Ventricular Tachycardia And Ventricular Fibrillation Research Articles

Prognostic significance of the Holter-derived T-wave variability in patients with ventricular tachyarrhythmias complicating acute coronary syndrome-TWIST study.

We aimed to investigate the association between ventricular repolarization instability and sustained ventricular tachycardia and ventricular fibrillation (VT/VF) occurring within 48 h (acute-phase VT/VF) after the onset of acute coronary syndrome (ACS) and the prognostic role of repolarization instability and heart rate variability (HRV) after discharge from the hospital. We studied 572 ACS patients with a left ventricular ejection fraction >35%. The ventricular repolarization instability was assessed by the beat-to-beat T-wave amplitude variability (TAV) using high-resolution 24-h Holter ECGs recorded at a median of 11 days from the date of admission. We calculated the HRV parameters including the deceleration capacity (DC) and non-Gaussian index calculated on a 25 s timescale (λ25s). The DC and λ25s were dichotomized based on previous studies' thresholds. Acute-phase VT/VF developed in 43 (7.5%) patients. In-hospital mortality was significantly higher among VT/VF patients (4.7% vs. 0.9%, p = .03). An adjusted logistic model showed that the maximum TAV (odds ratio 1.02, 95% confidence interval [CI] 1.00-1.29, p = .04) was associated with acute-phase VT/VF. During a median follow-up period of 2.1 years, 19 (3.3%) patients had cardiac deaths or resuscitated cardiac arrest. Acute-phase VT/VF (p = .12) and TAV (p = .72) were not significant predictors of survival. An age and sex-adjusted Cox model showed that the DC (p < .01), λ25s (p < .01), and emergency coronary intervention (p < .01) were independent predictors. T-wave amplitude variability was associated with acute-phase VT/VF, but the TAV was not predictive of survival post-discharge. The DC, λ25s, and emergency coronary intervention were independent predictors of survival.

A multicentre survey of paediatric out-of-hospital cardiac arrest incidence, aetiology, and survival in New South Wales over an 11-year period

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Out-of-hospital cardiac arrest (OOHCA) is commonly associated with pulseless ventricular tachycardia and ventricular fibrillation (VT/VF) and cardiac aetiologies. One New South Wales (NSW) ambulance registry reported(1) cardiac aetiologies with a prevalence of 31% among OOHCA cases. Multicentre OOHCA data and NSW’s well-developed services for cardiac genetic predisposition screening motivate us to consider the following study of paediatric OOHCA in this state. Purpose We present a multicentre, retrospective study summarizing the demographics, clinical characteristics, incidence, presenting rhythm, and survival-to-discharge status of paediatric OOHCA cases in NSW over an 11-year period. We also present and categorize diagnostic outcomes for patients presenting with VT/VF. Methods A retrospective case series of 298 patients admitted to one of three NSW PICUs (two in Sydney and one in Newcastle) under 18 years of age and presenting with OOHCA between January 2009 and December 2019. Results Out of 296 paediatric OOHCA patients that survived until PICU admission, 187 (63.2%) were male and 160 (54.1%) survived until hospital discharge. Of those surviving to discharge, 105 (65.6%) were male. Presenting rhythm was asystole or pulseless electrical activity in 240 patients (84.8%, aged 0–17 years, median age 2 years), VT/VF in 41 patients (14.5%, aged 0–16 years, median age 9 years), and complete heart block in 2 patients (0.7%, aged 4–4 years, median age 4 years). Survival was higher in the VT/VF group (82.9%) relative to the asystole and pulseless electrical activity group (50.0%). Of the 41 patients presenting with VT/VF, 13 (31.7%) had a predisposing cardiac condition (2 truncus arteriosus, 1 arrhythmogenic right ventricular cardiomyopathy, 1 double outlet right ventricle, 1 hypoplastic right ventricle, 1 left ventricular non-compaction, 2 asystolic syncope, 2 left ventricular intramyocardial fibroma, 1 familial dilated cardiomyopathy, and 2 undetermined cardiac conditions) and 20 (48.8%) had a genetic condition (9 catecholaminergic polymorphic ventricular tachycardia, 4 hypertrophic cardiomyopathies, 1 Nkx-2.5 mutation, 2 Long QT syndrome, 2 PPA2 mutation, 1 TANGO2 mutation, 1 supraventricular tachycardia). Toxins or trauma were involved in 4 (9.8%) cases, while no cause was determined in 4 (9.8%) other cases. Conclusions Overall, 54.1% of paediatric OOHCA patients admitted to PICU survived until hospital discharge, rising to 82.9% among those with VT/VF. Genetic conditions (48.8%), predominated by CPVT, were present in over one-third of VT/VF cases: this figure confirms the continued need for detailed cardiac/genetic assessment for paediatric OOHCA cases.

