Objective: This study was conducted to assess the incidence of sudden cardiac death (SCD) in post myocardial infarction patients and to determine the predictive value of various risk markers in identifying cardiac mortality and SCD. Methods: Left ventricular function, arrhythmias on Holter and microvolt T wave alternans (MTWA) were assessed in patients with prior myocardial infarction and ejection fraction ≤ 40%. The primary outcome was a composite of cardiac death and resuscitated cardiac arrest during follow up. Secondary outcomes included total mortality and SCD. Results: Fifty-eight patients were included in the study. Eight patients (15.5%) died during a mean follow-up of 22.3 ± 6.6 months. Seven of them (12.1%) had SCD. Among the various risk markers studied, left ventricular ejection fraction (LVEF) ≤ 30% (Hazard ratio 5.6, 95% CI 1.39 to 23) and non-sustained ventricular tachycardia (NSVT) in holter (5.7, 95% CI 1.14 to 29) were significantly associated with the primary outcome in multivariate analysis. Other measures, including QRS width, heart rate variability, heart rate turbulence and MTWA showed no association. Conclusions: Among patients with prior myocardial infarction and reduced left ventricular function, the rate of cardiac death was substantial, with most of these being sudden cardiac death. Both LVEF ≤30% and NSVT were associated with cardiac death whereas only LVEF predicted SCD. Other parameters did not appear useful for prediction of events in these patients. These findings have implications for decision making for the use of implantable cardioverter defibrillators for primary prevention in these patients.

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Aims: Sedation is not consistently used during electrophysiology procedures because of concerns regarding effects on tachycardia inducibility. We designed this study to assess the effect of conscious sedation on tachycardia inducibility and patient comfort during supraventricular tachycardia ablation. Methods and results: Patients with narrow QRS tachycardia and no pre-excitation undergoing an electrophysiology study were randomly assigned to sedation or placebo group. Patients in the sedation group received intermittent doses of midazolam and fentanyl, while those in the placebo group received normal saline as placebo. The physician and the patient were blinded to the allocation. Information was collected on tachycardia inducibility, patient discomfort, and complications. A total of 103 patients were included in the study. Proportion of patients with difficult tachycardia induction (27.4% vs. 32.7%) or with non-inducibility (5.8% vs. 3.8%) were not different between the sedation and placebo groups. Patient discomfort as measured by the Wong-Baker scale was significantly less in the sedation group (1.45 ± 1.08 vs. 2.24 ± 1.2, P < 0.0007) compared to the placebo group. There was no difference in incidence of hypotension or hypoxia between the two groups. Conclusions: Conscious sedation with intermittent midazolam- and fentanyl-reduced patient discomfort during electrophysiology study and ablation of supraventricular tachycardia without affecting tachycardia inducibility. Sedation administered in the absence of an anaesthetist was safe.

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Background: T wave alternans (TWA) is an electrocardiographic marker of heightened sudden death risk from ventricular tachyarrhythmias in patients with cardiomyopathy. TWA is evaluated from the 12-lead electrocardiogram, Frank lead, or Holter lead recordings, however these clinical lead configurations will not record TWA from adjacent regions of the body torso. Objective: We tested the hypothesis that changing heart rate or ventricular activation may alter the body surface distribution of TWA such that the clinical ECG leads fail to detect TWA in some patients; thereby producing a false-negative test. Methods: In 28 cardiomyopathy patients (left ventricular ejection fraction 28±6%), 114 unipolar electrograms were recorded across the body torso during incremental atrial pacing, followed by atrioventricular pacing at 100, 110 and 120bpm. TWA was measured from each unipolar electrogram using the spectral method. A clinically positive TWA test was defined as TWA magnitude (Valt) ≥1.9 uV with k ≥3 at ≤110bpm. Results: Maximum Valt (TWAmax) was greater from the body torso than clinical leads during atrial (p<0.005) and atrioventricular pacing (p<0.005). TWAmax was most prevalent in the right lower chest with atrial pacing 100 bpm and shifted to the left lower chest at 120 bpm. TWAmax was most prevalent in left lower chest with atrioventricular pacing at 100 bpm and shifted to the left upper chest at 120 bpm. Using the body torso as a gold standard, the false-negative rate for clinically positive TWA with clinical leads was 21% during atrial and 11% during atrioventricular pacing. Due to TWA signal migration outside the clinical leads, clinically positive TWA became false-negative when pacing mode was switched (atrial→atrioventricular pacing) in 21% of patients. Conclusions: The body surface distribution of TWA is modulated by heart rate and the sequence of ventricular activation in patients with cardiomyopathy, which can give rise to modest false-negative TWA signal detection using standard clinical leads.

