Renal Sympathetic Denervation (RSDN) for A-Fib?
Report by Steve S. Ryan, PhD Dr. Vivek Reddy of Mount Sinai School of Medicine, NY gave a presentation entitled “Renal Denervation for AF—Physiology, Mechanisms of Action and Rational in AF.”
RSDN Found Ineffective, Symplicity HTN-3 Trial
Background: (Before reading this report, it is recommended to first look at the our 2014 BAFS satellite presentation “Renal Denervation and Pulmonary Vein Isolation for PAF.)
Earlier in the Symposium, the results of the Medtronic Symplicity HTN-3 trial were announced and discussed. Medtronic’s renal denervation system was found to be basically no better than a sham procedure for reducing systolic blood pressure through six months.
Dr. Reddy described how previous surgical interventions (Thoracolumbar Surgical Sympathectomy—destroying some of the sympathetic nerve trunk) did reduce blood pressure by affecting the Sympathetic Nerves (Smithwick et al. JAMA 1953;152(16);1501-4). And the clinical trial Symplicity HTN-2 did work—84% of patients had a 10 mmHg or greater decrease in Systolic Blood Pressure (Esler et al. Lancet 2010;376(9756): 1903-9)
Then why was Symplicity HTN-3 a negative study? Was the catheter not properly employed? (Dr. Reddy described a new method of performing RSDN by using External Ultrasound Energy which has a minimal effect on the arterial wall.) Is refractory hypertension not primarily “sympathetically-driven?”
Does RSDN do anything?—Mechanistic Data
• In a small study of patients with refractory high blood pressure (HBN) that couldn’t be lowered by drugs and other methods, RSDN did significantly lower high blood pressure (Brandt et al. JACC 59:901 ).
• In another study RSDN lowered blood pressure and Muscle Sympathetic Nerve Activity (MSNA) (Achlaich et al. NEJM 36:932-934 )
• In another study RSDN lowered renal hormones like Aldosterone, Metanephrine and Normetanephrine (Ahmed H/Neuzil P/Reddy VY: JACC-CV Interv 5:758-65 )
• RSDN improved heart rate variability (F. Himmel et al. J.Clin.HTN 14:654 }
Supporting Evidence for RSDN Helping A-Fib
• Experimental studies of sheep show that high blood pressure (hypertension) produces fibrosis (interstitial collagen) and remodeling of the atria. (Heart Rhythm 2010;7:1282-1290)
• In the ARIC study of nearly 15,000 people followed for 17 years, high blood pressure accounted for 20%-25% of all A-Fib cases (other factors were Obesity, Diabetes, Smoking and Prior Cardiac Disease). (Huxley et al Circulation 123:1501-1508 )
• Hypertension was the most significant predictor of recurrence after A-Fib ablation (Takigawa et al. JRAS, DOI: 10.1177/1470320312446212 )
• Sympathetic Nervous System overactivity predicted A-Fib recurrence (Arimoto et al. JCE )
• In Dr. Pokushalov’s work described under 2014 BAFS Satellite Presentations-Siberia, PVI with RSDN had much less recurrence than just a PVI (Pokushalov et al. JACC )
But What About A-Fib Patients without High Blood Pressure—Would RSDN Help Them?
• In a small experimental study using dogs, RSDN kept the dogs from going into A-Fib and reduced renal hormones (Q.Zhao et al. JICE [2012; DOI 10.1007/s10840-012-9717-y).
• In another dog study, RSDN ameliorated pacing-induced changes in hormones and tissue structure (X.Wang et al. PloS ONE 8(5): e64611 )
• In a study of Obstructive Sleep Apnea in pigs, RSDN helped blood pressure and reduced A-Fib when the pigs had induced sleep apnea.(Linz et al. Hypertension 62:767 )
Renal Sympathetic Denervation as Upstream Therapy in A-Fib?
Dr. Reddy described a multi-center randomized study of A-Fib and Hypertension. Patients with A-Fib and hypertension will have a catheter ablation procedure (PVI). Then some will be in the placebo group and others will have a RSDN procedure. Follow-up will measure A-Fib recurrence. (H Ahmed/MA Miller/VY Reddy, JCE 25:503-9 ). The rational for this study is that Renal Denervation can dramatically affect sympathetic tone, is technically simple to do, and has minimal safety issues. In an earlier study, Renal Denervation significantly reduced blood pressure after three months (Ahmed H / Neuzil P / Reddy VY: JACC-CV Interv 5:758-65 )
Dr. Reddy’s Final Thoughts
• RSDN is a novel approach to modulate the sympathetic nervous system (one of several)
• Many animal studies demonstrate the electrophysiological effects of RSDN
• Potential Role for RSDN in A-Fib—Reduce A-Fib recurrence
In spite of the preliminary results of Symplicity HTN-3, Renal Denervation is not dead in the water. The full results of Symplicity HTN-3 haven’t been released and examined yet. And the new multi-center randomized study Dr. Reddy described may yet prove the effectiveness of RSDN.
Renal Denervation, in addition to helping people with high blood pressure and A-Fib, may benefit anybody with A-Fib. Because Renal Denervation is easy to do and relatively safe, RSDN may become another treatment option for A-Fib.
Return to Index of Articles: AF Symposium: Steve’s Summary Reports
Last updated: Wednesday, September 2, 2015
By Steve S. Ryan, PhD
Pulmonary Vein Ablation of A-Fib is a relatively new procedure whose techniques and language are evolving. What follows is perhaps an oversimplified, somewhat biased attempt at explaining the catheter ablation procedures from a patient’s perspective. (Pulmonary Vein Ablation differs from other types of Catheter Ablation used in treating A-Fib, such as ‘Ablation of the AV Node’.)
