Spontaneous Ventricular Fibrillation Research Articles

Inadvertently Developed Ventricular Fibrillation during Electrophysiologic Study and Catheter Ablation: Incidence, Cause, and Prognosis

Background and ObjectivesVentricular fibrillation (VF) can inadvertently occur during electrophysiologic study (EPS) or catheter ablation. We investigated the incidence, cause, and progress of inadvertently developed VF during EPS and catheter ablation.Subjects and MethodsWe reviewed patients who had developed inadvertent VF during EPS or catheter ablation. Patients who developed VF during programmed ventricular stimulation to induce ventricular tachycardia or VF were excluded.ResultsInadvertent VF developed in 11 patients (46.7±9.3 years old) among 2624 patients (0.42%); during catheter ablation for atrial fibrillation (AF) in nine patients, frequent ventricular premature beats (VPBs) in one, and Wolff-Parkinson-White (WPW) syndrome were observed in one. VF was induced after internal cardioversion in six AF patients due to incorrect R-wave synchronization of a direct current shock. Two AF patients showed spontaneous VF induction during isoproterenol infusion while looking for AF triggering foci. The remaining AF patient developed VF after rapid atrial pacing to induce AF, but the catheter was accidentally moved to the right ventricular (RV) apex. A patient with VPB ablation spontaneously developed VF during isoproterenol infusion. The focus of VPB was in the RV outflow tract and successfully ablated. A patient with WPW syndrome developed VF after rapid RV pacing with a cycle length of 240 ms. Single high energy (biphasic 150-200 J) external defibrillation was successful in all patients, except in two, who spontaneously terminated VF. The procedure was uneventfully completed in all patients. At a mean follow-up period of 17.4±15.5 months, no patient presented with ventricular arrhythmia.ConclusionAlthough rare, inadvertent VF can develop during EPS or catheter ablation. Special caution is required to avoid incidental VF during internal cardioversion, especially under isoproterenol infusion.

Abstract 341: Estrogen Prevents Sudden Death and Spontaneous Ventricular Fibrillation Associated with Pulmonary Hypertension via Estrogen Receptor Beta Mediated Mechanism

Introduction: Previously we showed that right ventricular failure (RVF) secondary to pulmonary hypertension (PH) is associated with spontaneous ventricular fibrillation (VF) and sudden death in rats. We also discovered that estrogen (E2) therapy rescues severe PH and RVF. Estrogen receptor b (ERb) has been shown to play a protective role both in heart and lung. Here we hypothesize that E2 prevents sudden death and abolishes spontaneous VF associated with RVF through ERb. Methods: Male rats were treated with monocrotaline (MCT 60 mg/kg, s.c.) or PBS (CTRL, n=9). At day 21, MCT rats were left untreated to develop RVF by day 30 (n=9), or treated with E2 (42.5 ug/kg/day, s.c., n=9) with or without ERb antagonist PHTPP (850 ug/kg/day, s.c., n=8) from day 21 to day 30. RV ejection fraction (RVEF) was serially monitord with echocardiography. Direct RV catheterisation was performed terminally to record RV pressure (RVP). At ~day 30, hearts were studied in isolated-perfused Langendorff setting and microelectrode recordings were made. RV-epicardial activation pattern was optically mapped using fluorescent voltage-sensitive dye (RH-237). Trichrome staining was performed to assess cardiac fibrosis. Values are expressed as Mean±SEM. Results: By day 30, MCT rats developed severe PH (RVP=72±4 vs. 30±2 mmHg in CTRL, p<0.05) and RV failure (RVEF=33±3% vs. 65±1 in CTRL, p<0.05) with moderate RV fibrosis and ∼30% of RVF rats died suddenly. Early after depolarization (EADs) and spontaneous VF were observed in RVF group during normal Tyrode perfusion with wave front dynamics supported by both focal and multiple wavelet patterns. E2 therapy resulted in complete rescue of PH (RVP=38±3 mmHg, p<0.05 vs. RVF; RVEF=60±2%, p<0.05 vs. RVF; no signs of fibrosis) and none of the rats died in E2-groups. No VF was initiated in any of the control or E2 treated rat hearts. In the presence of ERb antagonist PHTPP, E2 could not rescue PH (RVP=60±4 vs. 38±3 in E2; RVEF=42±2 vs. 60±2 % in E2; p<0.05 vs. E2); moderate RV fibrosis was present and spontaneous EADs and VF were observed in all the hearts similar to RVF group. Conclusions: In conclusion, E2-therapy rescues PH-induced RVF and prevents VF by reversing PH-induced RV-dysfunction and fibrosis most likely through ERb-mediated mechanism.