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Background: Syntax 1 and recently Syntax 2(SS2) scores are validated risk prediction models in coronary disease. Objectives: To find out the long term outcomes following stenting for unprotected left main bifurcation disease (LMD) and to validate and compare the performance of the SYNTAX scores 1 and 2(SS1 and SS2 PCI) for predicting major adverse cardiac events (MACE) in Indian population. Methods: Single-center, retrospective, observational study involving patients who underwent percutaneous coronary intervention (PCI) with at least one stent implanted for the LMD. Discrimination and calibration models were assessed by ROC curve and the Hosmer-Lemeshow test. Results: Data of 103 patients were analyzed. The mean SS1 and SS2 scores were 27.9 and 30.7 and MACE was 16.5{\%} at 4 years. The target lesion revascularization (TLR) rate at 4 years was 11(10.7{\%}). There were 4 deaths (3.8{\%}). The mean left ventricular ejection fraction (LV EF) was the only variable in SS2, which predicted cardiac events. ROC curve analysis showed both models to be accurate in predicting TLR and mortality following LM PCI. SS2 score showed a better risk prediction than SSI with AUC for TLR (SSI 0.560 and SS2PCI 0.625) and AUC for mortality (SS1 0.674 and SS2PCI 0.833). Hosmer-Lemeshow test validated the accuracy of both the risk models in predicting the events. Conclusions: Both risk models were applicable for Indian patients. The SS2 score was a better predictor for mortality and TLR. In the SS2 score, the LV EF was the most useful predictor of events after LM PCI.

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{\textcopyright} 2017 Wiley Periodicals, Inc. Background: The His-ventricular (HV) interval is an important index of atrioventricular conduction, but at present can be reliably measured only during an invasive electrophysiology (EP) study. Magnetocardiography (MCG) is a noninvasive measurement of weak magnetic fields generated by the heart. We compared HV interval noninvasively assessed using MCG with the corresponding values measured directly in an EP study. Methods: MCG was measured using a 37-channel system inside a magnetically shielded room in patients who had previously undergone an EP study. His-bundle potential was identified in the PR segment after signal averaging. Magnetic field maps representing the spatial distribution of ramp-like signals in the PR segment generated at various instants of time were used to identify His-bundle signals in cases where the deflection representing the His was ambiguous. Results: The study included 23 patients (14 male, nine female) with a wide range of HV intervals measured during EP study (49 ± 17 ms, range 35–120 ms). In 21 (91{\%}) subjects, discernible His-bundle signals are observed in the PR segment of MCG traces. HV intervals measured between the two methods showed a correlation (r 2 = 0.87, P {\textless} 0.0001) with a mean difference of 5.4 ± 3.2 ms. Conclusion: With the use of new criteria to identify the His-bundle deflection in signal-averaged MCG signals, we report a high success rate in noninvasive HV interval measurement and a good agreement with those from EP study. The results encourage the use of MCG as a noninvasive method for measurement of the HV interval.

OBJECTIVE Access to pacemakers remains poor among many patients in low/middle-income countries. Reuse of explanted pacemakers is a possible solution, but is still not widespread because of concerns regarding outcomes, especially infection. Our objective was to study early outcomes with implants using reused devices and compare them with those with implants using new devices. METHODS We studied all patients who underwent implantation of a new or reused pacemaker, cardiac resynchronisation therapy (CRT) device or implantable cardioverter defibrillator (ICD) in the last 5 years at a single institution. We analysed outcomes related to infection, device malfunction and device-related death within 6 months after initial implantation. RESULTS During the study period, 887 patients underwent device implant, including 127 CRT devices or ICDs. Of these, 260 devices (29.3{\%}) were reused and the others were new. At 6 months, there were three device-related infections in implants using a new device. There were no infections among patients receiving a reused device. There were no device malfunctions or device-related deaths in either group. CONCLUSIONS We found no difference in rate of infection or device malfunction among patients getting a reused device as compared with those with a new device. This study reinforces the safety of reusing devices for implant including CRT and ICDs.

Aim A national atrial fibrillation (AF) registry was conducted under the aegis of the Indian Heart Rhythm Society (IHRS), to capture epidemiological data-type of AF, clinical presentation and comorbidities, current treatment practices, and 1-year follow-up outcomes. Methods A total of 1537 patients were enrolled from 24 sites in India in the IHRS-AF registry from July 2011 to August 2012. Their baseline characteristics and follow-up data were recorded in case report forms and subsequently analyzed. Results The average age of Indian AF patients was 54.7 years. There was a marginal female preponderance – 51.5{\%} females and 48.5{\%} males. At baseline, 20.4{\%} had paroxysmal AF; 33{\%} had persistent AF; 35.1{\%} had permanent AF and 11{\%} had first AF episode. At one-year follow-up, 45.6{\%} patients had permanent AF. Rheumatic valvular heart disease (RHD) was present in 47.6{\%} of patients. Hypertension, heart failure, coronary artery disease, and diabetes were seen in 31.4{\%}, 18.7{\%}, 16.2{\%}, and 16.1{\%}, respectively. Rate control was the strategy used in 75.2{\%} patients, digoxin and beta-blockers being the most frequently prescribed rate-control drugs. Oral anticoagulation (OAC) drugs were used in 70{\%} of patients. The annual mortality was 6.5{\%}, hospitalization 8{\%}, and incidence of stroke 1{\%}. Conclusions In India, AF patients are younger and RHD is still the most frequent etiology. Almost two-third of the patients have persistent/permanent AF. At one-year follow-up, there is a significant mortality and morbidity in AF patients in India.

