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Biomedical subjects

Kumaraswamy Nanthakumar

Publications and source records attributed to Kumaraswamy Nanthakumar.

16 recordsLinked to original sources

Cardiac electrophysiological consequences of neuromuscular incapacitating device discharges.

OBJECTIVES: The purpose of this study was to evaluate the cardiac consequences of neuromuscular incapacitating device (NID)/stun gun discharge in an experimental model. BACKGROUND: The large-voltage electrical discharges from NIDs have been suggested to pose a risk for triggering cardiac arrhythmias. METHODS: Intracardiac catheters and blood pressure transducers were inserted before the application of NID discharges in six anesthetized pigs. Two different commercially available models (NID-1 and NID-2), two different vectors of discharges (thoracic: parallel to the long axis of the heart on the chest wall, and nonthoracic: away from the chest, across the abdomen), and two different durations of discharge (5 and 15 s) were tested. The effect of simulated adrenergic stress using epinephrine was also evaluated. RESULTS: We studied a total of 150 discharges to 6 pigs; 74 of these discharges resulted in stimulation of the myocardium, as documented by electrical capture (mean ventricular rate during stimulation and capture, 324 +/- 66 beats/min). Of the 94 thoracic discharges, 74 stimulated the myocardium, compared with none from 56 nonthoracic discharges (p < 0.0001). During 16 discharges with epinephrine, there were 13 episodes of stimulation of the myocardium, of which 1 induced ventricular fibrillation and 1 caused ventricular tachycardia. Thoracic discharges from NID-1 were more likely to stimulate the myocardium than those from NID-2 (98% vs. 54%, p = 0.0007). CONCLUSIONS: In an experimental model, NID discharges across the chest can produce cardiac stimulation at high rates. This study suggests that NIDs may have cardiac risks that require further investigation in humans.

Animals↗

Biventricular pacemaker upgrade in previously paced heart failure patients--improvements in ventricular dyssynchrony.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces symptoms and mortality in patients with left bundle branch block (LBBB) and severe chronic heart failure. There are few data demonstrating the effects of CRT on contemporary dyssynchrony variables in patients with advanced heart failure who have been chronically paced from the right ventricle (RV). METHODS AND RESULTS: We reviewed baseline and follow-up clinical and echocardiographic data on patients receiving CRT in a single centre. Indices of global left ventricular (LV) function and dyssynchrony before and after CRT were measured. Patients were then divided into those receiving their first device (n = 39) and those receiving CRT as an upgrade to existing RV pacemakers (n = 32). Baseline demographic variables, indices of global LV function, symptomatic status, renal function, hemodynamics, and diuretic requirements were not different between previously paced patients and nonpaced patients. Mean length of RV pacing in the previously paced patients was 59 months (range 12-167 months). Patients in the previously paced group had a broader QRS complex than patients with intrinsic LBBB. Aortopulmonary delay of longer than 40 ms was present in 68% of all subjects, 67% had intraventricular septal and posterior wall motion delay longer than 130 ms, and 59% had an intraventricular delay as measured by tissue Doppler imaging of longer than 65 ms. There was no difference between paced and nonpaced patients for any of these measures of dyssynchrony. QRS duration was reduced to a greater extent in the previously paced patients than those with no previous device therapy. CRT led to important reductions in each dyssynchrony variable in both patients with previous RV pacing and those with intrinsic LBBB. The magnitude of these changes in measures of dyssynchrony was not different between the 2 groups. In all patients undergoing CRT, 50% had a reduction in furosemide dose at 3 months, 56% an improvement of at least 1 grade in New York Heart Association status, and 66% an improvement of at least 5% in LVEF. Divided by group, previously paced patients were no more or less likely than newly implanted patients to achieve one or more of these clinical outcomes. CONCLUSION: Our data suggest that patients with RV pacing and heart failure have similar dyssynchrony as patients with intrinsic LBBB. CRT leads to improvements in LV global function, dyssynchrony variables and symptoms in patients chronically paced from the RV that are similar to those observed in patients with LBBB without preexisting devices.

Aged↗

Increased ventricular repolarization heterogeneity in patients with ventricular arrhythmia vulnerability and cardiomyopathy: a human in vivo study.