Empiric Quinidine for Asymptomatic Brugada Syndrome—Preliminary Results of an International Registry

<h3>Background</h3> Common practice for asymptomatic Brugada syndrome (BrS) has included risk stratification with electrophysiologic studies (EPS) and defibrillator implantation when the latter are positive. However, several multicenter studies show that EPS has limited value for predicting spontaneous ventricular fibrillation. Therefore, in 2008 we started this Prospective International Registry. <h3>Methods</h3> Patients with a type 1 Brugada ECG, who have no arrhythmia-related symptoms and no heart disease, are included in the Registry. They receive quinidine therapy or no therapy depending on physician's/patient's preference. EPS are not recommended. <h3>Results</h3> In total, 132 patients from the Netherlands (51), Italy (41), Israel (20), Germany (13), and Japan (7) have been recruited; 93 (70%) are male. Age at presentation is 43 ± 12 (11–79) years. Symptoms include palpitations (20%), chest pain (10%) and vagal syncope (20%); 54 patients have a family history of BrS or sudden death before age 50. The reason for index ECG was medical screening in 41 (31%), cardiac symptoms in 34 (26%), noncardiac symptoms (eg, fever) in 18 (14%), and screening for familial history of sudden death or BrS in 39 (30%). The type 1 ECG pattern was spontaneous in 45 patients (including spontaneous on "high leads" in 7 and fever-induced in 8) and drug-induced in 87. Disease-causing mutations were found in 23% and genetic variants of unknown significance in 5%. Nineteen patients received empiric quinidine therapy. Of them, 4 had presented with syncope (believed to be vasovagal) and 4 were asymptomatic but had familial history of sudden death or BrS. Nine patients had a spontaneous type 1 ECG pattern. Five (26%) patients discontinued quinidine because of asymptomatic QT prolongation (2 patients), diarrhea, asymptomatic abnormal liver function tests, and patient's preference (1 patient each). Follow-up >4 months (1.8 ± 0.9 years) is available for 59 patients. The only serious adverse event was syncope (leading to defibrillator implantation) in 1 untreated patient. <h3>Conclusions</h3> In our Prospective Registry of asymptomatic patients with BrS, most physicians and patients opt for no therapy. Long-term quinidine therapy is well tolerated by 74%. The risk of an arrhythmic event proved to be low.

Ventricular tachyarrhythmias in rats with acute myocardial infarction involves activation of small-conductance Ca2+-activated K+channels

In vitro experiments have shown that the upregulation of small-conductance Ca(2+)-activated K(+) (SK) channels in ventricular epicardial myocytes is responsible for spontaneous ventricular fibrillation (VF) in failing ventricles. However, the role of SK channels in regulating VF has not yet been described in in vivo acute myocardial infarction (AMI) animals. The present study determined the role of SK channels in regulating spontaneous sustained ventricular tachycardia (SVT) and VF, the inducibility of ventricular tachyarrhythmias, and the effect of inhibition of SK channels on spontaneous SVT/VF and electrical ventricular instability in AMI rats. AMI was induced by ligation of the left anterior descending coronary artery in anesthetized rats. Spontaneous SVT/VF was analyzed, and programmed electrical stimulation was performed to evaluate the inducibility of ventricular tachyarrhythmias, ventricular effective refractory period (VERP), and VF threshold (VFT). In AMI, the duration and episodes of spontaneous SVT/VF were increased, and the inducibility of ventricular tachyarrhythmias was elevated. Pretreatment in the AMI group with the SK channel blocker apamin or UCL-1684 significantly reduced SVT/VF and inducibility of ventricular tachyarrhythmias (P < 0.05). Various doses of apamin (7.5, 22.5, 37.5, and 75.0 μg/kg iv) inhibited SVT/VF and the inducibility of ventricular tachyarrhythmias in a dose-dependent manner. Notably, no effects were observed in sham-operated controls. Additionally, VERP was shortened in AMI animals. Pretreatment in AMI animals with the SK channel blocker significantly prolonged VERP (P < 0.05). No effects were observed in sham-operated controls. Furthermore, VFT was reduced in AMI animals, and block of SK channels increased VFT in AMI animals, but, again, this was without effect in sham-operated controls. Finally, the monophasic action potential duration at 90% repolarization (MAPD(90)) was examined in the myocardial infarcted (MI) and nonmyocardial infarcted areas (NMI) of the left ventricular epicardium. Electrophysiology recordings showed that MAPD(90) in the MI area was shortened in AMI animals, and pretreatment with SK channel blocker apamin or UCL-1684 significantly prolonged MAPD(90) (P < 0.05) in the MI area but was without effect in the NMI area or in sham-operated controls. We conclude that the activation of SK channels may underlie the mechanisms of spontaneous SVT/VF and susceptibility to ventricular tachyarrhythmias in AMI. Inhibition of SK channels normalized the shortening of MAPD(90) in the MI area, which may contribute to the inhibitory effect on spontaneous SVT/VF and inducibility of ventricular tachyarrhythmias in AMI.

