responsible.

The role of laser-induced fluorescence in myocardial tissue characterization: an experimental in vitro study.

OBJECTIVE: The fluorescence of tissue when stimulated by a laser beam is a well-known phenomenon. The resulting emission spectra depend on the biochemical and structural composition of the tissue. In this study, we examined the spectra of laser-induced fluorescence emitted by myocardial tissue. METHODS: We used an argon-ion laser to stimulate the myocardium of 20 intact sheep hearts. For each spectral emission, we calculated the intensity in specific regions in order to characterize the spectra and to reveal intercavitary and intracavitary morphologic differences. RESULTS: The statistical analysis showed significant differences in the emission spectra intensity between atria and ventricles. The intensity was higher in the atria than in the ventricles (p < 0.001). The atrial emission spectra were morphologically different from those of the ventricles. There was no difference in the intensity or morphology of emission spectra within each chamber. All measurements showed good reproducibility after a short period of time. CONCLUSIONS: Laser-induced fluorescence of myocardial tissue seems to have the characteristics necessary for tissue recognition. This might prove useful in identifying cardiomyopathies and transplant rejection, as well as for myocardial mapping, assisting electrophysiologists in discovering fibrotic arrhythmogenic foci.

Sotalol vs metoprolol for ventricular rate control in patients with chronic atrial fibrillation who have undergone digitalization: a single-blinded crossover study.

AIMS: To compare the effects of sotalol and metoprolol on heart rate, during isotonic (ITE) and isometric (IME) exercise and daily activities, in digitalized patients with chronic atrial fibrillation. METHODS AND RESULTS: The study had a randomized, single-blinded, crossover design. Twenty-three patients with chronic atrial fibrillation received placebo for 4 weeks, followed by a 4-week period of treatment with sotalol and metoprolol in random order. At the end of each period, the patients were assessed with 24-h ECG monitoring, a cardiopulmonary exercise test and a handgrip manoeuvre. Both agents produced a lower heart rate than placebo at rest and at all levels of isotonic exercise (P < 0.001) without affecting oxygen uptake. Sotalol produced a lower heart rate than metoprolol only at submaximal exercise (116 +/- 9 bpm for sotalol vs 125 +/- 11 bpm for metoprolol, P < 0.001). During isometric exercise, sotalol produced a lower maximum heart rate than did metoprolol (113 +/- 22 vs 129 +/- 18 bpm, respectively). Both agents produced a lower mean heart rate than placebo over 24 h (P < 0.001 for all), while sotalol produced a lower mean heart rate than metoprolol during the daytime (P < 0.01). CONCLUSION: Sotalol is a safe and effective agent for control of heart rate in digitalized patients with atrial fibrillation. Sotalol is superior to metoprolol at submaximal exercise, resulting in better rate control during daily activities.

Effects of asynchronous ventricular activation on myocardial adrenergic innervation in patients with permanent dual-chamber pacemakers; an I(123)-metaiodobenzylguanidine cardiac scintigraphic study.

AIMS: To evaluate myocardial sympathetic innervation abnormalities in patients with DDD pacemakers for complete heart block. METHODS: We studied 39 patients, chronically paced in DDD mode because of complete atrioventricular block. Twenty-three healthy individuals served as a control group. All patients underwent planar and single-photon emission computed tomography (SPECT) myocardial imaging 4 h after intravenous infusion of 185 MBq I(123)-MIBG. The heart to mediastinum ratio was calculated to quantify cardiac I(123)-MIBG accumulation, while the SPECT study was performed to investigate the regional distribution of adrenergic innervation. All patients underwent a SPECT thallium(201)myocardial study during the same week as the I(123)-MIBG study. RESULTS: The heart to mediastinum ratio was significantly smaller in paced patients than in the controls (P<0.001). 89.7% of paced patients had regional abnormalities of I(123)-MIBG uptake, mainly in the inferior (92.3%) and apical (38.5%) wall. 46.2% of paced patients had regional perfusion defects, also mainly in the inferior (46.2%) and apical (10.3%) wall. Neither the I(123)-MIBG abnormalities nor the perfusion defects were related to the duration of pacing. CONCLUSIONS: Stimulation from the apex of the right ventricle leads to regional disturbances of the adrenergic innervation of the left ventricular myocardium, as assessed by I(123)-MIBG activity.