Increased repolarization heterogeneity can provide the substrate for reentrant ventricular arrhythmias in animal models of cardiomyopathy. We hypothesized that ventricular repolarization heterogeneity is also greater in patients with cardiomyopathy and ventricular arrhythmia vulnerability (inducible ventricular tachycardia or positive microvolt T wave alternans, VT/TWA) compared with a similar patient population without ventricular arrhythmia vulnerability (no VT/TWA). Endocardial and epicardial repolarization heterogeneity was measured in patients with (n = 12) and without (n = 10) VT/TWA by using transvenous 26-electrode catheters placed along the anteroseptal right ventricular endocardium and left ventricular epicardium. Local activation times (AT), activation-recovery intervals (ARI), and repolarization times (RT) were measured from unipolar electrograms. Endocardial RT dispersion along the apicobasal ventricle was greater (P < 0.005) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.005). AT dispersion was similar between the two groups. Epicardial RT dispersion along the apicobasal ventricle was greater (P < 0.05) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.05). AT dispersion was similar between the two groups. A plot of AT as a function of ARI revealed an inverse linear relationship for no VT/TWA such that progressively later activation was associated with progressively shorter ARI. The AT-ARI relationship was nonlinear in VT/TWA. In conclusion, patients with cardiomyopathy and VT/TWA have greater endocardial and epicardial repolarization heterogeneity than those without VT/TWA without associated conduction slowing. The steep repolarization gradients in VT/TWA may provide the substrate for functional conduction block and reentrant ventricular arrhythmias.

Adult↗

Deployment of left ventricular lead from the ipsilateral side of central vein obstruction.

Cardiac resynchronisation therapy improves symptoms and reduces mortality in patients with chronic heart failure. In patients with previously implanted devices, particularly automatic defibrillators, central venous stenoses provide a challenge to upgrading to resynchronisation devices. We present a patient with central venous obstruction secondary to previously implanted defibrillator leads, in whom we achieved coronary sinus pacing through the ipsilateral internal jugular vein.

Aged↗

Systematic evaluation of the determinants of defibrillation efficacy.

OBJECTIVES: We studied the effect of varying shock capacitance, shock impedance, and pulse duration on defibrillation efficacy in a randomized, crossover manner for biphasic shocks. BACKGROUND: The relationship between the electrical determinants of defibrillation efficacy is incompletely understood. METHODS: Biphasic shocks were delivered to 12 dogs through epicardial patches (to vary impedance) after 15 seconds of ventricular fibrillation using one of 100- or 155-muF capacitors at each of four pulse durations (2.5, 5, 10, 20 ms), in a balanced random order. There were two impedance groups: six with higher impedance (mean 97 +/- 15 Omega, range 80-120) and six with lower impedance (mean 39 +/- 3 Omega, range 34-44). Voltage requirements were estimated as the average of three defibrillation threshold (DFT) tests. RESULTS: Shock capacitance, resistance, and pulse duration all had significant effects upon the minimum voltage DFT (P = .0065, P = .0066, and P = .0001, respectively). The tilt associated with the lowest voltage and current requirement for each of the four capacitance/resistance combinations varied widely, between 34 +/- 5% and 63 +/- 3%, depending on capacitance and impedance. The optimal pulse duration associated with minimum DFT lies between 5.11 and 5.34 ms. CONCLUSIONS: Defibrillation voltage requirements for biphasic shocks are affected by pulse duration, capacitance and impedance, but not "tilt."

Animals↗

Decrease in fluoroscopic cardiac silhouette excursion precedes hemodynamic compromise in intraprocedural tamponade.

BACKGROUND: Acute pericardial tamponade is a life-threatening complication of invasive cardiovascular procedures. Survival depends on early recognition and treatment. A diagnostic test to detect pericardial fluid accumulation before a significant fall in blood pressure and without contamination of the sterile field would be valuable. OBJECTIVE: We tested the hypothesis that fluoroscopic excursion of the cardiac silhouette decreases early in the course of acute pericardial tamponade and precedes hemodynamic compromise. METHODS: The pericardial space of seven pigs was accessed by a sub-xiphoid puncture. Tamponade was produced by intrapericardial saline infusion at 20-25 mL/minute until the pericardial pressure equalized with right ventricular end diastolic pressure or the systolic blood pressure reached 40 mmHg. Supine fluoroscopic images were obtained every 2 minutes in the left anterior oblique view with simultaneous echocardiography. The fluoroscopic heart silhouette was digitized, and the maximum excursion during the cardiac cycle was quantified by custom software. The qualitative excursion of the fluoroscopic heart silhouette on randomly selected video images was also graded by two independent observers who were blinded to the time course of the experiment and the hemodynamics. RESULTS: During progressive pericardial fluid accumulation, the cardiac silhouette excursion quantified by the custom software (p < 0.001) and by video rating (p < 0.0001) was significantly reduced within 2 minutes. A statistically significant fall in blood pressure compared with baseline did not occur until 6 minutes (89 +/- 21 vs. 121 +/- 15 mmHg, p < 0.001). The interobserver agreement was very close, with a kappa statistic of 0.78. The reduction in cardiac silhouette excursion was apparent as soon as the effusion was detected by echocardiography. CONCLUSION: Cardiac silhouette excursion becomes reduced early in the course of acute pericardial fluid accumulation. This fluoroscopic observation can be used to detect impending pericardial tamponade before hemodynamic collapse.