Clinician Preimplementation Perspectives of a Decision-Support Tool for the Prediction of Cardiac Arrhythmia Based on Machine Learning: Near-Live Feasibility and Qualitative Study.

BackgroundArtificial intelligence (AI), such as machine learning (ML), shows great promise for improving clinical decision-making in cardiac diseases by outperforming statistical-based models. However, few AI-based tools have been implemented in cardiology clinics because of the sociotechnical challenges during transitioning from algorithm development to real-world implementation.ObjectiveThis study explored how an ML-based tool for predicting ventricular tachycardia and ventricular fibrillation (VT/VF) could support clinical decision-making in the remote monitoring of patients with an implantable cardioverter defibrillator (ICD).MethodsSeven experienced electrophysiologists participated in a near-live feasibility and qualitative study, which included walkthroughs of 5 blinded retrospective patient cases, use of the prediction tool, and questionnaires and interview questions. All sessions were video recorded, and sessions evaluating the prediction tool were transcribed verbatim. Data were analyzed through an inductive qualitative approach based on grounded theory.ResultsThe prediction tool was found to have potential for supporting decision-making in ICD remote monitoring by providing reassurance, increasing confidence, acting as a second opinion, reducing information search time, and enabling delegation of decisions to nurses and technicians. However, the prediction tool did not lead to changes in clinical action and was found less useful in cases where the quality of data was poor or when VT/VF predictions were found to be irrelevant for evaluating the patient.ConclusionsWhen transitioning from AI development to testing its feasibility for clinical implementation, we need to consider the following: expectations must be aligned with the intended use of AI; trust in the prediction tool is likely to emerge from real-world use; and AI accuracy is relational and dependent on available information and local workflows. Addressing the sociotechnical gap between the development and implementation of clinical decision-support tools based on ML in cardiac care is essential for succeeding with adoption. It is suggested to include clinical end-users, clinical contexts, and workflows throughout the overall iterative approach to design, development, and implementation.

Biphasic Waveform External Defibrillation Starting Energy and In-Hospital Cardiac Arrest Survival: Retrospective Cohort Study From the Get With the Guidelines-Resuscitation Registry

ABSTRACT Biphasic waveform defibrillators permit effective defibrillation of ventricular tachycardia and ventricular fibrillation (VT/VF) at lower energies. Little data is available on trends in th...

Effectiveness of wearable defibrillators: systematic review and quality of evidence.

The objectives of this systematic literature review were to identify all published literature on wearable defibrillators, assess the wearable defibrillator's efficacy and effectiveness in general and among specific patient groups, including post-myocardial infarction, post coronary artery bypass grafting or percutaneous coronary intervention, non-ischemic cardiomyopathy, and ischemic cardiomyopathy, and to evaluate the quality of evidence. The search and synthesis was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation and the Newcastle Ottawa Scale. A total of thirty-six articles and conference abstracts from thirty-three studies were included in the review. It appears that wearable defibrillator use compared with no defibrillator use reduces the chance of ventricular tachycardia and ventricular fibrillation (VT/VF) associated deaths by an absolute risk reduction of approximately 1 percent, achieved by averting approximately 4/5th of all VT/VF associated deaths. The quality of evidence was low to very low quality, such that our confidence in the reported estimates is weak. To validate beneficial results, further investigation using robust study designs conducted by independent researchers is warranted.