Hemodynamic and Catecholamine Changes after Recurrent Ventricular Fibrillation

BackgroundPatients with recurrent ventricular fibrillation (VF) have a high mortality rate, which may be partly due to hemodynamic instability. ObjectivesThe aim of this study was to simulate spontaneous recurrent VF by repeated induction of VF in pigs, and to evaluate the subsequent changes in heart rate (HR), blood pressure (BP), and serum catecholamine levels. MethodsVF was induced four times in each of eight female pigs. Defibrillation was first attempted at 30 s after induction of each episode of VF. Circulation was allowed to stabilize for 30 min after return of spontaneous circulation (ROSC) before induction of the next episode of VF. HR and BP were measured before each induction of VF and at 1 min after each ROSC, and venous blood was drawn at the same times to measure serum catecholamine levels. ResultsVF was induced a total of 32 times. Serum epinephrine (EPI) and norepinephrine (NE) levels decreased (p all < 0.05) and dopamine (DA) levels gradually increased (p < 0.05) with repeated episodes of VF. Compared with baseline values before each episode of VF, BP increased significantly at 1 min after ROSC (p all < 0.05) and then gradually returned to baseline values. HR increased significantly after the first ROSC and stayed elevated. No significant correlations were found between catecholamine levels and HR or BP. ConclusionWith repeated episodes of VF, BP increased transiently and then gradually returned to baseline values, but HR stayed elevated. Serum DA levels increased, EPI and NE levels gradually decreased.

Effects of ganglionated plexi ablation on ventricular electrophysiological properties in normal hearts and after acute myocardial ischemia

BackgroundGanglionated plexi (GP) ablation has been shown to play an important role in atrial fibrillation (AF) initiation and maintenance. Also, GP ablation increases chances for prevention of AF recurrence. This study investigated the effects of GP ablation on ventricular electrophysiological properties in normal dog hearts and after acute myocardial ischemia (AMI). MethodsFifty anesthetized dogs were assigned into normal heart group (n=16) and AMI heart group (n=34). Ventricular dynamic restitution, effective refractory period (ERP), electrical alternans and ventricular fibrillation threshold (VFT) were measured before and after GP ablation in the normal heart group. In the AMI heart group, the incidence of ventricular arrhythmias and VFT were determined. ResultsIn the normal heart group, GP ablation significantly prolonged ERP, facilitated electrical alternans but did not increase ERP dispersion, the slope of restitution curves and its spatial dispersion. Also, GP ablation did not cause significant change of VFT. In the AMI heart group, the incidence of ventricular arrhythmias after GP ablation was significantly higher than that in the control group or the GP plus stellate ganglion (SG) ablation group (P<0.05). Spontaneous VF occurred in 8/12, 1/10 and 2/12 dogs in the GP ablation group, the GP plus SG ablation group and the control group, respectively (P<0.05). VFT in the GP ablation group showed a decreased trend though a significant difference was not achieved compared with the control or the GP plus SG ablation group. ConclusionsGP ablation increases the risk of ventricular arrhythmias in the AMI heart compared to the normal heart.

Selective inhibitors of cardiac ADPR cyclase as novel anti-arrhythmic compounds

ADP-ribosyl cyclases (ADPRCs) catalyse the conversion of nicotinamide adenine dinucleotide to cyclic adenosine diphosphoribose (cADPR) which is a second messenger involved in Ca2+ mobilisation from intracellular stores. Via its interaction with the ryanodine receptor Ca2+ channel in the heart, cADPR may exert arrhythmogenic activity. To test this hypothesis, we have studied the effect of novel cardiac ADPRC inhibitors in vitro and in vivo in models of ventricular arrhythmias. Using a high-throughput screening approach on cardiac sarcoplasmic reticulum membranes isolated from pig and rat and nicotinamide hypoxanthine dinuleotide as a surrogate substrate, we have identified potent and selective inhibitors of an intracellular, membrane-bound cardiac ADPRC that are different from the two known mammalian ADPRCs, CD38 and CD157/Bst1. We show that two structurally distinct cardiac ADPRC inhibitors, SAN2589 and SAN4825, prevent the formation of spontaneous action potentials in guinea pig papillary muscle in vitro and that compound SAN4825 is active in vivo in delaying ventricular fibrillation and cardiac arrest in a guinea pig model of Ca2+ overload-induced arrhythmia. Inhibition of cardiac ADPRC prevents Ca2+ overload-induced spontaneous depolarizations and ventricular fibrillation and may thus provide a novel therapeutic principle for the treatment of cardiac arrhythmias.

