Can QT/RR relationship differentiate between low- and high-risk patients with hypertrophic cardiomyopathy?

BACKGROUND: Abnormal dynamicity of repolarization is considered to be a marker of myocardial vulnerability contributing to increased risk of arrhythmic events and sudden death. However, little is known about QT dynamics in hypertrophic cardiomyopathy (HCM). In this study, we aimed to evaluate ventricular repolarization by QT dynamicity in patients with HCM, focusing on its value to define if it is able to differentiate among low- and high-risk HCM patients. METHODS: The linear regression slopes of the QT interval, measured to the apex and to the end of the T wave plotted against RR intervals (QTapex/RR and QTend/RR slopes, respectively) were calculated from 24-hour Holter recordings using a standard algorithm in 36 HCM patients and 64 control subjects. RESULTS: QTapex/RR and QTend/RR slopes were significantly steeper in the HCM patients in contrary to healthy control subjects (QTapex/RR = 0.22 + 0.08 vs 0.20 + 0.05, P = 0.0367; QTend/RR = 0.25 + 0.10 vs 0.20 + 0.06, P = 0.023). Moreover, the slopes of QTend/RR and QTapex/RR of high-risk patients were significantly steeper than those of control subjects while no significant differences were found among low-risk HCM patients and control subjects and only QTe/RR of high-risk patients was significantly different between low- and high-risk HCM patients. CONCLUSIONS: Our study results suggest that QT dynamicity is impaired in patients with HCM and may help to differentiate among low- and high-risk patients. Further studies are needed to elucidate the prognostic significance and clinical implications of impaired ventricular repolarization in patients with HCM.

Unsupervised classification of ventricular extrasystoles using bounded clustering algorithms and morphology matching.

Ventricular extrasystoles (VE) are ectopic heartbeats involving irregularities in the heart rhythm. VEs arise in response to impulses generated in some part of the heart different from the sinoatrial node. These are caused by the premature discharge of a ventricular ectopic focus. VEs after myocardial infarction are associated with increased mortality. Screening of VEs is typically a manual and time consuming task that involves analysis of the heartbeat morphology, QRS duration, and variations of the RR intervals using long-term electrocardiograms. We describe a novel algorithm to perform automatic classification of VEs and report the results of our validation study. The proposed algorithm makes use of bounded clustering algorithms, morphology matching, and RR interval length to perform automatic VE classification without prior knowledge of the number of classes and heartbeat features. Additionally, the proposed algorithm does not need a training set.

Gender differences in electrical remodeling and susceptibility to ventricular arrhythmias in rabbits with left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is associated with an increased risk of death, vulnerability to ventricular arrhythmia, and multiple electrophysiological abnormalities. OBJECTIVES: The purpose of the present study was to determine the gender-dependent differences in electrical remodeling and the susceptibility to ventricular arrhythmias in a rabbit model of renovascular hypertension. METHODS: Rabbits of both sexes underwent unilateral renal artery banding and contralateral nephrectomy or were placed in the control group. Data are expressed as mean +/- standard error of the mean. RESULTS: The duration of action potentials was prolonged in the LVH group compared with the control group in both male (123 +/- 2.4 ms and 151 +/- 2.3 ms vs. 180 +/- 5.1 ms and 196 +/- 3.1 ms for action potential duration [APD](90 Epi) and APD(90 Endo) of control [n = 5] and LVH rabbits [n = 8], respectively; P<.05) and female rabbits (131 +/- 1.9 ms and 166 +/- 2.0 ms vs. 156 +/- 4.2 ms and 175 +/- 2.2 ms for APD(90 Epi) and APD(90 Endo) of control [n = 5] and LVH rabbits [n = 7], respectively; P<.05). Moreover, the gender-dependent differences in repolarization were opposite to those seen under control conditions. In LVH rabbits, APD(90) was greater in males than in females. The changes induced in APD lead to a greater transmural dispersion of repolarization (38 +/- 6.6 ms vs. 19 +/- 6.5 ms for males and females, respectively; P<.05). In addition, while control rabbits did not show induction of arrhythmias, an enhanced susceptibility to ventricular arrhythmia was seen in LVH male rabbits (6/8 male vs. 1/7 female LVH rabbits; P<.05). CONCLUSION: We conclude that the electrical remodeling associated with LVH inverted the gender-dependent differences, with male rabbits now exhibiting action potentials with longer durations both in the endocardial and epicardial surface of the left ventricle, increased dispersion of repolarization, and increased vulnerability to ventricular arrhythmia induction.