Malignant ventricular arrhythmias after off-pump coronary artery bypass

Sustained ventricular tachycardia and ventricular fibrillation (VT/VF) are rare complications after coronary surgery. Off-pump coronary artery bypass (OPCAB) was developed to decrease postoperative complications. No studies to date have specifically addressed VT/VF after OPCAB. We sought to assess the incidence, risk factors, and outcome of VT/VF after OPCAB. The study included a retrospective review of 1010 patients undergoing OPCAB between 2000 and 2012. Data were compared between the VT/VF patients and control patients who were the first cases of OPCAB in each month during the study period and did not have VT/VF. Twenty-three patients (2.3%) developed VT/VF after OPCAB. The hospital mortality rate was 17.4%. In univariate analysis, the risk factors for VT/VF were old age, rapid heart rate, prolonged corrected QT interval, severe congestive heart failure, poor left ventricular ejection fraction, large left ventricular end-diastolic diameter, chronic kidney disease, preoperative dialysis, low blood hemoglobin level, preoperative intubation, recent myocardial infarction, high European System for Cardiac Operative Risk Evaluation, urgent/emergent operation, use of intra-aortic balloon pump, conversion to on-pump beating heart, postoperative dialysis, and no use of beta-blockers after operation. Multivariate analysis identified preoperative corrected QT interval>426 milliseconds [odds ratio (OR)=4.501; 95% confidence interval (CI)=1.153-17.570] and estimated glomerular filtration rate<30mL/minute/1.73m(2) (OR=4.876; 95% CI=1.112-21.374) as independent risk factors. Postoperative VT/VF was rare after OPCAB but was associated with high mortality. Prolonged corrected QT interval and chronic kidney disease were independent risk factors. Recognition of these risk factors, proper prevention, and early intervention may improve survival.

Abstract 7: Myocardial Electrical Remodeling and Arrhythmogenic Substrate in Hemorrhagic Shock-Induced Heart

Rationale: Lethal arrhythmias such as ventricular tachycardia and ventricular fibrillation (VT/VF) is one of the most serious complications after the resuscitation of severe hemorrhagic shock, even though systemic hemodynamics seems to recover. Objectives: To investigate the mechanisms of arrhythmogenesis after hemorrhagic shock and a role of oxygenated hemoglobin transfusion, optical mapping analysis (OMP), electrophysiological study (EPS), and pathological examination were performed using an acute hemorrhagic shock model of rats. Measurement and Main Results: After cannulating 22G catheter into the lower abdominal aorta, rats were subjected to acute hemorrhagic shock by withdrawing 30% of total blood volume (TBV) for 25 min, and observed for 15 min (shock alone). After acute hemorrhagic shock, the rats were immediately resuscitated by transfusing exactly the same amount of saline, 5% albumin (5%ALB), oxygenated liposome-encapsulated human hemoglobin (LHb), or oxygenated autologous washed red blood cells (wRBC) (n = 7, per group). After excising the heart, OMP and EPS were performed in isolated Langendorff-perfused hearts. OMP revealed abnormal ventricular conduction delay in conjunction with impaired action potential duration (APD) dispersion in both ventricles in shock alone, saline, and 5%ALB. In contrast, myocardial conduction velocity and APD dispersion in both ventricles were substantially attenuated in LHb or wRBC. VT/VF spontaneously occurred in shock alone. Furthermore, sustained VT/VF was easily provoked by burst pacing stimulus to the LV in saline and 5%ALB. No VT/VF was induced in the LV when the heart was resuscitated with oxygenated LHb or wRBC. Pathology including electron microscopy and immunohistochemistry demonstrated myocardial structural damages characterized by degradation of sarcometric actin and connexin43 in shock, saline, and 5%ALB. However, these histological changes were substantially attenuated in LHb and wRBC. Conclusion: Ventricular structural remodeling after hemorrhagic shock causes VT/VF only in the presence with APD dispersion. Oxygenated hemoglobin transfusion prevents VT/VF by preserving myocardial structures caused by ischemia-reperfusion injury in hemorrhagic shock.