Letter by Casado-Arroyo et al Regarding Article, “Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization”

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 5, No. 2Letter by Casado-Arroyo et al Regarding Article, “Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Casado-Arroyo et al Regarding Article, “Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization” Rubén Casado-Arroyo, MD, Moisés Rodriguez-Mañero, MD, Andrea Sarkozy, MD, PhD and Pedro Brugada, MD, PhD Rubén Casado-ArroyoRubén Casado-Arroyo Search for more papers by this author , Moisés Rodriguez-MañeroMoisés Rodriguez-Mañero Search for more papers by this author , Andrea SarkozyAndrea Sarkozy Search for more papers by this author and Pedro BrugadaPedro Brugada Search for more papers by this author Originally published1 Apr 2012https://doi.org/10.1161/CIRCEP.112.970673Circulation: Arrhythmia and Electrophysiology. 2012;5:e59To the Editor:We have read “Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization” by Watanabe and colleagues1 with great interest and congratulate the authors for their publication. However, there are some aspects that in our opinion should be clarified.The authors state in the “Methods” section, “Patients with Brugada type ST-segment elevations at baseline or after sodium channel blocker challenge were excluded.”1 As has been previously published, the diagnosis of Brugada syndrome (BS) should be strongly considered if there is appearance of Type 1 ST segment elevation (coved type) in at least 1 of the precordial leads or in the inferior leads in the presence or absence of a sodium channel blocker plus at least 1 clinical symptom.2,3We disagree with the electrocardiographic interpretation in Patient 1 (Figure 2B): the basal electrocardiogram shows a spontaneous Type I Brugada pattern in lead V2. After pilsicainide, the patient presents an inferior–lateral early repolarization pattern. This pattern and the response to sodium channel blockers are specific of patients with BS and interestingly have been associated with a more severe phenotype.3 Patient 2 (Figure 2C) illustrates a classical coved-type electrocardiographic pattern after the infusion of the drug in lead V2. These 2 patients presented spontaneous ventricular fibrillation after the infusion of the drug and also during programmed stimulation, because it has been previously described in patients with BS.3,4 On the other hand, the third patient presents a typical case of spontaneous Type 1 at baseline in lead V2 (Figure 2E). Accordingly, it is important to mention that the SCN5A mutation (R367H) had been previously described in patients with BS, specifically in a large European family with 18 members4 and is internationally recognized as a mutation causative of BS.5 This amino acid substitution is associated with high incidence of spontaneous Type 1, as is the case in the third patient.Although differentiation between idiopathic ventricular fibrillation and BS may be difficult, frequent overlap between these 2 entities is possible. From our point of view, BS has not been properly excluded. These patients discussed by Wanatabe et al fit all phenotype and genotype characteristics of BS.Rubén Casado-Arroyo, MDMoisés Rodriguez-Mañero, MDAndrea Sarkozy, MD, PhDPedro Brugada, MD, PhD Heart Rhythm Management Center Cardiovascular Division Free University of Brussels (UZ Brussel) VUB Brussels, BelgiumSources of FundingFunded by a grant for international research post-residency, Spanish Society of Cardiology (R.C.-A.).DisclosuresNone.

Inhibition of Small‐Conductance Ca2+‐activated K+ Channels Protects Against Ventricular Fibrillation (VF) In Rats With Acute Myocardial Infarction (AMI)

In vitro study has shown that up‐regulation of SK channels in the ventricular epicardial myocytes is responsible for the spontaneous VF in failing ventricle. The present study determined the role of SK channels in regulating VF in AMI rats. AMI was induced by coronary artery ligation and ventricular programmed stimulation was used to evaluate ventricular vulnerable period (VVP), VF threshold (VFT) and ventricular effective refractory period (VERP) in anesthetized rats. In AMI animals, VVP was prolonged and VERP was shortened (p&lt;0.05, n=6). Pre‐treatment in the AMI group with the SK channel blocker UCL1684 significantly shortened VVP and prolonged VERP (p&lt;0.05, n=6). No effects were observed in sham‐operated controls (n=9). Additionally, VT was reduced in the AMI group, and UCL1684 increased VFT in the AMI group (p&lt;0.05, n=6), but, again, was without effect in sham‐operated controls (n=9). Finally, monophasic action potential duration (MAPD90) was examined using an electrode placed on the left ventricular epicardium. The data showed that MAPD90 was shortened in AMI group (p&lt;0.05, n=7), and UCL1684 significantly prolonged the MAPD90 (p&lt;0.05, n=5), but was without effect in sham‐operated controls (n=9). We conclude that activation of SK channels may underlie the mechanisms of VF. Inhibition of SK channels reduced shorting of MAPD90, which may be responsible for the inhibitory effect on VF in AMI rats. Support: NNSF‐30971223 (JHZ); AHA 10SDG2640130 (QHC).

