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Biomedical subjects

Prashanthan Sanders

Publications and source records attributed to Prashanthan Sanders.

At least 19 recordsLinked to original sources

High-density mapping of spontaneous pulmonary vein activity initiating atrial fibrillation in humans.

INTRODUCTION: High-density three-dimensional (3D) mapping of the pulmonary vein (PV)-left atrial (LA) junction was performed to characterize spontaneous PV activity in humans. METHODS AND RESULTS: The activation patterns of ectopic beats and of the initial 2 seconds of atrial fibrillation (AF) from the PVs were analyzed using a 64-poles basket catheter. A focal mechanism was defined as a discrete site of early and centrifugal activation. Continuous activity was considered as an activation covering > or = 80% of the tachycardia beat-to-beat cycle length within the mapping field. In 35 patients, 123 spontaneous focal ectopic beats that did not induce AF and 95 that did induce AF were mapped. The mean coupling interval of ectopic discharges not inducing AF was 281 +/- 70 msec versus 236 +/- 90 msec for ectopies initiating AF (P < or = 0.01). The first ectopic activity of all 218 arrhythmogenic events showed exclusively a focal mechanism. During the 95 episodes of AF initiation, one or two ectopic beats from the PVs initiated AF in the LA in 39%, a stable focal tachycardia was recorded in 14%, continuous activity with important changes in cycle length (35 +/- 15 msec) suggestive of decremental or fibrillatory conduction was found in 18%, and in 29% the activation pattern could not be classified. No stable and sustained reentrant circuit could be identified by our mapping tool in the PV-LA junction. CONCLUSIONS: Arrhythmogenic activity from PVs in humans is predominantly due to discrete focal activity.

Atrial Fibrillation↗

The stepwise ablation approach for chronic atrial fibrillation--evidence for a cumulative effect.

Treatment options for atrial fibrillation (AF) have evolved from simple, fluoroscopy-guided pulmonary vein isolation for those patients with paroxysmal AF to complex, multi-modality procedures targeting not only anatomic structures but also electrophysiologic phenomena including complex fractionated electrograms, sites of dominant frequency and local non-venous drivers in patients with persistent and permanent AF. The stepwise ablation approach is a novel technique whereby structures contributing to initiation and maintenance of AF are sequentially targeted by radiofrequency ablation. Broadly divided into pulmonary veins, left atrial (LA) roof, left atrium (incorporating all anatomic regions of the chamber), mitral isthmus and non-LA structures, each region is targeted in sequence and the impact of ablation upon the global fibrillatory process assessed by measurement of AF cycle length (AFCL) at a site remote from the ablation target. In addition to pulmonary vein electrical disconnection and demonstrable complete conduction block across the roof and mitral isthmus lines (when performed), ablation is performed at those sites displaying continuous electrical and complex fractionated activity, with the endpoint of local organization, as well as at sites displaying electrograms consistent with focal sources driving AF. Ablation is accompanied by a cumulative increase in the AFCL prior to termination of AF by conversion either directly to sinus rhythm or to an atrial tachycardia which is then mapped conventionally and ablated. There is a ceiling of ablation within the LA beyond which further ablation is unlikely to result in a clinical benefit and should prompt evaluation of the contribution of the right atrium to maintenance of AF. The stepwise approach benefits from the integration of anatomic and electrophysiologic information to achieve a high level of success in termination of chronic AF by catheter ablation.

Atrial Fibrillation↗

Atrial electrical and structural abnormalities in an ovine model of chronic blood pressure elevation after prenatal corticosteroid exposure: implications for development of atrial fibrillation.

