Krishnakumar Nair

Phase Mapping of Cardiac Fibrillation

Received January 25, 2009; accepted October 6, 2009. Phase is a descriptor that tracks the progression of a defined region of myocardium through the action potential and has been demonstrated to be an effective parameter in analyzing spatiotemporal changes during fibrillation. In this review, the basic principles behind phase mapping are presented mainly in the context of ventricular fibrillation (VF), atrial fibrillation (AF), and fibrillation from experimental monolayer data. During fibrillation, the phase distribution changes over time, depending on activation patterns. Analyzing these phase patterns provides us insight into the fibrillatory dynamics and helps clarify the mechanisms of cardiac fibrillation and modulation by interventions. Winfree1 introduced the phase analysis to study cardiac fibrillation in the late eighties. This time-encoding technique deals with a scenario where the activation periods are the same over the surface being mapped. To deal with the scenario of varying activation period over the mapped surface (common in animal and human fibrillation models), Gray et al2,3⇓ introduced the state-space encoding concept from nonlinear dynamics. In analyzing spatiotemporal phase maps constructed from electric or optical mapping of the surface of heart during VF, points around which the phase progresses through a complete cycle from −π to +π are of great interest. At these points, the phase becomes indeterminate and the activation wave fronts hinge to these points and rotate around them in an organized fashion. These points in the phase map are called phase singularity (PS) points. Bray et al4 developed a procedure to locate PS points in a phase map. Nash et al5 used phase mapping to study the entire ventricular epicardium of human hearts with a sock containing 256 unipolar contact electrodes. The development of this phase mapping tool has led to better understanding of fibrillation dynamics as evidenced by the …

Role of KATP Channels in the Maintenance of Ventricular Fibrillation in Cardiomyopathic Human Hearts

Rationale: Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF. Objective: We addressed the hypotheses that there is regional disease-related expression of KATP channels in human cardiomyopathic hearts and that KATP channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness. Methods and Results: In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 &mgr;mol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. KATP subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (P=0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (P=0.001), which was attenuated by glibenclamide. There was greater gene expression of all KATP subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (&Dgr;ERPTransmural=ERPEpicardium−ERPEndocardium) was verified with pacing protocols. &Dgr;ERPTransmural in control was 5±2 ms and increased to 36±5 ms with ischemia. This effect was greatly attenuated by glibenclamide (&Dgr;ERPTransmural for glibenclamide+ischemia=4.9±4 ms, P=0.019 versus control ischemia). Conclusions: KATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of KATP channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.

Escape capture bigeminy: Phenotypic marker of cardiac sodium channel voltage sensor mutation R222Q

BACKGROUND Electrocardiographic signature of escape capture bigeminy that spans generations and clusters in a family has not been linked to a sodium channel voltage sensor mutation. OBJECTIVE To characterize the clinical and biophysical consequences of the R222Q mutation in the voltage sensor of cardiac sodium channels. METHODS Comprehensive clinical assessment, invasive electrophysiologic study, genetic analysis, and patch-clamp studies were undertaken. RESULTS Uniquely, 5 members had the same electrocardiographic pattern of a junctional escape ventricular capture bigeminy. Genetic analysis of 3 family members revealed the same mutation (R222Q) in the cardiac sodium channel gene, SCN5A (nucleotide change was 665 G→A that led to missense amino acid substitution Arg 222 Gln, located in the S4 voltage sensor in domain I). Catheterization and mapping revealed that there was no consistent evidence of bundle branch reentry or fascicular potentials preceding ectopic beats. The bigeminy was suppressed by the intravenous administration of the sodium channel blocker, lidocaine. Patch-clamp studies revealed unique differential leftward voltage-dependent shifts in activation and inactivation properties of human voltage-gated Na(+) channels with the R222Q mutation, consistent with increasing channel excitability at precisely the voltages corresponding to the resting membrane potential of cardiomyocytes. CONCLUSIONS The R222Q mutation enhances cardiac sodium channel excitability, resulting in an unusual, highly penetrant phenotype of escape capture bigeminy and cardiomyopathy. These findings support the conclusion that a mutation in the voltage sensor of cardiac sodium channels can cause bigeminal arrhythmia associated with cardiomyopathy.