Successful Reduction of a High Defibrillation Threshold by a Combined Implantation of a Subcutaneous Array and Azygos Vein Lead

A 72-year-old man with nonischemic cardiomyopathy was referred because his implantable cardioverter defibrillator had failed to terminate spontaneous ventricular fibrillation (VF). Defibrillation threshold (DFT) testing confirmed that 830-V shocks failed to defibrillate VF despite optimization of the biphasic waveform and reversal of shock polarity. The placement of a new right ventricular lead and the addition of a subcutaneous array failed to defibrillate VF at 830 V. The combination of a subcutaneous array and azygos vein coil successfully defibrillated VF. The mechanism for successful DFT reduction was likely greater current supplied to the posterior basal left ventricle by the azygos vein lead.

Imaging Arrhythmogenic Calcium Signaling in Intact Hearts

Protein complex of the cardiac junctional sarcoplasmic reticulum (SR) membrane formed by type 2 ryanodine receptor, junction, triadin, and calsequestrin is responsible for controlling SR calcium (Ca) release. Increased intracellular calcium (Ca(i)) activates the electrogenic sodium-Ca exchanger current, which is known to be important in afterdepolarization and triggered activities (TAs). Using optical-mapping techniques, it is possible to simultaneously map membrane potential (V (m)) and Ca(i) transient in Langendorff-perfused rabbit ventricles to better define the mechanisms by which V (m) and Ca(i) interactions cause early afterdepolarizations (EADs). Phase 3 EAD is dependent on heterogeneously prolonged action potential duration (APD). Electrotonic currents that flow between a persistently depolarized region and its recovered neighbors underlies the mechanisms of phase 3 EADs and TAs. In contrast, "late phase-3 EAD" is induced by APD shortening, not APD prolongation. In failing ventricles, upregulation of apamin-sensitive Ca-activated potassium (K) channels (I(KAS)) causes APD shortening after fibrillation-defibrillation episodes. Shortened APD in the presence of large Ca(i) transients generates late-phase 3 EADs and recurrent spontaneous ventricular fibrillation. The latter findings suggest that I (KAS) may be a novel antiarrhythmic targets in patients with heart failure and electrical storms.

Estrogen Therapy Abolishes Spontaneous Ventricular Arrhythmias in Right Ventricular Failure Induced by Pulmonary Hypertension

We previously have shown that pulmonary hypertension (PH)-induced right ventricular failure (RVF) is associated with increased incidence of sudden death caused by spontaneous ventricular fibrillation (VF). We also discovered that estrogen (E2) therapy rescues severe PH and RVF and results in 100% survival. Here we hypothesized that E2 abolishes spontaneous VF associated with RVF by restoring RVEF, reversing fibrosis and restoring PH-induced downregulation of repolarizing K-channel proteins Kv1.5 and KCNE-2 and SERCA-2a expression. Chronic PH-associated RVF was induced in male rats by s.c. monocrotaline (MCT, 60 mg/kg, n=10). Some MCT-rats were treated with E2 (42.5 ug/kg/day, s.c.) from day 21 (severe PH-stage) to day-30 (n=8). Saline treated rats served as control (n=8). At ∼day 30, hearts were studied in isolated-perfused Langendorff setting. RV-epicardial activation pattern was optically mapped using fluorescent voltage-sensitive dye (RH-237). By ∼day 30, 30% RVF rats died suddenly but none in the control or E2-groups. RVF hearts manifested EADs and spontaneous VF during normal Tyrode’s perfusion with wavefront dynamics supported by both focal and multiple wavelet patterns. No VF was initiated in any of the control or E2-treated hearts. SERCA-2a was reduced (∼15-fold) in RVF (0.06±0.01 vs. 1±0.26 control) that was reversed in E2-group (0.77±0.13, p<0.05 vs. RVF). Kv1.5 was reduced ∼8 fold in RVF (0.12±0.03 vs. 1±0.18 in control, p<0.05) and E2 partially restored Kv1.5 (0.46±0.06, p<0.05). KCNE2, an ancillary K-channel subunit, was reduced ∼3-fold in RVF (0.3±0.1 vs. 1±0.1, p<0.05) that was reversed by E2 (0.9±0.05, p<0.05). RVF was associated with moderate RV-fibrosis and severe reduction in RV-ejection fraction (RVEF) from 65±1 to 33±3%. E2- group did not show any fibrosis and RVEF was preserved (60±2%). In conclusion, E2-therapy rescues RVF and prevents VF by reversing PH-induced RV-fibrosis and reduced repolarization-reserve.

