Original-clinical

Genetic: Editorial commentary

Cutting nerves and saving lives

Patients who present with electrical storms (ES) due to rapid recurrence of ventricular tachycardia/ventricular fibrillation represent major medical emergencies without easy solutions. Antiarrhythmic drugs have limited value, and ES need to be stopped quickly to prevent irreversible patient deterioration and death. Since the mid-1970s, we have provided the rationale for interrupting cardiac sympathetic nerves and evidence of its antifibrillatory action in different clinical settings. Slowly but progressively, from isolated clinical reports to small case series, increasing evidence has indicated that pharmacologic stellate ganglion block (SGB) is highly effective in interrupting ES. However, medical guidelines have largely ignored SGB, and few centers are prepared to perform SGB in actual emergencies. Our own experience shows that a direct anatomic approach that does not require echocardiographic assistance can be performed rapidly, thus saving time in highly critical patients. In this review, we retrace the evolution in our understanding of the mechanism of action of SGB, discuss the current approaches and their limitations, and review the correct indications that overcome still existing biases. Furthermore, we propose a practical solution to increase the availability of SGB to more patients by extending the number of centers where this approach can be rapidly implemented.

This study sought to report our single-center experience with left cardiac sympathetic denervation (LCSD) for long QT syndrome (LQTS) since 1973.

LCSD is still underutilized because clinicians are often uncertain whether to use it versus an implantable cardioverter-defibrillator (ICD).

We performed LCSD in 125 patients with LQTS (58% women, mean QT interval corrected for frequency [QTc] 527 ± 60 ms, 90% on beta blockers) with a follow-up of 12.9 ± 10.3 years. They were retrospectively divided into 4 groups according to the clinical/genetic status: very high risk (n = 18, symptomatic in the first year of life or with highly malignant genetics), with aborted cardiac arrest (ACA) (n = 31), with syncope and/or ICD shocks on beta blockers (n = 45), in primary prevention (n = 31).

After LCSD, 17% in the very high risk group remained asymptomatic, compared with 52%, 47%, and 97% in the other 3 groups (P < 0.0001), with an overall 86% decrease in the mean yearly cardiac event rate (P < 0.0001). Among 45 patients with only syncope/ICD shocks before LCSD, none had ACA/sudden death as first symptom after LCSD and a 6-month post-LCSD QTc <500 ms predicted excellent outcome. Patients with a QTc ≥500 ms have a 50% chance of shortening it by an average of 60 ms. LCSD results are not affected by common genotypes.

We provide definitive evidence for the long-term efficacy of LCSD in LQTS. The degree of antiarrhythmic protection is influenced by patient’s specificity and amount of QTc shortening. This novel approach to the analysis of the outcome allows cardiologists to rationally decide and tailor their management strategies to the individual features of their patients.

The prevention and management of QT interval prolongation and torsades de pointes often depends on the underlying etiology. Drugs and electrolyte imbalances are the major causes of acquired long QT syndrome, and prevention strategies include identifying and discontinuing or substituting the offending drug and correcting electrolyte abnormalities. Lifestyle modification, genetic testing, and β-adrenergic receptor blockade are risk mitigation strategies for patients with the congenital long QT syndrome. Left cardiac sympathetic denervation, implantable cardioverter-defibrillator, magnesium sulfate and overdrive cardiac pacing are currently used in the management of TdP, although a significant number of cases are not adequately managed. This chapter discusses the approaches and current therapies for the prevention and management of long QT syndrome. The chapter also explores novel approaches such genome editing, RNA interference, and hormone therapy in the management of QT interval prolongation and torsades de pointes.

Long QT syndrome (LQT) represents a heterogeneous family of cardiac electrophysiologic disorders characterized by QT prolongation and T-wave abnormalities on the electrocardiogram. It is commonly associated with syncope, however, sudden cardiac death can occur due to torsades de pointes. LQT is a clinical diagnosis and should be suspected in individuals on the basis of clinical presentation, family history and ECG characteristics. Management is focused on the prevention of syncope and ultimately sudden death. Complete cessation of symptoms is the goal. Life-style modification, beta blockers and ICD implantation are the most important therapeutic modalities in proper management of patients with LQT. Awareness should be raised regarding possible circumstances that could increase the risk of QT prolongation. Advanced age, hypokalemia, a history of heart failure, and structural heart disease are often mentioned in this context. Prudent consideration is needed before making a decision to recommend an ICD implantation in a young, active patient. Medical and/or device therapy still represent important therapeutic modalities in the management of patients with LQT with careful clinical judgement for the substrate of patients who will benefit. Insights from benchside to bedside have facilitated progress toward better therapeutic strategies, there also remains a need for tailoring management toward individuals in a mechanism-specific manner to optimize care. In addition, continued progress toward fundamental understanding of mechanisms of ion channel function and drug-channel interaction will guide the development of more effective, mechanism-based molecular agents in the treatment of LQT.

The main causes of mortality in patients with chronic heart failure include sudden cardiac death (SCD) and progressive heart failure. Autonomic dysfunction plays a detrimental role in the progression of chronic heart failure. Left cardiac sympathetic denervation (LCSD) is an inexpensive and safe procedure which modifies autonomic innervation of the heart and is associated with a significant antifibrillatory effect. Whether LCSD reduces the risk of SCD, delays progression of heart failure and improves quality of life in patients with heart failure with reduced ejection fraction (HFrEF) is not known.

This is a 2-phased prospective, randomized trial to test the efficacy and safety of LCSD as an adjunct to guideline recommended medical therapy for patients with HFrEF. Once the safety and feasibility of conducting a large LCSD study have been demonstrated in the pilot phase, a phase III efficacy trial to assess the impact on ventricular arrhythmias, heart failure outcomes, and mortality will be completed. Outcome data from the pilot study will remain blinded and added to the results of phase III study for analysis.

To date the study has received approval from local and national ethics and regulatory bodies and recruitment has commenced, and 4 patients have been randomized so far.

If LCSD is proven to be safe, feasible and effective in this first ever study using this novel approach in patients with HFrEF it may be a cost-effective alternative to the implantable cardioverter defibrillator therapy especially in regions where ICDs and cardiac transplantation are unavailable.