Myocardial perfusion in patients with permanent ventricular pacing and normal coronary arteries.

OBJECTIVES: The purposes of this study were to test the specificity of dipyridamole myocardial perfusion scintigraphy in patients with permanent ventricular pacing (PVP) and to evaluate coronary blood flow and reserve in these patients. BACKGROUND: Permanent ventricular pacing is associated with exercise perfusion defects on myocardial scintigraphy in the absence of coronary artery disease (CAD). On the basis of studies in patients with left bundle brunch block, coronary vasodilation with dipyridamole has been proposed as an alternative to exercise testing for detecting CAD in paced patients, but this approach has never been tested. METHODS: Fourteen patients with a PVP and normal coronary arteries underwent stress thallium-201 scintigraphy and cardiac catheterization. In these patients and in eight control subjects, coronary flow velocities were measured in the left anterior descending coronary artery (LAD) and in the dominant coronary artery before and after adenosine administration. RESULTS: In the paced patients, coronary flow velocities in the LAD and in the dominant coronary artery were significantly lower than those in the control subjects. In addition, seven patients showed perfusion defects on dipyridamole thallium-201 single-photon emission computed tomography, with a specificity of 50% for this test. The defect-related artery in these patients had lower coronary flow reserve (2.6 +/- 0.5) as compared with those without perfusion defects (3.9 +/- 1.0, p < 0.05) or the control group (3.5 +/- 0.5, p < 0.05). CONCLUSIONS: Permanent ventricular pacing is associated with alterations in regional myocardial perfusion. Furthermore, abnormalities of microvascular flow, as indicated by reduced coronary flow reserve in the defect-related artery, are at least partially responsible for the uncertain specificity of dipyridamole myocardial perfusion scintigraphy.

Occult aorto-iliac disease in patients with symptomatic coronary artery disease.

BACKGROUND: Atherosclerosis may affect the entire cardiovascular system despite absence of symptoms. Early changes in the wall of the carotid artery have been related to a higher morbidity and mortality from coronary artery disease (CAD). This study was conducted to investigate the relationship between the presence of occult aorto-iliac disease (OAID) and certain risk factors with the severity of CAD. METHODS: Two hundred and eighty-four consecutive patients subjected to coronary angiography (CA) were studied. Additional images of the aorto-iliac arterial segment were taken. Patients with negative CA or symptomatic lower limb arterial disease (LLAD) were excluded from further analysis. In the remaining patients, the risk factors (age, smoking, diabetes mellitus, hypertension, hyperlipidemia and positive family history for atherosclerosis) and the severity of coronary artery disease (CAD) were analyzed in relation to the presence or absence of OAID. RESULTS: Twelve patients with impaired renal function were excluded from the study. Negative CA was found in 12% (32/272) and symptomatic LLAD was present in 14% (37/272). Eligible for further analysis were 203 patients with positive CA and no LLAD. A hundred and ten of them had a positive CA and the presence of OAID whereas the remaining 93 patients had only a positive CA. The patients with OAID had more severe CAD on CA (p=0.003). There was no difference between the two groups concerning age and gender. The most common risk factors in both groups were hypercholesterolemia and a positive family history but with a significantly higher prevalence in the patients with OAID (p=0.008 and p<0.001, respectively). CONCLUSIONS: The presence of OAID in coronary patients was associated with more severe CAD and with a significantly higher prevalence of hypercholesterolemia and positive family history for atherosclerosis. This subset of patients may represent those with more aggressive atherosclerosis.

Atrial and ventricular refractoriness in paced patients; circadian variation and its relationship to autonomic nervous system activity.

