A classification scheme for ventricular arrhythmias using wavelets analysis

Identification and classification of ventricular arrhythmias such as rhythmic ventricular tachycardia (VT) and disorganized ventricular fibrillation (VF) are vital tasks in guiding implantable devices to deliver appropriate therapy in preventing sudden cardiac deaths. Recent studies have shown VF can exhibit strong regional organizations, which makes the overlap zone between the fast paced rhythmic VT and VF even more ambiguous. Considering that implantable cardioverter-defibrillator (ICD) are primarily rate dependent detectors of arrhythmias and that there may be patients who suffer from arrhythmias that fall in the overlap zone, it is essential to identify the degree of affinity of the arrhythmia toward VT or organized/disorganized VF. The method proposed in this work better categorizes the overlap zone using Wavelet analysis of surface ECGs. Sixty-three surface ECG signal segments from the MIT-BIH database were used to classify between VT, organized VF (OVF), and disorganized VF (DVF). A two-level binary classifier was used to first extract VT with an overall accuracy of 93.7 % and then the separation between OVF and DVF with an accuracy of 80.0 %. The proposed approach could assist clinicians to provide optimal therapeutic solutions for patients in the overlap zone of VT and VF.     

基于短时心率变异性信号两种熵测度的过速型室性心律失常的预测分析

目的:过速型室性心律失常［持续性室性心动过速或心室纤颤（VT/VF）］是心脏猝死的主要诱因,测试VT/VF发生前心率变异性信号是否有明显改变可作为VT和VF发生的提前预报信号。方法:以78名患者体内心脏复律除颤器记录的VT/VF事件发生前心率变异性信号（VT/VF序列）和来自同一患者的正常窦性节律（CON序列）组成的135个样本对作为实验序列。通过预处理消除实验序列的伪差、异位心搏等干扰,采用两种基于熵的非线性复杂度测度——样本熵和逐点多尺度熵（PPMSE）,分析VT和VF发生前十几分钟的VT/VF序列,以及心率增加和减小的VT/VF序列复杂性,并采用PPMSE方法讨论了接近VT/VF发生时VT/VF序列复杂性变化。结果:与正常对照组CON序列相比,在一定匹配容差内,VT/VF发生前心率变异性信号的样本熵明显减小（r<0.25×SD, P<0.000 5）,心率增加的VT/VF序列减小更显著（r<0.3×SD, P<0.000 1）;VT/VF序列的PPMSE在越接近VT/VF发生时刻减小越显著,提取的CI指数存在显著差异（如1~30尺度,N=986、500、250时,P=1.5×10-2、P=4.3×10-3、P=1.3×10-5）,心率增加的VT/VF序列区分性能更好。结论:过速型心律失常的自然发作并不是突发现象,在其发作前或许存在某种生理预兆,两种熵测度可能是短时预报恶性室性心律失常事件的有效非线性参数。     

Ruthenium red-induced transition from ventricular fibrillation to tachycardia in isolated rat hearts:: possible involvement of changes in mitochondrial calcium uptake

