Treatment of Reflex Syncope

Management of

REFLEX SYNCOPE

heartRhythmBox.com

Thin Line between Syncope and SCD

Van Dijk et al. Front. Cardiovasc. Med., 13 March 2020.

What is ?

REFLEX SYNCOPE

REFLEX SYNCOPE is
- Syncope due to failure of neural reflex to control BP.
- Including vasovagal syncope, situational syncope, and carotid sinus syndrome.

J Cardiovasc Electrophysiol. 2017 Sep;28(9):1088-1097.

The interplay between sym- and parasympathetic nervious system

Mechanism of Reflex Syncope

How to Reverse Reflex Syncope

#1 Counterpressure Maneuover to delay or prevent reflex syncope.

J R Army Med Corps 2015;161:180–186.

15mmHg increase in standing SBP
34% relative reduction in recurrence rate
Less effective in the elderly and those with minimal prodromal period.

Front. Cardiovasc. Med., 13 October 2022

#2 Pharmacological Treatment of Reflex Syncope

Treatment 1	Mechanism of Action	Results from RCT(s)	Guidelines Recommendation 2
De-prescribing of antihypertensive meds	Reduce orthostatic hypotension	HR (syncope/pre-syncope) 0.40 (0.16- 1.00) 3	IIa (older w/ htn meds)
Midodrine	Selective alpha-receptor agonist	HR (time to 1st syncope) 0.59 (0.37-0.96) 4	IIb (younger & low BP)
Fludrocortisone	Mineralocorticoid-like action	HR (syncope; after 2wk of drug) 0.51 (0.28-0.89) 5	IIb (younger & low BP)
Theophylline	Adenosine blockade	No RCT. In a case series, asystolic pause reduced from 9.6 to 1.1/yr. 6	No recommendation
Atomoxetine	NE transporter inhibition	Episodes of syncope/presyncope at 3mos 2 (drug) vs 4 (placebo); p<0.0017 7	No recommendation
Droxidopa	Synthetic NE prodrug	Symptoms improvement in neurogenic OH (assessed by questionnaire), P=0.0038 8	No recommendation

1. Brignole M, Rivasi G. Heart 2021;107:864–873.	2. 2018 ESC Guidelines for Syncope
3. Solari, et al. Heart 2017;103:449-455.	4. Sheldon et al. POST 4. Ann Intern Med. 2021 Oct;174(10):1349-1356.
5. Sheldon et al. POST 2. J Am Coll Cardiol 2016;68:1–9.	6. Brignole et al. Int J Cardiol. 2019 Aug 15;289:70-73.
7. Tajdini et al. Int J Cardiol Heart Vasc. 2021 May 8;34:100789.	8. Kaufmann et al. Neurology. 2014 Jul 22; 83(4): 328–335.

#3 Pacemaker for Cardio-inhibitory type of Reflex Syncope

PPM vs. No PPM

Trials	1yr Recurrence Rate (PPM vs. No PPM)	Statistical Significance
RCT: PPM vs no PPM 1	0% vs. 36%	P <0.001
RCT: PPM vs Atenolol 2	3% vs. 24%	OR 0.13 95%CI 0.03-0.63

1. Brignole et al. Am J Cardiol. 1992 Apr 15;69(12):1039-43.

2. Ammirati et al. Circulation. 2001 Jul 3;104(1):52-7.

PPM ON vs. PPM OFF

Trials	1yr Recurrence Rate (PPM ON vs OFF)	HR (95%CI)
ISSUE 3 1	25% vs. 37%	0.43 (0.04-0.81)
BIOSYNC CLS 2	19% vs. 53%	0.23 (0.11-0.47)

1. Brignole et al. Circulation. 2012 May 29;125(21):2566-71.

2. Brignole et al. Eur Heart J. 2021 Feb 1;42(5):508-516.

#4 Cardioneural Ablation for Reflex Syncope

The small brain within the heart

The heart is not just a pump. It has its neural network or intrinsic cardiac nervous system.

Aksu et al. JACC Case Rep 2021.

Circ Arrhythm Electrophysiol. 2017.

Targets for Cardioneual Ablation is...

SUPERIOR PARASEPTAL AND THE INFERIOR PARASEPTAL GANGLIA.

Targets for Cardioneual Ablation can be identified by...

ANATOMY, FRAGMENTED SIGNALS, AND RESPONSE TO STIMULATION.

Hu et al. J Atr Fibrillation. 2020. and Calo et al. J Interv Card Electrophysiol. 2021.

CNA for Cardio-inhibitory Syncope after Failure of Pharmacologic and Non-pharmacologic Treatment

JACC Clin Electrophysiol. 2023

Knowns & Unknowns of CardioNeural Ablation

Knowns

Not for vasodepressor type.
Not for patients with intrinsic SA or AV node dysfunction.
Complications included injury to phrenic nerve, coronary artery, and other complications similar to SVT ablation
Reflex syncope has a benign prognosis.

Unknowns

Long-term effects of re-innervation and high heart rate.
RA vs. Bi-atrial Approach
Endpoint???
Therapeutic Fashion vs. Evidence-based Treatment

Rivarola et al. Circ Arrhythm Electrophysiol. 2017.	Debruyne et al. Circ Arrhythm Electrophysiol. 2021
Scanavacca et al. JACC Case Rep. 2022.	Brignole et al. Europace 2023.
Mandrola JM. Medscape 2023.

#5 Yoga therapy to prevent recurrent reflex syncope

Yoga is known to improve balance of autonomic nervous system and recommended as an adjunctive therapy in cardiovascular conditions such as hypertension and heart failure.

J Clin Hypertens 2021. Circulation 2023.

Trials	Inclusions	Yoga Protocol	Mean Syncope Episodes (Yoga vs. Control)
			6wks	1yr
RCT, N=97	Reflex syncope 3+/yr, age 12-60 yr	Instructed; breathing & postures exercises 60mins/d x 5/wk	0.8 vs 1.8 P <0.001	1.1 vs 3.8 P <0.001
RCT, N=55	Reflex syncope 2+/3mo, age 15-70yr		0.17 vs 0.45 P =0.04	0.70 vs 2.52 P <0.01

Shenthar et al. Europace 2021. Sharma et al. JACC Clin Electrophysiol 2022.

"Tadasana" Yoga Maneuver

a very simple yoga pose for prevention of reflex syncope: an RCT

Rao et al. JACC Clin Electrophysiol 2022.

#6 Avoid Triggers

CONCLUSIONS

Reflex Syncope is a benign condition.
Current strategy to prevent reflex syncope include medications, pacemaker, exercise maneuvers, and etc.
None of the above is highly effective.
Cardioneural ablation is a novel and promising treatment option for patients who have failed conventional treatments. Long-term effects and side effects have yet to be established.

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