AIMS: Elevated blood pressure (EBP) is the most prevalent and potentially modifiable risk factor for AF, yet little is known of its atrial effects. We aimed to characterize the atrial electrical and structural changes in a chronic ovine model of EBP after prenatal corticosteroid exposure. METHODS AND RESULTS: Twelve sheep with chronically EBP (mean arterial pressure 94+/-3 mmHg) and six controls (71+/-4 mmHg, P<0.01) underwent acute open chest electrophysiologic and pathologic studies. We measured refractoriness at the atrial appendages at 3 cycle lengths (CL); conduction velocities at Bachmann's bundle, both atrial appendages and free walls at 4 CLs; conduction heterogeneity; atrial wavelength and AF duration. We performed light microscopy (LM) and electron microscopy (EM) and collagen and apoptosis studies. EBP was associated with widespread conduction abnormalities, shortening of atrial wavelength, and increased AF. There was no significant change in refractoriness. LM demonstrated atrial myocyte hypertrophy and myolysis in all EBP sheep and focal scarring in six. EM demonstrated mitochondrial and nuclear enlargement and increased collagen fibrils in EBP sheep, findings not present in any controls. Atrial collagen and apoptosis were increased in EBP animals. CONCLUSION: This study demonstrates that chronically, EBP is associated with significant atrial electrical and structural remodelling. These changes may explain the increased propensity to atrial arrhythmias observed with long-standing EBP.

Adrenal Cortex Hormones↗

Theoretical modeling of micro-scale biological phenomena in human coronary arteries.

This paper presents a mathematical model of biological structures in relation to coronary arteries with atherosclerosis. A set of equations has been derived to compute blood flow through these transport vessels with variable axial and radial geometries. Three-dimensional reconstructions of diseased arteries from cadavers have shown that atherosclerotic lesions spiral through the artery. The theoretical framework is able to explain the phenomenon of lesion distribution in a helical pattern by examining the structural parameters that affect the flow resistance and wall shear stress. The study is useful for connecting the relationship between the arterial wall geometries and hemodynamics of blood. It provides a simple, elegant and non-invasive method to predict flow properties for geometrically complex pathology at micro-scale levels and with low computational cost.

Biomechanical Phenomena↗

Characterization of conduction recovery across left atrial linear lesions in patients with paroxysmal and persistent atrial fibrillation.

BACKGROUND: Left atrial (LA) linear lesions are effective in substrate modification for atrial fibrillation (AF). However, achievement of complete conduction block remains challenging and conduction recovery is commonly observed. The aim of the study was to investigate the localization of gap sites of recovered LA linear lesions. METHODS AND RESULTS: Forty-eight patients with paroxysmal (n = 26) and persistent/permanent (n = 22) AF underwent repeat ablation after pulmonary vein (PV) isolation and LA linear ablation at the LA roof and/or mitral isthmus due to recurrences of AF or flutter. In 35 patients, conduction through the mitral isthmus line (ML) had recovered whereas roof-line recovery was observed in 30 patients. The gaps within the ML were distributed to the junction between left inferior PV and left atrial appendage in 66%, the middle part of the ML in 20%, and in 8% to the endocardial aspect of the ML while only 6% of lines showed an epicardial site of recovery. The RL predominantly recovered close to the right superior PV (54%) and less frequently in the mid roof or close to the left PV (both 23%). Reablation of lines required significantly shorter RF durations (ML: 7.24 +/- 5.55 minutes vs 24.08 +/- 9.38 minutes, RL: 4.24 +/- 2.34 minutes vs 11.54 +/- 6.49 minutes; P = 0.0001). Patients with persistent/permanent AF demonstrated a significantly longer conduction delay circumventing the complete lines than patients with paroxysmal AF (228 +/- 77 ms vs 164 +/- 36 ms, P = 0.001). CONCLUSIONS: Gaps in recovered LA lines were predominantly located close to the PVs where catheter stability is often difficult to achieve. Shorter RF durations are required for reablation of recovered linear lesions. Conduction times around complete LA lines are significantly longer in patients with persistent/permanent AF as compared to patients with paroxysmal AF.

Atrial Fibrillation↗

Phrenic nerve injury after atrial fibrillation catheter ablation: characterization and outcome in a multicenter study.

