Ranjan K. Thakur

Statins and the reduction of sudden cardiac death: antiarrhythmic or anti-ischemic effect?

Sudden cardiac death is an important cause of cardiovascular mortality with the majority of cases occurring in low-risk groups. HMG-CoA reductase inhibitors (statins) have recently been shown to reduce the incidence of ventricular tachycardia (VT)/fibrillation (VF) and sudden cardiac death, and this has been attributed to their pleiotropic effects. However, it is unclear whether this occurs through an ‘indirect’ anti-ischemic or ‘direct’ antiarrhythmic effect. We systematically reviewed articles published on MEDLINE between January 1996 and December 2009 focusing on the reduction of VT/VF and sudden cardiac death by statins and the potential mechanisms. Studies reporting sudden cardiac death or VT/VF outcomes with statin use (n = 23) or the pathophysiology of sudden cardiac death reduction by statins (n = 19) were included. We found that statins have been shown to reduce VT/VF and sudden cardiac death only in subjects with underlying coronary artery disease or ischemic cardiomyopathy. No definite benefits were seen with statins in sudden cardiac death and VT/VF in patients with non-ischemic cardiomyopathy. There is insufficient evidence to point toward a benefit in populations at low risk for VT/VF. In conclusion, an anti-ischemic rather than a primary antiarrhythmic effect emerges as the likely mechanism of sudden cardiac death reduction with statins.

Reduction in the Intensity Rate of Appropriate Shocks for Ventricular Arrhythmias With Statin Therapy

Higher rate of implantable cardioverter-defibrillator (ICD) shocks has been associated with increased mortality and morbidity. The aim of our study was to determine whether statins reduced the intensity rate of appropriate shock therapy for ventricular tachycardia/fibrillation in patients with an ICD placed for left ventricular systolic dysfunction. In this retrospective single center analysis, patients with an ejection fraction ≤35% who underwent ICD implantation were divided into treatment and control groups based on statin use. A zero-inflated negative binomial model was used to compare the intensity rate of appropriate ICD shocks between the 2 groups. Characteristics associated with shock-free follow-up were assessed using a stepwise logistic regression model. We found 699 patients eligible for inclusion, with 412 (59%) in the statin treatment group. The adjusted mean intensity rate of shocks was lower in patients on statin therapy (intensity rate ratio = 0.22; 95% confidence interval, 0.12-0.41; P < 0.001). Statin use was associated with a significantly higher probability of shock-free follow-up (odds ratio = 1.64; 95% confidence interval, 1.09-2.48; P = 0.019). In conclusion, statins reduced the intensity rate of appropriate shock therapy for ventricular tachycardia/fibrillation and increased probability of shock-free follow-up in patients with cardiomyopathy. Larger randomized trials are needed to confirm this relationship.

Statins reduce appropriate implantable cardioverter-defibrillator shocks in ischemic cardiomyopathy with no benefit in nonischemic cardiomyopathy

Statins have been hypothesized to decrease ventricular arrhythmias through a direct antiarrhythmic effect. Clinical studies have demonstrated a clear reduction only in populations with underlying ischemic heart disease. This study was designed to compare the effect of statins on appropriate shocks between ischemic and nonischemic cardiomyopathy. Patients with an ejection fraction 35% or less who received an implantable cardioverter–defibrillator and had follow-up for at least 1 month were included. The ischemic and nonischemic groups were divided into statin treatment and control subgroups and the occurrence of appropriate shocks was compared. The frequency of shocks was analyzed using negative binomial models to account for overdispersion of the “count” data (number of appropriate shocks) and an adjusted intensity rate ratio was calculated for statin use. A total of 676 patients were included, of which statins were used by 65% (329 of 506) of the ischemic and 42% (72 of 170) of the nonischemic groups. Occurrence of appropriate shocks was significantly reduced with statins in ischemic (13.4% vs 20.9%; relative risk 0.64, P = 0.028), but not in the patients with nonischemic cardiomyopathy. Similarly, although use of statins lowered the intensity rate of appropriate shocks in ischemic patients (intensity rate ratio, 0.23; 95% confidence interval, 0.12–0.47), no such benefit was noted in the nonischemic group (intensity rate ratio, 1.27; 95% confidence interval, 0.37–4.40). In conclusion, statins reduced the occurrence and frequency of appropriate shocks for ventricular arrhythmias in ischemic but not in nonischemic cardiomyopathy. Larger, randomized controlled trials are needed to confirm these findings.

Adenosine-induced tachycardia acceleration: an unusual proarrhythmia.

Adenosine is an effective agent for termination of most re-entrant supraventricular arrhythmias involving the atrioventricular node and often also used as a diagnostic agent for wide QRS tachycardias. Adenosine terminates 90–99% of re-entrant supraventricular tachycardias but it may rarely accelerate tachycardias. Adenosine-induced tachycardia acceleration is a rare phenomenon, as only a handful of cases have been described in the literature. We present a case of a 36-year-old man with a narrow complex, short RP tachycardia at a rate of 165u2005bpm and an initial blood pressure of 110/78u2005mmu2005Hg. A bolus of 12u2005mg of adenosine resulted in slowing of the tachycardia to 150u2005bpm for 2–3u2005s, followed by acceleration of the tachycardia to 185u2005bpm that lasted for approximately 20u2005s and returned to baseline at 165u2005bpm. The main mechanism of adenosine-induced acceleration may be the secondary sympathetic stimulation, which may be preceded by transient bradycardia and/or hypotension.

Foreword: From Genes to the Bedside

We are pleased to introduce the one-year anniversary issue of theCardiac Electrophysiology Clinics, entitled “Genetics of Cardiac Arrhythmias,” edited by Sylvia Priori. All clinicians recognize that our understanding of cardiac arrhythmias has progressed beyond the “phenotype.” Early on, we learned the correlation between physiology, pathology, and clinical presentation. Then, our understanding progressed to the level of the cell, correlating cellular physiology and pathology to the genesis and sustenance of cardiac arrhythmias and how to select pharmacologic agents for therapeutic effect. Although we did not fully attain the original promise of the “Sicilian Gambit,” our understanding was clearly at a higher level. While there is still much to learn at the phenotype level, as we delve deeper, our next level of understanding will be focused on elucidating the genetic bases of certain arrhythmias and the responsible molecular mechanisms. We clearly see this in our understanding of the long and short QT syndromes, the Brugada syndrome, cardiomyopathies, etc. Dr Priori has been a leader in this field, and in this issue of the Clinics, she has assembled esteemed contributors who have summarized what we know today about the genetics of some common arrhythmias seen in practice. In this