Meral Kayikcioglu

Effect of Fluid Management Guided by Bioimpedance Spectroscopy on Cardiovascular Parameters in Hemodialysis Patients: A Randomized Controlled Trial

BACKGROUND Fluid overload is the main determinant of hypertension and left ventricular hypertrophy in hemodialysis patients. However, assessment of fluid overload can be difficult in clinical practice. We investigated whether objective measurement of fluid overload with bioimpedance spectroscopy is helpful in optimizing fluid status. STUDY DESIGN Prospective, randomized, and controlled study. SETTING & PARTICIPANTS 156 hemodialysis patients from 2 centers were randomly assigned to 2 groups. INTERVENTION Dry weight was assessed by routine clinical practice and fluid overload was assessed by bioimpedance spectroscopy in both groups. In the intervention group (n = 78), fluid overload information was provided to treating physicians and used to adjust fluid removal during dialysis. In the control group (n = 78), fluid overload information was not provided to treating physicians and fluid removal during dialysis was adjusted according to usual clinical practice. OUTCOMES The primary outcome was regression of left ventricular mass index during a 1-year follow-up. Improvement in blood pressure and left atrial volume were the main secondary outcomes. Changes in arterial stiffness parameters were additional outcomes. MEASUREMENTS Fluid overload was assessed twice monthly in the intervention group and every 3 months in the control group before the mid- or end-week hemodialysis session. Echocardiography, 48-hour ambulatory blood pressure measurement, and pulse wave analysis were performed at baseline and 12 months. RESULTS Baseline fluid overload parameters in the intervention and control groups were 1.45 ± 1.11 (SD) and 1.44 ± 1.12 L, respectively (P = 0.7). Time-averaged fluid overload values significantly decreased in the intervention group (mean difference, -0.5 ± 0.8 L), but not in the control group (mean difference, 0.1 ± 1.2 L), and the mean difference between groups was -0.5 L (95% CI, -0.8 to -0.2; P = 0.001). Left ventricular mass index regressed from 131 ± 36 to 116 ± 29 g/m(2) (P < 0.001) in the intervention group, but not in the control group (121 ± 35 to 120 ± 30 g/m(2); P = 0.9); mean difference between groups was -10.2 g/m(2) (95% CI, -19.2 to -1.17 g/m(2); P = 0.04). In addition, values for left atrial volume index, blood pressure, and arterial stiffness parameters decreased in the intervention group, but not in the control group. LIMITATIONS Ambulatory blood pressure data were not available for all patients. CONCLUSIONS Assessment of fluid overload with bioimpedance spectroscopy provides better management of fluid status, leading to regression of left ventricular mass index, decrease in blood pressure, and improvement in arterial stiffness.

Benefits of statin treatment in cardiac syndrome-X

AIMS The pathophysiological mechanism in cardiac syndrome-X (anginal chest pain, positive exercise test, and angiographically normal coronary arteries) has been suggested as an impairment in normal endothelial function of the coronary microvasculature, resulting in inadequate flow reserve. The aim of this study was to determine whether statins with proven beneficial effects on endothelium, have any effect on endothelial functions and exercise induced ischaemia in cardiac syndrome-X. METHODS AND RESULTS Study population consisted of prospectively enrolled 40 patients with cardiac syndrome-X. Patients with left ventricular hypertrophy, hypertension, diabetes mellitus, and LDL levels >/=160 mg/dl were excluded. Half of the patients received pravastatin (40 mg/day) for 3 months irrespective of their lipid values, according to a single-blind, randomized, placebo-controlled design. Endothelial functions were assessed with high-resolution vascular ultrasound, which measured the brachial artery flow mediated dilatation (FMD). Lipid measurements, symptom limited exercise tests and vascular ultrasound images were obtained before and at the end of 3 months. After the treatment, FMD improved significantly in pravastatin group. Exercise duration, and time to 1mm-ST depression were significantly prolonged after statin therapy. Ischaemic symptoms and ECG findings during exercise test disappeared completely in 5 (26%) patients in the statin group. However, there were no significant changes in FMD and exercise parameters in placebo group. CONCLUSIONS Statin therapy resulted in beneficial effects on both exercise induced ischaemia and FMD in cardiac syndrome-X. The mechanism of this beneficial effect is probably the result of improvement in endothelial functions.

