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Background: The main objective of this study was to determine whether myocardial strain and myocardial work are altered in hypertension and whether the strain is independent of hypertension-induced left ventricular hypertrophy. Methods: Two systematic literature searches were conducted using Medline and EMBASE through to June 30, 2022. In the first, search terms left ventricular strain or speckle tracking AND hypertension and left ventricular hypertrophy were used in conjunction with Boolean operators to identify articles reporting left ventricular strain in patients with hypertension. In the second, the terms Global cardiac or myocardial work AND hypertension were used to identify articles. Publication bias was assessed by examination of funnel plots and calculation of the Failsafe N and Duval and Tweedie's Trim and fill. The results were presented as Forrest plots. Results: Global longitudinal strain (GLS) was significantly lower in patients with hypertension compared to those without hypertension with a mean difference of 2.0 ± 0.1 (standard error of mean(SEM)) in the fixed effect model. Global circumferential strain (GCS) was significantly lower in hypertension. The mean difference between the hypertensive and non-hypertensive groups was 1.37 ± 0.17. Global radial strain (GRS) was significantly (p < 0.05) greater in hypertension. However, this difference was significant in only 3 and of borderline significance in 3 of 14 studies where GRS was measured. The mean difference between the hypertensive and non-hypertensive groups was 1.5 ± 0.5 using the fixed effects model. There was a significant relationship between GLS and GCS as well as between GCS and GRS but no significant relationship between GLS and GRS. There was no significant difference in left ventricular ejection fraction (LVEF) between the hypertension and no hypertension groups. There was no significant relationship between LVEF and either GLS or GCS but a significant negative correlation was found between LVEF and GRS. GLS was further reduced in persons with hypertension and left ventricular hypertrophy (LVH) compared to hypertension without LVH. In contrast, there were no or minimal differences in GCS and GRS for individuals with hypertension and LVH compared to those without LVH. Global myocardial work index (GWI) and Global constructive work (GCW) were significantly greater in patients with hypertension compared to controls. Global wasted work (GWW) indicated significantly less wasted work in controls compared to hypertension. In contrast, Global work efficiency (GWE) was significantly lower in hypertension compared to the control. Conclusions: There was a significant reduction in GLS and GCS in hypertension while GRS was increased. The reduction in GLS in hypertension was not dependent on the presence of LVH. GLS was further reduced in persons with hypertension when LVH was present. In contrast, there were no or minimal differences in GCS and GRS for individuals with LVH compared to those without LVH. GLS was independent of left ventricle (LV) ejection fraction. GWI, GCW and GWW were greater in hypertension while GWE was lower in hypertension compared to controls. These data support the contention that GLS and indices of global work are early markers of hypertensive heart disease.
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PURPOSE OF REVIEW: The purpose of this review was to synthesize the evidence on non-traditional biomarkers from proteomic and metabolomic studies that may distinguish heart failure (HF) with preserved ejection fraction (HFpEF) from heart failure with reduced ejection fraction (HFrEF) and non-HF. RECENT FINDINGS: Understanding the pathophysiology of HFpEF continues to be challenging. A number of inflammatory and metabolic biomarkers that have recently been suggested to be involved include C-reactive protein (CRP), interleukin-6 (IL-6), trimethylamine-N-oxide (TMAO), syndecan-1 (SDC-1), nitric oxide (NO), and tumor necrosis factor receptor-1 (TNFR-1). A systematic search was conducted using Medline, EMBASE, and Web of Science with search terms such as "HFpEF," "metabolomics," and "proteomics," and a meta-analysis was conducted. The results demonstrate significantly higher levels of TMAO, CRP, SDC-1, and IL-6 in HFpEF compared to controls without HF and significantly higher levels of TMAO and CRP in HFrEF compared to controls. The results further suggest that HFpEF might be distinguishable from HFrEF based on higher levels of IL-6 and lower levels of SDC-1 and NO. These data may reflect pathophysiological differences between HFpEF and HFrEF.