Acute Disease↗

Regional variation in capture of fibrillating swine left ventricle during electrical stimulation.

INTRODUCTION: While it has been shown that electrical stimulation can capture a region of myocardium during ventricular fibrillation (VF), the ideal location to stimulate to maximize capture of the fibrillating in vivo left ventricle (LV) is not known. We previously demonstrated a mean directionality to the propagation of VF wavefronts in swine from posterior to anterior LV. We hypothesized that this directionality of VF wavefronts would affect capture of the LV epicardium while stimulating during VF. METHODS AND RESULTS: In seven open-chest swine, during different VF episodes, electrical stimulation was performed singly or simultaneously from two lines of 26 epicardial electrodes, one on the posterior LV adjacent to the posterior descending coronary artery and another on the anterior LV adjacent to the left anterior descending coronary artery. Mapping was performed between the line of stimulating electrodes with 768 recording electrodes 2-mm apart. The incidence and extent of epicardium captured by stimulation through the lines of stimulating electrodes were determined in the mapped region. Capture occurred during 67% of 78 VF episodes. Capture from the posterior LV line was achieved in 88% of the episodes and from the anterior LV line in 44% of the episodes (P = 0.001). The maximum amount of myocardium captured was also much greater for stimulating from the posterior as compared to the anterior LV line (232 +/- 168 mm(2) vs 64 +/- 124 mm(2), P = 0.003). A significant part of the variability in capture was related to the direction of the mean VF wavefront velocity vector in each animal (r = 0.84, P < 0.05). CONCLUSION: Electrical stimulation from the posterior LV resulted in a greater incidence and extent of LV capture than stimulation from the anterior LV. A significant component of the variability in capture is related to the mean direction of VF wavefronts.

Animals↗

Prophylactic implantable cardioverter-defibrillator therapy in patients with left ventricular systolic dysfunction: a pooled analysis of 10 primary prevention trials.

Strategies to decrease sudden cardiac death in patients with left ventricular systolic dysfunction are evolving. Recent clinical trials have evaluated the role of prophylactic implantable cardioverter-defibrillators (ICDs) in patients with and without additional risk stratifiers. We pooled studies comparing treatment with and without ICDs from published data and presented abstracts, irrespective of QRS duration and etiology of systolic dysfunction. On the basis of the available clinical trials, implantation of an ICD for primary prevention of death provides a 7.9% absolute mortality reduction (p = 0.003) in patients with left ventricular (LV) systolic dysfunction who were receiving optimized medical therapy. This finding was not sensitive to the exclusion of any individual trial. The ICD is an effective primary preventative measure in patients who are at risk for death; however, the application of this therapy needs to be individualized for the patient, similar to drug therapies in LV systolic dysfunction. In health care settings without unlimited resources, optimal use of this therapy will require better risk stratification methods or lowering of the initial device cost.

Confounding Factors, Epidemiologic↗

Electrophysiological findings in adolescents with atrial fibrillation who have structurally normal hearts.