The aim was to study the angiographic profile in patients presented as acute coronary syndrome and its relation with risk factors and comparison between genders. This prospective observational study was performed on total 352 patients of acute coronary syndrome were analyzed for various risk factors, angiographic pattern in Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, South India from January 2015 to July 2016. Mean age of presentation was 52.62±11.63 years. Male were 271(77.0%) and female were 81(23.0%). Majority of patients were STEMI (67.6%) followed by UA (24.4%) and NSTEMI (8%). Smoker was 117(33.3%) patients. Hypertensive were 124(35.2%) of patients and 149(42.3%) were diabetics. Family history of CAD was positive in 45(12.8%). On angiographic evaluation left main reference diameter was lower in females (4.02±0.72) than males (4.07±0.82). LAD was most commonly involved followed by RCA and LCX among all three group of acute coronary syndrome. Left main was least involved (8.3%). In STEMI SVD (40.3%) was most common presentation, after that DVD was seen in 22.3%, TVD in 10.5%, non-obstructive coronary was seen in 16% of patients and normal coronary was seen in 11% of patients. In UA 28%, 22.8%, 13.2%, 15.8%, 20.2% was seen in SVD, DVD, TVD, non-obstructive and normal coronary respectively. Long length coronary lesions (>20mm) were seen in majority in all type of acute coronary syndrome. Coronary lesion length was not associated with presentation acute coronary syndrome and genders. Male were most commonly presented as acute coronary syndrome. STEMI was most common presentation. Diabetic was most prevalent risk factor. SVD was most common angiographic pattern and LAD was most common involved arteries.

Optimal stent deployment attaining larger lumen area with image guidance (IVUS/OCT) may reduce the risk of re-stenosis. However imaging based optimization is often not performed in emergency procedures. We planned to prospectively evaluate intra vascular ultrasound (IVUS) findings in patients with in stent restenosis (ISR) who underwent emergency PCI for ACS. Methods To find out the intra vascular ultrasound findings in drug eluting stent restenosis (DES-ISR). We enrolled consecutive patients with DES-ISR who had index PCI for ACS (NSTEMI/STEMI). IVUS analysis of individual lesions was performed for sub optimal stent deployment. Results Of the 1823 patients who had ACS PCI during the 5-year period, 172 patients {74 (9.4%) females and 88 males (8.4%)} had ISR. Eighty-two lesions in women were compared with 84 ISR lesions men. Baseline characteristics were similar except for presence of diabetes mellitus and multivessel disease. Females had more focal ISR (48 focal, 34 diffuse) compared to males (23 focal, 61 diffuse) (P < 0.001). The prevalence {38(46%) females and 33(39%)} and IVUS pattern of different mechanical factors (MF) with suboptimal stent deployment was not different between both sexes (P = 0.2). Conclusions The occurrence of ISR was higher in women. Women had higher TLR and lower mean vessel size. In 46% of women and 39% men, a mechanical factor with sub optimal stent deployment was found. Longer stented length, diffuse disease, calcification and Type B/C lesion type were associated with under expanded and undersized stents.

PURPOSE: Posteroseptal accessory pathways may be associated with a coronary sinus (CS) diverticulum. Our purpose was to describe the clinical characteristics, mapping and ablation of these pathways. METHODS: This was a retrospective study of all patients who underwent ablation of posteroseptal accessory pathways in a single centre. Patients with a diverticulum of the CS or one of its tributaries were included in group I, while the other patients formed group II. Clinical presentation, ablation procedure and outcome were compared between the two groups. RESULTS: A total of 51 patients were included, 16 in group I and 35 in group II. There were no significant differences in age or sex distribution. Atrial fibrillation (AF) and previous unsuccessful ablation were more common in group I. A negative delta wave in lead II was the ECG finding with best sensitivity and specificity for the presence of a diverticulum. A pathway potential was common at the successful site in group I, and the interval between local ventricular electrogram and delta wave onset was shorter (19.5 +/- 8 vs 33.1 +/- 7.6 ms, p {\textless} 0.001). There was a trend toward lower procedural success rate and higher recurrence rate in group I, although this was not significant. CONCLUSIONS: CS diverticula should be suspected in patients with manifest posteroseptal accessory pathways who have a previous failed ablation, documented AF or typical electrocardiographic signs. A discrete potential is frequently seen at the successful site, but the local ventricular electrogram is not as early as in other accessory pathways.