Comparison of 4- and 8-h dialysis sessions in thrice-weekly in-centre haemodialysis A prospective, case-controlled study

BACKGROUND Longer dialysis sessions may improve outcome in haemodialysis (HD) patients. We compared the clinical and laboratory outcomes of 8- and 4-h thrice-weekly HD. METHODS Two-hundred and forty-seven HD patients who agreed to participate in a thrice-weekly 8-h in-centre nocturnal HD (NHD) treatment and 247 age-, sex-, diabetes status- and HD duration-matched control cases to 4-h conventional HD (CHD) were enrolled in this prospective controlled study. Echocardiography and psychometric measurements were performed at baseline and at the 12th month. The primary outcome was 1-year overall mortality. RESULTS Overall mortality rates were 1.77 (NHD) and 6.23 (CHD) per 100 patient-years (P = 0.01) during a mean 11.3 ± 4.7 months of follow-up. NHD treatment was associated with a 72% risk reduction for overall mortality compared to the CHD treatment (hazard ratio = 0.28, 95% confidence interval 0.09-0.85, P = 0.02). Hospitalization rate was lower in the NHD arm. Post-HD body weight and serum albumin levels increased in the NHD group. Use of antihypertensive medications and erythropoietin declined in the NHD group. In the NHD group, left atrium and left ventricular end-diastolic diameters decreased and left ventricular mass index regressed. Both use of phosphate binders and serum phosphate level decreased in the NHD group. Cognitive functions improved in the NHD group, and quality of life scores deteriorated in the CHD group. CONCLUSIONS Eight-hour thrice-weekly in-centre NHD provides morbidity and possibly mortality benefits compared to conventional 4-h HD.

Effect of Obesity on Left Ventricular Structure and Myocardial Systolic Function: Assesment by Tissue Doppler Imaging and Strain/Strain Rate Imaging

Background: Obesity is associated with heart failure, cardiovascular morbitity, and mortality. A direct effect of weight on left ventricle (LV) structure and myocardial function is not well‐established. Aim: The aim of our study is to determine the effect of obesity on LV morphology and systolic function by using LV standard Doppler echocardiographic indices, myocardial Doppler imaging and strain/strain rate imaging indices. Methods: We studied 33 obese and 34 age, sex‐adjusted control subjects who had no other pathological conditions. Standard transthorasic Doppler echocardiographical measurements, reconstructed spectral pulsed wave tissue Doppler velocities, strain and strain rate imaging of six different myocardial regions were obtained. Peak systolic velocity (SR), peak systolic strain (Î), peak systolic strain rate (SR) for each region and as a global systolic longitidunal LV function mean of peak systolic strain of six myocardial regions (glsca) were compared. Results: Age, body surface area, blood pressure, and heart rate were comparable between the two groups. Obese subjects had significantly increased LV end‐diastolic volume, septal wall thickness, left atrial diameter, and decreased transmitral early to late diastolic velocity ratio. In obese subjects, reconstructed spectral pulsed‐wave tissue Doppler analysis showed significantly decreased basal lateral peak systoic (Sm) velocity (6.68 ± 1.89 vs. 8.08 ± 2.50, P < 0.05), mid lateral Sm (5.01 ± 2.17 vs. 6.78 ± 3.22, P < 0.05). Differences in regional strain rate (mid septal SR, 1.45 ± 0.23 vs. 1.63 ± 0.18, P < 0.05), regional strain (basal septum Î, 19.13 ± 3.83 vs. 22.09 ± 4.60, P < 0.05; mid‐septum Î, 18.03 ± 2.91 vs. 20.25 ± 4.77, P < 0.05; radial Î, 27.50 ± 7.32 vs. 35.53 ± 9.48, P < 0.05), and global strain (glsca, 19.38 ± 1.34 vs. 21.24 ± 2.82, P < 0.05) were identified between obese and the referent subjects. Conclusions: Obesity is associated with morphologic alterations in left ventricle and left atrium and subclinical changes in left ventricle systolic function which can be detected by strain and strain rate imaging even without overt heart disease.