INTRODUCTION: Ventricular tachycardia (VT) is considered to be the most common precursor of ventricular fibrillation (VF) and sudden cardiac death. However, the mechanisms underlying the transition from VT to VF remain unclear despite more than a century of study. Here, we investigated whether perfusion of the heart with blockers of mitochondrial Ca(2+) uniporter changed the macrodynamics of the heart between VT and VF. METHODS: The experiments were performed using Langendorff perfused isolated rat hearts in which left ventricular pressure (LVP) and left ventricular cardiomyogram (LVCMG) were measured. Sustained VT or VF was induced by burst pacing of the left ventricular muscles. RESULTS: During pacing-induced sustained VF, perfusion of the heart with ruthenium red (RR) or Ru 360, blockers of mitochondrial Ca(2+) uniporter, resulted in the reversible conversion of VF to VT. In contrast, during pacing-induced sustained VT, perfusion of the heart with spermine, an activator of mitochondrial Ca(2+) uptake, resulted in the reversible conversion of VT to VF, and the effect was antagonized by cotreatment with RR. In addition, RR-induced conversion of VF to VT was antagonized by cotreatment with S(-)-Bay K8644 (Bay K), an activator of L-type Ca(2+) channels, suggesting that the inactivation of L-type Ca(2+) channels was responsible for the RR-induced effect on the macrodynamics of hearts. In fact, perfusion with verapamil, an antagonist of L-type Ca(2+) channels, during pacing-induced sustained VF, resulted in the conversion of VF to VT. CONCLUSION: This study demonstrated that perfusion of isolated rat hearts with blockers of Ca(2+) uptake by mitochondria resulted in the reversible conversion of pacing-induced sustained VF to VT, suggesting that changes in mitochondrial Ca(2+) uptake were possibly involved in the transition between VT and VF.     

Pathological analysis of myocardial cell under ventricular tachycardia and fibrillation based on symbolic dynamics

Ventricular fibrillation (VF) is one of the most serious malignant arrhythmias usually resulting from immediate degeneration of ventricular tachycardia (VT). In order to analyse the nonlinear dynamics of the cardiac micro-mechanism under VT and VF rhythm, at the cellular level, myocardial cell action potentials are investigated under different rhythm, normal sinus rhythm, VT and VF. On the basis of nonlinear chaotic theory and symbolic dynamics, we put forward new definitions, complexity rate, etc, and obtained some useful properties for cellular electrophysiological analysis. The results of the experiments and computation show that the myocardial cellular signals under VT and VF rhythm are different kinds of chaotic signals in that the cardiac chaos attractor under VF is higher than that under VT. The analytical complexity theory has been promising in the clinical application.     

Clinical assessment of the risk for sudden cardiac death in patients with sickle cell anemia

BACKGROUND: Previous studies suggest that patients with sickle cell anemia (SCA) have an increased risk of sudden cardiac death; however, its etiology and mechanism are not well defined. Left ventricular hypertrophy (LVH), ventricular tachycardia (VT) and poor left ventricular systolic function are known risk factors for sudden cardiac death. An abnormal microvolt T-wave alternans (TWA) test is also a predictor of sudden cardiac death risk, but it has not been applied to this patient population. METHODS: We performed a 12-lead electrocardiogram, 24-hour Holter monitor, two-dimensional echocardiogram, nuclear stress test and microvolt TWA test to determine whether markers of sudden cardiac death could be identified. RESULTS: Twenty-six patients were evaluated with a mean age of 40 +/- 12 years. The two-dimensional echocardiogram revealed a normal ejection fraction in 23 patients and LVH in 17 (65%), whereas hypertension was noted in only five (19%). Microvolt TWA testing was abnormal in six of 22 patients (27%). Holter monitor revealed VT in two patients. Among the clinical variables tested, only LVH was predictive of an abnormal TWA test. The sensitivity, specificity, positive and negative predictive value of LVH for and abnormal TWA test was 100, 56, 46 and 100%. CONCLUSION: LVH was common in patients with SCA and disproportional to the number of patients with hypertension. Microvolt TWA tests were abnormal in 27% of patients; however, LVH was the only clinical variable that predicted an abnormal TWA test. Risk stratification of SCA patients may require echocardiographic detection of LVH and an abnormal TWA test due to the high negative predictive value. The significance of an abnormal TWA test should be further evaluated in a large study, with a longer follow-up period.     

