Showing papers by "Marek Malik published in 2014"

Risk stratification for sudden cardiac death: current status and challenges for the future

Abstract: Sudden cardiac death (SCD) remains a daunting problem. It is a major public health issue for several reasons: from its prevalence (20% of total mortality in the industrialized world) to the devastating psycho-social impact on society and on the families of victims often still in their prime, and it represents a challenge for medicine, and especially for cardiology. This text summarizes the discussions and opinions of a group of investigators with a long-standing interest in this field. We addressed the occurrence of SCD in individuals apparently healthy, in patients with heart disease and mild or severe cardiac dysfunction, and in those with genetically based arrhythmic diseases. Recognizing the need for more accurate registries of the global and regional distribution of SCD in these different categories, we focused on the assessment of risk for SCD in these four groups, looking at the significance of alterations in cardiac function, of signs of electrical instability identified by ECG abnormalities or by autonomic tests, and of the progressive impact of genetic screening. Special attention was given to the identification of areas of research more or less likely to provide useful information, and thereby more or less suitable for the investment of time and of research funds.

Risk of sudden cardiac death in chronic kidney disease

Abstract: The review discusses the epidemiology and the possible underlying mechanisms of sudden cardiac death (SCD) in chronic kidney disease (CKD), and highlights the unmet clinical need for noninvasive risk stratification strategies in these patients. Although renal dysfunction shares common risk factors and often coexists with atherosclerotic cardiovascular disease, the presence of renal impairment increases the risk of arrhythmic complications to an extent that cannot be explained by the severity of the atherosclerotic process. Renal impairment is an independent risk factor for SCD from the early stages of CKD; the risk increases as renal function declines and reaches very high levels in patients with end-stage renal disease on dialysis. Autonomic imbalance, uremic cardiomyopathy, and electrolyte disturbances likely play a role in increasing the arrhythmic risk and can be potential targets for treatment. Cardioverter defibrillator treatment could be offered as lifesaving treatment in selected patients, although selection strategies for this treatment mode are presently problematic in dialyzed patients. The review also examines the current experience with risk stratification tools in renal patients and suggests that noninvasive electrophysiological testing during dialysis may be of clinical value as it provides the necessary standardized environment for reproducible measurements for risk stratification purposes.

Electrocardiographic Data Quality in Thorough QT/QTc Studies

Abstract: Background Most drugs with systemic bioavailability have to undergo a thorough QT (TQT) study, which includes a pharmacologic positive control. A set of QTc-quality tests was recently proposed with the possible aim of removing the need for a positive control.

Postextrasystolic Blood Pressure Potentiation Predicts Poor Outcome of Cardiac Patients

Abstract: Background Postextrasystolic blood pressure potentiation (PESP), the pulse wave augmentation after an extrasystolic beat, is typically enhanced in heart failure (HF) patients. This study prospectively tested the association of PESP and mortality in cardiac patients. Methods and Results Consecutive patients (n=941; mean age, 61 years; 19% female) presenting with acute myocardial infarction were enrolled between May 2000 and March 2005 and followed up until August 2010. The main study outcome was 5-year all-cause mortality. Patients underwent noninvasive 30-minute recordings of ECG and continuous blood pressure. PESP presence was based on the ratio between the first postectopic pulse wave amplitude and the mean of the subsequent 9 pulse wave amplitudes. A ratio above 1 was prospectively defined as PESP present. Ventricular premature complexes (VPCs) suitable for PESP quantification were present in recordings of 220 patients. PESP was present in 62 of these patients. Patients without suitable VPCs were classified as PESP absent. During the follow-up, 72 patients died. Among the 220 patients in whom PESP was measurable, 27 died. Under univariable analysis, PESP was a significant predictor of death ( P P P P P P P =0.001) were independently associated with outcome. The combination of PESP presence and LVEF ≤35% identified a subgroup of patients with a particularly high mortality of 46.7%. Separate validation reproduced the finding in an unrelated population of 146 HF patients. Conclusions PESP, which likely reflects abnormalities of myocardial calcium cycling, predicts the mortality risk in postinfarction patients. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00196274.

Impact of Electrocardiographic Data Quality on Moxifloxacin Response in Thorough QT/QTc Studies

Abstract: Thorough QT studies are typically conducted for drugs with systemic bioavailability and include a positive control, typically moxifloxacin, with a well-described QTc effect. This study tested two hypotheses: that (i) re-measuring the QT intervals based on electrocardiogram (ECG) pattern similarity improves the moxifloxacin time profile, and (ii) that study conduct influences the ability to detect a typical moxifloxacin time profile. ECGs from 65 studies with available moxifloxacin plasma concentrations were obtained, including four studies with an unexpected moxifloxacin response. Residual error of a concentration–QT model was evaluated before and after re-measuring the QT interval based on ECG pattern similarity. Intra-replicate heart rate differences were calculated using the original heart rate measurements and the 10-s average heart rates. Similarity re-measurements reduced the residual error of the model (before vs. after of 8.43 ± 2.00 vs. 7.55 ± 1.86 ms; p < 0.001). For both original and averaged 10-s heart rate, intra-replicate heart rate differences were significantly lower (p < 0.001) in studies with the expected response than in those with an unexpected time profile. The pattern similarity measurement methodology reduces the residual error of the model, which influences the time profile of the moxifloxacin response. Accuracy of study conduct, represented by intra-replicate heart rate differences, separated studies with and without the expected moxifloxacin time profile.