Time-dependent effect of cardiac resynchronization therapy on ventricular repolarization and ventricular arrhythmias

Cardiac resynchronization therapy (CRT) improves the clinical status of patients with congestive heart failure, although left ventricular epicardial pacing may increase transmural dispersion of repolarization (TDR). The aim of this study was to investigate the time-dependent effect of CRT on ventricular repolarization and ventricular arrhythmia at mid-term follow-up. The study group consisted of 84 patients treated with CRT. Twelve-lead electrocardiogram was digitally recorded and Tpeak-to-Tend interval (Tp-e) was measured at baseline, 1 week, 1 month, and 3, 6, and 12 months after device implantation. We determined the time-dependent changes in Tp-e, ventricular tachycardia and ventricular fibrillation (VT/VF) during 12 months of follow-up, in both CRT responders and non-responders. Seventeen of 84 patients (20%) had VT/VF during first year. Six of those 17 patients (35%) experienced VT/VF within 1 month of implantation and diminished over time. Tp-e decreased significantly at 6 and 12 months after implantation compared with 1 week [108 ± 14 ms at 1 week vs. 97 ± 21 ms at 6 months (P = 0.03) and 95 ± 19 ms at 12 months (P = 0.01)]. Responders demonstrated a greater time-dependent reduction of Tp-e at 6 and 12 months of CRT and had a lower rate of VT/VF compared with non-responders (log-rank test, P = 0.004). Transmural dispersion of repolarization and the number of patients with VT/VF decreased over time after CRT. Patients with reverse remodelling demonstrated a lower rate of VT/VF and a greater time-dependent reduction of TDR.

Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs

Chronic hyperglycemia in type-1 diabetes mellitus is associated with oxidative stress (OS) and sudden death. Mechanistic links remain unclear. We investigated changes in electrophysiological (EP) properties in a model of chronic hyperglycemia before and after challenge with OS by GSH oxidation and tested reversibility of EP remodeling by insulin. Guinea pigs survived for 1 mo following streptozotocin (STZ) or saline (sham) injection. A treatment group received daily insulin for 2 wk to reverse STZ-induced hyperglycemia (STZ + Ins). EP properties were measured using high-resolution optical action potential mapping before and after challenge of hearts with diamide. Despite elevation of glucose levels in STZ compared with sham-operated (P = 0.004) and STZ + Ins (P = 0.002) animals, average action potential duration (APD) and arrhythmia propensity were not altered at baseline. Diamide promoted early (<10 min) formation of arrhythmic triggers reflected by a higher arrhythmia scoring index in STZ (P = 0.045) and STZ + Ins (P = 0.033) hearts compared with sham-operated hearts. APD heterogeneity underwent a more pronounced increase in response to diamide in STZ and STZ + Ins hearts compared with sham-operated hearts. Within 30 min, diamide resulted in spontaneous incidence of ventricular tachycardia and ventricular fibrillation (VT/VF) in 3/6, 2/5, 1/5, and 0/4 STZ, STZ + Ins, sham-operated, and normal hearts, respectively. Hearts prone to VT/VF exhibited greater APD heterogeneity (P = 0.010) compared with their VT/VF-free counterparts. Finally, altered EP properties in STZ were not rescued by insulin. In conclusion, GSH oxidation enhances APD heterogeneity and increases arrhythmia scoring index in a guinea pig model of chronic hyperglycemia. Despite normalization of glycemic levels by insulin, these proarrhythmic properties are not reversed, suggesting the importance of targeting antioxidant defenses for arrhythmia suppression.