Background Pace mapping is a useful tool but is of limited utility for the atrium because of poor spatial resolution. We investigated the use of bipolar electrograms recorded from widely spaced electrodes in order to improve the resolution of pace mapping. Methods This prospective study included patients undergoing a clinical electrophysiology study. Unipolar pacing from either the superior or inferior lateral right atrium was performed to simulate atrial tachycardia. Twelve-lead electrocardiograms were recorded during pacing as a template. In addition, three intracardiac bipolar electrograms from a set of widely spaced electrodes were also recorded. Subsequently, unipolar pacing was performed from electrodes at known distances from the initial pacing site, and the morphology of P waves in the electrocardiogram and bipolar electrograms were compared with that of the template. Morphological comparison was performed by a cardiologist and by automated computerized matching. Spatial resolution was calculated as the minimum distance at which there was no match. Results Fifteen patients participated in the study. Distance at which differences in morphology were noted was smaller in the bipolar electrograms compared to that indicated by P waves in the electrocardiogram, when matched by the cardiologist (6.1±3.8 mm vs. 9.9±5.2 mm, p=0.012) or by automated analysis (4±0 mm vs. 9.9±4 mm, p{\textless}0.001). Conclusions Use of three bipolar electrograms recorded from a set of widely spaced electrodes in the right atrium improves the resolution of pace mapping compared to that using P waves from surface electrocardiograms alone.

Background Cardiac syndrome X includes a heterogenous group of patients with angina but normal epicardial coronaries in angiography. Objective Our objective was to study the clinical characteristics of patients with cardiac syndrome X. Methods Data of patients who underwent coronary angiography over a period of one year was retrospectively analyzed. Those with normal or non-obstructive coronaries in angiography with chest pain were included in this study. Results 1203 patients underwent coronary angiography during the study period. 105 (8.7{\%}) patients fulfilled the inclusion criteria. There were 52 (49.5{\%}) males and 53 (50.5{\%}) females including 31 (29.5{\%}) postmenopausal women. Many patients had atherosclerotic risk factors. Typical angina and atypical chest pain were reported by 63 (60{\%}) and 42 (40{\%}) patients, respectively. ECG was normal in 46 (43.8{\%}) and abnormal in 59 (56.2{\%}) patients. The most common abnormal finding in ECG was ST-T changes seen in 49 (46.7{\%}) patients. Regional wall motion abnormality with mild left ventricular systolic dysfunction was seen in 4 (3.8{\%}) patients while 101 (96.2{\%}) patients had normal ventricular function in echocardiography. TMT was positive for inducible ischemia in 35 (33.3{\%}) patients and inconclusive in 10 (9.5{\%}) patients. Angiography showed normal epicardial coronaries in 85 (80.9{\%}) patients. Conclusions Cardiac syndrome X constitutes a significant subset of patients undergoing coronary angiography. It is essential to identify and treat them specifically for microvascular angina. Many of them have atherosclerotic risk factors but their presentation is different from those with obstructive coronaries.

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BACKGROUND: Coronary sinus (CS) has been shown to be larger in patients with atrioventricular nodal reentrant tachycardia (AVNRT). We sought to determine if echocardiographically measured CS diameter can help identify the mechanism of tachycardia in patients with narrow complex tachycardia without preexcitation before the invasive electrophysiology study. METHODS: Forty four patients with documented narrow complex, short RP tachycardia who were scheduled for an electrophysiology study were included. Based on the electrophysiology study, patients were divided into those with AVNRT and those with a concealed accessory pathway and atrioventricular reentrant tachycardia (AVRT). Proximal CS diameter (CSp) measured at the ostium and mid CS diameter (CSm) 1 cm distal to the ostium using transthoracic echocardiography. RESULTS: CSp was significantly larger in patients with AVNRT than AVRT (14.1 +/- 5 vs. 9.9 +/- 2 mm, p {\textless} 0.0001). CSm diameter was not significantly different between the two groups. A cut-off of CSp {\textgreater} 11.2 mm identified AVNRT with a sensitivity of 92.6{\%} and specificity of 76.9{\%}. CSp was a better discriminant (AUC 0.89, 95{\%} CI 0.75-0.97) compared to age (AUC 0.74, 95{\%} CI 0.58-0.87) or tachycardia rate (AUC 0.60, 95{\%} CI 0.44-0.76). CONCLUSIONS: Echocardiographic measurement of the diameter of CS ostium can help in identifying the mechanism of the tachycardia before the invasive electrophysiology study.

Objective To prospectively study the techniques and outcomes of transcatheter closure of complex Atrial septal defects (ASD). Study design and settings Prospective single center study with experience in catheter closure of ASD. All patients with complex ASD suitable for device closure. Objective Analysis of outcomes of transcatheter closure of complex ASD in JIPMER Hospital over the past 5-year period. Methods Complex ASD was predefined and patients satisfying inclusion and exclusion criteria are included. All the patients had meticulous Transesophageal echocardiography (TEE) imaging beforehand. Modifications of the conventional techniques were allowed on a case per case basis according to operator preference. Successfully intervened patients were followed up clinically. Results Out of the 75 patients enrolled, 69 patients had successful device closure (success rate 92{\%}) despite challenging anatomy. Fifty-six (74{\%}) patients had ASD ≥25 mm. Fifteen patients (20{\%}) had defect size ≥35 mm and 20 patients (26.6{\%}) had devices implanted with ≥35 mm waist size. Fifty percent of patients had complete absence of aortic rim and 25{\%} had deficient posterior rim. Twenty percent of patients had malaligned septum. Mean follow up period was 3.2 years. Conclusions Trans catheter closure is feasible in anatomically complex substrates of Secundum ASD. Careful case selection, scrupulous imaging protocol, and expertise in modified techniques are mandatory for successful outcomes. Copyright {\textcopyright} 2013, Cardiological Society of India. All rights reserved.