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Proteína C-Reactiva , Insuficiencia Cardíaca , Humanos , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Interleucina-6 , Péptido Natriurético Encefálico/metabolismo , Óxido Nítrico , Pronóstico , Proteómica , Volumen Sistólico/fisiología , Sindecano-1RESUMEN
An 87-year-old man with a history of transcatheter aortic valve replacement, pulmonary hypertension, diastolic dysfunction with preserved systolic function, and myelofibrosis had a 12-lead ECG showed a prolonged QT interval of 508 ms with heart-rate correction placing it in the 99th percentile of the population. Reduction in the dose of furosemide and calcium supplementation increased serum calcium and shortened the QT interval. This case provides an opportunity to examine newer concepts for the understanding of the mechanisms by which hypocalcemia might induce QT prolongation. Hypocalcemia likely produces corrected QT interval prolongation primarily through a calcium-dependent inactivation (CDI) mechanism on the L-type calcium channel (LTCC). Lower extracellular calcium leads to a decreased ICaL, subsequently causing intracellular calcium to take longer to reach the critical threshold to induce CDI of the LTCC. The resulting prolonged repolarization of the ventricular myocyte can lead to early after-depolarizations and ensuing life-threatening ventricular arrhythmias. Genetic polymorphisms in Ca2+-binding protein calmodulin which can prolong QT, underscore the role for disturbances of intracellular myocardial calcium handling in arrhythmogenesis. Hypocalcemia is an under-recognized cause of QT prolongation and should be taken into careful consideration in patients presenting with incidental findings of a prolonged QT interval.
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Hipocalcemia , Síndrome de QT Prolongado , Anciano de 80 o más Años , Arritmias Cardíacas , Electrocardiografía/métodos , Frecuencia Cardíaca , Humanos , Hipocalcemia/complicaciones , MasculinoRESUMEN
The objective was to evaluate the diagnosis of heart failure with preserved ejection fraction (HFpEF) using the biomarkers, growth differentiation factor-15 (GDF-15), galectin-3 (Gal-3), and soluble ST2 (sST2), and to determine whether they can differentiate HFpEF from heart failure with reduced ejection fraction (HFrEF). Medline and Embase databases were searched with the terms diastolic heart failure or HFpEF, biomarkers, and diagnosis, limited to years 2000 to 2019. There were significantly and consistently higher levels of GDF-15, Gal-3, and sST2 in HFpEF compared to no heart failure. Importantly, the magnitude of the increase in GDF-15 or Gal-3 and possibly sST2,correlated with a greater degree of diastolic dysfunction. There were no significant differences between GDF-15, Gal-3, and sST2 in patients with HFpEF vs HFrEF. In the studies assessing these three biomarkers, BNP was significantly greater in heart failure than controls. Furthermore, BNP was significantly higher in HFrEF compared to HFpEF. The diagnostic utility of GDF-15, Gal-3, and sST2 compared to BNP was evaluated by comparing ROC curves. The data supports the contention that to distinguish HFpEF from HFrEF, an index is needed that incorporates GDF-15, Gal-3, or sST2 as well as BNP. The three biomarkers GDF-15, Gal-3, or sST2 can identify patients with HFpEF compared to individuals without heart failure but cannot differentiate HFpEF from HFrEF. BNP is higher in and is better at differentiating HFrEF from HFpEF. Indices that incorporate GDF-15, Gal-3, or sST2 as well as BNP show promise in differentiating HFpEF from HFrEF.
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Biomarcadores/sangre , Insuficiencia Cardíaca , Proteínas Sanguíneas , Galectina 3/sangre , Galectinas , Factor 15 de Diferenciación de Crecimiento/sangre , Insuficiencia Cardíaca/diagnóstico , Humanos , Proteína 1 Similar al Receptor de Interleucina-1/sangre , Volumen SistólicoRESUMEN
BACKGROUND: Whether the QT interval displays circadian rhythm after heart rate correction is unresolved and the relationship of QT interval to heart rate variability (HRV) is uncertain. OBJECTIVES: To test the hypothesis that there is a circadian rhythm to QT interval and HRV and determine the relationship between QTc and HRV. METHODS: The hourly average ECG data from 24-h ECGs were examined in individuals (50 without medications and 9 on beta blockers only) with no evidence of coronary artery disease or structural heart disease. The QT duration of normal QRS complexes from a series of 30-s windows was measured. The presence of circadian rhythm was tested by the data analytic approach of goodness of fit to a cosine function. RESULTS: QT interval with and without heart rate correction showed a circadian rhythm for five heart rate adjustment formulae except for the Bazett formula. HRV also showed circadian rhythm but with different acrophages and nadirs depending on the HRV component. There were significant (p < 0.05) positive correlations of QTc with pNN50 rms-SD and SDNN and significant (p < 0.05) negative correlations with SDANN and Tri. The beta blocker group did not generally show circadian rhythm for QT interval or HRV. CONCLUSION: QT, after heart rate adjustment, and HRV have circadian rhythmicity. There are significant correlations between QT interval and HRV indices. Circadian rhythm was blunted with beta blockers. The data are consistent with the concept of a predominance of parasympathetic activity to increase QTc and sympathetic activity to shorten QTc, even after 'correction' of the QT interval for heart rate.