Demonstration of ventricular myocardial extensions into the pulmonary artery and aorta beyond the ventriculo-arterial junction.

Background: A subgroup of outflow tract (OT) ventricular tachycardias (VT) originate from the aortic sinuses or the main stem of the pulmonary artery. The anatomic substrate for these tachycardias is unknown. The aim of this study was to investigate the presence of ventricular myocardial extensions (VME) into the pulmonary artery (PA) and aorta (Ao) beyond the ventriculo‐arterial junction (VAJ) and determine the anatomical and histological characteristics of these muscle extensions.

Tachycardia-induced cardiomyopathy in patients with idiopathic ventricular arrhythmias: the incidence, clinical and electrophysiologic characteristics, and the predictors.

Idiopathic Ventricular Arrhythmias and Cardiomyopathy. Introduction: Idiopathic ventricular arrhythmias in the form of monomorphic premature ventricular contractions (PVC) and/or ventricular tachycardia (VT) can cause tachycardia‐induced cardiomyopathy (TICMP). The aim of this study was to determine the incidence, clinical and electrophysiologic characteristics, and the predictors of TICMP in patients with idiopathic ventricular arrhythmias.

Familial hypercholesterolaemia: A global call to arms.

Familial Hypercholesterolaemia (FH) is the commonest autosomal co-dominantly inherited condition affecting man. It is caused by mutation in one of three genes, encoding the low-density lipoprotein (LDL) receptor, or the gene for apolipoprotein B (which is the major protein component of the LDL particle), or in the gene coding for PCSK9 (which is involved in the degradation of the LDL-receptor during its cellular recycling). These mutations result in impaired LDL metabolism, leading to life-long elevations in LDL-cholesterol (LDL-C) and development of premature atherosclerotic cardiovascular disease (ASCVD) [1], [2] and [3]. If left untreated, the relative risk of premature coronary artery disease is significantly higher in heterozygous patients than unaffected individuals, with most untreated homozygotes developing ASCVD before the age of 20 and generally not surviving past 30 years [2], [3], [4] and [5]. Although early detection and treatment with statins and other LDL-C lowering therapies can improve survival, FH remains widely underdiagnosed and undertreated [1], thereby representing a major global public health challenge.

The effect of statin therapy on ventricular late potentials in acute myocardial infarction

AIMS To determine whether early statin therapy in acute myocardial infarction has any effect on ventricular late potentials which are considered as a noninvasive tool for evaluation of arrhythmogenic substrate. METHODS AND RESULTS Study population consisted of prospectively enrolled 72 patients presenting with acute myocardial infarction (<6 h). Thirty-four of the patients were randomized to pravastatin (40 mg/day) on admission irrespective of lipid levels. All patients received thrombolytic therapy. Signal-averaged ECG recordings were obtained serially prior to thrombolytic therapy, 48 h after and 10 days later. Late potentials were defined as positive if signal-averaged ECG met at least two of Gomes criteria: filtered total QRS duration >114 ms, root mean square voltage of the last 40 ms of the QRS <20 mV, or the duration of the terminal low (<40 mV) amplitude signals >38 ms. Changes observed in signal-averaged ECG recordings after thrombolysis were evaluated statistically with regard to statin usage. There were no significant differences between the clinical characteristics of the two randomized groups. There was a significant decrease in the rates of late potentials between the first and third signal-averaged ECG recordings after thrombolytic therapy in pravastatin group. Pravastatin group also had lower incidence of ventricular arrhythmias compared with control group (26 vs. 63%, P=0.021). The in-hospital cardiovascular event rates were also lower in statin group. CONCLUSION Early use of pravastatin reduces the incidence of late potentials following thrombolytic therapy in acute myocardial infarction. Statin therapy also seems to be reducing the incidence of in-hospital ventricular arrhythmias. These beneficial effects of statins might be explained through prevention of new myocardial ischemic episodes due to early plaque stabilization or regulation of endothelial and platelet functions.