Frequency domain analysis of highly amplified ECG on the basis of maximum entropy spectral estimation

Recognition of patients with high risk for ventricular tachycardia (VT) or sudden cardiac death is of high clinical importance. We have investigated the efficiency of maximum entropy spectral estimation (MES) to detect such risk patients on the basis of highly amplified surface ECG. In comparison with the traditionally applied periodogram (fast Fourier transform), the MES produces sharper and more pronounced peaks in the power density spectrum (PS). The main problem is the influence of residual noise (after averaging), which often leads to additional components in the PS. To completely avoid this negative noise influence we developed a new algorithm, called the variance subtraction method. In a first clinical investigation 86 per cent of patients with myocardial infarction and ventricular tachycardia have shown frequency components above 80 Hz in the PS compared with healthy persons where no frequency components above this 80 Hz level could be detected.     

Pathological analysis of myocardial cell under ventricular tachycardia and fibrillation based on symbolic dynamics.

Ventricular fibrillation (VF) is one of the most serious malignant arrhythmias usually resulting from immediate degeneration of ventricular tachycardia (VT). In order to analyse the nonlinear dynamics of the cardiac micro-mechanism under VT and VT rhythm, at the cellular level, myocardial cell action potentials are investigated under different rhythm, normal sinus rhythm, VT and VT. On the basis of nonlinear chaotic theory and symbolic dynamics, we put forward new definitions, complexity rate, etc, and obtained some useful properties for cellular electrophysiological analysis. The results of the experiments and computation show that the myocardial cellular signals under VT and VF rhythm are different kinds of chaotic signals in that the cardiac chaos attractor under VF is higher than that under VT. The analytical complexity theory has been promising in the clinical application.     

基于心室动作电位的三维心肌组织模型算法研究

心肌电折返是引起心律失常的重要因素之一,它会导致心动过速(VT)乃至室颤(VF)的发生,从而引起心源性猝死。随着计算机仿真在定量电生理研究中的广泛应用,迫切需要建立三维心肌组织实验平台。本文就这种组织模型的数值解方法进行了研究。文中利用Luo-Rudy 1991心室肌细胞模型结合扩散方程形成三维组织模型,利用算子分裂法求其数值解。分别采用ADI格式和七点差分格式求解描述电扩布的偏微分方程,边界条件采用二阶精度的离散格式。实验结果表明,以上两种格式均可成功地解算出细胞膜电位的变化以及电兴奋的活动,且具有良好的稳定性。但ADI格式可较大幅度地缩短计算时间。因此ADI格式下增加时间步长以提高计算效率的方法更具优势。     

Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary-artery spasm.

BACKGROUND. Silent myocardial ischemia in patients with coronary atherosclerosis is associated with an increased risk of adverse cardiac events, including sudden death. The relation between silent ischemia and the initiation of potentially fatal ventricular arrhythmias has not been defined, however. METHODS. As part of a long-term study of sudden cardiac death, data on arrhythmias, coronary anatomy, and responses to ergonovine testing to provoke coronary-artery spasm were collected prospectively among survivors of out-of-hospital cardiac arrest who had no flow-limiting coronary-artery lesions, prior myocardial infarctions, or other structural causes of cardiac arrest and no angina pectoris. Associations between silent myocardial ischemia due to coronary-artery spasm and the occurrence and characteristics of life-threatening ventricular arrhythmias were studied by both invasive and noninvasive techniques. RESULTS. Silent ischemic events were associated with the initiation of life-threatening ventricular arrhythmias in five patients with induced or spontaneous focal coronary-artery spasm (or both). These patients were identified among a group of 356 survivors of out-of-hospital cardiac arrest who were evaluated between 1980 and 1991. In two of the five patients reperfusion, rather than ischemia itself, correlated with the onset of the ventricular arrhythmia. Only one of the five had an inducible arrhythmia during electrophysiologic testing. Titration of the dose of a calcium-entry-blocking agent (verapamil, diltiazem, or nifedipine) against the ability of ergonovine to provoke spasm was successful in preventing both the provocation of spasm and arrhythmias in all four patients who were tested. CONCLUSIONS. Silent myocardial ischemia due to coronary-artery spasm can initiate potentially fatal arrhythmias in patients without flow-limiting structural coronary-artery lesions. The role of silent ischemia, reperfusion, or both in the initiation of fatal arrhythmias in larger groups of patients with advanced coronary-artery lesions remains to be defined.     