Validation of the 2014 European Society of Cardiology Sudden Cardiac Death Risk Prediction Model in Hypertrophic Cardiomyopathy in a Reference Center in South America.

Sudden cardiac death (SCD) is a common cause of death in hypertrophic cardiomyopathy (HC). Our aim was to conduct an external and independent validation in South America of the 2014 European Society of Cardiology (ESC) SCD risk prediction model to identify patients requiring an implantable cardioverter defibrillator. This study included 502 consecutive patients with HC followed from March, 1993 to December, 2014. A combined end point of SCD or appropriate implantable cardioverter defibrillator therapy was assessed. For the quantitative estimation of individual 5-year SCD risk, we used the formula: 1 - 0.998(exp(Prognostic index)). Our database also included the abnormal blood pressure response to exercise as a risk marker. We analyzed the 3 categories of 5-year risk proposed by the ESC: low risk (LR) <4%; intermediate risk (IR) ≥4% to <6%, and high risk (HR) ≥6%. The LR group included 387 patients (77%); the IR group 39 (8%); and the HR group 76 (15%). Fourteen patients (3%) had SCD/appropriate implantable cardioverter defibrillator therapy (LR: 0%; IR: 2 of 39 [5%]; and HR: 12 of 76 [16%]). In a receiver-operating characteristic curve, the new model proved to be an excellent predictor because the area under the curve for the estimated risk is 0.925 (statistical C: 0.925; 95% CI 0.8884 to 0.9539, p <0.0001). In conclusion, the SCD risk prediction model in HC proposed by the 2014 ESC guidelines was validated in our population and represents an improvement compared with previous approaches. A larger multicenter, independent and external validation of the model with long-term follow-up would be advisable.

Developmental changes of cardiac repolarization in rabbits: implications for the role of sex hormones.

OBJECTIVES: Firstly, to compare gender-dependent differences of cardiac repolarization in both adult and young rabbits. Secondly, to analyze the effect of gonadectomy on these gender differences in cardiac repolarization. METHODS: We evaluated potential gender differences in cardiac repolarization with both microelectrode and ECG recordings. QT(end), JT(end), and T(peak-end) intervals and action potential durations at 30%, 50% and 90% of full repolarization were used to assess ventricular repolarization in adult (normal and gonadectomized) and young rabbits of both sexes. RESULTS: Adult rabbits exhibited clear gender-related differences in repolarization evidenced by significantly longer JT(end) and T(peak-end) intervals and significantly longer APD30, APD50 and APD90 in females. These gender-related differences in repolarization were absent in young rabbits and were abolished by gonadectomy. CONCLUSIONS: Developmental changes of repolarization are present in rabbits. These changes are in agreement with those reported in humans and may further support the role played by sex hormones in the modulation of cardiac repolarization.

Enhanced modified moving average analysis of T-wave alternans using a curve matching method: a simulation study.

T-wave alternans (TWA) are beat-to-beat amplitude oscillations in the T-waves of electrocardiograms (ECGs). Numerous clinical studies have demonstrated the link between these oscillations and ventricular arrhythmias. Several methods have been developed in recent years to detect and quantify this important feature. Most methods estimate the amplitude differences between pairs of consecutive T-waves. One such method is known as modified moving average (MMA) analysis. The TWA magnitude is obtained by means of the maximum absolute difference of even and odd heartbeat series averages computed at T-waves or ST-T complexes. This method performs well for different levels of TWA, noise, and phase shifts, but it is sensitive to the alignment of the T-waves. In this paper we propose a preprocessing stage for the MMA method to ensure an optimal alignment of such averages. The alignment is performed by means of a continuous time warping technique. Our assessment study demonstrates the improved performance of the proposed algorithm.

T-wave alternans analysis improvement by means of curve alignment prior to distance calculation.

Tracking of repolarization instabilities in the ECG, such as T-wave alternans (TWA), has become a popular non-invasive method to assess the vulnerability to malignant arrhythmic events. These instabilities are usually characterized by small amplitude changes and their measurement is difficult due to the presence of noise and artifacts. Several methods have been recently proposed to address this problem. Most of them are based on amplitude analysis of beat-to-beat alternation of the T wave. This paper describes a preprocessing stage intended to be used prior to amplitude analysis and aimed at improving the alignment between consecutive T waves. This increases the accuracy of the difference calculation.

Lack of effect of conduction direction on action potential durations in anisotropic ventricular strips of pig heart.