Oxidative stress, fibrosis, and early afterdepolarization-mediated cardiac arrhythmias

Animal and clinical studies have demonstrated that oxidative stress, a common pathophysiological factor in cardiac disease, reduces repolarization reserve by enhancing the L-type calcium current, the late Na, and the Na-Ca exchanger, promoting early afterdepolarizations (EADs) that can initiate ventricular tachycardia and ventricular fibrillation (VT/VF) in structurally remodeled hearts. Increased ventricular fibrosis plays a key facilitatory role in allowing oxidative-stress induced EADs to manifest as triggered activity and VT/VF, since normal non-fibrotic hearts are resistant to arrhythmias when challenged with similar or higher levels of oxidative stress. The findings imply that antifibrotic therapy, in addition to therapies designed to suppress EAD formation at the cellular level, may be synergistic in reducing the risk of sudden cardiac death.

Impact of Systemic Acidosis on the Development of Malignant Ventricular Arrhythmias After Reperfusion Therapy for ST-Elevation Myocardial Infarction

The aim of the present study was to examine the effect of systemic acidosis on the development of malignant ventricular arrhythmias, including sustained ventricular tachycardia and ventricular fibrillation (VT/VF), after reperfused ST-elevation myocardial infarction (STEMI). A total of 157 consecutive patients with a reperfused STEMI were examined. Patients were divided into 2 groups according to the presence or absence of systemic acidosis, defined as arterial blood pH <7.40 on admission. Serum creatine kinase and C-reactive protein (CRP) levels were serially measured. Systemic acidosis was observed in 53 patients (34%). There was no significant difference in coronary risk factors and arrival time from onset between the 2 groups. Estimated glomerular filtration rate (eGFR) on admission was lower in patients with acidosis than in those without (P=0.001). Patients with acidosis had a higher incidence of VT/VF (26% vs 4%, P<0.0001), especially within 48 h after STEMI (23% vs 3%, P=0.0002), than those without. The peripheral white blood cell count on admission was higher in patients with than in those without acidosis. Multivariate analysis showed that systemic acidosis was a strong independent predictor of VT/VF (relative risk =8.79, P=0.002) among variables including prior MI and eGFR <60 ml . min(-1) . 1.73 m(-2). Systemic acidosis was a significant determinant of VT/VF after reperfused STEMI and was associated with elevated serum CRP level. Systemic acidosis and subsequent inflammation after ischemia reperfusion may play an important role in the development of VT/VF.

Role of Ischemic Preconditioning and Inflammatory Response in the Development of Malignant Ventricular Arrhythmias After Reperfused ST-Elevation Myocardial Infarction

Background Sustained ventricular tachycardia and ventricular fibrillation (VT/VF) are major complications of ST-elevation myocardial infarction (STEMI), even in the era of reperfusion therapy. We sought to clarify the determinants of VT/VF after reperfused STEMI. Methods and Results Consecutive STEMI patients treated with primary percutaneous coronary intervention (n = 457) were divided into 2 groups by the presence or absence of VT/VF during hospitalization. Serum C-reactive protein (CRP) level and peripheral white blood cell (WBC) count were serially measured. VT/VF was observed in 54 patients (12%). Prior infarction was more common and preinfarction angina was less in patients with VT/VF than those without. Peak CRP level ( P < .0001), WBC count on admission ( P = .008), and maximum WBC count ( P = .0014) were higher in patients with VT/VF than those without. VT/VF, especially VT/VF later than 48 hours after onset, was associated with greater left ventricular (LV) dimension during convalescence. Kaplan-Meier curves and log-rank test revealed VT/VF to be a significant determinant of long-term major adverse cardiac events. Multivariate analysis revealed that prior infarction, absence of preinfarction angina, and peak CRP ≥10 mg/dL were independent determinants of VT/VF. Conclusions Lack of ischemic preconditioning, enhanced inflammatory response, and subsequent LV dysfunction are related to the development of VT/VF after STEMI.