Background Very few published data is available on the outcomes of balloon assisted techniques (BATs) for trans catheter closure (TCC) of very large (Defined as≥ 35 mm size) ostium secundum atrial septal defect (ASD). Objective To study the utility of BAT as against conventional techniques (CT) in TCC of very large ostium secundum ASD (≥ 35 mm) over the past 5-year period and to find out the association of different morphological features of the defects in relation to TCC outcomes.

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BACKGROUND: The arrhythmogenic substrate in survivors of unexplained cardiac arrest (UCA) has not been defined. OBJECTIVES: We tested the hypothesis that UCA patients have latent repolarization abnormalities, in particular T wave alternans (TWA), which may be unmasked with epinephrine (EPI) challenge. METHODS: We prospectively studied 10 UCA survivors (46±9 yr) and 11 first degree relatives (FDR) of sudden death victims (37±14 yr). UCA patients underwent standard clinical testing which was normal. FDR had normal clinical history and testing. All subjects underwent an EPI infusion (0.05, 0.1, 0.2 ug/kg/min, 5 min each dose) while recording continuous digital 12-lead ECGs. QTc and QT variability index (QTVI) were evaluated at each EPI dose. TWA magnitude (V(alt)) was assessed at each dose using the spectral method. Positive (+) TWA at each dose was defined as V (alt) {\textgreater}0 with k ≥3 in one or more 128-beat segment in ≥2 ECG leads. A novel metric, TWA burden, reflecting V(alt) integrated over time (s), was also evaluated for each EPI dose. RESULTS: There was no difference between UCA and FDR with respect to heart rate, QT, QTc, or QTVI at baseline or during EPI. At baseline, +TWA was similar between UCA and FDR (10 vs. 0{\%}, p=NS). During EPI, +TWA was more prevalent in UCA than FDR (80 vs. 18{\%}, p=0.009). TWA burden was greater in the UCA than FDR during EPI 0.1 (p=0.039) and EPI 0.2 ug/kg/min (p=0.009). CONCLUSIONS: UCA survivors are more likely to demonstrate latent TWA compared to FDR, which becomes manifest with epinephrine. This novel finding provides evidence for an arrhythmogenic substrate in UCA survivors.

Premature beats can trigger ventricular arrhythmias in heart disease, but the mechanisms are not well defined. We studied the effect of premature beats on activation and repolarization dispersion in seven patients with cardiomyopathy (57 ± 10 yr, left ventricular ejection fraction 31 ± 7{\%}). Activation time (AT), activation-recovery interval (ARI), and total repolarization time (TRT) were measured from 26 unipolar electrograms during right ventricle (RV) endocardial (early) to left ventricle epicardial (late) activation in response to RV apical extrastimulation (S1S2). Early TRT dispersion increased significantly with shorter S1S2 (1.0 ± 0.2 to 2.3 ± 0.4 ms/mm, P {\textless} 0.0001), with minimal change in late TRT dispersion (0.8 ± 0.1 to 1.0 ± 0.3 ms, P = 0.02). This was associated with an increase in early AT dispersion (1.0 ± 0.1 to 1.5 ± 0.2 ms/mm, P = 0.05) but no change in late AT dispersion (0.6 ± 0.1 to 0.7 ± 0.2 ms/mm, P = 0.4). Early and late ARI dispersion did not change with shorter S1S2. AT restitution slopes were similar between early and late sites, as was slope heterogeneity. ARI restitution slope was greater in early vs. late sites (1.3 ± 0.6 vs. 0.8 ± 0.6, P = 0.03), but slope heterogeneity was similar. With shorter S1S2, AT-ARI slopes became less negative (flattened) at both early (-0.4 ± 0.1 to +0.04 ± 0.2) and late (-1.5 ± 0.2 to +0.3 ± 0.2) sites, implying less activation-repolarization coupling. There was no difference in AT-ARI slopes between early and late sites at short S1S2. In conclusion, high-risk patients with cardiomyopathy have greater TRT dispersion at tightly coupled S1S2 due to greater AT dispersion and activation-repolarization uncoupling. Modulated dispersion is more pronounced at early vs. late activated sites, which may predispose to reentrant ventricular arrhythmias.