INTRODUCTION: The influence of activation sequence on the rate of rise of the depolarization phase of action potentials in atrial or ventricular muscles has been well established. However, whether myocardial fiber orientation is important in modulating the repolarization process is unclear. METHODS AND RESULTS: We examined the influence of activation sequence on the repolarization phase of action potentials in epicardial tissues from the right and left ventricles of domestic pigs. Whereas cells from the right ventricle exhibited direction-dependent differences in action potential duration at 30%, 50%, and 90% of full repolarization (190.6 +/- 31.1 msec vs 181.8 +/- 32.8 msec, 240.3 +/- 23.5 msec vs 236.7 +/- 25.4 msec, and 291.3 +/- 23.7 msec vs 287.4 +/- 25.1 msec for longitudinal and transverse propagation, respectively; P < 0.001), a similar duration of repolarization during both directions of propagation was observed in cells from the left ventricle at 50% and 90% of full repolarization (241.4 +/- 39.4 msec and 285.5 +/- 39.5 msec vs 240.4 +/- 38.9 msec and 284.9 +/- 39.6 msec for longitudinal and transverse propagation respectively; P = NS). A slight but significant difference was found at 30% of full repolarization in cells from the left ventricle (190.4 +/- 39.0 msec vs 187.0 +/- 38.0 msec for longitudinal and transverse propagation, respectively; P < 0.05). In the left ventricle, the duration of repolarization did not change as the distance between the recording site and stimulation site increased. CONCLUSION: The direction of wavefront propagation with respect to fiber orientation may not play an important role in modulating the duration of repolarization in epicardial cells from the left ventricle.

Role of dipolar and nondipolar components of the T wave in determining the T wave residuum in an isolated rabbit heart model.

INTRODUCTION: Repolarization heterogeneity has been shown to constitute a substrate for malignant ventricular arrhythmias. Noninvasive measurement of abnormal repolarization through assessment of QT interval dispersion from the resting standard 12-lead ECG initially had shown promise in assessing arrhythmia risk but was challenged recently. The relative T wave residuum (TWR) has been proposed recently to reflect regional repolarization dispersion more accurately. We analyzed the role played by the dipolar and nondipolar components in determining TWR. METHODS AND RESULTS: Singular value decomposition was applied to the repolarization signals obtained from isolated rabbit hearts using a 5 x 8 array multielectrode recording system during premature beats (N = 11) and after d-sotalol (N = 9) exposure. Both the dipolar and nondipolar components of the T wave increased significantly during premature stimulation and after d-sotalol exposure. The relative TWR decreased significantly during premature stimulation but did not change after d-sotalol. Changes in the dipolar and nondipolar components of the second half of the T wave were significantly greater than those corresponding to the first half during premature stimulation, and a significant correlation was observed between the nondipolar components of the second half of the T wave and the T(peak-end) interval. CONCLUSION: Conditions exist during which both the dipolar and nondipolar components can change simultaneously. Under these conditions, the relative TWR may not reflect regional heterogeneity of repolarization with accuracy. The nondipolar components of the second half of the T wave can be linked to assessment of the transmural dispersion of repolarization.

Beat-to-beat repolarization variability measured by T wave spectral variance index in chronic infarcted animals.

BACKGROUND: Recent experimental and clinical studies have shown that beat-to-beat variability of repolarization morphology is associated with an increased risk for developing malignant ventricular arrhythmias. However, few data exist on the relationship between beat-to-beat repolarization variability and myocardial infarction itself. METHODS AND RESULTS: In the present work we tested the algorithm of T wave spectral variance (TWSV) using the two dimension fast Fourier transform, in an animal model of myocardial infarction to extend the evidences that support the existence of beat-to-beat alteration in repolarization during the chronic stage of myocardial infarction. Thirty-four New Zealand rabbits were included in the study and divided in two groups. Group I (N = 24) exposed to surgical ligation of the left anterior descendent coronary artery. Group II (N = 10) sham operated animals. The TWSV index was calculated before and after 15 and 45 days of surgery. Both groups showed significant increments in TWSV after 15 days postsurgery. However, while the sham animals return to its control value, the infarcted group exhibited values of the TWSV index that remains significantly high after 45 days of surgery, with a mean increment of 28.7% (P < 0.05 against sham). Moreover, when the infarcted group was qualitatively divided in three subgroups, according to its infarction areas, a trend was found in the correlation between the magnitude of the infarcted area and the TWSV index. CONCLUSION: This noninvasive measure confirms the presence of temporal repolarization variability associated with chronic myocardial infarction and further contributes to identify the infarcted animals.