Michael Kyriakidis

Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation

BACKGROUND The prolongation of intraatrial and interatrial conduction time and the inhomogeneous propagation of sinus impulses are well known electrophysiologic characteristics in patients with paroxysmal atrial fibrillation (PAF). METHODS To search for possible electrocardiographic markers that could serve as predictors of idiopathic PAF, we measured the maximum P-wave duration (P maximum) and the difference between the maximum and the minimum P-wave duration (P dispersion) from the 12-lead surface electrocardiogram of 60 patients with a history of idiopathic PAF and 40 age-matched healthy control subjects. RESULTS P maximum and P dispersion were found to be significantly higher in patients with idiopathic PAF than in control subjects. A P maximum value of 110 msec and a P dispersion value of 40 msec separated patients from control subjects, with a sensitivity of 88% and 83% and a specificity of 75% and 85%, respectively. CONCLUSIONS P maximum and P dispersion are simple electrocardiographic markers that could be used for the prediction of idiopathic PAF.

Left Atrial Mechanical Function in the Healthy Elderly: New Insights From a Combined Assessment of Changes in Atrial Volume and Transmitral Flow Velocity

To assess left atrial mechanical function in the elderly, 35 old (age > 70 years) and 18 sex-matched young (age < 50 years) healthy subjects were studied. Transmitral flow velocities were recorded with pulsed Doppler echocardiography. Left atrial volumes were measured echocardiographically at mitral valve opening (maximal) and closure (minimal) and at onset of atrial systole (P wave of the electrocardiogram) according to the biplane area-length method. Left atrial passive emptying was assessed with the passive emptying volume (maximal-volume at onset of atrial systole) and fraction (passive emptying volume/maximal). Left atrial active emptying was assessed with the active emptying volume (volume at onset of atrial systole-minimal) and fraction (active emptying volume/volume at onset of atrial systole) and with left atrial ejection force = 0.5.blood density.volume at onset of atrial systole.active emptying fraction.(A velocity)2/A integral. Left atrial volumes were greater in old compared with young subjects (maximal: 31 +/- 10 cm3/m2 vs 24 +/- 8 cm3/m2, p = 0.02; at onset of atrial systole: 23 +/- 8 cm3/m2 vs 15 +/- 5 cm3/m2, p = 0.0002; minimal: 13 +/- 5 cm3/m2 vs 9 +/- 4 cm3/m2, p = 0.001). Passive emptying volume and fraction were lower (7.8 +/- 1.7 cm3/m2 vs 9.2 +/- 3.2 cm3/m2 [p = 0.04] and 26.4% +/- 9.8% vs 37.9% +/- 11.2% [p = 0.003], respectively), whereas atrial ejection force and active emptying volume were greater in old compared with young subjects (6.8 +/- 3.3 kdynes/m2 vs 4.2 +/- 2.8 kdynes/m2 [p = 0.007] and 9.2 +/- 4.1 cm3/m2 vs 5.7 +/- 2.9 cm3/m2 [p = 0.002], respectively). The active emptying fraction was similar in the two groups (39.7% +/- 11% vs 38.4% +/- 13%; difference not significant). Thus advanced age is associated with depressed left atrial passive emptying function and increased left atrial volume. Left atrial dilation contributes to an increase in atrial ejection force and the amount of blood ejected during left atrial systole and may represent an important compensatory mechanism in this age population.

Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: A prospective, parallel-group, randomized, controlled study with 36-month follow-up†

Anthracyclines have contributed to a marked increase in survival in different types of cancer [1,2]. Unfortunately, they are associated with dose-dependent cardiotoxicity and heart failure (HF) [3–8]. Change to a weekly dosage schedule with slow infusions has been tested, a strategy that requires more frequent hospital visits and increased storage resources[7,9]. Liposomal anthracycline formulations with reduced drug exposure and lower plasma concentrations may still be cardiotoxic at higher cumulative doses [10]. Beta-blockers and angiotensin converting enzyme(ACE) inhibitors have been shown to reduce anthracycline-induced cardiotoxicity,but have not been tested in long-term prospective, randomized,controlled studies with well defined cardiotoxicity criteria and careful cardiac function monitoring [11–16]. We investigated doxorubicin-induced clinical or subclinical cardiotoxicity in lymphoma patients after concomitant prophylactic therapy with metoprolol or enalapril or no concomitant treatment. We examined whether cardiotoxicity was related to the treatment or any other variable. We found that HF was less frequent under concomitant treatment than no treatment, especially in the metoprolol group, but the differences were not significant. No association was found between the presence of cardiotoxicity and concomitant treatment or other variable apart of age that had a significant impact. The marginal benefit seen with metoprolol should be investigated further.

Fibrinolytic/hemostatic variables in arterial hypertension: response to treatment with irbesartan or atenolol

Essential hypertension is often accompanied by abnormalities of the coagulation/fibrinolytic system, predisposing to a procoagulant state. The aim of the present study was to compare the effects of atenolol (beta1-blocker agent) and irbesartan (angiotensin II type 1 receptor antagonist) on plasma levels of hemostatic/fibrinolytic and endothelial function markers in a cohort of previously untreated hypertensives. Fifty-four patients were randomly assigned to atenolol 25 to 150 mg (26 patients) or irbesartan 75 to 300 mg (28 patients). The plasma levels of plasminogen activator inhibitor-1 antigen, thrombomodulin, tissue factor pathway inhibitor antigen, fibrinogen, and factor XII were determined before and after 6 months of therapy. Age, gender distribution, body mass index, lipid profile, and baseline values of the measured markers were similar in both groups. Baseline values for systolic and diastolic blood pressure, as well as the reduction after treatment, were not significantly different between the two groups. Treatment with irbesartan was associated with a significant decrease in the levels of all the parameters. Similar findings were observed in the atenolol group, except for factor XII and tissue factor pathway inhibitor levels, which were not significantly decreased in this group. The reduction, however, of fibrinogen, plasminogen activator inhibitor-1, and thrombomodulin was significantly greater in the irbesartan than in the atenolol group. In conclusion, the results indicated that, despite an equally controlled blood pressure, 6-month therapy with irbesartan was associated with a more favorable modification of hemostatic/fibrinolytic status than atenolol.

P Wave Dispersion: A Valuable Electrocardiographic Marker for the Prediction of Paroxysmal Lone Atrial Fibrillation

Background: The prolongation of atrial conduction time and the inhomogeneous propagation of sinus impulses are well known electrophysiological characteristics in patients with paroxysmal atrial fibrillation.

Relation between changes in blood flow of the contralateral coronary artery and the angiographic extent and function of recruitable collateral vessels arising from this artery during balloon coronary occlusion

OBJECTIVES The purpose of this study was to investigate changes in the magnitude of blood flow through the contralateral coronary artery in relation to the development of recruitable collateral vessels arising from this artery to supply a balloon-occluded coronary vessel. BACKGROUND Recruitable collateral vessels have been shown to emerge suddenly to supply an occluded coronary artery, but their physiologic effect cannot always be predicted angiographically. METHODS Twenty-four patients were studied during four successive balloon dilations for single left anterior descending coronary artery stenosis. Before and during each balloon occlusion, blood flow in the proximal right coronary artery was measured by intracoronary Doppler flow velocimetry and quantitative coronary angiography. Estimates of chest pain and ST segment elevation were also obtained. RESULTS Fourteen patients developed angiographically visible recruitable collateral vessels (high grade in 6 [group III], low grade in 8 [group II]), whereas 10 patients (group I) did not. During the four successive balloon occlusions, the right coronary artery flow showed transient reproducible increases in group III (first occlusion 66.4 +/- 36.8%, fourth occlusion 64 +/- 23.9%, all p = 0.036), progressive increases in group II (from first occlusion 17.9 +/- 26.6% [p = 0.08] to fourth occlusion 60.4 +/- 35.9% [p = 0.014]) and no significant changes in group I. Between the first and the fourth occlusion, the severity of chest pain and the magnitude of ST segment elevation declined significantly in group II but did not change in groups I and III. CONCLUSIONS During balloon coronary artery occlusion, the transient appearance of recruitable collateral vessels is associated with a transient increase in blood flow through the collateral donor artery. This increase in coronary flow appears to reflect collateral function better than the angiographic assessment, especially in patients with poor collateral vessel recruitment.