We have studied the effects of cleistanthin A and cleistanthin B, phytoconstituents isolated from the leaves of Cleistanthus collinus Roxb. (Euphorbiaceae), on blood pressure, electrocardiogram, and barium chloride-induced arrhythmia in Wistar rats. The two compounds were isolated by column chromatography and their identity was confirmed spectroscopically. A healthy, male Wistar rat was used to record the invasive blood pressure and electrocardiograph. The antiarrhythmic effects of cleistanthins A and B were studied using the barium chloride model. Both cleistanthin A and cleistanthin B showed a dose-dependent hypotensive effect. Both compounds reduced the mean blood pressure significantly although the dose required for the effect was higher in the case of cleistanthin B. In the electrocardiogram, cleistanthins A and B significantly altered the electrical activity of the heart, the changes were transient and of no further consequence. Intravenous injection of 64 microg or more of cleistanthins A and B caused a sudden respiratory depression without affecting the electrocardiogram. Cleistanthins A and B did not display any antiarrhythmic effect against barium chloride-induced arrhythmia. In conclusion, both cleistanthin A and cleistanthin B exert a hypotensive effect and have no antiarrhythmic effect against barium chloride-induced arrhythmia in Wistar rats.

Each year 400,000 North Americans die from sudden cardiac death (SCD). Identifying those patients at risk of SCD remains a formidable challenge. T wave alternans (TWA) evaluation is emerging as an important tool to risk stratify patients with heart diseases. TWA is a heart rate dependent phenomenon that manifests on the surface electrocardiogram (ECG) as a change in the shape or amplitude of the T wave every second heart beat. The presence of large magnitude TWA often presages lethal ventricular arrhythmias. Because the TWA signal is typically in the microvolt range, accurate detection algorithms are required to control for confounding noise and changing physiological conditions (i.e. data nonstationarity). In this study, we address the limitations of two common TWA estimation methods, spectral method (SM) and modified moving average (MMA). To overcome their limitations, we propose a modified TWA quantification framework, called Adaptive SM, that uses non-linear time-frequency distribution (TFD). In order to increase the robustness of TWA detection in ambulatory ECGs, we also propose a new technique, called non-negative matrix factorization (NMF)-Adaptive SM. We present the analytical background of these methods, and evaluate their accuracy in detecting synthetic TWA signal in simulated and real-world ambulatory ECG recordings under conditions of noise and data non-stationarity. The results of the numerical simulations support the effectiveness of the proposed approaches for TWA analysis, which may ultimately improve SCD risk assessment. {\textcopyright} 2011 IPEM.

Background In patients with severe left ventricular (LV) dysfunction, visible pulsus alternans coincides with visible T-wave alternans (TWA), but a similar relationship has not been described for nonvisible microscopic systolic pressure alternans (MSPA) and microvolt TWA (MTWA). Objective The purpose of this study was to determine the prevalence of MSPA and its relationship to MTWA in patients with cardiomyopathy. Methods Using the spectral method, MSPA was measured from finger pressure during incremental atrial pacing and then validated against MSPA measured from the LV pressure in 12 patients. In 23 other patients with cardiomyopathy (LV ejection fraction {\textless}40{\%}), noninvasive MSPA and MTWA were measured simultaneously during incremental atrial pacing. Results MSPA ({\textless}1 mm Hg) was detected in 80{\%} of patients with cardiomyopathy and in 43{\%} of controls. The presence of finger MSPA showed 100{\%} positive concordance with LV MSPA; however, finger MSPA was 20{\%} larger due to peripheral augmentation. Finger MSPA was highly concordant (96{\%} positive concordance and 90{\%} negative concordance) with MTWA. The magnitudes of MSPA and MTWA showed a linear correlation (R = 0.66, P {\textless}.001), and the k value, a measure of signal-to-noise ratio, was significantly larger for MSPA compared to MTWA (108 ± 88 vs 24 ± 48, P {\textless}.001). Premature beats resulted in concordant and coincident changes in MSPA and MTWA. During follow-up (454 ± 274 days), 2 (8.6{\%}) patients experienced ventricular tachycardia, and both manifested MSPA and MTWA during pacing at 600 ms. Conclusion MSPA can be detected noninvasively in patients with cardiomyopathy and is coupled to MTWA, suggesting a common mechanism. The high signal-to-noise ratio of MSPA may provide a novel robust metric of sudden cardiac death risk in these patients. {\textcopyright} 2011 Heart Rhythm Society. All rights reserved.

T wave alternans (TWA) has been associated with ventricular arrhythmias. Hence, TWA detection can risk stratify patients with heart disease who may experience sudden death from ventricular arhythmias. However, accurate TWA detection is technically challenging due to the low microvolt TWA signal and the confounding effect of biological noise such as movement, myopotentials or respiration. In this paper, we propose nonnegative matrix factorization (NMF)-Adaptive spectral method to increase the robustness of TWA detection in ambulatory electrocardiograms (ECGs). The proposed method applies a non-linear time-frequency (TF) analysis and NMF to the aligned ST-T waveforms. This method separates the TWA signal from the other non-desired ECG signal components, and detects TWA with high accuracy. The performance of our proposed method is validated in a clinical study using ECGs which confirms a TWA detection of 92{\%} compared to 47{\%} using the conventional spectral method.