Genetic predisposition and cellular basis for ischemia-induced ST-segment changes and arrhythmias

Recent reports have highlighted the importance of a family history of sudden death as a risk for ventricular fibrillation (VF) in patients experiencing acute myocardial infarction (AMI), pointing to the possibility of a genetic predisposition. This report briefly reviews 2 recent studies designed to examine the hypothesis that there is a genetic predisposition to the development of arrhythmias associated with AMI. Ventricular tachycardia and VF (VT/VF) complicating AMI as well as arrhythmias associated with Brugada syndrome, a genetic disorder linked to SCN5A mutations, have both been linked to phase 2 reentry. Because of these mechanistic similarities in arrhythmogenesis, we examined the contribution of SCN5A mutations to VT/VF complicating AMI in patients developing VF during AMI. A missense mutation in SCN5A was found in a patient who developed an arrhythmic electrical storm during an evolving myocardial infarction. All VT/VF episodes were associated with ST-segment changes and were initiated by short-coupled extrasystoles. G400A mutation and H558R polymorphism were on the same allele, and functional expression in TSA201 demonstrated loss of function of sodium channel activity. These results suggest that a subclinical mutation in SCN5A resulting in a loss of function may predispose to life-threatening arrhythmias during acute ischemia. In another cohort of patients who developed long-QT intervals and torsade de pointes arrhythmias in days 2 to 11 after an AMI, a genetic screening of all long-QT genes was performed. Of 8 patients in this group, 6 (75%) displayed the same polymorphism in KCNH2, which encodes the α-subunit of the rapidly activating delayed rectifier potassium current, I Kr. The K897T polymorphism was detected in only 3 of 14 patients with uncomplicated myocardial infarction and has been detected in 33% of the white population. Expression of this polymorphism has previously been shown to cause a loss of function in HERG current consistent with the long-QT phenotype. These observations suggest a genetic predisposition to the development of long-QT intervals and torsade de pointes in the days after an AMI. These preliminary studies provide support for the hypothesis that there is a genetic predisposition to the type and severity of arrhythmias that develop during and after an AMI, and that additional studies are warranted.

Abstract 3207: Role of Ischemic Preconditioning and Inflammatory Response in the Development of Malignant Ventricular Arrhythmias after Reperfused Acute Myocardial Infarction

Background: Malignant ventricular arrhythmias, such as sustained ventricular tachycardia and ventricular fibrillation (VT/VF), are fatal complications after acute myocardial infarction (MI) even in the era of reperfusion therapies. We sought to clarify the determinants of VT/VF after reperfused MI. Methods: A total of 528 consecutive acute MI patients, who were treated with primary percutaneous coronary intervention, were divided into 2 groups according to the presence or absence of VT/VF during hospitalization. Serum C-reactive protein (CRP) level and peripheral white blood cell (WBC) count were serially measured for every 24 hours. As a substudy, left ventricular (LV) function and long-term clinical outcome were compared between patients with early (&gt;48 hours after the onset) and late VT/VF (&gt;48 hours). Results: VT/VF was observed in 58 patients (11%). Prior MI and anterior MI are more common in patients with VT/VF than those without. Prevalence of preinfarction angina was less in patients with VT/VF than those without. Peak CRP (14.7±10.1 vs. 8.8±7.1 mg/dl, p&lt; 0.0001), WBC on admission (12833±3513 vs. 10906±4771 /mm 3 , p=0.03) and maximum WBC (14808±5335 vs. 12531±4348 /mm 3 , p=0.009) were higher in patients with VT/VF than those without. Multivariate analysis revealed that prior MI (RR=4.57, p=0.02), absence of preinfarction angina (RR=2.44, p=0.02) and peak serum CRP ≥10 mg/dl (RR=3.37, p=0.003) were independent determinants of VT/VF. Early VT/VF was observed in 49 patients, while late VT/VF in 9 patients. Prevalence of prior MI, preinfarction angina or peak CRP ≥10mg/dl was comparable between early and late VT/VF. LV end-diastolic and end-systolic dimensions are greater in patients with late VT/VF than those with early VT/VF (p&lt; 0.05). Incidence of readmission for heart failure and sudden cardiac death tended to be higher in patients with late VT/VF than those with early VT/VF. Conclusions: VT/VF after reperfused acute MI was associated with prior history of MI, absence of preinfarction angina and increased inflammatory markers. VT/VF occurred in late phase was related to depressed LV function. Lack of ischemic preconditioning, enhanced inflammatory response and subsequent LV remodeling could contribute to the development of VT/VF after MI.