PON1 activities and oxidative markers of LDL in patients with angiographically proven coronary artery disease

BACKGROUND There is growing evidence that ox-LDL plays an important role during the atherosclerosis process and PON1 can significantly inhibit generation of lipid peroxidation during LDL oxidation and thus play a role in the in vivo protection by HDL against atherosclerosis. METHODS Twenty-four healthy volunteers and one-hundred and one patients were taken into study, sixty-eight patients had coronary artery disease which was confirmed by coronary angiography. Serum PON1, erythrocyte superoxide dismutase and catalase activities, oxidative markers of LDL were determined along with the routine biochemical parameters in all groups. RESULTS The indicators of oxidative stress were higher in the patients compared with the controls. No statistically significant difference in any of parameters were observed between the patients who had obstruction with different degrees except for erythrocyte TBARS [24.5 nM/g Hb in patients with one vessel disease (VD) (n=22), 29.6 nM/g Hb in patients with two VD (n=26) and 33.5 nM/g Hb in patients with three VD (n=20)]. Basal and stimulated diene levels were higher in patients who had more diseased vessels than those who had less. CONCLUSION The increase in erythrocyte TBARS and CRP levels with the severity of disease supports the reports that showed the inflammatory and oxidative nature of atherosclerosis. In the light of the fact that the well-known classical risk factors for atherosclerosis are closely associated with increased oxidative stress, we propose that the elevation in TBARS levels might be a more marked indicator for the degree of atherosclerosis than the insufficiency in antioxidant enzymes such as SOD and PON1.

Early use of pravastatin in patients with acute myocardial infarction undergoing coronary angioplasty.

AIM To determine whether statin therapy initiated early in acute myocardial infarction together with thrombolytic therapy in patients with acute myocardial infarction results in clinical benefit through early plaque stabilization. METHODS AND RESULTS The study population consisted of 77 patients who underwent coronary balloon angioplasty of the infarct-related artery during the first month of acute myocardial infarction. These patients belonged to the cohort of the Pravastatin Turkish Trial (PTT). Forty of them were assigned randomly to have immediate pravastatin (40 mg/day) therapy adjunctive to thrombolytic therapy regardless of serum lipid levels and received statin treatment throughout the study. Lipid levels were determined immediately after admission and before angioplasty and at the end of 6 months. Patients were re-evaluated clinically and angiographically for cardiovascular adverse events and restenosis after a 6-month follow-up period. The baseline angiographic and clinical characteristics of the two groups were similar. The incidence of angina was significantly lower in the pravastatin group (30.0%, 12 patients) compared to the control group (59.5%, 22 patients) (p = 0.018). The cumulative major adverse cardiac events in the pravastatin group were significantly lower when compared to the control group (32.5% vs. 75.6%, p = 0.0001). CONCLUSIONS Early initiation of pravastatin therapy immediately after an acute myocardial infarction significantly decreased the frequency of major cardiac adverse events. Such early potential clinical benefits further strengthen the rationale for starting statin treatment as soon as possible after acute coronary events particularly in patients in whom invasive intervention is planned.Aim — To determine whether statin therapy initiated early in acute myocardial infarction together with thrombolytic therapy in patients with acute myocardial infarction results in clinical benefit through early plaque stabilization. Methods and results — The study population consisted of 77 patients who underwent coronary balloon angioplasty of the infarct-related artery during the first month of acute myocardial infarction. These patients belonged to the cohort of the Pravastatin Turkish Trial (PTT). Forty of them were assigned randomly to have immediate pravastatin (40 mg/day) therapy adjunctive to thrombolytic therapy regardless of serum lipid levels and received statin treatment throughout the study. Lipid levels were determined immediately after admission and before angioplasty and at the end of 6 months. Patients were re-evaluated clinically and angiographically for cardiovascular adverse events and restenosis after a 6-month follow-up period.The baseline angiographic and clinical characteristics of the two groups were similar.The incidence of angina was significantly lower in the pravastatin group (30.0%, 12 patients) compared to the control group (59.5%, 22 patients) (p = 0.018).The cumulative major adverse cardiac events in the pravastatin group were significantly lower when compared to the control group (32.5% vs. 75.6%, p = 0.0001). Conclusions — Early initiation of pravastatin therapy immediately after an acute myocardial infarction significantly decreased the frequency of major cardiac adverse events. Such early potential clinical benefits further strengthen the rationale for starting statin treatment as soon as possible after acute coronary events particularly in patients in whom invasive intervention is planned.