Browsing by Author "Brink, Paul A."
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- ItemLong-term follow-up of R403W MYH7 and R92W TNNT2 HCM families : mutations determine left ventricular dimensions but not wall thickness during disease progression(Clinics Cardiv Publishing, 2007-06) Revera, Miriam; Van der Merwe, Lize; Heradien, Marshall; Goosen, Althea; Corfield, Valerie A.; Brink, Paul A.; Moolman-Smook, Johanna C.The clinical profile and prognosis of patients with hypertrophic cardiomyopathy, a primary cardiac muscle disease caused mostly by mutations in sarcomeric protein-encoding genes, have been linked to particular disease-causing mutations in the past. However, such associations are often based on cross-sectional observations, as longitudinal studies of the progression of the disease in genotypically defined patients are sparse. Most importantly, the relative contribution of age, gender and genetic cause to disease profile and progression has not yet been reported, and the question remains whether one or more of these factors could mask the effect of the other(s). Methods: We previously described cross-sectional family studies of two hypertrophic cardiomyopathy (HCM)-causing mutations, R92WTNNT2 and R403WMYH7, both associated with minimal hypertrophy, but with widely different life expectancies. We re-investigated 22 and 26 R92WTNNT2 and R403WMYH7 mutation carriers in these and additional South African R92WTNNT2 families after a mean 11.08 ± 2.79 years, and compared the influence of the two mutations, in the context of age and gender, on disease progression. Results: We demonstrated a positive correlation between age and interventricular septal thickness for both mutations, with more than a third of all mutation carriers developing clinically recognised hypertrophy only after the age of 35 years. This period of hypertrophically silent HCM also coincided with the years in which most sudden cardiac deaths occurred, particularly in male R92WTNNT2 carriers. Statistical analyses indicated that the particular mutation was the strongest determinant of left ventricular remodelling; particularly, LVESD increased and EF reduction was noted in the majority of R403WMYH7 carriers, which may require clinical follow-up over the longer term. Conclusions: Statistical modelling of follow-up data suggests that an interplay between unidentified, possibly genderassociated factors, and the causal mutation are the determinants of eventual cardiac function and survival, but not of the extent of hypertrophy, and emphasises the need for long-term follow-up even in individuals with apparently mild disease.
- ItemLow-Pass filtering approach via empirical mode decomposition improves short-scale entropy-based complexity estimation of QT interval variability in long QT syndrome type 1 patients(MDPI, 2014-09-05) Bari, Vlasta; Marchi, Andrea; De Maria, Beatrice; Girardengo, Giulia; George, Alfred L.; Brink, Paul A.; Cerutti, Sergio; Crotti, Lia; Schwartz, Peter J.; Porta, AlbertoEntropy-based complexity of cardiovascular variability at short time scales is largely dependent on the noise and/or action of neural circuits operating at high frequencies. This study proposes a technique for canceling fast variations from cardiovascular variability, thus limiting the effect of these overwhelming influences on entropy-based complexity. The low-pass filtering approach is based on the computation of the fastest intrinsic mode function via empirical mode decomposition (EMD) and its subtraction from the original variability. Sample entropy was exploited to estimate complexity. The procedure was applied to heart period (HP) and QT (interval from Q-wave onset to T-wave end) variability derived from 24-hour Holter recordings in 14 non-mutation carriers (NMCs) and 34 mutation carriers (MCs) subdivided into 11 asymptomatic MCs (AMCs) and 23 symptomatic MCs (SMCs). All individuals belonged to the same family developing long QT syndrome type 1 (LQT1) via KCNQ1-A341V mutation. We found that complexity indexes computed over EMD-filtered QT variability differentiated AMCs from NMCs and detected the effect of beta-blocker therapy, while complexity indexes calculated over EMD-filtered HP variability separated AMCs from SMCs. The EMD-based filtering method enhanced features of the cardiovascular control that otherwise would have remained hidden by the dominant presence of noise and/or fast physiological variations, thus improving classification in LQT1.
- ItemMolecular genetics of cardiomyopathy: changing times, shifting paradigms(Clinics Cardiv Publishing, 2003-06) Moolman-Smook, Johanna C.; Mayosi, Bongani M.; Brink, Paul A.; Corfield, Valerie A.Congestive heart failure is a major problem in developed and developing countries alike. Primary dysfunction of the heart muscle accounts for a significant proportion of patients with a non-ischaemic cause of heart failure. Application of genetic techniques has facilitated identification of some molecular causes of the inherited form of these diseases, dramatically increasing our understanding of the pathogenesis of these primary, previously termed ‘idiopathic’, cardiomyopathies over the last few decades. Knowledge of the different causes is beginning to coalesce into aetiological principles underlying the clinically distinguished cardiomyopathies. Hypertrophic cardiomyopathy (HCM) now appears to be a disease caused by a dysfunctional sarcomere, dilated cardiomyopathy (DCM), a disease of myocytic structural instability, and arrhythmogenic right ventricular cardiomyopathy, a disease of accelerated myocyte death. The aetiology of both HCM and DCM probably also involves cardiac energy imbalances, while additional factors modify the clinical expression in all cardiomyopathies. Even though our knowledge of the genetic aetiology of the cardiomyopathies is still incomplete, it already has relevant clinical significance. Elucidation of the full genetic contribution to the development and progression of the cardiomyopathies represents a new challenge in the study of these diseases, and will undoubtedly lead to new therapeutic approaches in the not-too-distant future.