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Ritmo Circadiano , Electrocardiografía , Antagonistas Adrenérgicos beta , Corazón , Frecuencia Cardíaca , HumanosRESUMEN
OBJECTIVE: To determine the effect of exercise and heart rate on the early repolarization (ER) pattern; focusing on the new criteria for identification of ER. METHODS: The ECG measurements on the terminal QRS notch or slur found in early repolarization were quantitated before, during and after exercise; specifically: (i) the amplitude at the onset of the notch (Jo) (ii) the amplitude at the peak of the notch (Jp), (iii) the amplitude at the end of the notch (Jt), (iv) the duration from Jo to Jp (D1) and (v) the duration from Jo to Jt (D2). RESULTS: All individuals (Nâ¯=â¯21) fulfilling the criteria for ER showed complete disappearance of ER after 3â¯min of exercise. After 5â¯min of recovery, 29% of subjects showed return of the ER. The return of ER was dynamic with QRS notching of varying extent, without ST elevation, being evident first. The relationship between heart rate and ER was significant and nonlinear, best fit by a second-order polynomial, suggesting that changes in heart rate with exercise was a factor influencing the presence of the ER pattern and the parameters that define ER. CONCLUSION: Each of the newly defined characteristics of the ER are modified and eventually disappear with exercise. The return of ER was dynamic with QRS notching of varying extent being evident first. The changes correlated with variations in heart rate, during both exercise and recovery, suggesting, in part, a role in the underlying mechanism of ER.
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Arritmias Cardíacas , Electrocardiografía , Ejercicio Físico , Frecuencia Cardíaca , HumanosRESUMEN
OBJECTIVE: The objective of the study was to determine the optimal formula to estimate QT interval adjusting for QRS prolongation during right ventricular (RV) pacing. METHODS: This observational study included individuals (nâ¯=â¯43) with a newly implanted permanent ventricular pacemaker, who had a narrow QRS complex before pacemaker insertion. QT interval with RV pacing was related to QT interval before pacemaker implantation. The validation cohort (nâ¯=â¯442) had permanent RV pacing in DDD mode. RESULTS: A new QTc formula was derived utilizing the constants from the relationship between the spline heart rate QT correction (QTcRBK) before and after pacing; specifically, QTcRBKPACEDâ¯=â¯QTcRBKâ¯×â¯0.86. The JT interval from paced complexes was highly heart rate (HR) dependent and was not accurate for QT assessment. Previous, QTc formula for paced complexes were not highly correlated with QT before pacing unless a robust HR correction is added. Formulae subtracting a fixed amount from QTcPACED markedly overestimated QTc before pacing. CONCLUSION: We proposed a new, simple formula for QT estimation in RV pacing. JT interval in paced complexes is highly HR dependent and is not accurate for QT assessment. The new spline approach for HR correction for the QT, once incorporated into some previously proposed formulae, blunts HR dependency and improves prediction of QT before pacing. QTcRBKPACED*0.86 and QTcRBKPACED - (QRS*0.5) demonstrated the best balance of relatively strong correlation to QTc before pacing and accurate QTc prolongation identification. Abnormal QT for QTcRBKPACED*0.86 as defined by the 97.5th and 99th percentile are 469 and 479â¯ms respectively.