OBJECTIVES: The purpose of this study was to characterize the occurrence of phrenic nerve injury (PNI) and its outcome after radiofrequency (RF) ablation of atrial fibrillation (AF). BACKGROUND: It is recognized that extra-myocardial damage may develop owing to penetration of ablative energy. METHODS: Between 1997 and 2004, 3,755 consecutive patients underwent AF ablation at five centers. Among them, 18 patients (0.48%; 9 male, 54 +/- 10 years) had PNI (16 right, 2 left). The procedure consisted of pulmonary vein (PV) isolation in 15 patients and anatomic circumferential ablation in 3 patients, with additional left atrial lesions (n = 11) and/or superior vena cava (SVC) disconnection (n = 4). RESULTS: Right PNI occurred during ablation of right superior PV (n = 12) or SVC disconnection (n = 3). Left PNI occurred during ablation at the left atrial appendage. Immediate features were dyspnea, cough, hiccup, and/or sudden diaphragmatic elevation in 9, and in the remaining the diagnosis was made after ablation owing to dyspnea (n = 7) or on routine radiographic evaluation (n = 2). Four patients (22%) were asymptomatic. Complete recovery occurred in 12 patients (66%). Recovery occurred within 24 h in the two patients with left PNI and in one patient with right PNI occurring with SVC disconnection. In the other nine patients, right PNI recovery occurred after 4 +/- 5 months (1 to 12 months) with respiratory rehabilitation. After a mean follow-up of 36 +/- 33 months, six patients have persistent PNI (three with partial and three with no recovery). CONCLUSIONS: In this multicenter experience, PNI was a rare complication (0.48%) of AF ablation. Ablation of the right superior PV, SVC, and left atrial appendage were associated with PNI. Complete (66%) or partial (17%) recovery was observed in the majority.

Adult↗

Sites of focal atrial activity characterized by endocardial mapping during atrial fibrillation.

OBJECTIVES: The aim of the present study was to assess the feasibility of identifying sites of focal atrial activity by localized high-density endocardial mapping during atrial fibrillation (AF). BACKGROUND: Sites of focal activity in the left atrium have been demonstrated by epicardial mapping during AF. METHODS: Twenty-four patients (15 with paroxysmal, 3 with persistent, and 6 with permanent AF) underwent endocardial mapping during AF. A 20-pole catheter with five radiating spines was used to map both atria for 30 s in each of 10 pre-determined segments. A focal activity was defined as > or =3 atrial cycles with activation spreading from center to periphery of the mapping catheter. Catheter ablation was performed independent of the mapping results. RESULTS: Spontaneous focal activities were observed in 13 sites in the left atrium (9%; anterior 1, roof 2, posterior 6, inferior 4) in 12 patients (9 paroxysmal, 3 persistent). Focal activity was observed continuously (two sites) or intermittently (11 sites, median 5 episodes), and associated with shortening of the cycle length (from 183 +/- 33 ms to 172 +/- 29 ms; p < 0.05). The mean duration of an intermittent episode was 1.5 s (range 0.4 to 7.1 s). Atrial fibrillation terminated without ablation at the foci in all of 12 patients, but in 2 of them, re-initiated arrhythmia was successfully ablated at these foci. Nine of these 12 patients (75%) were arrhythmia-free without antiarrhythmic drugs during a follow-up period of 7.0 +/- 3.1 months. CONCLUSIONS: Termination of AF without ablation at the sites of atrial focal activity suggests that this activity may be triggered by impulses originating from other regions, such as the pulmonary veins.

Adult↗

An approach to catheter ablation of cavotricuspid isthmus dependent atrial flutter.

Much of our understanding of the mechanisms of macro re-entrant atrial tachycardia comes from study of cavotricuspid isthmus (CTI) dependent atrial flutter. In the majority of cases, the diagnosis can be made from simple analysis of the surface ECG. Endocardial mapping during tachycardia allows confirmation of the macro re-entrant circuit within the right atrium while, at the same time, permitting curative catheter ablation targeting the critical isthmus of tissue located between the tricuspid annulus and the inferior vena cava. The procedure is short, safe and by demonstration of an electrophysiological endpoint - bidirectional conduction block across the CTI - is associated with an excellent outcome following ablation. It is now fair to say that catheter ablation should be considered as a first line therapy for patients with documented CTI-dependent atrial flutter.