Unmasking of J waves during Right Coronary Angiography in Patients with Spontaneous Coronary Spasms and Ventricular Fibrillation

We encountered two consecutive cases with spontaneous ST elevation due to right coronary spasms and subsequent ventricular fibrillation (VF). Their 12-lead ECGs on anterior chest pain showed elevation of ST-segments in the inferior leads, but coronary angiography (CAG) revealed no significant stenosis. Both cases showed dramatically evolving J waves in the inferior leads during the right CAG, but it was not observed during angiography of the left CAG. Neither Brugada-type ECG nor long-QT was evident. In summary, J waves can be produced without ST-segment elevation, and contrast media-induced J waves might be related to the arrhythmogenesis of subsequent VF evoked by right coronary spasms.

Spontaneous Ventricular Fibrillation in Right Ventricular Failure Secondary to Chronic Pulmonary Hypertension

Right ventricular failure (RVF) in pulmonary hypertension (PH) is associated with increased incidence of sudden death by a poorly explored mechanism. We test the hypothesis that PH promotes spontaneous ventricular fibrillation (VF) during a critical post-PH onset period characterized by a sudden increase in mortality. Rats received either a single subcutaneous dose of monocrotaline (MCT, 60 mg/kg) to induce PH-associated RVF (PH, n=24) or saline (control, n=17). Activation pattern of the RV-epicardial surface was mapped using voltage-sensitive dye in isolated Langendorff-perfused hearts along with single glass-microelectrode and ECG-recordings. MCT-injected rats developed severe PH by day 21 and progressed to RVF by approximately day 30. Rats manifested increased mortality, and ≈30% rats died suddenly and precipitously during 23-32 days after MCT. This fatal period was associated with the initiation of spontaneous VF by a focal mechanism in the RV, which was subsequently maintained by both focal and incomplete reentrant wave fronts. Microelectrode recordings from the RV-epicardium at the onset of focal activity showed early afterdepolarization-mediated triggered activity that led to VF. The onset of the RV cellular triggered beats preceded left ventricular depolarizations by 23±8 ms. The RV but not the left ventricular cardiomyocytes isolated during this fatal period manifested significant action potential duration prolongation, dispersion, and an increased susceptibility to depolarization-induced repetitive activity. No spontaneous VF was observed in any of the control hearts. RVF was associated with significantly reduced RV ejection fraction (P<0.001), RV hypertrophy (P<0.001), and RV fibrosis (P<0.01). The hemodynamic function of the LV and its structure were preserved. PH-induced RVF is associated with a distinct phase of increased mortality characterized by spontaneous VF arising from the RV by an early afterdepolarization-mediated triggered activity.

Thirteen Reasons not to Give up Using Quinidine and to Avoid its Withdrawal from the Market