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Síndrome de QT Prolongado , Marcapaso Artificial , Estimulación Cardíaca Artificial , Electrocardiografía , Frecuencia Cardíaca , Ventrículos Cardíacos , HumanosRESUMEN
Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-ß1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1ß, ß-MHC, ECE1, MMP14, AGT, and MMP9. In contrast, GLUT4, VEGF, eNOS, HIF-1α, and PGC1-α were significantly decreased in expression. The top biological process clusters identified in Database for Annotation, Visualization and Integrated Discovery, ToppGene, and PANTHER were collagen metabolic process, cellular ion homeostasis, regulation of cell migration, and response to decreased oxygen levels. These data suggest refocusing understanding of the pathophysiology of HFpEF to pathways involved in collagen metabolism, cell migration likely for inflammatory cells, and responses to decreased oxygen levels. Abbreviations Inducible nitric oxide synthase (INOS), neutrophil cytosolic factor 1 (p47phox), adrenomedullin (ADM), atrial natriuretic peptide (ANP), osteopontin (OPN/SPP1), angiotensin converting enzyme (ACE), monocyte chemotactic protein 1 (MCP-1), cytochrome b-245 beta polypeptide (gp91phox), intercellular adhesion molecule 1 (ICAM-1), transforming growth factor beta 1 (TGF-ß1), connective tissue growth factor (CTGF), endothelin-1 (ET-1), cytochrome B-245, alpha polypeptide (p22phox), endothelin receptor type B (ETB/EDNRB), brain natriuretic peptide (BNP), endothelin receptor type A (ETA/EDNRA), matrix metallopeptidase 13 (MMP13), type I collagen (Col1a1), matrix metallopeptidase 2 (MMP2), TIMP metallopeptidase inhibitor 1 (TIMP1), Type III collagen (Col3a1), interleukin 1 beta (IL-1ß), beta myocin heavy chain (ß-MHC), endothelin converting enzyme 1 (ECE1) matrix metallopeptidase 14 (MMP14), angiotensinogen (AGT), angiotensin II receptor Type 1 (AT1R), cytochrome C oxidase I (COX1), fms-like tyrosine kinase 1 (FLT1), TIMP metallopeptidase inhibitor 2 (TIMP2), phospholamban (PLN), vascular cell adhesion molecule 1 (VCAM1), extracellular matrix (ECM).
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Expresión Génica , Insuficiencia Cardíaca/fisiopatología , Hipertensión/fisiopatología , Animales , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/genética , Hipertensión/genética , Masculino , Ratas , Ratas Endogámicas Dahl , Volumen SistólicoRESUMEN
The objective is to investigate the relationship between arterial stiffness measured by arterial tonometry and echocardiographic indices of diastolic dysfunction-a basis for the diagnosis of heart failure with preserved ejection fraction (HFpEF). OvidSP Medline, Embase and PubMed were systematically searched. Eligible articles correlated arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV), carotid-femoral pulse wave velocity (cfPWV), augmentation index (AIx) or cardio-ankle vascular index (CAVI) with indices of diastolic dysfunction, E/A ratio, peak early mitral annular velocity (e') and E/e' ratio. Correlation coefficients were determined using a random-effects model. Twenty-seven studies with 6,626 patients were included. baPWV was significantly correlated with E/A ratio (r = -0.434, 95 % CI -0.387 to -0.479), e' (r = -0.499, 95 % CI -0.448 to -0.548) and E/e' ratio (r = 0.372, 95 % CI 0.251-0.481). cfPWV was significantly correlated with E/A ratio (r = -0.391, 95 % CI -0.304 to -0.470) and E/e' ratio (r = 0.210, 95 % CI 0.300-0.116), but not e'. AIx was significantly correlated with E/A ratio (r = -0.356, 95 % CI -0.255 to -0.450), e' (r = -0.313, 95 % CI -0.195 to -0.423) and E/e' ratio (r = 0.321, 95 % CI 0.250-0.388). CAVI was significantly correlated with E/A ratio (r = -0.405, CI -0.324 to -0.481), e' (r = -0.449, 95 % CI -0.340 to -0.630), but not E/e'. baPWV showed significantly greater correlation with diastolic dysfunction compared to most other tonometric techniques. Arterial stiffness measured by arterial tonometry is an indicator of diastolic dysfunction with baPWV demonstrated the most consistent and strongest association. These data suggest a refocusing on the impact of arterial stiffness on the left ventricle as a potential causative factor leading to HFpEF.
