John C. Somberg, MD I have no real or apparent conflicts of interest to report.

Nonpharmacologic Treatment of Hypertension John Somberg, MD 80 million Americans have hypertension 1 billion people world wide have hypertension 30% or 24 million patients have drug resistant hypertension 20% are intolerant to medical therapy due to adverse side effects Hypertension if left untreated is a major contributing factor to myocardial infarction, heart failure, stroke and sudden death

Targets for Reduction of Arterial Hypertension Reduce Sympathetic Neural Activation Inhibit central cardio acceleratory centers Stimulate central cardio inhibitory centers Increase cardiopulmonary stretch receptors Increase Peripheral Parasympathetic Tone Stimulate central parasympathetic centers Stimulate baroreceptors Inhibit Sympathetic Mediated Activation of the Renin Angiotensin System Decrease central sympathetic neural outflow Decease (interrupt) renal sympathetic innervation Activate baroreceptors

Limitations to Pharmacologic Therapy for Hypertension Compliance Side effects Protracted costs Tolerance development Inability to treat to goal Inefficacy in drug resistant patients Drug interactions

Alternative Non-Pharmacologic Therapy Would be Useful Clinician’s Viewpoint for Non-Pharmacologic Therapy Assessment Efficacy Durability of Effect Procedural Adverse Effects Costs

Renal Sympathetic – Nerve Ablation 1940’s – 1950’s radical sympathectomy popular, but severe side effects, adversity and costs associated Krum & associates 2010 have studies 50 drug resistant (failed 4.7 drugs) with renal artery radiofrequency ablation, BP > 160 mm systolic with BP reduction of -27/-17 mmHg at 12 months with one intraprocedural renal artery dissection Krum study did not have a placebo or sham-operated comparator, did not account for “white coat” hypertension, only partially evaluated durability of effect and needs to have cost effectiveness evaluated

Murray Esler et al. Symplicity HTN-2 Study Abstract No: 21826. Late Breaking Clinical Trials, AHA Scientific Sessions 2010, Chicago IL

Carotid Barroreceptor Stimulation From the early work in man by Bilgutay and Lillehei (1960), stimulation of the carotid baroreceptor has been known to cause a lowering in BP. Braumwald, Epstein and colleagues (1967) showed that relief of angina pectoris could be achieved by BP lowering after carotid – sinus nerve stimulation. Wustman et al. (2009) reported that in 21 hypertensive patients BP was lowered from a mean of 185 ± 31 / 109 ± 24 mmHg to 154 ± 23 / 95 ± 16 mmHg (p<0.0001). Heusser et al. (2010) reported that in 12 patients with treatment resistant hypertension the Rheos stimulator with bilateral intra- arterial stimulation caused a 32 ± 10 mmHg mean fall in BP (p<0.01). Scheffers et al. (2010) reporting the results of the European Multi-Center Feasibility Study found that in 40 patients with systolic BP > 160 mmHg despite at least 3 anti hypertensive drugs, after 3 months stimulation the mean BP was reduced 21/12 mmHg and the results were sustained in 17 patients over 2 years.

RHEOS BAROREFLEX HYPERTENSION THERAPY SYSTEM Maria M. Ng et al. Cardiology in Review 2011;19(2): 52–57

Deep Brain Stimulation Green and associates (2005) report that electrical stimulation of the periventricular/periqueductal grey matter in 15 awake individuals caused a 14 + 4 mmHg reduction in SBP. Green and associates (2006) report that in a 61 yo male hypertensive, stimulation of the periventricular / periaqueductal grey area for relief of neuropathic pain could increase or decrease BP depending on electrode placement. Pereiva and associates (2009) report that in a 58 yo male with chronic pain, left periaqueductal grey matter stimulation a 13 mmHg (systolic) and 11 mmHg (diastolic) BP reduction sustained over one year.

Respiratory Rate Modulation to Control BP Reducing respiratory rate to 6-10 bpm increases tidal volume while maintaining minute ventilation resulting in increased cardio pulmonary stretch receptor stimulation, reducing sympathetic outflow (Parati et al 2008). RESPeRate – electronic device to assist in slow breathing training. Viskoper et al (2003) studied 17 patients with resistant hypertension (140-160 mmHg despite 3 drugs) over 8 weeks with a 13 + 11 systolic and 7 + 6 mmHg diastolic fall in BP. Schein et al 2001 found a 78% of the treatment group compared with 57% of the active control group achieved a 7 mm fall in BP using RESPeRate – a non significant difference. This negative finding is supported by Grossman et al (2001) and Longtenberg et al (2007).

The RESPeRATE Device Sharma et a. Cardiology in Review 2011;19 (2): 47–51