Parathyroid Hormone and Heart Rate Variability in Haemodialysis Patients

Abstract: Background: Depressed heart rate variability (HRV) reflects abnormal cardiac autonomic regulation and has been linked with increased cardiovascular risk and sudde

Riskstratificationforsuddencardiacdeath:current status and challenges for the future †

Abstract: Cardiovascular Research Center, Maastricht, The Netherlands; IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy; Medtronic Bakken Research Center, Maastricht, The Netherlands; Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Division of Cardiology, Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Division of Clinical Electrophysiology, Department of Cardiology, J. W. Goethe University, Frankfurt, Germany; Medical Research Center Oulu, University and University Hospital of Oulu, Oulu, Finland; Department of Medicine I, University Hospital, Ludwig-Maximilians-University, Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany; Department of Cardiology, Fondazione ‘Salvatore Maugeri’, IRCCS, Istituto Scientifico di Montescano, Montescano, Pavia, Italy; St Paul’s Cardiac Electrophysiology, University of London and Imperial College, London, UK; Cardiovascular Division, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA; Thoraxcentrum, Erasmus MC, Cardiology, Rotterdam, The Netherlands; University of Gothenburg, Gothenburg, Sweden; Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; University Medical Center Groningen, Groningen, The Netherlands; Department of Clinical and Experimental Cardiology, Academic Medical Center, Amsterdam, The Netherlands; and Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia

ICH E14-compatible holter bin method and its equivalence to individual heart rate correction in the assessment of drug-induced QT changes.

Abstract: E14-Compatible Holter Bin and QTcI Introduction The Holter bin method evaluates QT interval changes in the presence of heart rate changes without correcting the QT interval. However, the method does not allow time-matched comparisons, thus contradicting available guidance and good practice. We report a modification of the methods that allows time-matched comparisons without any heart rate correction. Methods and Results The modified Holter bin method (a) finds matching baseline heart rates for each QT reading on treatment and (b) calculates ΔQT values from the QT intervals on baseline and on treatment that match in heart rates. The difference between ΔQT values on active treatment and placebo provides the ΔΔQT value. The method was compared with the individual correction method in the data of the mirabegron thorough QT study in which supratherapeutic doses of this β3-adrenoceptor agonist led to substantial heart rate changes. The modified Holter bin method reproduced closely the results obtained with the individual heart rate correction. At all time points of the mirabegron study, the differences between the mean ΔΔQT values by the Holter bin method and the individual correction method were below 1 millisecond. Compared to the individual correction, the Holter bin method led to slight increases in the standard deviations of ΔΔQT values, but these were on average below 0.25 millisecond. Conclusions The Holter bin methodology can be modified to make it compatible with the available guidance and with good practice of clinical investigations. The results obtained with the modified Holter bin method are practically the same as with individualized heart rate corrected QT intervals. The close correspondence between the 2 methods demonstrates that the present possibilities of comparing QT interval duration in the presence of experiment-induced heart rate differences are not influenced by methodological artifacts.

Sex-Dependent Association between Heart Rate Variability and Pulse Pressure in Haemodialysis Patients

Abstract: Aims: Increased pulse pressure (PP) is associated with increased cardiovascular mortality in haemodialysis (HD) patients. Autonomic imbalance is common in HD patients and predisposes to sudden cardiac death, but its relationship to PP is unknown. We investigated the relationship between cardiac autonomic modulation assessed by heart rate variability (HRV) and PP in HD patients. Methods: Continuous electrocardiograms recorded during HD sessions were repeated 5 times at 2-week intervals in stable HD patients. The high-frequency (HF) and low-frequency (LF) components and the LF/HF ratio of HRV were calculated during the first and last hour of the recordings. These values and the corresponding systolic blood pressure (SBP), diastolic blood pressure (DBP) and PP measurements were averaged in repeated recordings of each patient. Results: Seventy-six patients were included in the final analysis (aged 61 ± 15 years, 32% females, 37% diabetics). In male patients, LF/HF correlated inversely with pre- and post-HD PP (r = -0.369, p = 0.007 and r = -0.546, p = 0.000, respectively), positively with pre- and post-HD DBP (r = 0.358, p = 0.009 and r = 0.306, p = 0.028, respectively) and inversely with post-HD SBP (r = -0.350, p = 0.011). In female patients, LF/HF correlated positively with post-HD SBP (r = 0.422, p = 0.040). Conclusion: We observed an association between PP and HRV in male HD patients. Sex differences may be important for cardiac risk assessment.

Circadian pattern and sex differences of QT/RR and T-peak-to-end/RR curvatures and slopes in chronic heart failure patients

Abstract: Increased QT/RR and T pe /RR slopes have been shown to be independent predictors of sudden cardiac death (SCD) when analyzed over a 24-hour ECG recording. The circadian influence on the QT/RR slope is well-known but it has never been tested on the T pe /RR slope. This work studied the inter-individual variability of the curvature and slope of QT/RR and T pe /RR, as well as their circadian pattern in women and men. Holter ECG recordings of 385 patients with chronic heart failure (CHF) from the “MUSIC” database were analyzed. ECGs were delineated using a single-lead procedure over the first principal component lead derived to emphasize the T-wave. RR, QT and T pe series were obtained and for each patient, a regression equation was fitted, where λ is the QT/RR or T pe /RR curvature, and Δ is the slope of the regression pattern evaluated at the medium RR value. The median (IQR) slope was Δ QT = 0.194 (0.11), and Δ Tpe = 0.018 (0.04). The median (IQR) curvature was γ QT = 0.993 (0.17) and γ Tpe = 1.000 (0.04), respectively. The circadian pattern modulated the QT/RR and T pe /RR curvature and slope, with statistically significant differences between day and night for QT/RR slope. No statistically significant differences in gender were found in this study. According to the results in this work, the time of the day should be considered when using QT/RR slope for SCD risk prediction, but the T pe /RR slope is less sensitive to the circadian pattern.