BACKGROUND: Atrial fibrillation (AF) is uncommon in children, and its mechanisms are unknown. This study describes the electrophysiological findings in children and adolescents with AF and the outcome of catheter ablation. METHODS AND RESULTS: Nine adolescents with symptomatic, lone AF who failed antiarrhythmic drug therapy were evaluated. All patients had ECG-documented AF and underwent invasive electrophysiological testing. Intracardiac mapping was performed to determine the site of spontaneous onset of AF and rapidly firing atrial foci. Only the triggering focus was targeted for ablation or isolation. The patients' mean age was 15.9+/-3.3 (range, 8 to 19 years). The most common finding was rapid, irregular atrial tachycardias in the region of the pulmonary veins (n=5), left atrium (n=2), or crista terminalis (n=3). One patient had foci in both the pulmonary veins and crista terminalis. The cycle lengths ranged from 108 to 280 ms. Catheter ablation was acutely successful in 8 patients (88.9%), whereas 1 patient with multiple left atrium foci was treated with the surgical maze operation. Over a mean of 35+/-22 months, 7 patients (77.8%) were arrhythmia free on no medications, while AF recurred in 2 patients who are controlled on antiarrhythmic medications. Two patients with tachycardia-induced cardiomyopathy had resolution of their left ventricular dysfunction after ablation. CONCLUSIONS: AF in adolescents with structurally normal hearts is usually due to foci in the pulmonary veins, crista terminalis, or left atrium. These foci usually induce irregular atrial tachycardias. Catheter ablation of the foci is effective in eliminating recurrent AF.

Adolescent↗

Resumption of electrical conduction in previously isolated pulmonary veins: rationale for a different strategy?

BACKGROUND: Atrial fibrillation (AF) may recur after pulmonary vein isolation (PVI) as the result of either recurrent PV conduction or non-PV foci. This study characterized the electrophysiological findings of patients with recurrent AF after initially successful PVI and the clinical outcome after a repeat procedure. METHODS AND RESULTS: Among 185 patients undergoing PVI, 52 reported no significant improvement in their clinical course. We analyzed PV conduction in 51 PVs (15 patients) at repeat PVI. All PVs were isolated with either RF (30 W, 50 degrees C, 60 seconds) or cryoablation (-80 degrees C for 5 minutes). At repeat study, 42 of the previously isolated 51 PVs had return of conduction. All patients had recurrent conduction in > or =2 PVs, with only 1 non-PV focus identified. The mean number of RF applications required to re-isolate the PVs was fewer at the repeat compared with the initial procedure (10+/-6 versus 4+/-2, P<0.005). Over a period of 15+/-6 months, all but 1 patient was clinically improved by the second procedure. CONCLUSIONS: In patients with recurrent AF after PVI, return of PV conduction can be expected. Repeat PVI provides significant clinical benefit for these patients. These results suggest that if permanent PV isolation is the ablation strategy, different techniques may be required to improve long-term efficacy.

Atrial Fibrillation↗

Epicardial organization of human ventricular fibrillation.

OBJECTIVE: The objective of this study was to test the hypothesis that on the epicardium of the in vivo human heart, ventricular fibrillation (VF) consists of chaotic small wavefronts that constantly change paths. BACKGROUND: Despite the significance of VF to cardiovascular mortality, little is known about the wavefronts that constitute VF in humans. METHODS: In 9 patients undergoing cardiac surgery, a single VF episode was induced by rapid pacing immediately after institution of cardiopulmonary bypass while recordings were made from 504 electrodes spaced 2 mm apart in a 20 cm(2) plaque held against the anterior left ventricle epicardium. A total of 26 segments of VF, each 2 s long, were analyzed. A computer algorithm identified individual wavefronts and classified them into groups that followed similar activation sequences. RESULTS: The mean activation rate was 5.8 +/- 1.8 (mean +/- SD) cycles/s. The wavefronts during each epoch were grouped into 9.4 +/- 7.1 different activation pathways, and 8.3 +/- 2.3 wavefronts followed each pathway. Individual wavefronts spread to activate an area of 5.1 +/- 3.0 cm(2) in the mapped region. The majority of the wavefronts propagated into the mapped region and/or propagated out of the mapped region into adjacent tissue, suggesting that the wavefronts were larger than 5.1 cm(2). Reentry was identified in only 16 of the 26 (62%) 2-s segments, always completed <2 cycles, and lasted for 9.5 +/- 6.6% of these 16 epochs, which is 5.8% of the total duration of all the segments analyzed. CONCLUSION: VF wavefronts on the human epicardium are usually large, repeatedly follow distinct pathways, and only occasionally reenter. If these results for the left ventricular epicardium are representative of those for the entire ventricular mass, they do not support the hypothesis that human VF consists of small, constantly changing wavefronts, but rather suggest that there is significant organization of human VF.

Action Potentials↗

Functional assessment of pulmonary vein stenosis using radionuclide ventilation/perfusion imaging.