AIMS: Dispersion of repolarization (DOR) in the human heart is minimized by activation-repolarization coupling. Adrenergic stimulation can be proarrhythmic in patients with impaired left-ventricular function and its effect on repolarization dispersion has not been systematically investigated. Our objective was to study the effect of dobutamine on repolarization dispersion and activation-repolarization coupling in patients with cardiomyopathy. METHODS AND RESULTS: Activation recovery intervals (ARI) and activation times (AT) were measured from unipolar electrograms at 10 sites along the apicobasal right ventricle (RV) in 14 patients with cardiomyopathy (LVEF {\textless} 40{\%}). These measurements were made during control, dobutamine 2.5-5.0 microg/kg/min, and a recontrol phase while maintaining constant heart rates with atrial pacing. Dispersion of repolarization was calculated from the total recovery time (TRT, AT+ARI). Activation-repolarization coupling was assessed by linear regression of ARI and AT. Dispersion of repolarization across all 10 sites and between adjacent sites increased with dobutamine compared with control (whole DOR: range 15 +/- 2 vs. 12 +/- 2 ms, P = 0.06 and standard deviation 5.5 +/- 0.9 vs. 4.3 +/- 0.9 ms, P = 0.04; adjacent DOR: 5.9 +/- 0.8 vs. 4.5 +/- 0.6 ms, P = 0.04). This was associated with shallower ARI/AT slopes (-0.3 +/- 0.2 vs. -0.8 +/- 0.2, P = 0.05) and a decrease in ARI-AT correlation (R(2) 0.4 +/- 0.1 vs. 0.6 +/- 0.1, P = 0.05) with dobutamine compared with control. CONCLUSION: Adrenergic stimulation increases apicobasal RV DOR and reduces coupling between activation and repolarization in patients with cardiomyopathy. This may provide a mechanism for the proarrhythmic potential of heightened adrenergic states in these patients.

Traditional time-frequency (TF) signal representations are not appropriate for parametric analysis ofmost real world signals. In this study, we describe Adaptive time-frequency distribution (TFD) as a robust approach to TF signal decomposition for non-stationary signal processing. This approach has not been utilized for TF signal analysis other than feature extraction. We introduce T wave altemans (TWA) analysis as a new application for this approach. In order to test the robustness of the proposed technique, we challenge it under conditions of non-stationary dynamics that are expected with real world TWA. The results of the numerical simulation support the effectiveness of this approach for TWA estimation. {\textcopyright} 2009 IEEE.

Background: Action potential duration alternans (APDA) can vary regionally in magnitude and phase. The influence of APDA heterogeneity on T-wave alternans (TWA) has not been defined. Objective: Our objectives were: (1) to determine how APDA affects the magnitude and spatial distribution of TWA, and (2) to optimize electrocardiographic (ECG) lead configuration accordingly to improve TWA detection. Methods: Global, regional, and discordant APDA were simulated in a 257-node heart model. Using a forward solution, body surface potentials were derived at 300 points on the thorax and TWA was computed at each point. In 22 patients with cardiomyopathy (left ventricular ejection fraction 28{\%} ± 6{\%}), TWA was measured from a 114-electrode body surface map using the spectral method during atrial pacing at 110 beats/min. Results: An increase in global APDA from 4 to 12 ms resulted in an increase in maximum TWA from 10 to 30 $\mu$V. TWA magnitude varied with the size and location of the alternating myocardium, but was largest with discordant APDA compared with regional or global APDA. Irrespective of the location or phase of APDA, TWA was largest over the precordium and correlated with T-wave amplitude in the simulation (R2= 0.56 ± 0.24, P {\textless}.01) and clinical study (R2= 0.45 ± 0.23, P {\textless}.02). A novel lead configuration (12 precordial leads + limb leads) significantly improved maximum TWA detection compared with the conventional 12-lead ECG+ Frank lead configuration. Conclusion: TWA magnitude is dependent on the interaction of concordant and discordant alternating sources within the heart. Maximum TWA consistently localizes to the precordium and a novel lead configuration using 12 precordial leads improves TWA quantification. {\textcopyright} 2009 Heart Rhythm Society.

BACKGROUND The modified moving average (MMA) and spectral method (SM) are commonly used to measure T-wave alternans (TWA), but their accuracy has not been compared in ambulatory electrocardiograms (ECGs) where TWA signal-to-noise ratio is low. Our objective was to compare the effect of noise and signal nonstationarity on the accuracy of TWA measurement using MMA versus SM when applied to synthetic and ambulatory ECGs. METHODS Periodic and nonperiodic noise were added to noiseless synthetic ECGs. Simulated TWA (0-20 microV) was added to synthetic ECGs and ambulatory ECG recordings. TWA was measured using SM and MMA, and the measurement error relative to added TWA was compared. An MMA ratio was used to discriminate TWA signal from noise. Signal nonstationarity was simulated by changing heart rate, TWA magnitude, and TWA phase. RESULTS With no added TWA, MMA falsely measured TWA in synthetic and ambulatory ECGs, while false measurement was not seen with SM. An MMA ratio {\textgreater} 1.2 eliminated false TWA detection. In the presence of low TWA magnitude ({\textless}10 microV), TWA was overestimated by MMA and underestimated by SM in proportion to the noise level. In synthetic ECGs with periodic noise and 10-microV added TWA, MMA was less accurate than SM. The effects of simulated signal nonstationarity on the TWA magnitude measured with MMA versus SM were similar using a 64-beat analysis window. CONCLUSIONS In the presence of noise, MMA falsely detects or overestimates simulated TWA in ambulatory ECG recordings. In this setting, the proposed MMA ratio improves the specificity of MMA.