Intermittent milrinone effect on long-term hemodynamic profile in patients with severe congestive heart failure

BACKGROUND Many reports have suggested that intermittent milrinone infusion (IMI) may be efficacious in the management of end-stage congestive heart failure (CHF), but this issue has not been clearly established. The aim of our study was to investigate the effectiveness of IMI in hospitalized patients with severe CHF undergoing long-term (4 months) post-therapy hemodynamics. METHODS Thirty-six patients (28 men, 8 women; mean age 65.6 +/- 8.2 years old) with end-stage CHF (New York Heart Association functional class III-IV) were studied. Each patient received 4 cycles of 3 days per week with milrinone therapy. Each cycle consisted of a loading dose of 50 microgram/kg over 10 minutes and a 72-hour continuous infusion of 0.5 microgram/kg per minute under close monitoring. Hemodynamic changes were determined during the first and fourth cycles and on 4-month reexamination. Full clinical examination was performed at the beginning (baseline) and at the end of 4-month follow-up. RESULTS The values of mean pulmonary arterial pressure, pulmonary capillary wedge pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased (P <.01) and cardiac index was significantly increased (P <.01) compared with the baseline of first and fourth cycles. At the end of the 4-month follow-up period all hemodynamic parameters sustained the improvement. Clinical examination at the end of the 4-month period showed that 21 (58.3%) of 36 patients remained in New York Heart Association functional class IV but were hemodynamically improved, 13 (36.2%) of 36 were in functional class III, and 2 (5.5%) of 36 were in class II-III. There were no deaths during the study period. CONCLUSIONS Our findings suggest that IMI in hospitalized patients with severe CHF is hemodynamically efficacious. This beneficial hemodynamic effect is maintained for at least 4 months after discontinuation of therapy. These promising results raised the possibility that given appropriately, milrinone may have an important role in end-stage CHF.

Elevated plasma immunoreactive leptin levels preexist in healthy offspring of patients with essential hypertension.

BACKGROUND Plasma leptin levels and plasma insulin levels have been found to be elevated in patients with essential hypertension (EH) and have been suggested to be components of the metabolic syndrome. Increased heart rate (HR) may predict the development of EH in normal or borderline-hypertensive individuals. The aim of our study was to test the hypothesis that elevated plasma leptin and insulin levels as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP) and increased resting HR preexist in the healthy offspring of patients with EH. METHODS AND RESULTS Twenty-six (12 male, 14 female) healthy offspring of hypertensive patients, mean age 16 +/- 2.5 years and body mass index (BMI) of 21.5 +/- 2.8 kg/m(2) (group A), and 30 (14 male, 16 female) healthy offspring of normotensive patients, mean age 17 +/- 2.3 years and BMI of 21.9 +/- 2.4 kg/m(2) (group B), were studied. (The two groups were matched for sex, age, and BMI). Mean SBP, DBP, resting HR, plasma leptin, and plasma insulin levels (radioimmunoassay method) were determined in the whole study population. Mean SBP, DBP, and resting HR were significantly higher in group A than in group B (120 +/- 12 vs 112 +/- 9.5 mm Hg, 77 +/- 9 vs 72 +/- 7 mm Hg, 79 +/- 8 vs 75 +/- 5 beats/min, P <.01, P <.05, and P <.05, respectively). Plasma leptin and insulin levels were significantly higher in group A than in group B (9 +/- 5.06 vs 5.6 +/- 2.5 ng/mL and 20.11 +/- 11.3 vs 14.8 +/- 5.2 microIU/mL, P <.01 and P <.05, respectively). CONCLUSIONS Our findings support the hypothesis that hyperleptinemia, hyperinsulinemia, and elevated blood pressure and resting HR preexist in the healthy offspring of patients with EH.