Pulmonary vein (PV) stenosis following catheter ablation of atrial fibrillation (AF) is a new clinical syndrome. The optimal method of assessing this syndrome is not known. We evaluated radionuclide perfusion imaging, anatomic imaging, and direct measurements of PV-left atrial (LA) pressure gradients in patients suspected of having PV stenosis after catheter ablation for the treatment of AF. The study included 11 consecutive patients who were referred to a tertiary referral center for the evaluation of symptoms suggesting or imaging evidence of PV stenosis following catheter ablation for AF. All patients underwent anatomic imaging of their PVs with direct pulmonary venography or CT scanning as well as radionuclide perfusion imaging. PV stenosis (> 50% diameter) was diagnosed by venography in 6 of the 11 patients and in 16 of 44 PVs. All six patients with PV stenosis had perfusion defects in the affected pulmonary lobe. In contrast, all of the patients without anatomic evidence of PV stenosis had normal perfusion. There were 14 PVs with stenoses of > 80% of the luminal diameter, all of which had a corresponding perfusion abnormality ascertained by perfusion scanning. In all 14 PVs with a resting PV-LA gradient of > 5 mm Hg, there was a corresponding perfusion defect. PV stenosis results in decreased perfusion in the affected lobe when the resting PV-LA pressure gradient is at least 5 mm Hg or when there is 80% luminal stenosis. A perfusion scan may serve as an effective screening tool for PV stenosis and may be most useful in assessing the hemodynamic significance of an anatomic PV stenosis.

Adult↗

Is inappropriate implantable defibrillator shock therapy predictable?

OBJECTIVE: To identify implantable cardioverter defibrillator (ICD) patients who are at risk of receiving inappropriate shock. BACKGROUND: Inappropriate ICD shock, usually from atrial fibrillation (AF) or sinus tachycardia (ST), is a common problem. We hypothesized that clinical variables would predict which patients with single chamber ICDs would be more likely to receive inappropriate therapy and be candidates for more accurate discriminators such as those available in dual chamber ICDs. METHODS: The ICD registry at St. Michael's Hospital has it's clinical information and demographic data updated after each clinic visit. Inappropriate shock was considered as the outcome variable. Possible predictors considered were age, gender, ejection fraction, NYHA class, prior CABG and prior history of AF. Univariate predictors were identified using t-test for continuous variables and Chi-square test for categorical variables. Multivariate predictors were identified using stepwise logistic regression analyses. RESULTS: Of 299 patients, 261 had complete data for analysis. In this population 78% were male, mean age was 60 +/- 13 years, mean ejection fraction was 37 +/- 15% and mean follow up was 53 +/- 36 months. One hundred and sixteen of the 261 patients (44%) received one or more inappropriate therapies (73% within 2 years of receiving their device), and 140 (51%) received one or more appropriate therapies. Significant predictors of inappropriate therapy by multivariate model were prior AF (OR 2.6, 95% CI 1.5-4.5) and NYHA class 1 vs. classes 2-4 (OR 2.2, 95% CI 1.2-3.7). CONCLUSION: Clinical characteristics of ICD patients can predict those at risk for inappropriate shock and should be considered for interventions to decrease such shocks.

Aged↗

Regional differences in ventricular fibrillation in the open-chest porcine left ventricle.

It has been hypothesized that during ventricular fibrillation (VF), the fastest activating region, the dominant domain, contains a stable reentrant circuit called a mother rotor. This hypothesis postulates that the mother rotor spawns wavefronts that propagate to maintain VF elsewhere and implies that the ratio of wavefronts propagating off a region to those propagating onto it (propoff/propon) should be >1 for the dominant domain but <1 elsewhere. To test this prediction in the left ventricular (LV) epicardium of a large animal, most of the LV free wall was mapped with 1008 electrodes in 7 pigs. VF activation rate was faster in the posterior than in the anterior LV (10.0+/-1.3Hz versus 9.3+/-1.3Hz; P<0.001). The anterior LV had a higher fraction of wavefronts that blocked than did the posterior LV and had a propoff/propon ratio <1 (P<0.001). The mean conduction velocity vectors of the VF wavefronts pointed in the direction from the posterior to the anterior LV. Although these findings favor a dominant domain in the posterior LV, the facts that the anterior LV had a higher incidence of reentry than did the posterior LV and that the posterior LV did not have propoff/propon significantly different from 1 do not. Thus, quantitative regional differences are present over the porcine LV epicardium during VF. Although these differences are not totally consistent with the presence of a dominant domain within the LV free wall, the mean conduction velocity vector is consistent with one in the septum.

Animals↗