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Arterias/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Volumen Sistólico , Rigidez Vascular , Velocidad del Flujo Sanguíneo , Ecocardiografía Doppler , Humanos , Función Ventricular IzquierdaRESUMEN
BACKGROUND: It is believed that the balance of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs), in the aorta, play a critical role in aneurysm formation. The objective of this study was to perform a meta-analysis of studies reporting protein expression of MMPs and TIMPs in the ascending aorta of thoracic aortic aneurysms (TAA) cases and to examine this expression in persons with TAA and bicuspid aortic valves (BAV). METHODS: OvidSP Medline and EMbase were systematically searched for studies that were: human ascending TAA cases with measurement of MMP or TIMP protein expression in the aorta and a control group. A similar search was conducted for BAV compared to those with a normal or trileaflet aortic valve (TAV). RESULTS: Eight studies fulfilled the inclusion criteria. There was a significant increase in MMP-9 and no change in MMP-2, in the aorta from persons with TAA (N = 106) compared to control (N = 30). There was also a highly significant reduction in TIMP-1 and TIMP-2 in TAA (N = 93) compared to control (N = 24) resulting in a MMP-9 to TIMP-1 or TIMP-2 ratio over 3.5 fold greater than controls. There was a highly significant increase in MMP-2 but not MMP-9 in TAA with BAV (N = 112) compared to TAV (N = 53). There was a significant reduction for TIMP-1 in BAV compared to TAV but no change in TIMP-2, TIMP-3 or TIMP-4. CONCLUSIONS: These data suggest that MMP may be implicated in the pathogenesis of TAA and there is a differential expression with MMP-9 increased and TIMP-1 and -2 reduced in the most common forms of TAA. MMP-2 is increased and only TIMP-1 decreased in TAA with BAV compared to TAV.
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Aorta/enzimología , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/enzimología , Válvula Aórtica/anomalías , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/enzimología , Metaloproteinasa 2 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/análisis , Inhibidores Tisulares de Metaloproteinasas/análisis , Válvula Aórtica/enzimología , Enfermedad de la Válvula Aórtica Bicúspide , Humanos , PronósticoRESUMEN
While the link between aging and mortality from dementia is widely appreciated, the mechanism is not clear. The objective of this study was to determine whether there is a direct relationship between Alzheimer dementia (AD) and the QT interval, because the latter has been related to cardiac mortality. A systematic review and meta-analysis were conducted after a Medline and EMBASE search using terms "Alzheimer disease or Dementia AND QT interval, QT dispersion or cardiac repolarization." Four studies with control groups were identified. There were significant differences in QT interval between individuals with AD vs individuals without dementia (controls) (odds ratio (OR)1.665 [random effects model] and 1.879 [fixed effect model]) (p < 0.001). There were significant differences in QT interval between individuals with AD vs individuals with mild cognitive impairment (MCI) (OR 1.760 [random effects] and 1.810 [fixed effect]) (p < 0.001). A significant (p <0.001) correlation exists between the QTc and the Mini-Mental State Exam (MMSE), a test of cognitive function. Two studies examined QT variability (the difference between the longest and shortest QT interval on a 12 lead ECG); the OR for QT variability AD vs MCI was 3.858 [random effects model] and 3.712 [fixed effects model] (p < 0.001). When compared to the control group, the OR for QT dispersion in AD was 6.358 [random effects model] or 5.143 ( P< 0.001) [fixed effects model]. A qualitative analysis of the data raised questions about paucity of data defining the nature of the control groups, the pathophysiologic mechanism, and the uniform use of a poor QT heart rate correction factor. The longer QT in AD, greater QT variability in AD, and the direct relationship between QT interval and AD severity supports a brain-heart connection in AD that might be fundamental to aging-induced AD and mortality. Issues with defining the control group, limited number of studies, conflicting data in population studies, and the lack of a strong electrophysiological basis underscore the need for additional research in this field.