- ItemMultiscale complexity analysis of the cardiac control identifies asymptomatic and symptomatic patients in long QT syndrome type 1(PLoS, 2014-04-04) Bari, Vlasta; Valencia, Jose F.; Vallverdu, Montserrat; Girardengo, Giulia; Marchi, Andrea; Bassani, Tito; Caminal, Pere; Cerutti, Sergio; George, Alfred L.; Brink, Paul A.; Crotti, Lia; Schwartz, Peter J.; Porta, AlbertoThe study assesses complexity of the cardiac control directed to the sinus node and to ventricles in long QT syndrome type 1 (LQT1) patients with KCNQ1-A341V mutation. Complexity was assessed via refined multiscale entropy (RMSE) computed over the beat-to-beat variability series of heart period (HP) and QT interval. HP and QT interval were approximated respectively as the temporal distance between two consecutive R-wave peaks and between the R-wave apex and T-wave end. Both measures were automatically taken from 24-hour electrocardiographic Holter traces recorded during daily activities in non mutation carriers (NMCs, n = 14) and mutation carriers (MCs, n = 34) belonging to a South African LQT1 founder population. The MC group was divided into asymptomatic (ASYMP, n = 11) and symptomatic (SYMP, n = 23) patients according to the symptom severity. Analyses were carried out during daytime (DAY, from 2PM to 6PM) and nighttime (NIGHT, from 12PM to 4AM) off and on beta-adrenergic blockade (BBoff and BBon). We found that the complexity of the HP variability at short time scale was under vagal control, being significantly increased during NIGHT and BBon both in ASYMP and SYMP groups, while the complexity of both HP and QT variability at long time scales was under sympathetic control, being smaller during NIGHT and BBon in SYMP subjects. Complexity indexes at long time scales in ASYMP individuals were smaller than those in SYMP ones regardless of therapy (i.e. BBoff or BBon), thus suggesting that a reduced complexity of the sympathetic regulation is protective in ASYMP individuals. RMSE analysis of HP and QT interval variability derived from routine 24-hour electrocardiographic Holter recordings might provide additional insights into the physiology of the cardiac control and might be fruitfully exploited to improve risk stratification in LQT1 population.
- ItemA refined multiscale self-entropy approach for the assessment of cardiac control complexity : application to long QT syndrome type 1 patients(MDPI, 2015-11-13) Bari, Vlasta; Girardengo, Giulia; Marchi, Andrea; De Maria, Beatrice; Brink, Paul A.; Crotti, Lia; Schwartz, Peter J.; Porta, AlbertoENGLISH ABSTRACT: The study proposes the contemporaneous assessment of conditional entropy (CE) and self-entropy (sE), being the two terms of the Shannon entropy (ShE) decomposition, as a function of the time scale via refined multiscale CE (RMSCE) and sE (RMSsE) with the aim at gaining insight into cardiac control in long QT syndrome type 1 (LQT1) patients featuring the KCNQ1-A341V mutation. CE was estimated via the corrected CE (CCE) and sE as the difference between the ShE and CCE. RMSCE and RMSsE were computed over the beat-to-beat series of heart period (HP) and QT interval derived from 24-hour Holter electrocardiographic recordings during daytime (DAY) and nighttime (NIGHT). LQT1 patients were subdivided into asymptomatic and symptomatic mutation carriers (AMCs and SMCs) according to the severity of symptoms and contrasted with non-mutation carriers (NMCs). We found that RMSCE and RMSsE carry non-redundant information, separate experimental conditions (i.e., DAY and NIGHT) within a given group and distinguish groups (i.e., NMC, AMC and SMC) assigned the experimental condition. Findings stress the importance of the joint evaluation of RMSCE and RMSsE over HP and QT variabilities to typify the state of the autonomic function and contribute to clarify differences between AMCs and SMCs.
- ItemRenal denervation : mechanisms and clinical aspects(African Association of Nephrology, 2020) Heradien, Marshall J.; Van Der Bijl, Pieter; Brink, Paul A.ENGLISH ABSTRACT: Hypertension is a global health issue of paramount importance, which has not spared the African continent where an unacceptably high prevalence of uncontrolled blood pressure prevails among its population. Renal denervation (RD) represents an invasive management option for resistant hypertension, acting via several different physiological pathways – mostly predicated on modification of the renal autonomic nervous system. The evidence base for RD has recently been expanded by three randomised, sham-controlled clinical trials, which demonstrated significant blood pressure reductions under a variety of clinical conditions. In this review, both the renal mechanisms underlying RD, as well as the clinical aspects of its application to hypertension, are discussed.