Characteristics and Relevance of Clustering Ventricular Arrhythmias in Defibrillator Recipients

Studies of recurrent ventricular tachycardia and ventricular fibrillation (VT/VF) have been limited to "electrical storms," where recurrent arrhythmias necessitate repeated external cardioversions or defibrillations. Patients with an implantable cardioverter-defibrillator (ICD) may also suffer frequently recurrent arrhythmias. The aim of this study was to analyze the temporal pattern and the clinical relevance of clustering ventricular arrhythmias in ICD recipients. The incidence and the type of arrhythmias were determined by reviewing stored electrograms. VT/VF clusters were defined as the occurrence of three or more adequate and successful ICD interventions within 2 weeks. Two hundred and fourteen consecutive ICD recipients were followed during an average of 3.3 +/- 2.2 years (698 patient-years). Fifty-one patients (24%) suffered 98 VT/VF clusters 21 +/- 22 months after ICD implantation, 93% of these clusters consisting of recurrent regular VT. Monomorphic VT as index event leading to ICD implantation was the only factor predicting VT/VF clusters. Kaplan-Meier estimates of the combined end-point of death or heart transplantation showed a 5-year event-free survival of 67% versus 87% in patients with and without clusters, respectively (P = 0.026). Adjusted hazard ratios for death or heart transplantation in the group with arrhythmia clusters was 3.5 (95% confidence interval 1.5-7.9 P = 0.003). VT/VF clusters are frequent late after ICD implantation particularly in patients who had VT as index-event. As arrhythmias and recurrent ICD interventions are responsible for an important morbidity, there is a possible role for a prophylactic intervention. Furthermore, VT/VF clusters are an independent marker of increased risk of death or need for heart transplantation.

Not Everyone With an Ejection Fraction ≤30% Should Receive an ICD

Although the total number of deaths attributed to cardiovascular disease has decreased during recent decades, an increase in the percentage of cardiac deaths occurring suddenly (from 56% in 1989 to 63% in 1998) has actually resulted in an increase in the total number of sudden deaths in the United States.1 The problem of sudden death spans all racial and cultural groups and is equally important in men and women. It is now 40 years since continuous ECG monitoring revealed that ventricular tachycardia and ventricular fibrillation (VT/VF) are responsible for the majority of sudden deaths. Dissemination of this information resulted in a marked change in practice. Until the 1970s, physicians treated only symptomatic VTs. Therapeutic options were limited to a few antiarrhythmic drugs, administered empirically. With the advent of telemetric ECG monitoring and continuous ambulatory (Holter) ECG monitoring came the recognition that frequent and multiform ventricular ectopy often preceded episodes of VF in the acute phase of myocardial infarction (MI). Ventricular ectopy and nonsustained VT was documented 1 to 2 weeks after MI in many patients. The presence of frequent ventricular premature complexes and runs of nonsustained VT in patients with significant left ventricular dysfunction were then demonstrated to be an independent predictor of sudden cardiac death late after MI. This information then led to the practice of administering antiarrhythmic drugs to suppress ventricular ectopy under the presumption that suppression of asymptomatic ectopy would prevent sudden death. This fashion lasted almost 20 years, until the results of the Cardiac Arrhythmia Suppression Trial (CAST) trial demonstrated the harm caused by this approach.2 Thus, a sea change in the practice of cardiology had occurred, from treating only symptomatic patients to therapy aimed at primary prevention of sudden death. The initial efforts using antiarrhythmic drugs failed to reduce mortality. While many physicians …

Combined Effects of Nifekalant and Lidocaine on the Spiral-Type Re-Entry in a Perfused 2-Dimensional Layer of Rabbit Ventricular Myocardium