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Background: Left ventricular hypertrophy (LVH) is a powerful predictor of future cardiovascular events. Objectives: The objectives of this study were to conduct a systematic review of machine learning (ML) algorithms for the identification of LVH and compare them with respect to the classical features of test sensitivity, specificity, accuracy, ROC and the traditional ECG criteria for LVH. Methods: A search string was constructed with the operators "left ventricular hypertrophy, electrocardiogram" AND machine learning; then, Medline and PubMed were systematically searched. Results: There were 14 studies that examined the detection of LVH utilizing the ECG and utilized at least one ML approach. ML approaches encompassed support vector machines, logistic regression, Random Forest, GLMNet, Gradient Boosting Machine, XGBoost, AdaBoost, ensemble neural networks, convolutional neural networks, deep neural networks and a back-propagation neural network. Sensitivity ranged from 0.29 to 0.966 and specificity ranged from 0.53 to 0.99. A comparison with the classical ECG criteria for LVH was performed in nine studies. ML algorithms were universally more sensitive than the Cornell voltage, Cornell product, Sokolow-Lyons or Romhilt-Estes criteria. However, none of the ML algorithms had meaningfully better specificity, and four were worse. Many of the ML algorithms included a large number of clinical (age, sex, height, weight), laboratory and detailed ECG waveform data (P, QRS and T wave), making them difficult to utilize in a clinical screening situation. Conclusions: There are over a dozen different ML algorithms for the detection of LVH on a 12-lead ECG that use various ECG signal analyses and/or the inclusion of clinical and laboratory variables. Most improved in terms of sensitivity, but most also failed to outperform specificity compared to the classic ECG criteria. ML algorithms should be compared or tested on the same (standard) database.
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BACKGROUND: Understanding the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF) continues to be challenging. Several inflammatory and metabolic biomarkers have recently been suggested to be involved in HFpEF. OBJECTIVES: The purpose of this review was to synthesize the evidence on non-traditional biomarkers from metabolomic studies that may distinguish HFpEF from heart failure with reduced ejection fraction (HFrEF) and controls without HF. METHODS: A systematic search was conducted using Medline and PubMed with search terms such as "HFpEF" and "metabolomics", and a meta-analysis was conducted. RESULTS: Myeloperoxidase (MPO) levels were significantly (p < 0.001) higher in HFpEF than controls without HF, but comparable (p = 0.838) between HFpEF and HFrEF. Carnitine levels were significantly (p < 0.0001) higher in HFrEF than HFpEF, but comparable (p = 0.443) between HFpEF and controls without HF. Derivatives of reactive oxidative metabolites (DROMs) were not significantly (p = 0.575) higher in HFpEF than controls without HF. CONCLUSION: These data suggest that MPO is operative in HFpEF and HFrEF and may be a biomarker for HF. Furthermore, circulating carnitine levels may distinguish HFrEF from HFpEF.
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Insuficiencia Cardíaca , Humanos , Carnitina , Volumen Sistólico/fisiología , Biomarcadores/metabolismo , Peroxidasa , Estrés Oxidativo , PronósticoRESUMEN
Objectives: To examine the relationship of QRS voltages and left ventricular (LV) mass across the spectrum of individuals with different LV mass. Methods: Twenty QRS voltage measurements or combinations were determined in a consecutive series of 159 adults with an ECG and echocardiogram without previous myocardial infarction, left or right bundle branch block, pre-excitation, or electronic pacemaker. Results: The four strongest and significant correlations between QRS and LV mass were S in V4, deepest S wave in any precordial lead plus S in V4, S in V3, and S in V3 plus R in AVL times QRS duration. For men, the strength of the relationships were S in V3 (F = 33.8), deepest S wave in any precordial lead plus S V4 (F = 33.7), S in V3 plus R aVL (F = 29.9), S in V4 (F = 29.79), and deepest S in precordial leads (F = 17.9). The R wave in AVL alone did not correlate with LV mass. Criteria using the R wave in lateral precordial leads did not correlate as strongly with LV mass. For women, only S in V4 significantly correlated with LV mass. Overall, the R wave voltage in limb leads (AVL I or II) did not correlate with precordial S wave amplitudes. Univariate and multivariate analysis showed that some but not all QRS voltages correlated with each other. In multivariate analysis, using only single variables and not combination of QRS variables, the only significant relationship between QRS voltage and left ventricular mass was for men the S in V3 (p = 0.04) and for women S in V4 (p = 0.016) and R in V6 (p = 0.04). Conclusion: The S wave in V3 and V4 correlate most strongly with LV mass while the R wave in limb leads, including AVL, do not correlate.