Effect of global ischemia and reperfusion during ventricular fibrillation in myopathic human hearts

The effect of lack of global coronary perfusion on myocardial activation rate, wavebreak, and its temporal progression during human ventricular fibrillation (VF) is not known. We tested the hypothesis that global myocardial ischemia decreases activation rate and spatiotemporal organization during VF in myopathic human hearts, while increasing wavebreak, and that a short duration of reperfusion can restore these spatiotemporal changes to baseline levels. The electrograms were acquired during VF in a human Langendorff model using global mapping consisting of two 112-electrode arrays placed on the epicardium and endocardium simultaneously. We found that global myocardial ischemia results in slowing of the global activation rate (combined endo and epi), from 4.89+/-0.04 Hz. to 3.60+/-0.04 Hz. during the 200 s of global ischemia (no coronary flow) (P<0.01) in eight myopathic hearts. Two minutes of reperfusion contributed to reversal of the slowing with activation rate value increasing close to VF onset (4.72+/-0.04 Hz). In addition, during the period of ischemia, an activation rate gradient between the endocardium (3.76+/-0.06 Hz) and epicardium (3.45+/-0.06 Hz) was observed (P<0.01). There was a concomitant difference in wavebreak index (that provides a normalized parameterization of phase singularities) between the epicardium (11.29+/-2.7) and endocardium (3.25+/-2.7) during the 200 s of ischemia (P=0.02). The activation rate, gradient, and wavebreak changes were reversed by short duration (2 min) of reperfusion. Global myocardial ischemia of 3 min leads to complex spatiotemporal changes during VF in myopathic human hearts; these changes can be reversed by a short duration of reperfusion.

Controlled Exposure Study of Air Pollution and T-Wave Alternans in Volunteers without Cardiovascular Disease

Background: Epidemiological studies have assessed T-wave alternans (TWA) as a possible mechanism of cardiac arrhythmias related to air pollution in high-risk subjects and have reported associations with increased TWA magnitude. Objective: In this controlled human exposure study, we assessed the impact of exposure to concentrated ambient particulate matter (CAP) and ozone (O3) on T-wave alternans in resting volunteers without preexisting cardiovascular disease. Methods: Seventeen participants without preexisting cardiovascular disease were randomized to filtered air (FA), CAP (150 μg/m3), O3 (120 ppb), or combined CAP + O3 exposures for 2 hr. Continuous electrocardiograms (ECGs) were recorded at rest and T-wave alternans (TWA) was computed by modified moving average analysis with QRS alignment for the artifact-free intervals of 20 beats along the V2 and V5 leads. Exposure-induced changes in the highest TWA magnitude (TWAMax) were estimated for the first and last 5 min of each exposure (TWAMax_Early and TWAMax_Late respectively). ΔTWAMax (Late–Early) were compared among exposure groups using analysis of variance. Results: Mean ± SD values for ΔTWAMax were –2.1 ± 0.4, –2.7 ± 1.1, –1.9 ± 1.5, and –1.2 ± 1.5 in FA, CAP, O3, and CAP + O3 exposure groups, respectively. No significant differences were observed between pollutant exposures and FA. Conclusion: In our study of 17 volunteers who had no preexisting cardiovascular disease, we did not observe significant changes in T-wave alternans after 2-hr exposures to CAP, O3, or combined CAP + O3. This finding, however, does not preclude the possibility of pollution-related effects on TWA at elevated heart rates, such as during exercise, or the possibility of delayed responses.

Non-linear image registration for correction of motion artifacts during optical imaging of human hearts

Optical imaging of cardiac electrical activity can be used to elucidate patho-physiological mechanisms of cardiac arrhythmias. However, cardiac motion during optical imaging causes significant error in electrophysiological measurements such as action potential duration. In particular, cardiac tissue in fibrillation introduces highly non-linear imaging artifacts. We present a novel approach that uses non-linear image registration to correct for in-plane cardiac motion, particularly of non-linear origin found during cardiac arrhythmias. The algorithm is performed entirely post-acquisition and does not require a complicated optical setup. It is computationally fast, and available as open source. The algorithm was tested with images acquired from five excised dilated myopathic human hearts and the results show that the image registration method significantly reduces both non-linear and linear motion-related artifacts in both sinus rhythm and ventricular fibrillation. This algorithm corrects for non-linear imaging artifacts caused by cardiac motion that are impossible to correct using linear registration methods.

Percutaneous transmitral commissurotomy in juvenile mitral stenosis--comparison of long term results of Inoue balloon technique and metallic commissurotomy.