AIMS: To examine whether atrial and ventricular effective refractory periods exhibit circadian variation and whether the latter is correlated with fluctuations in autonomic nervous system tone. METHODS AND RESULTS: We studied 24 patients aged 67.1 +/- 9.6 years, 11 of whom were paced for complete heart block and 13 for sick sinus syndrome. Atrial and ventricular effective refractory periods were measured bihourly over a 24-h period, using the pacemaker programming capabilities, at basic cycle lengths of 600 ms and 500 ms. During the same time period we evaluated autonomic nervous system activity in patients paced for complete heart block, expressed by spectral power indexes in low frequency and high frequency areas of heart rate variability. Atrial and ventricular effective refractory periods showed significant circadian variation at both basic cycle lengths, with the highest values occurring between 22:00 and 06:00. At times, the atrial and ventricular effective refractory periods of the patients with sick sinus syndrome differed significantly from those with complete heart block. Furthermore, atrial and ventricular effective refractory periods in patients with complete heart block exhibited a strong negative correlation with the low frequency/high frequency ratio. CONCLUSION: Our data show that atrial and ventricular effective refractory periods in DDD paced patients exhibit significant circadian variation that is strongly correlated with variations in autonomic nervous system activity in patients with complete heart block.

Aortic atherosclerotic lesions in the thoracic aorta detected by multiplane transesophageal echocardiography as a predictor of coronary artery disease in elderly patients.

BACKGROUND: The presence of atherosclerotic lesions in the thoracic aorta by transesophageal echocardiography (TEE) appears to be a marker for the presence of significant coronary artery disease (CAD) in the general population. HYPOTHESIS: We investigated whether atherosclerotic lesions in the thoracic aorta, by multiplane TEE, could be a marker for CAD in elderly patients. METHODS: In all, 127 patients (67 men, 60 women, aged 68 +/- 13 years), underwent a TEE study with imaging of the thoracic aorta and cardiac catheterization with coronary angiography. The presence of a distinct, linear, or focal, highly echogenic mass protruding into the vessel lumen was the criterion for the diagnosis of atherosclerotic plaque. RESULTS: Atherosclerotic lesions were found in 30 of 36 patients (83.3%) with and in 20 of 91 (22%) without CAD. Of the 41 patients > or = 70 years, atherosclerotic lesions were detected in 14 of 17 (82.3%) with and in 13 of 24 patients (54%) without CAD. The sensitivity, specificity, and positive and negative predictive values in this group were 82.3, 46, 52, and 78.6%, respectively. Multivariate logistic regression analysis revealed that in patients aged > or = 70 years only advanced atherosclerotic lesions were independent predictors of significant CAD. However, the high negative predictive value of the method indicates that the absence of aortic plaque is a strong predictor of the absence of CAD. CONCLUSIONS: The presence of atherosclerotic lesions in the thoracic aorta is a strong predictor of CAD only in patients < 70 years old. However, the negative predictive value of the method is high for all patients regardless of age.

Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study.

OBJECTIVE: To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation. DESIGN: Prospective, randomised, single blind, placebo controlled study. SETTING: Tertiary cardiac referral centre. PATIENTS: 186 consecutive patients (97 men, 89 women; mean (SD) age, 63 (10) years) with recurrent, symptomatic atrial fibrillation. INTERVENTIONS: 65 patients were randomised to amiodarone, 61 to sotalol, and 60 to placebo. Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase. The sotalol dose was 160-480 mg daily, as tolerated. MAIN OUTCOME MEASURES: Recurrence of atrial fibrillation or side effects. RESULTS: In the amiodarone group, 31 of the 65 patients developed atrial fibrillation after an average of six months, while 15 (11 in sinus rhythm and four in atrial fibrillation) experienced significant side effects after an average of 16 months. In the sotalol group, relapse to atrial fibrillation occurred in 47 of the 61 patients after an average of eight months; three experienced side effects during the titration phase. In the placebo group, 53 of the 60 patients developed atrial fibrillation after an average of four months (p < 0.001 for amiodarone and sotalol v placebo; p < 0.001 for amiodarone v sotalol). CONCLUSIONS: Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation. Amiodarone is more effective but causes more side effects.

Left ventricular diastolic filling pattern predicts cardiopulmonary determinants of functional capacity in patients with congestive heart failure.