Increased susceptibility of spontaneously hypertensive rats to ventricular tachyarrhythmias in early hypertension

Key points

• Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation.
• Whether hypertension in its early stage is associated with an increased risk of ventricular tachyarrhythmias is not known.
• Based on experiments performed at the cellular and whole heart levels, we show that, even early in chronic hypertension, the hypertrophied and fibrotic ventricles of spontaneously hypertensive rats aged 5 to 6 months have already developed increased stress‐induced arrhythmogenicity, and this increased susceptibility to ventricular arrhythmias is primarily a result of tissue remodelling rather than cellular electrophysiological changes.
• Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.

Abstract

Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that, in early hypertension, the susceptibility to stress‐induced VT/VF increases. We compared the susceptibility of 5‐ to 6‐month‐old male spontaneously hypertensive rats (SHR) and age/sex‐matched normotensive rats (NR) to VT/VF during challenge with oxidative stress (H₂O₂; 0.15 mmol l⁻¹). We found that only SHR hearts exhibited left ventricular fibrosis and hypertrophy. H₂O₂ promoted VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage‐calcium optical mapping of Langendorff‐perfused SHR hearts revealed that H₂O₂‐induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)‐mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR ventricular myocytes, except with larger EAD amplitude. During the early stages of hypertension, when challenged with oxidative stress, SHR hearts showed an increased ventricular arrhythmogenicity that stems primarily from tissue remodelling (hypertrophy, fibrosis) rather than cellular electrophysiological changes. Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.

Abbreviations

AP

action potential

APD

action potential duration

APD₉₀

action potential at 90% duration

CaMKII

calcium/calmodulin‐dependent protein kinase II

CaT

calcium transient

CaTD₉₀

calcium transient at 90% duration

CI

confidence interval

DBP

diastolic blood pressure

EAD/DAD

early/delayed after‐depolarization

HR

heart rate

ICC

interclass correlation

I_Ca,L

L‐type calcium current

I_Ks

slow delayed rectifier potassium current

I_Na

sodium current

I_to

transient outward potassium current

IVS(d,s) interventricular septum thickness (during diastole

during systole)

LV

left ventricle

LVEF

left ventricular ejection fraction

LVFS

left ventricular fractional shortening

LVH

left ventricular hypertrophy

LVID(d,s) left ventricular internal diameter (during diastole

during systole)

MV

mitral valve

NR

normotensive rats

PA peak vel

pulmonary artery peak velocity

(P)CL

(pacing) cycle length

PW

posterior wall

P‐ECG

pseudo‐electrocardiogram

RV

right ventricle

RWT

relative wall thickness

SHR

spontaneously hypertensive rats

SHHF

spontaneously hypertensive heart failure

SBP

systolic blood pressure

VT/VF

ventricular tachycardia and fibrillation

     

The fibrosis and atrial fibrillation: is the transforming growth factor-beta 1 a candidate etiology of atrial fibrillation

Atrial fibrillation (AF) is the most commonly occurring arrhythmia in clinical practice, however, the mechanism of atrial fibrillation is not well explained. It has been considered that myocardial fibrosis plays a role in atrial fibrillation. Within the heart, this fibrosis is thought to be mediated by transforming growth factor-beta 1 (TGF-beta 1), a potent stimulator of collagen-producing cardiac fibroblasts. Recent studies indicate that atrial fibrillation is associated with elevated serum concentrations of TGF-beta 1 and C-terminal propeptide of procollagen type I (a marker of collagen type I synthesis). TGF-beta 1 was not only associated with the presence of atrial fibrillation but may also predict patients at increased risk for future development of atrial fibrillation. Why TGF-beta 1 in atrial fibrillation is high is a puzzling problem. We hypothesized that TGF-beta 1 is a possible cause of atrial fibrillation by initiating fibrosis response. Atrial interstitial fibrosis has been seen in patients with CHF and in animal models of pacing-induced heart failure. It was demonstrated that TGF-beta 1 levels were increased in the atria after the development of congestive heart failure in dogs. In a similar study, mice with increased expression of TGF-beta 1 were prone to atrial fibrillation development as a result of raised levels of atrial fibrosis. If the hypothesis is confirmed, administration of TGF-beta 1 monoclonal antibodies may be used to eliminate the etiology. It will be a new target point to treat atrial fibrillation.     