To compare the immediate and long term results of percutaneous mitral valvotomy using metallic commissurotome and Inoue balloon in juvenile mitral stenosis.

Ventricular septal rupture following myocardial infarction. Long-term survival of patients who did not undergo surgery. Single-centre experience.

Long-term survival is rare in patients not undergoing surgery after post-myocardial infarction ventricular septal rupture.We report our experience of seven patients out of 27, who did not undergo surgery and were followed up for a mean period of 2.8 years.They were evaluated after a mean period of 2.2 months after infarction in our centre. The septal defects measured 9.8 mms on average and the mean left-to-right shunt ratio was 1.98:1. The mean pulmonary artery, right atrial and left ventricular end diastolic pressures were 28.3 ± 10.6, 4 ± 3 and 15.8 ± 4.8 mm Hg, respectively. Only three out of seven patients had LV aneurysm and all patients had single-vessel disease. Smaller defect size, minimal left-to-right shunt and preserved right ventricular function may be the factors responsible for long-term survival.

Phenotype, management and predictors of outcome in a large cohort of adult congenital heart disease patients with heart failure

OBJECTIVE Although heart failure (HF) is the leading cause of premature death in adult congenital heart disease (ACHD), little population-specific data exist. This study reports early experience from a dedicated, sub-specialty adult congenital heart disease-heart failure (ACHD-HF) clinic, aiming to identify risk factors for adverse outcome. METHODS Between 2012 and 2015, 126 patients (57% male) attended the ACHD-HF clinic. Baseline and follow-up data were analysed and compared across 4 anatomical/physiological subgroups: cyanotic ACHD, Fontan circulation (1V), biventricular circulation with a subaortic right ventricle (2V-RV) and biventricular circulation with a subaortic left ventricle (2V-LV). Predictors of the composite primary outcome: death, transplant or ventricular assist device (VAD) were identified using multivariable Cox proportional hazard models. RESULTS Mean age at first visit was 38±13years. Patients were grouped as follows: cyanotic ACHD 10%, 1V 24%, 2V-RV 29% and 2V-LV 37%. During a median follow-up of 1.7 (IQR 0.8-2.9) years, 38 patients (30%) reached the primary outcome. Event-free survival was 89%, 78% and 63% at 1, 2 and 3years. Forty (31.7%) patients experienced 69 HF hospitalisations. Between-group differences were noted for systolic function, valvular regurgitation, pacing prevalence and invasive hemodynamics. Multivariable analysis revealed 2V-RV subgroup (p=0.001), NYHA class (p=0.002) B-type natriuretic peptide >164pg/ml (p=0.003) and sodium <136mmol/L (p=0.036) as independently associated with death, transplant or VAD. CONCLUSIONS Our young ACHD-HF patients experienced high adverse event rates during a short period of follow-up. The prognostic markers identified will aid clinicians to stratify short-term risk and thereby guide advanced HF management decisions in ACHD.

Chasing Red Herrings: Making Sense of the Colors While Mapping

A 50-year-old man presented with sustained wide complex tachycardia and was treated with cardioversion. He gave a history of 2 such episodes within the past 7 years, requiring cardioversion each time. Ten years previously, he had undergone surgical repair of tetralogy of Fallot. Review of operative notes indicated that the procedure included patch closure of the ventricular septal defect, right ventricular outflow tract resection, repair with a transannular patch, and pulmonary valve replacement with a porcine valve. Editor’s Perspective see p 557 ECG recorded during the tachycardia showed a regular wide complex tachycardia at a rate of 240 beats per minute of left bundle branch block morphology with left axis deviation. ECG in sinus rhythm showed PR interval of 200 ms, right bundle branch block with normal axis, and QRS duration of 170 ms. Echocardiography showed mild right ventricular dilatation with normal left and right ventricular function. The ventricular septum was intact, there was no pulmonary regurgitation, and the peak gradient across the pulmonary valve was 32 mm Hg. Mapping was performed using an electroanatomic system (CARTO 3, Biosense Webster, Diamond Bar, CA). Wide complex tachycardia at a cycle length of 260 ms with the same morphology as the clinical tachycardia was induced during catheter placement and could not be pace terminated. ventriculo-atrial dissociation and negative His-ventricular interval confirmed ventricular tachycardia. Surface ECG was used …