BACKGROUND: Abnormalities of diastolic function are an important determinant of exercise intolerance in patients with heart failure. However, the relation between left ventricular filling pattern and cardiopulmonary exercise performance has not been adequately studied. METHODS: Thirty-one patients with idiopathic (n = 14) or ischemic (n = 17) dilated cardiomyopathy, demonstrated by coronary angiography, and radionuclide ejection fraction 30.5% +/- 9% underwent cardiopulmonary exercise testing with a modified Naughton protocol and a complete echocardiographic study. Patients were subdivided into restrictive and nonrestrictive groups according to their Doppler transmitral flow pattern. Gas exchange data were measured during exercise testing. The relation of left ventricular filling pattern to cardiopulmonary parameters was assessed in both groups. RESULTS: Exercise duration was similar in the restrictive and nonrestrictive groups but significant differences were found in oxygen consumption (VO(2)) at peak exercise (14.3 +/- 2.4 vs 20.4 +/- 4.7 mL/kg per minute; P <.001) and at the anaerobic threshold (VO(2AT)) (13 +/- 2.2 vs 17.3 +/- 3 mL/kg per minute; P <.001). Simple linear regression analysis revealed that both peak VO(2) and VO(2AT) were significantly correlated with the ratio of peak early (E wave) to late (A wave) transmitral filling velocity, early filling deceleration time, atrial filling fraction, and A-wave velocity but not with left ventricular ejection fraction. Multivariate regression analysis gave only the peak A-wave velocity as an independent predictor for both peak VO(2) and VO(2AT). CONCLUSIONS: In patients with heart failure, abnormalities of diastolic function are the most important determinant of exercise intolerance. A restrictive transmitral flow pattern by Doppler echocardiography is a marker of diminished cardiopulmonary exercise performance in these patients.

Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study.

STUDY OBJECTIVES: To investigate the efficacy and safety of amiodarone administered as the drug of first choice in the conversion of atrial fibrillation, regardless of its duration. DESIGN: : Prospective, randomized, controlled clinical study. SETTING: : Tertiary cardiac referral center. PATIENTS: Two-hundred eight consecutive patients (102 men; mean [+/- SD] age, 65 +/- 10 years) with atrial fibrillation. INTERVENTIONS: One-hundred eight patients received amiodarone, and 100 patients received placebo treatment. Patients randomized to amiodarone received 300 mg IV for 1 h, and then 20 mg/kg for 24 h. They were also given 600 mg/d orally, divided into three doses, for 1 week, and thereafter 400 mg/d for 3 weeks. Patients randomized to placebo treatment received an identical amount of saline solution IV over 24 h, and oral placebo treatment for 1 month. MEASUREMENTS AND RESULTS: Baseline clinical characteristics were similar in the two groups. Conversion to sinus rhythm was achieved in 87 of 108 patients (80.05%) who received amiodarone, and in 40 of 100 patients (40%) in the placebo group (p < 0.0001). Statistical analysis showed that the duration of the arrhythmia and the size of the left atrium affected both the likelihood of conversion to sinus rhythm and the time to conversion in both groups. No side effects requiring discontinuation of treatment were observed in either group. CONCLUSIONS: Amiodarone appears to be safe and effective in the termination of atrial fibrillation. However, extreme cases with a large left atrium and long-lasting arrhythmia need long-term therapy.

Effect of pericardial pressure on human coronary circulation.

A 52-year-old patient underwent percutaneous balloon pericardiotomy because of rapid fluid accumulation. During the procedure, we calculated the amount of blood flow to the nondiseased left anterior descending coronary artery while pericardial pressure was gradually increased by the infusion of warmed normal saline solution. Coronary vasodilator reserve was assessed by intracoronary adenosine. With increasing pericardial pressure, there was a continuous decline in coronary blood flow, due to an increase in coronary vascular resistance, and an unaffected hyperemic response throughout. The maximal hyperemic flow was far less under increased pericardial pressure than at normal pressure, which implies an augmented susceptibility to myocardial ischemia.