Design Considerations for Clinical Trials of Autonomic Modulation Therapies Targeting Hypertension and Heart Failure

Zannad, Faı̈ez; Stough, Wendy Gattis; Mahfoud, Felix; Bakris, George L.; Kjeldsen, Sverre E.; Kieval, Robert S.; Haller, Hermann; Yared, Nadim; Ferrari, Gaetano M. De; Piña, Ileana L.; Steín, Kenneth M.; Azizi, Michel

doi:10.1161/hypertensionaha.114.04057

Cited by 26 publications

(8 citation statements)

References 96 publications

(99 reference statements)

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“…Despite the promising clinical outcomes observed with surgical denervation, and favorable association between SGB and VA burden, the efficacy and safety of a sympathetic nerve block for VAs have not been tested in randomized prospective trials. Furthermore, the available surgical and percutaneous data cannot exclude a placebo effect as seen with other autonomic modulation procedures such as renal denervation . On one side, the proof of efficacy of the percutanoues SGB could provide an urgently needed alternative therapy for patients at greatest risk for cardiovascular morbidity and mortality; on the other side, continuous use of percutanoues SGB without proven efficacy and safety could result in harm of patients at an already increased risk without any potential benefit.…”

Section: Discussionmentioning

confidence: 99%

Stellate ganglion blockade for the treatment of refractory ventricular arrhythmias: A systematic review and meta‐analysis

Fudim

Boortz-Marx

Garg

et al. 2017

Cardiovasc electrophysiol

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Section: Discussionmentioning

confidence: 99%

Stellate ganglion blockade for the treatment of refractory ventricular arrhythmias: A systematic review and meta‐analysis

Fudim

Boortz-Marx

Garg

et al. 2017

Cardiovasc electrophysiol

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“…8,9 Importantly, it makes sense to determine the efficacy and short-term safety of a new renal denervation device in a smaller well-characterized sample before it is tested in a larger heterogeneous randomized trial population with increased cardiorenal risk. 6,10 Patients, caregivers, and those assessing BP were blinded to randomization assignments. Blinding of study patients and BP assessors was maintained for up to 12 months after randomization.…”

Section: What Does This Important Study Show?mentioning

confidence: 99%

“…Because of the multiple measurements obtained with ABP monitoring and removal of observer bias seen in clinical measurements, ABP is more reproducible than clinic measurements and has the ability to determine nocturnal BP values at a time when sympathetic nervous system activity is theoretically lower than while awake. 10,11 SPYRAL HTN-OFF MED was also performed with more than 1 catheter per site, according to international consensus recommendations. 5,6 Results of SPYRAL HTN-OFF MED showed that the renal-denervation group had small but both statistically and clinically significant reductions from baseline to 3 months in both clinic BPs and ABPs, whereas the sham group did not.…”

Section: What Does This Important Study Show?mentioning

confidence: 99%

A New Era of Renal Denervation Trials for Patients With Hypertension?

Jalil

White

2018

American Journal of Kidney Diseases

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“…( 1) Is SGB more than just an elaborate placebo? The available surgical and percutaneous experience does not exclude a placebo effect as has been seen with other autonomic modulation procedures such as renal denervation . For this and several other reasons, testing SGB in a randomized clinical trial is of paramount importance.…”

mentioning

confidence: 99%

Treating cardiac dysrhythmias by targeting the neck: Off target or on the right track?

Fudim

Piccini

2017

Cardiovasc electrophysiol

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The history of cardiology provides many examples of attempts to target cardiovascular pathophysiology by modulating the autonomic nervous system (ANS). The most widely used form of nonspecific and global autonomic modulation is beta-receptor blockade. Beta-blockers are proven to improve outcomes in patients with heart failure and myocardial infarction 1,2 and prevent ventricular arrhythmias and sudden cardiac death. 3 However, beta-blockade is not perfect. It often is ineffective for the prevention of ventricular arrhythmias. Moreover, on occasion, excessive or nonspecific sympathetic blockade may not be helpful. 4,5 In theory, targeted modulation of the ANS has the potential to restore autonomic balance in organs affected by autonomic dysfunction. Autonomic modulation has several potential and beneficial mechanisms, including sympathetic and parasympathetic effects via either the efferent and/or afferent limbs of each system. Examples of targeted autonomic modulation therapies for cardiovascular disorders include: (1) thoracolumbar sympathectomy and renal denervation for the treatment of hypertension 6 ; (2) baroreceptor stimulation for the management of heart failure and hypertension 7 ; (3) vagus nerve stimulation for the treatment of heart failure 8 ; and (4) carotid body modulation for the treatment of heart failure and hypertension. 9,10 Despite promising phase II studies for each of the aforementioned interventions, there are no conclusive phase III data to support their clinical use.In the last several years the field of neuromodulation has increasingly focused on cardiac autonomics as a potential therapeutic target in the treatment of heart rhythm disorders. For example, in the case of atrial fibrillation, several approaches to modulate the ANS directly 11,12 or indirectly via sensory input from the periphery 13,14 are in continued development. Ventricular arrhythmia is one of the last (but not new) frontiers for neuromodulation. Ventricular arrhythmias are complex electrical phenomenon that can occur in patients with or without structural heart disease. Electrical storm (≥3 episodes of ventricular tachycardia or fibrillation in 24 hours) represents a particularly complicated and life-threatening emergency. Electrical storm is more common than often appreciated, as recently shown in a meta-analysis of 5,600 patients with implanted cardiac defibrillators, where 15% experienced electrical storm during 30-month followup. 15 Not surprisingly, electrical storm is more common in secondary prevention patients and its occurrence is associated with a threefold increased risk of mortality. 15,16 However, it is also notable that electrical storm carries a 2.5-fold higher risk of death compared with isolated VT/VF episodes. This suggests that electrical storm is not just the frequent occurrence of ventricular arrhythmias in a 24-hour window but is an indicator of severe cardiac dysfunction and global autonomic imbalance. Early therapeutic intervention is the key to successful management of electrical storm, given th...

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Design Considerations for Clinical Trials of Autonomic Modulation Therapies Targeting Hypertension and Heart Failure

Cited by 26 publications

References 96 publications

Stellate ganglion blockade for the treatment of refractory ventricular arrhythmias: A systematic review and meta‐analysis

Stellate ganglion blockade for the treatment of refractory ventricular arrhythmias: A systematic review and meta‐analysis

A New Era of Renal Denervation Trials for Patients With Hypertension?

Treating cardiac dysrhythmias by targeting the neck: Off target or on the right track?

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