Since 2006, the news about the withdrawal from the market of quinidine sulfate produced by Astra Zeneca began to go around the internet. (1) More recently, the same happened with quinidine polygalacturonate (Ritmocor, Malesci, Bagno A Ripoli, Italy) in Italy where quinidine sulfate was not in circulation any more. Only hydroquinidine was available, from which its real correspondence with polygalacturonate is known; 275 mg of polygalacturonate are equivalent to 200 mg of quinidine sulfate, but, as it was mentioned before, in Italy there is no quinidine sulfate. (2) In several countries, quinidine is difficult to be found and the decision to withdraw this drug from the market was not consulted with prestigious societies in charge of gathering worldwide experts in cardiac arrhythmias. (3) This decision had a commercial basis and not a scientific one, as it is shown in the following evidences: 1. Quinidine is the only antiarrhythmic agent with significant inhibiting properties of Ito that exists in the market. (4) 2. Quinidine prevents ventricular fibrillation (VF) induced by programmed electrical stimulation (5-8) and in patients with Brugada syndrome and idiopathic VF at long-term. (8) 3. Quinidine is effective to avoid arrhythmic storm in Brugada syndrome (6, 7), and idiopathic VF, (9) apart from reducing appropriate shocks of the implantable cardioverter defibrillator (ICD) which makes more bearable the coexistence with the equipment. 4. Quinidine could be the indication in asymptomatic Brugada syndrome with positive electrophysiologic study, since more recent evidences have not shown that these cases could be risky, (9, 10) generating an unnecessary expense due to ICD implantations which will never work (only 1% per year of these patients will have a spontaneous VF) and complications related to the implantation (prevalence of 28-32% in young patients). (7) 5. Quinidine may represent a temporary state until ICD implantation in young patients with short QT syndrome. (11) 6. Oral quinidine may offer an alternative to ICD in old asymptomatic patients with short QT syndrome and negative history of sudden cardiac death. (12) 7. Belhassen et al. have used quinidine successfully for more than 20 years in idiopathic VF. (13) 8. Quinidine and verapamil used together may reduce afterdepolarizations produced by class I and II antiarrhythmic agents. Afterdepolarizations induce torsade de pointes, apart from preventing high ventricular frequencies that may be generated due to vagolytic effect of quinidine. (4) 9. The aforementioned combination may be compared with sotalol in the prevention of atrial fibrillation recurrence after electrical cardioversion. (4) 10. Quinidine for pharmacological cardioversion of atrial fibrillation is safe and effective (successful in 84% of the cases) in patients with coronary disease and recent myocardial revascularization or percutaneous coronary intervention, even with previous myocardial infarction; besides, this kind of cardioversion is also safe and effective in patients with valvular disease who underwent valve replacement with revascularization or without it and in other structural heart diseases already operated. (14) 11. According to the biggest series of pharmacological cardioversion with quinidine published up to now (501 patients), the risk of proarrhythmia is minimized if the following factors are controlled (14): LVEF ≥ 35%. Absolute QT interval 4.3 mEq/L. Concomitant use with verapamil or beta blockers. 12. A significant part of lethal complications observed before the eighties could have been associated with the combination quinidine-digoxin, since quinidine reduces renal tubular secretion of the digital and there is a need to reduce the dose of digoxin in up to 50%, so that some complications could have been secondary to lethal digitalis toxicity due to an increase in the concentration of this drug. Besides, high doses of digoxin (800-1800 mg/day) were used in old studies. (4) 13. Quinidine is indicated as the first option of pharmacological treatment of class IA of antiarrhythmic agents in a pregnant woman with ventricular and supraventricular tachycardias, atrial fibrillation in particular, atrial flutter and atrioventricular reciprocal tachycardia. Quinidine is useful in the woman that is feeding the baby due to the concentration of it in the mother’s milk is less than 70% in comparison with the mother’s blood. (15) There is certainty that the use of this drug is safe during pregnancy, the use is backed by a worldwide medical experience Abbreviations > ICD Implantable cardioverter defibrillator LVEF Left ventricular ejection fraction VF Ventricular fibrillation

Abstract 8784: Mechanisms of Recurrent Spontaneous Ventricular Fibrillation in a Rabbit Model of Electrical Storm

Introduction: Electrical storm (ES) is defined as recurrent spontaneous ventricular fibrillation (SVF) within a short period of time. The mechanism of ES remains unclear. Objective: To develop a model of ES in normal rabbit ventricles and to test the hypothesis that ATP-sensitive K + current ( I KATP ) activation underlies the mechanisms of ES. Methods and Results: Intracellular Ca 2+ (Ca i ) and membrane voltage were optically mapped in 32 Langendorff-perfused rabbit ventricles. At baseline, no SVF was observed after 5 attempts of the VF-defibrillation episodes. During the post-shock period, isoproterenol (0.3 μ mol/L) heterogeneously shortened 50% recovery of action potential duration (APD 50 ) while lowering [K + ] o during isoproterenol infusion prolonged Ca i transient duration (Ca i TD 50 ). Increased difference between Ca i TD and APD (ΔCa i TD 50 -APD 50 ) lead to late phase 3 early afterdepolarization, triggered activity and SVF. In 11 (69%) of 16 SVF episodes, the VF originated from a focal site with maximal or next to maximal ΔCa i TD 50 -APD 50 (Figure A). The focal wavefronts developed wavebreak at sites with large voltage gradient, leading to SVF. Suppression of I Ca,L with nifedipine (10 μ mol/L) reliably prevented ES when given before, but not after, the development of SVF. I KATP blockade with glibenclamide (5 μ mol/L) prolonged post-shock APD 50 and suppressed ES in all ventricles (Figure B). An I Kr blocker E-4031 (1 μ mol/L) failed to terminate ES. The lactate concentration did not increase after 5 VF episodes. Conclusions: VF during beta-adrenergic stimulation causes non-ischemic activation of I KATP and abbreviated APD 50 . Low [K + ] o increases Ca i TD 50. These two factors synergistically enlarge the postshock ΔCa i TD 50 -APD 50 and induce late phase 3 afterdepolarization, triggered activity, wavebreaks and recurrent SVF (electrical storm). I KATP blockade effectively prolongs post-shock APD 50 and suppresses ES.