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BACKGROUND: Identifying prolonged QT interval in RBBB has been problematic. METHODS: Four approaches were compared to adjust for the QT prolongation in intermittent RBBB. The implications were assessed in a separate group of 200 persons with established RBBB. RESULTS: In 12 individuals, mean age 74.5 years with intermittent RBBB, the presence of RBBB significantly (p < 0.05) increased the QT interval in each of six different heart rate correction formulae by an amount ranging from 35.4 ms in the Hodges formula to 50.2 ms in the Bazett formula. Four different equations were tested to adjust the QT interval and one approach QTcRBBB = 0.945*QTcRBBB - 26 was the best method to adjust for the increased QT in RBBB as it produced a QT value that was not significantly different from the QT interval in the absence of RBBB in intermittent RBBB.Failure to adjust the QT interval in RBBB produces an overestimate of the QT interval which in some heart rate adjustment formulae was marked. For the Bazett heart rate adjustment approach QTc 450 ms was found in 73.9% of men and QTc over 460 ms was found in 60.6% of women. CONCLUSION: These data suggest the implementation of a new approach to recalculate the QT intervals in RBBB. QTcRBBB = 0.945*QTcRBBB - 26 with an appropriate heart rate adjustment formula (other than the Bazett formula) accurately predicts the QT interval in the absence of RBBB.
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Bloqueo de Rama , Síndrome de QT Prolongado , Masculino , Humanos , Femenino , Anciano , Bloqueo de Rama/diagnóstico , Electrocardiografía , Frecuencia Cardíaca/fisiología , Síndrome de QT Prolongado/diagnósticoRESUMEN
Arterial stiffness has been linked to impaired cognitive function and dementia but the reason for the association is uncertain. This review proposes that collagen type IV is a critical factor linking arterial stiffness and dementia. Several genome wide association studies have related arterial stiffness to Collagen type IVα. Proteomic studies of arteries, demonstrated higher levels of collagen IVα1 in persons with high arterial stiffness. Collagen type IV defects are associated genetic causes of dementia as well as dementia of a variety of other causes. There are plausible causal roles for collagen type IV in dementia. Disorders of Collagen type IV can produce (I) fibro-hyalinosis and elastosis of small arterioles leading to cerebral ischemia and infarction; (II) dysfunction of the blood brain barrier leading to cerebral hemorrhage; (III) carotid artery stiffness with increase pulse pressure induces cerebral blood vessel damage leading to cerebral atrophy. The mechanisms by which Collagen type IV can lead to vascular stiffness include its degradation by matrix metalloprotease type 2 that (a) stimulates vascular smooth muscle cells to produce more extracellular matrix or (b) liberates peptides that damage the subendothelial space. Factors, such as TGF-ß1, and LDL cholesterol especially oxidized LDL can increase collagen type IV and produce vascular stiffness and dementia. Fibroblast growth factor 23, and abnormal NO signaling have been linked to collagen type IV or increased vascular stiffness and an increased risk of dementia. Recognition of the central role of collagen type IV in arterial stiffness and dementia will inspire new research focused on determining whether its modification can benefit arterial and brain health.
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This review will focus on epigenetic modifications utilizing the DNA methylation mechanism, which is potentially involved in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). The putative pathways of HFpEF will be discussed, specifically myocardial fibrosis, myocardial inflammation, sarcoplasmic reticulum Ca2+-ATPase, oxidative-nitrosative stress, mitochondrial and metabolic defects, as well as obesity. The relationship of HFpEF to aging and atrial fibrillation will be examined from the perspective of DNA methylation.