Journal Article↗

Localized sources maintaining atrial fibrillation organized by prior ablation.

BACKGROUND: Endocardial mapping of localized sources driving atrial fibrillation (AF) in humans has not been reported. METHODS AND RESULTS: Fifty patients with AF organized by prior pulmonary vein and linear ablation were studied. AF was considered organized if mapping during AF showed irregular but discrete atrial complexes exhibiting consistent activation sequences for >75% of the time using a 20-pole catheter with 5 radiating spines covering 3.5-cm diameter or sequential conventional mapping. A site or region centrifugally activating the remaining atrial tissue defined a source. During AF with a cycle length of 211+/-32 ms, activation mapping identified 1 to 3 sources at the origin of atrial wavefronts in 38 patients (76%) predominantly in the left atrium, including the coronary sinus region. Electrograms at the earliest area varied from discrete centrifugal activation to an activity spanning 75% to 100% of the cycle length in 42% of cases, the latter indicating complex local conduction or a reentrant circuit. A gradient of cycle length (>20 ms) to the surrounding atrium was observed in 28%. Local radiofrequency ablation prolonged AF cycle length by 28+/-22 ms and either terminated AF or changed activation sequence to another organized rhythm. In 4 patients, the driving source was isolated, surrounded by the atrium in sinus rhythm, and still firing at high frequency (228+/-31 ms) either permanently or in bursts. CONCLUSIONS: AF associated with consistent atrial activation sequences after prior ablation emanates mostly from localized sources that can be mapped and ablated. Some sources harbor electrograms suggesting the presence of localized reentry.

Aged↗

Shortening of fibrillatory cycle length in the pulmonary vein during vagal excitation.

OBJECTIVES: The goal of the present prospective study is to evaluate the impact of vagal excitation on ongoing atrial fibrillation (AF) during pulmonary vein (PV) isolation. BACKGROUND: The role of vagal tone in maintenance of AF is controversial in humans. METHODS: Twenty-five patients (18 with paroxysmal AF, 7 with chronic AF) were selected by occurrence of vagal excitation during AF (atrioventricular [AV] block: R-R interval >3 s) produced by PV isolation. Fibrillatory cycle length (CL) in the targeted PV and coronary sinus (CS) were determined before, during, and after vagal excitation. The CL was available at PV ostium during vagal excitation in 11 patients. RESULTS: Forty-eight episodes of vagal excitation were observed. During vagal excitation, CL abruptly decreased both in CS and PV (CS, 164 +/- 20 ms to 155 +/- 23 ms, p < 0.0001; PV, 160 +/- 22 ms to 143 +/- 28 ms, p < 0.0001), and both returned to the baseline value with resumption of AV conduction. The decrease in PVCL occurred earlier (2.5 +/- 1.5 s vs. 4.0 +/- 2.6 s, p < 0.01) and was of greater magnitude than that in CSCL (16 +/- 16 ms vs. 8 +/- 9 ms, p < 0.01). A sequential gradient of CL was observed from PV to PV ostium and CS during vagal excitation (138 +/- 29 ms, 149 +/- 24 ms, and 159 +/- 26 ms, respectively). The decrease in CL was significantly greater in paroxysmal than in chronic AF (CS, 11 +/- 9 ms vs. 5 +/- 7 ms, p < 0.05; PV, 23 +/- 25 ms vs. 8 +/- 14 ms, p < 0.05). CONCLUSIONS: Vagal excitation is associated with shortening of fibrillatory CL. This occurs earlier in PV with a sequential gradient to PV ostium and CS, suggesting that vagal excitation enhances a driving role of PV.

Atrial Fibrillation↗

High-density activation mapping of fractionated electrograms in the atria of patients with paroxysmal atrial fibrillation.