Role of K ATP Channels in the Maintenance of Ventricular Fibrillation in Cardiomyopathic Human Hearts

Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF. We addressed the hypotheses that there is regional disease-related expression of K(ATP) channels in human cardiomyopathic hearts and that K(ATP) channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness. In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 μmol/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. K(ATP) 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 K(ATP) subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (ΔERP(Transmural)=ERP(Epicardium)-ERP(Endocardium)) was verified with pacing protocols. ΔERP(Transmural) in control was 5 ± 2 ms and increased to 36 ± 5 ms with ischemia. This effect was greatly attenuated by glibenclamide (ΔERP(Transmural) for glibenclamide+ischemia=4.9 ± 4 ms, P=0.019 versus control ischemia). K(ATP) channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of K(ATP) channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.

Vagal activity modulates spontaneous augmentation of J-wave elevation in patients with idiopathic ventricular fibrillation

Although J-wave elevation in the inferolateral leads could be related to idiopathic ventricular fibrillation (IVF), little is known about the pathophysiologic characteristics of J-wave elevation in patients with IVF. This study aimed to determine the relationship between augmentation of J-wave elevation and changes in RR interval or autonomic nervous activities in patients with IVF. Eight patients with IVF and 22 controls with J-wave elevation (≥0.1 mV) in lead V5 were studied. The J-wave amplitude was automatically measured in lead CM5 of a digital Holter electrocardiogram, and the J-RR relationship was determined. Based on the analysis of heart rate variability, the relationship between the J-wave amplitude and the natural logarithm of high-frequency (HF) components (J-ln HF relationship) or the ratio of low frequency (LF) components to HF components (J-LF/HF relationship) was also determined. The J-RR slope (mm/s) was greater in patients with IVF than in controls (3.5 ± 0.7 vs 2.4 ± 0.8; P <.01), as was J-wave amplitude (mm) at an RR interval of 1.2 seconds (2.8 ± 0.9 vs 2.0 ± 0.6; P <.05). The J-wave amplitude was correlated positively with ln HF and negatively with LF/HF, and the slopes of both J-ln HF and J-LF/HF regression lines were greater in patients with IVF than in controls. During an entire 24-hour period, there was no difference between the 2 groups in either HF or LF/HF. Nine of the total 11 episodes (82%) of spontaneous ventricular fibrillation occurred between 18:00 and 6:00. In patients with IVF as compared with control subjects, J-wave elevation was more strongly augmented during bradycardia and was associated with an increase in vagal activity. This could be related to the occurrence of ventricular fibrillation predominantly at night in patients with IVF.

Ventricular fibrillation in loop recorder memories in a patient with early repolarization syndrome

We report the first documentation of spontaneous ventricular fibrillation by a loop recorder in a patient with an ECG pattern of early repolarization (ER) in the inferior leads and presenting with syncope.

Association among intracardiac T-wave alternans, ischemia, and spontaneous ventricular arrhythmias after coronary artery occlusion in a canine model

T-wave alternans (TWA) has been investigated as a marker for susceptibility to lethal ventricular arrhythmia. In this article, we studied intracardiac TWA and ischemia as predictors of spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) in a canine model of coronary artery occlusion (CAO). Anesthetized, open-chest dogs were studied. Electrograms from intracardiac bipolar electrodes (IBEs) were assessed for TWA and spontaneous VT or VF. TWA was defined on IBE as T wave voltage change on every other complex. In each heart, we examined 62 electrograms measured in the risk zone and surrounding normal sites, filtered from 3 to 1300 Hz. Ischemia was measured as percent of all IBE recorded that had QRS voltage drop >45%. Mapping localized the three-dimensional origin of spontaneous VT or VF. The data from dogs with VF (n = 5), VT (n = 8), or controls (no VT or VF, n = 8) were analyzed before left CAO, at the 20th min after CAO and times immediately preceding VT and VF. We found a correlation between intracardiac TWA and ischemia. More importantly, increases in intracardiac TWA peaked immediately preceding spontaneous VF and VT and were significantly higher compared to controls at comparable times. At VT/VF origins and adjacent sites, the mean TWA magnitude and discordance of TWA distinguished between VT/VF and controls at comparable times but not between VT and VF or between reentry and focal mechanisms. TWA was more common than ischemia at VT/VF origins. In summary, changes in intracardiac TWA and ischemia correlate with impending spontaneous VT/VF in a clinically applicable canine model of CAO.