Arrhythmia and impaired myocardial function in heritable thoracic aortic disease: An international retrospective cohort study

BackgroundHeritable thoracic aortic diseases (HTAD), typically entailing aortic complications, can be caused by pathogenic variants or likely pathogenic variants (PV/LPVs) in several genes, including fibrillin1 (FBN1), Actin Alpha2 (ACTA2) and genes encoding components of the transforming growth factor (TGF)-β signaling pathway. In addition to aortic complications, non-aortic cardiac disease such as impaired myocardial function and/or arrhythmia have been increasingly reported, mainly in Marfan syndrome with underlying FBN1 PV/LPVs and are acknowledged as additional causes of morbidity and mortality. The prevalence of these manifestations in the various HTAD entities is largely unknown.MethodsThis international multicentre retrospective study collected data on patients with HTAD presenting non-aortic cardiac disease. A total of 9 centers from 7 different countries participated. Patients 12 years or older carrying a PV/LPV in one of the following genes: FBN1, TGFBR1, TGFBR2, TGFB2, TGFB3, SMAD3 and ACTA2 were screened. Non-aortic cardiac disease included impaired myocardial function and/or arrhythmia. Impaired myocardial function was defined as (a)symptomatic reduced ejection fraction (EF<50%). Arrhythmias included atrial fibrillation (AF), atrial flutter (AFL), ventricular tachycardia (VT), ventricular fibrillation (VF) and (aborted) sudden cardiac death (presumed arrhythmogenic) (SCD).ResultsMedical records of 3219 patients with HTAD were screened (2761, 385 and 73 carrying a PV/LPV in FBN1, in a TGF-β signaling gene and in ACTA2 respectively). Non-aortic cardiac disease was reported 142 times in 101 patients (3.1%) (age 37 [range 12–77] years, 39% female): 88 patients carrying an FBN1 PV/LPV and 13 carrying a PV/LPV in one of the TGF-β signaling genes. Neither impaired myocardial function nor arrhythmia was reported in screened patients carrying a PV/LPV in ACTA2. Among the 142 reported non-aortic cardiac diseases, 68 (48%) were impaired myocardial function, 47 (33%) were AF/AFL and 27 (19%) were VT/VF/SCD. Among the patients with non-aortic cardiac disease, prior cardiac surgery was noted in 80% and severe valvular disease (valvular surgery or severe valvular regurgitation) in 58%, while 18% of the patients developed non-aortic cardiac disease in the absence of any of the latter.ConclusionsIn patients with HTAD, arrhythmia and impaired myocardial function was reported in patients with PV/LPVs in FBN1 and in the TGF-β signaling genes and not in patients harboring PV/LPVs in ACTA2. Though infrequent, non-aortic cardiac disease should be acknowledged as potentially severe, also occurring in young patients with no underlying significant valvular or aortic disease.     

Clinical use of magnetic resonance imaging for the diagnosis of acute myocardial infarction in the survivors of cardiac arrest

The ventricular arrhythmias with underlying coronary artery disease are a leading cause of sudden cardiac death (SCD). While the SCD survivors with proven AMI are considered to be at low risk of SCD recurrence, those without the evidence of AMI represent a high risk group that benefits from implantable cardioverter defibrillator. Therefore, the evaluation of SCD survivors for the presence of acute myocardial infarction (AMI) as a triggering factor of cardiac arrest is essential. In SCD survivors, the use of the standard diagnostic criteria of AMI may be difficult, as both serum cardiac biomarkers and electrocardiogram can be influenced by previous cardiac arrest. A novel technique that may be used for the diagnosis of AMI is magnetic resonance imaging (MRI). We report its use in four patients after cardiopulmonary resuscitation where the diagnosis of AMI could not be definitely established or excluded by means of other diagnostic procedures.     