Changes in Phasic Coronary Blood Flow Velocity Profile in Relation to Changes in Hemodynamic Parameters During Stress in Patients With Aortic Valve Stenosis

BACKGROUND Alterations in phasic coronary flow profile have been demonstrated at rest in patients with aortic valve stenosis (AVS) but have never been studied under conditions of hemodynamic stress. METHODS AND RESULTS Thirty-four patients with significant pure AVS (21 with exertional symptoms [group 1], 13 asymptomatic [group 2]) and 9 control subjects (group 3), all with normal coronary arteries, were studied successively at rest, during rapid atrial pacing, and after dobutamine infusion (5 to 30 micrograms.kg-1.min-1 i.v.) by proximal left anterior descending (LAD) intracoronary Doppler flow velocimetry concomitant with hemodynamic measurements. Systolic retrograde coronary flow velocity (CFV) was recorded only in patients with AVS, and its resting peak value was positively correlated with peak aortic pressure gradient (APG) (r = .63, P < .001). In group 1, there was lower aortic valve area (0.58 +/- 0.10 versus 0.75 +/- 0.08 cm2, P < .001) and higher resting APG and peak systolic retrograde CFV than in group 2, and also higher resting peak diastolic and mean CFV than in groups 2 and 3. In the two AVS groups, there were no changes from rest in APG and retrograde CFV at peak pacing rate; however, these parameters increased concomitantly and significantly at peak dobutamine stress. The ratio of the resting systolic to diastolic CFV curve area was inversely correlated with mean APG (r = -.54, P < .001); it was significantly lower in group 1 than in groups 2 and 3 (0.19 +/- 0.07 versus 0.29 +/- 0.10 and 0.30 +/- 0.04, respectively, both P < .005) and increased at peak pacing (group 1, to 0.29 +/- 0.14; group 2, to 0.39 +/- 0.12; group 3, to 0.38 +/- 0.07; all P < .001). At peak dobutamine stress, it decreased in patients with AVS (group 1, to 0.05 +/- 0.05; group 2, to 0.08 +/- 0.03; both P < .001) but did not change in group 3 (0.25 +/- 0.05). From rest to peak dobutamine stress, in both AVS groups there was increased retrograde systolic (group 1, 441 +/- 483%; group 2, 681 +/- 356%; both P < .001), decreased total systolic (group 1, -66 +/- 25%, P < .001; group 2, -19 +/- 24%; P = NS), and increased diastolic (group 1, 33.4 +/- 31.7%; group 2, 197.7 +/- 105.1%; both P < .001; group 1 versus group 2, P < .001) CFV curve area. In contrast, group 3 showed comparable increases in both systolic (143.5 +/- 44.4%) and diastolic (197.1 +/- 75.2%) CFV area (both P < .001). The stress-induced increases in the mean CFV and blood flow exceeded or were comparable with the concomitant increases in the estimated myocardial metabolic demand in groups 2 and 3 but were significantly lower in group 1. CONCLUSIONS Stress-induced changes in LAD phasic CFV profile differ significantly between patients with and without AVS. In AVS, these changes are closely related to the concomitant stress-induced changes in hemodynamic parameters.

Cardiac Arrhythmias in Chronic Renal Failure

25 patients undergoing regular haemodialysis for chronic renal failure underwent Holter ECG monitoring for a continuous 48-hour period covering dialysis and the intermediate period of everyday activit