Background— Action potential duration (APD) variation is an important determinant of wave break and reentry. The determinants of APD variability during early ventricular fibrillation (VF) in myopathic human hearts have not been studied. The objective of this study was to study the role of APD restitution and short-term cardiac memory on variation in human VF. Methods and Results— The study consisted of 7 patients (67±9 years old) with ejection fraction <35%. Monophasic action potentials were recorded from the right and/or left ventricular septum during VF. APD60/90 was measured in sinus beat preceding induction of VF, and its amplitude was used to define 60%/90% repolarization in VF. The monophasic action potential upstroke (dV/dtmax) was used to characterize local excitability. Simple linear regression showed that variability in APDn60 was determined by APD/diastolic interval restitution (R2=0.48, P<0.0001) and short-term memory (APD60 n−1, n−2, n−3, n−4; R2=0.55, 0.40, 0.33, and 0.27 respectively; P<0.001). Using multiple stepwise regression, short-term memory and restitution accounted for 62% of variance in APD60 (P<0.001). Individually, memory effect had the greatest contribution to APD variability (R2=0.55, P<0.0001). Conclusions— In early human VF, short-term memory and APD/diastolic interval restitution explain most of the APD variability, with memory effects predominating. This suggests that in early human VF, short-term cardiac memory may provide a novel therapeutic target to modulate progression of VF in myopathic patients.

Objectives: The aim of this study was to define the spatiotemporal distribution of intracardiac alternans and its relationship to body surface alternans in humans. Background: Spatial heterogeneity of alternans exists in the animal heart owing to nonuniform calcium cycling and restitution kinetics. Patients with cardiomyopathy manifest similar myocardial substrate, which might influence the distribution of intracardiac alternans and its projection onto the body surface. Methods: Repolarization alternans was simultaneously measured from unipolar electrograms in the right ventricular endocardium, left ventricular (LV) epicardium, and the surface electrocardiogram in patients with cardiomyopathy (n = 14, LV ejection fraction 29 ± 2{\%}) during atrial pacing at cycle length (CL) 800, 600, and 500 ms. Alternans was determined from the entire JT interval as well as the early, mid, and late JT interval with spectral analysis. Results: Alternans was not uniformly distributed within the heart, with alternating and nonalternating myocardial segments lying adjacent to one another. A greater number of epicardial sites exhibited alternans than endocardial sites at CL 600 ms. Temporal heterogeneity in alternans was present along the JT interval, and apical segments had proportionately less alternans in the late JT interval than mid or basal segments, resulting in apicobasal alternans heterogeneity in late JT interval. Discordant alternans was seen in 5 patients confined to the epicardium. Patients with surface alternans had a greater proportion of intracardiac sites with alternans when compared with those patients without surface alternans. Conclusions: Spatiotemporal heterogeneity and discordant alternans are evident in patients with cardiomyopathy. Greater spatial distribution of intracardiac alternans is associated with measurable body surface alternans. {\textcopyright} 2007 American College of Cardiology Foundation.

Steep action potential duration (APD) restitution slopes ({\textgreater}1) and spatial APD restitution heterogeneity provide the substrate for ventricular fibrillation in computational models and experimental studies. Their relationship to ventricular arrhythmia vulnerability in human cardiomyopathy has not been defined. Patients with cardiomyopathy [left ventricular (LV) ejection fraction {\textless}40{\%}] and no history of ventricular arrhythmias underwent risk stratification with programmed electrical stimulation or T wave alternans (TWA). Low-risk patients (n = 10) had no inducible ventricular tachycardia (VT) or negative TWA, while high-risk patients (n = 8) had inducible VT or positive TWA. Activation recovery interval (ARI) restitution slopes were measured simultaneously from 10 right ventricular (RV) endocardial sites during an S1-S2 pacing protocol. ARI restitution slope heterogeneity was defined as the coefficient of variation of slopes. Mean ARI restitution slope was significantly steeper in the high-risk group compared with the low-risk group [1.16 (SD 0.31) vs. 0.59 (SD 0.19), P = 0.0002]. The proportion of endocardial recording sites with a slope {\textgreater}1 was significantly larger in the high-risk patients [47{\%} (SD 35) vs. 13{\%} (SD 21), P = 0.022]. Spatial heterogeneity of ARI restitution slopes was similar between the two groups [29{\%} (SD 16) vs. 39{\%} (SD 34), P = 0.48]. There was an inverse linear relationship between the ARI restitution slope and the minimum diastolic interval (P {\textless} 0.001). In cardiomyopathic patients at high risk of ventricular arrhythmias, ARI restitution slopes along the RV endocardium are steeper, but restitution slope heterogeneity is similar compared with those at low risk. Steeper ARI restitution slopes may increase the propensity for ventricular arrhythmias in patients with impaired left ventricular function.