‘Focal Catheter Ablation’ or ’Focal Point Catheter Ablation’
In this early procedure doctors mapped the sources of ectopic beats (beats that come from any region of the heart that ordinarily should not produce heart beat signals), then used a Radiofrequency (RF) catheter to “ablate” or burn off areas or points within the heart producing these ectopic beats. But if you weren’t in A-Fib at the time, it was difficult to identify the Focal Points or areas of the heart producing ectopic beats.
Doctors discovered that when a patient was not in A-Fib, the Focal Points producing A-Fib signals could still be found by identifying and mapping electrical potentials coming from these points. A potential is an electrical charge or energy—like the battery energy in your car. Even if your car isn’t running, you can still measure 12 volts “potential” at the battery. Similarly, in your heart any potential can be measured and pinpointed, even if you aren’t in A-Fib. When the area is ablated, the potential disappears. Like taking the battery out of your car, removing this potential eliminates your A-Fib. (Doctors today do not usually ablate within the Pulmonary Veins because of the risk of causing Stenosis (swelling). Instead they determine where the A-Fib signal(s) exits the Pulmonary Vein opening and ablate there to “Isolate” the A-Fib signal.)
‘Circumferential Ablation ‘or ‘Circumferential Pulmonary Vein Ablation’ (CPVA)
A circular catheter is used to make Circular Radiofrequency Ablation lines around each of the four Pulmonary Vein openings (ostia) in the left atrium of the heart. This procedure isolates the Pulmonary Veins from the rest of the heart and prevents any A-Fib signals from these veins from getting into the rest of the heart.
‘Anatomically-Based Circumferential PV Ablation’ or ‘Wide Area Circumferential Ablation’ (WACA)
Instead of trying to make continuous, perfect linear lesions around the Pulmonary Viens which can be difficult and time consuming, doctors use a “drop and drag” technique with a larger tip catheter which leaves gaps that are usually closed over time with scar tissue. This procedure originated in Italy. It has a good success rate with very few side effects both for Paroxysmal and for Chronic A-Fib.
The ‘Anatomically Based Circumferential PV Ablation’ procedure is faster, easier, requires less operator’s skill, and is more cost effective for doctors. But from a patient’s perspective it involves a lot of scarring of the heart by high wattage wide tipped catheters. And 20% of patients have atrial flutter after the procedure because of all the gaps in the lesion lines, though most of this flutter eventually disappears as these gaps fill in with scar tissue. Probably because of the gaps which caused patients a lot of problems, WACA doesn’t seem to be used much any more.
‘Pulmonary Vein (Wide Area) Antrum Isolation’(PVAI)
Instead on encircling each of the four Pulmonary Vein openings, one large encircling set of lesions isolates both the upper and lower left vein openings, another the upper and lower right vein openings. The encircling lesions are in the Antrum rather than near the vein openings.
Almost everyone doing RF ablations today seems to be using Antrum Isolation, for the main reason that the ablations are so far outside the Pulmonary Vein openings that the danger of creating stenosis (swelling of the pulmonary vein openings) is virtually eliminated.
In January 2014, I was privileged to observe doctors doing PVIs in their cath labs. Two of the leading EPs in Florida, Dr. Robert Fishel at JFK Medical Center in Atlantis/West Palm Beach, FL, and Dr. Sidney Peykar at Fawcett Memorial Hospital in Port Charlotte, FL, graciously let me observe, explained their procedures and answered my questions. Though they use different catheters and imaging systems, they both do PVAI and ablate in the antrum far away from the Pulmonary Vein openings as do most EPs today. Their point-by-point ablations burns are amazingly precise, consistent and normally leave no gaps. See my report, Visiting EP Labs as an Observer Instead of as a Patient.
‘Pulmonary Vein Ablation’ (PVA) or ‘Pulmonary Vein Isolation’ (PVI)
In general, types of PVA/PVI include: ‘Segmental Ablation’, ‘Circumferential Ablation’, ‘Anatomically-Based Circumferential PV Ablation’ and ‘Pulmonary Vein Antrum Isolation’. They are all similar in their approach. Their primary emphasis is the ablation/isolation of the Pulmonary Vein openings.
Note: Many use the term “Catheter Ablation” of A-Fib to include all of the above different ablation techniques.
Newer types of ablation have somewhat different ablation targets:
• ’Complex Fractionated Atrial Electrograms’ [CFAE]
• ‘Autonomic Ganglionated Plexi'[AGP]
Terms that still need to be re-defined
• Rather than ‘Isolation’, the term ‘electrical disconnection’ (used by The French Bordeaux group) may more aptly describes what ‘ablation’ does.
• The terms ‘Pulmonary Vein Potentials’ and ‘Pulmonary Vein Isolation’ both need to be re-defined because not all Potentials come from the Pulmonary Vein openings.
Which of the above procedures is the best? They all have somewhat similar success rates. Though the jury is still out on this, ‘Circumferential Ablation’ is quicker and faster for doctors and requires less mapping, but it’s difficult to make good circular ablations. The Pulmonary Vein openings aren’t always smooth, and the surfaces are not always easy to ablate. The inside of the heart is not a continuously smooth surface. Any gap in the circular ablation may result in more A-Fib. And not all A-Fib comes from the Pulmonary Veins. From a patient’s perspective, you’re better off with a doctor who will carefully map your heart to find out where exactly your A-Fib signals are coming from, and who will check for both Entrance and Exit Block (Isolation).
Also, with ‘Circumferential Ablation’ there might be a greater danger of Stenosis, a swelling of the Pulmonary Vein openings after ablation. PV Stenosis restricts blood flow into the heart and can lead to fatigue, flu-like symptoms and pneumonia. Most EPs now use Pulmonary Vein (Wide Area) Antrum Isolation and stay well away from ablating near the Pulmonary Vein openings.
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