BACKGROUND: Areas of complex fractionated atrial electrograms (CFAEs) have been implicated in the atrial substrate of atrial fibrillation (AF). The mechanisms underlying CFAE in humans are not well investigated. OBJECTIVES: The purpose of this study was to investigate the regional activation pattern associated with CFAE using a high-density contact mapping catheter. METHODS: Twenty patients with paroxysmal AF were mapped using a high-density multielectrode catheter. CFAE were mapped at 10 different sites (left atrium [LA]: inferior, posterior, roof, septum, anterior, lateral; right atrium [RA]: anterior, lateral, posterior, septum). Local atrial fibrillation cycle length (AFCL) was measured immediately before and after the occurrence of CFAE, and the longest electrogram duration (CFAEmax) was assessed. RESULTS: Longer electrogram durations were recorded in the LA compared with the RA (CFAEmax 118 +/- 21 ms vs 104 +/- 23 ms, P = .001). AFCL significantly shortened before the occurrence of CFAEmax compared with baseline (LA: 174 +/- 32 ms vs 186 +/- 32 ms, P = .0001; RA: 177 +/- 31 ms vs 188 +/- 31 ms, P = .0001) and returned to baseline afterwards. AFCL shortened by >or=10 ms in 91% of mapped sites. Two different local activation patterns were associated with occurrence of CFAEmax: a nearly simultaneous activation in all spines in 84% indicating passive activation, and a nonsimultaneous activation sequence suggesting local complex activation or reentry. CONCLUSION: Fractionated atrial electrograms during AF demonstrate dynamic changes that are dependent on regional AFCL. Shortening of AFCL precedes the development of CFAE; thus, cycle length is a major determinant of fractionation during AF. High-density mapping in AF may help to differentiate passive activation of CFAE from CFAE associated with an active component of the AF process.

Atrial Fibrillation↗

Long-term evaluation of atrial fibrillation ablation guided by noninducibility.

BACKGROUND: Pulmonary vein (PV) isolation and linear lesions are effective in eliminating paroxysmal atrial fibrillation (AF), but linear lesions probably are not required in all patients. Noninducibility of AF has been shown to be associated with freedom from arrhythmia in 87% of patients. OBJECTIVES: The purpose of this study was to prospectively evaluate the role of noninducibility in guiding a stepwise approach tailored to the patient. METHODS: In 74 patients (age 53 +/- 8 years) with paroxysmal AF, PV isolation was performed during induced or spontaneous AF. If AF was inducible after PV isolation, one to two additional linear lesions were placed at the mitral isthmus and/or left atrial roof, with the endpoint of noninducibility of AF or atrial flutter. Inducibility (AF/atrial flutter, lasting > or = 10 minutes) was assessed using burst pacing at an output of 20 mA down to refractoriness from the coronary sinus and both atrial appendages. RESULTS: In 42 patients (57%), PV isolation restored sinus rhythm and rendered AF noninducible. In the 32 patients with persistent or inducible AF after PV isolation, a single linear lesion achieved noninducibility in 20, whereas two linear lesions were required in 12 and resulted in conversion to sinus rhythm and noninducibility in 10. Using this stepwise approach, a total of 69 patients (93%) were rendered noninducible. During follow-up of 18 +/- 4 months, 67 patients (91%) were free from arrhythmia without antiarrhythmic drugs. Repeat procedures were performed in 23 patients: repeat ablation was required to consolidate prior targets in 15 patients (20%), and "new" linear lesions, which were not predicted by inducibility during the index procedure, were required in 8 (11%). CONCLUSION: Noninducibility can be used as an endpoint for determining the subset of patients with paroxysmal AF who require additional linear lesions after PV isolation. This tailored approach is effective in 91% of patients while preventing delivery of unnecessary linear lesions.

Anticoagulants↗

Progressive and persistent atrial inexcitability.