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BACKGROUND: Measurement of the QT interval in the ECG (QT interval) is important in evaluating risk for cardiac death and for assessing the impact of drugs on the heart. The objective of this study is to determine whether the time of day affects the QT interval, QT interval variability and whether these relationships are influenced by an individual's sex. METHODS: Twenty-four hour ECGs were analyzed in detail on 50 individuals, 49 years of age, without evidence of coronary artery disease, structural heart disease, or significant arrhythmias. Four different QT-heart rate adjustment formulae were calculated and compared. RESULTS: There were significant (P=0.0014) differences between the QT-heart rate relationship during three different time-periods (night 00:00 to 08:00 h, day 08:00 to 14:00 h and evening 14:00 to 24:00 h). Women, compared to men, had a steeper relation of QT to RR interval indicating that when heart rate slows at night, the QT interval is more prolonged which is consistent with a greater susceptibility to fatal arrhythmias. The variability of the QT interval (the SD) was significantly (P<0.01) greater in men than women at night and in the evening but not during the day. There were differences in the ability of different QT heart rate adjustment formulae to blunt the effect of heart rate changes on the QT interval during the day. CONCLUSION: The time of the day that the QT interval is assessed should be considered. The QT heart rate relationship is different in women than in men especially at night. QT interval variability is greater at night especially in men. There are differences in the ability of QT heart rate adjustment formulae to blunt the effect of heart rate on the QT interval. Differences in the QTc at night might be the basis for the higher prevalence of sudden death in women at night.
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Clozapine, a superior treatment for treatment-resistant schizophrenia can cause potentially life-threatening myocarditis and dilated cardiomyopathy. While the occurrence of this condition is well known, its molecular mechanisms are unclear and may be multifactorial. Putative mechanisms warrant an in-depth review not only from the perspective of toxicity but also for understanding the molecular mechanisms of the adverse cardiac effects of clozapine and the development of novel therapeutic approaches. Clozapine-induced cardiac toxicity encompasses a diverse set of pathways, including (i) immune modulation and proinflammatory processes encompassing an IgEmediated (type I hypersensitivity) response and perhaps a cytokine release syndrome (ii) catecholaminergic activation (iii) induction of free radicals and oxidative stress (iv) activation of cardiomyocyte cell death pathways, including apoptosis, ischemia through impairment in coronary blood flow via changes in endothelial production of NO and vasoconstriction induced by norepinephrine as well as other factors released from cardiac mast cells. (v) In addition, an extensive examination of the effects of clozapine on non-cardiac cellular proteins demonstrates that clozapine can impair enzymes involved in cellular metabolism, such as pyruvate kinase, mitochondrial malate dehydrogenase, and other proteins, including α-enolase, triosephosphate isomerase and cofilin, which might explain clozapine-induced reductions in myocardial energy generation for cell viability as well as contractile function. Pharmacologic antagonism of these cellular protein effects may lead to the development of strategies to antagonize the cardiac damage induced by clozapine.
Asunto(s)
Clozapina , Miocarditis , Humanos , Miocarditis/inducido químicamente , Clozapina/efectos adversos , Miocardio , Miocitos Cardíacos , ApoptosisRESUMEN
BACKGROUND: Current inferences about the site of origin (SOO) of premature ventricular complexes (PVC) from the surface ECG have not been subjected to newer data analytic techniques that identify signals that are not recognized by visual inspection. AIMS: The objective of this study was to apply data analytics to PVC characteristics. METHODS: PVCs from 12-lead ECGs of a consecutive series of 338 individuals were examined by unsupervised machine learning cluster analysis, and indexes were compared to a composite criterion for SOO. RESULTS: Data analytics found that V1S plus V2S ≤ 9.25 of the PVC had a LVOT origin (sensitivity 95.4%; specificity 97.5%). V1R + V2R + V3R > 15.0 (a RBBB configuration) likely had a LVOT origin. PVCs with V1S plus V2S > 12.75 (LBBB configuration) likely had a RVOT origin. PVC with V1S plus V2S > 14.25 (LBBB configuration) and all inferior leads positive likely had a RVOT origin. CONCLUSION: Newer data analytic techniques provide a non-invasive approach to identifying PVC SOO, which should be useful for the clinician evaluating a 12-lead ECG.