Spiral re-entry plays the principal role in the genesis of ventricular tachycardia and ventricular fibrillation (VT/VF). The specific I(Kr) blocker, nifekakant (NIF) has, often in combination with lidocaine (LID), recently been used in Japan to prevent recurrent VT/VF, but the combined effects of these drugs on spiral re-entry had never been investigated. A ventricular epicardial sheet was obtained from 13 Langendorff-perfused rabbit hearts by means of a cryoprocedure, and epicardial excitations were analyzed with a high-resolution optical mapping system. Nifekakant (0.5 micromol/L) caused significant prolongation of action potential duration (APD) and LID (3 micromol/L) attenuated the APD prolongation without affecting the conduction velocity. VT were induced in 6 hearts by cross-field stimulation, and single- or double-loop spirals circulating around variable functional block lines were visualized during the VT. Nifekakant reduced VT cycle length and caused early termination in association with destabilization of the spiral dynamics (prolongation of functional block line, frequent local conduction block, and extensive meandering). These modifications of spiral-type re-entrant VT by NIF were prevented by addition of LID. The effects of NIF on the spiral excitations are reversed by LID. This interaction should be taken into account when these drugs are used in combination to treat VT/VF.

Acute management of ventricular arrhythmias: role of antiarrhythmic agents.

When treating life-threatening ventricular arrhythmias such as symptomatic ventricular tachycardia and ventricular fibrillation (VT/VF), the nature of the arrhythmia must be precisely defined and the approach must be tailored to it. For hemodynamically unstable ventricular arrhythmias, DC cardioversion or high-energy defibrillation remains the approach of choice. Determining the specific role of intravenous drugs in acute conversion of VT/VF and the most appropriate long-term therapy (pharmacologic or nonpharmacologic) to prevent recurrence can be difficult. Pharmacologic conversion of stable VT/VF presents an even greater challenge, as the role of lidocaine considered the first-line agent for many decades, is now being reevaluated. Lidocaine appears to be effective in converting no more than 20% of stable VTs, compared with 70% for intravenous sotalol. The precise efficacies of parenteral procainamide, beta-blockers, and newer class III agents, including intravenous amiodarone, remain to be defined; however, intravenous amiodarone, available recently, can control unstable, recurrent VT/VF that is resistant to lidocaine or procainamide. A standard regimen of concomitant intravenous and oral amiodarone may be given for rapid and sustained control, and allows oral amiodarone to be continued in a significant number of patients.

Action potential alternans and irregular dynamics in quinidine-intoxicated ventricular muscle cells. Implications for ventricular proarrhythmia.

Cardiac cells display rate-dependent beat-to-beat variations in action-potential duration (APD), action potential amplitude (APA), and excitability during periodic stimulation. We hypothesized that quinidine causes a marked increase in the variability of APD, APA, and excitability of ventricular cells isolated from quinidine-toxic, arrhythmic ventricles. Action potentials were recorded from right ventricular endocardial tissues (2 x 1 cm, < 2 mm thick) isolated from dogs in which ventricular tachycardia and ventricular fibrillation (VT/VF) were induced with intravenous quinidine (80-100 mg/kg) over a 5-hour period in vivo (n = 7). As the basic cycle length (BCL) of stimulation was progressively shortened, rate-dependent variations in APD and APA occurred. The initial dynamic change was alternans of APD and APA that could be either in or out of phase between two cells. The magnitude of alternans was a function of the BCL and the strength of the stimulation current. At critically short BCLs, irregular APD and APA behavior emerged in the quinidine-intoxicated cells. In control cells (n = 16) isolated from three nontreated dogs, APD and APA remained constant at all BCLs tested (2,000-300 msec). Quinidine increased the slope of the APD restitution curve compared with control. The observed quinidine APD restitution curve was fitted with a biexponential equation, and computer simulation using the fitted restitution curve reproduced the aperiodic APD seen in the quinidine toxic cells during periodic stimulation. Thus, the observed irregular APD behavior was predictable from the restitution curve. Quinidine toxicity increases the temporal and spatial variability of APD and APA in the ventricle that may promote the initiation of reentrant VT/VF in vivo. The slope of the APD restitution curve provides a method to quantitate inhomogeneities in repolarization time and could be a useful marker for proarrhythmia.