Sinus node disease is characterized by the presence of significant sinus bradycardia or prolonged sinus pauses, and is attributed to either primary failure of sinus node automaticity or sino-atrial conduction disturbance. We present two patients with symptomatic bradycardia due to idiopathic global atrial inexcitability.

Adolescent↗

Flutter localized to the anterior left atrium after catheter ablation of atrial fibrillation.

INTRODUCTION: Organized atrial arrhythmias following atrial fibrillation (AF) ablation are typically due to recovered pulmonary vein (PV) conduction or reentry at incomplete ablation lines. We describe the role of nonablated anterior left atrium (LA) in arrhythmias observed after AF ablation. METHODS: A total of 275 consecutive patients with paroxysmal (n = 200) or chronic (n = 75) AF had PV isolation with/without additional linear ablation at the mitral isthmus (n = 106), LA roof (n = 23), or both (n = 88). Organized arrhythmias occurring after ablation were evaluated utilizing activation and entrainment mapping. RESULTS: Fourteen patients (11 female, 65 +/- 13 years, 10 chronic AF, 10 structural heart disease) demonstrated tachycardia localized to the anterior LA, an area not targeted by prior ablation. Eight had ECG features during sinus rhythm suggestive of impaired anterior LA conduction at baseline. These arrhythmias demonstrated a distinctive ECG flutter morphology in 7 of 10 (70%) with discrete -/+ or +/-/+ aspect in inferior leads. Mapping the anterior LA revealed electrograms spanning the entire tachycardia cycle length (325 +/- 125 msec). Entrainment was possible in all with a postpacing interval exceeding the tachycardia cycle length by 9 +/- 10 msec. Electroanatomic mapping in 6 demonstrated small reentrant circuits rotating clockwise in 4 and counterclockwise in 2. Low-amplitude, fractionated mid-diastolic potentials with long duration (200 +/- 80 msec) occupying 63 +/- 22% of the cycle length were targeted for ablation resulting in termination and subsequent noninducibility. CONCLUSION: Organized arrhythmias occurring after AF ablation can be due to reentrant circuits localized to the anterior LA, predominantly in females with chronic AF, structural heart disease, and abnormal atrial conduction. They are characterized by a distinctive surface ECG and highly responsive to RF ablation at the slow conduction area.

Aged↗

Organization of frequency spectra of atrial fibrillation: relevance to radiofrequency catheter ablation.

INTRODUCTION: We hypothesized that the frequency spectra of fibrillatory electrograms may reflect the complexity of activities perpetuating atrial fibrillation (AF). To test this hypothesis, we evaluated the frequency spectra in patients with paroxysmal AF in relation to catheter ablation. METHODS AND RESULTS: This study comprised two protocols: 25 patients undergoing pulmonary vein (PV) isolation in protocol I, and 20 patients undergoing mitral isthmus linear ablation after PV isolation in protocol II. The mean of dominant frequency (DF) and organization index (the ratio of the area under the DF and its harmonics to the total power) were determined from 32-second recordings in the coronary sinus. In protocol I, a PV was considered "driver" of AF if isolation of the PV resulted in termination or slowing of AF (decrease in DF by > or =0.25 Hz). Twenty-one patients had AF termination during four PV isolation. Among these 21 patients, 13 patients with single driving PV showed significantly higher baseline organization index than eight patients with multiple driving PVs (0.45 +/- 0.08 vs 0.35 +/- 0.07, P = 0.009). Patients with multiple driving PVs showed a significant increase in the organization index to 0.45 +/- 0.11 (P < 0.05) after isolation of the initial driving PVs. In protocol II, the baseline organization index was significantly higher in seven patients who had termination of AF during mitral isthmus ablation than 13 patients who did not (0.50 +/- 0.10 vs 0.38 +/- 0.07, P < 0.008). The baseline DF was not associated with outcomes of ablation in both protocols. CONCLUSIONS: A higher organization index of atrial electrograms is associated with termination of AF during limited ablation. This parameter may be useful to anticipate the extent of ablation.

Atrial Fibrillation↗