QT dispersion in adult hypertensives

Increased QT dispersion is associated with sudden cardiac death in congestive cardiac failure, hypertrophic cardiomyopathy and following myocardial infarction. Patients with hypertension--in particular, those with left ventricular hypertrophy (LVH)--are also at greater risk of sudden cardiac death. We examined whether QT dispersion, which is easily obtained from a routine ECG, correlates with LVH. One-hundred untreated patients with systemic hypertension and 78 normotensives had QT dispersion measured manually from a surface 12-lead electrocardiogram and two-dimensional echocardiography performed to measure interventricular septal thickness, posterior wall thickness and left ventricular internal diameter. Office blood pressure was also recorded. Multivariate analysis demonstrated significant relationships between QT dispersion and office systolic blood pressure, and left ventricular mass index. Manual measurement of QT dispersion might be a simple, noninvasive screening procedure to identify those hypertensives at greatest risk of sudden cardiac death in a third-world country.     

Cardial fibrosis and the functional activity of leukocytes in patients with essential arterial hypertension

The study revealed an increase in the serum levels of TGF-beta1 and the N-terminal peptide procollagen type III in patients with essential arterial hypertension (EAH), as well as an association between this increase and the duration of the disease, mean day arterial pressure profile, and left ventricular hypertrophy. An increased leukocyte functional activity is associated with disturbances in left ventricular diastolic function and an increase in TGF-beta1 serum concentration in EAH. The authors conclude that leukocytes participate in the development of myocardial hypertrophy and cardial fibrosis through the secretion of pro-inflammatory cytokines and peptide growth factors within the process of their activation.     

Altered electrical activity of fibrillation process following thrombolytic therapy in out-of-hospital cardiac arrest patients with sustained ventricular fibrillation

The likelihood of successful defibrillation in patients with sustained ventricular fibrillation (VF) is increased after administering thrombolytics during cardiopulmonary resuscitation (CPR). While dissolution of coronary artery thrombosis resolves the underlying cause of myocardial infarction in the majority of patients, improved microcirculatory reperfusion and alteration of the electrical activity of the fibrillation process may increase the likelihood of restoring spontaneous circulation in cardiac arrest patients. Electrocardiography is a sensitive means of displaying current myocardial perfusion in VF using changes in the frequency and amplitude of fibrillation. Our hypothesis postulates that thrombolytic therapy during CPR increases fibrillation frequency, fibrillation amplitude and amplitude spectrum area, thus improving ventricular fibrillation status and the chance of successful defibrillation.     

Cardiac arrest in Stockholm with special reference to the ambulance organization

During a one-year period all patients with cardiac arrest (CA) taken care of by three ambulances were studied. An incidence of 110 cardiac arrests/100,000 inhabitants/year was found. The majority of CAs affected the elderly and occurred during the day in their homes. The majority of CAs were witnessed but cardiopulmonary resuscitation (CPR) had been initiated by bystanders in only a few cases. The ambulance arrived within a mean time of 7.7 +/- 4.0 min. Forty-eight per cent of the CA patients showed ventricular tachycardia or ventricular fibrillation (VT/VF) on ambulance arrival. Patients with a prolonged ambulance delay showed a lower incidence of VT/VF than patients with a short delay. Patients in whom CPR had been initiated by bystanders showed a significantly higher incidence of VT/VF (67%) than unattended patients (45%). Bystander CPR was furthermore associated with an increased incidence of VT/VF in patients with prolonged ambulance delay. VT/VF was present at the time when the ambulance arrived in 86% of the CA patients who had received CPR from a bystander and were reached within 8 min by the ambulance.     

Cardiac sarcoidosis and sudden death. The heart may look normal or mimic other cardiomyopathies

Cardiac sarcoidosis has been known to give rise to heart failure, arrhythmias and sudden cardiac death. We have a large database of sudden cardiac death cases at the CRY Centre for Cardiac Pathology at Imperial College, London, UK in which we found 17 of 1,720 cases with a diagnosis of cardiac sarcoid. Macroscopic examination showed a variety of findings including left ventricular hypertrophy, a dilated thin-walled left ventricle ,areas of fibrosis, changes resembling arrhythmogenic right ventricular cardiomyopathy and in some cases, no gross abnormalities. Histological examination revealed large areas of fibrosis and focal lymphocytic inflammation mimicking infarction/myocarditis. Careful search had to be made for non-necrotizing granulomata, since the lymphocytic foci, fibrosis and granulation tissue often predominated throughout the heart. The conduction tissue is often not sampled at autopsy despite the history of heart block. The heterogeneous nature of the macroscopic appearance and histological findings means that widespread sampling of the heart and the conduction system is essential in cases of sudden death in order that a diagnosis of myocardial sarcoidosis is not missed.     

Substrate stiffness-regulated matrix metalloproteinase output in myocardial cells and cardiac fibroblasts: Implications for myocardial fibrosis

Cardiac fibrosis, an important pathological feature of structural remodeling, contributes to ventricular stiffness, diastolic dysfunction, arrhythmia and may even lead to sudden death. Matrix stiffness, one of the many mechanical factors acting on cells, is increasingly appreciated as an important mediator of myocardial cell behavior. Polydimethylsiloxane (PDMS) substrates were fabricated with different stiffnesses to mimic physiological and pathological heart tissues, and the way in which the elastic modulus of the substrate regulated matrix-degrading gelatinases in myocardial cells and cardiac fibroblasts was explored. Initially, an increase in cell spreading area was observed, concomitant with the increase in PDMS stiffness in both cells. Later, it was demonstrated that the MMP-2 gene expression and protein activity in myocardial cells and cardiac fibroblasts can be enhanced with an increase in PDMS substrate stiffness and, moreover, such gene- and protein-related increases had a significant linear correlation with the elastic modulus. In comparison, the MMP-9 gene and protein expressions were up-regulated in cardiac fibroblasts only, not in myocardial cells. These results implied that myocardial cells and cardiac fibroblasts in the myocardium could sense the stiffness in pathological fibrosis and showed a differential but positive response in the expression of matrix-degrading gelatinases when exposed to an increased stiffening of the matrix in the microenvironment. The phenomenon of cells sensing pathological matrix stiffness can help to increase understanding of the mechanism underlying myocardial fibrosis and may ultimately lead to planning cure strategies.     

Defibrillation threshold testing: Is it necessary during implantable cardioverter-defibrillator implantation?

Defibrillation threshold (DFT) testing has traditionally been a routine part of implantable cardioverter-defibrillator (ICD) implantation. DFT testing was developed in the early days of the ICD when failure of defibrillation was common, recipients had a high-risk of ventricular tachycardia (VT) or ventricular fibrillation (VF), and the only therapy for rapid VT or VF was a shock. However, modern ICD systems have such a high rate of successful defibrillation that many electrophysiologists now question whether DFT testing is still worthwhile. Studies found that long-term mortality was not higher among patients not undergoing DFT testing. Moreover, there was no survival difference between patients with a lower DFT and a higher DFT. Other studies have demonstrated that DFT testing poses some risk to the patient such as myocardial damage, embolic stroke in patient with atrial fibrillation and DFT testing-related death. If DFT testing is abandoned, more patients may have the opportunity to be treated with ICD, especially in regions with few or no electrophysiologists. It may be argued that other physicians, such as those currently implanting pacemakers, would more readily implant ICDs if not for the requirement of DFT testing.