Novel Neuromodulation Approach to Improve Left Ventricular Contractility in Heart Failure: A First-in-Human Proof-of-Concept Study

Morbidity and mortality outcomes for patients admitted for acute decompensated heart failure are poor and have not significantly changed in decades. Current therapies are focused on symptom relief by addressing signs and symptoms of congestion. The objective of this study was to test a novel neuromo...

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Published inCirculation. Arrhythmia and electrophysiology Vol. 13; no. 11; p. e008407
Main Authors Y. Reddy, Vivek, Petrů, Jan, Málek, Filip, Stylos, Lee, Goedeke, Steve, Neužil, Petr
Format Journal Article
LanguageEnglish
Published United States American Heart Association, Inc 01.11.2020
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Abstract Morbidity and mortality outcomes for patients admitted for acute decompensated heart failure are poor and have not significantly changed in decades. Current therapies are focused on symptom relief by addressing signs and symptoms of congestion. The objective of this study was to test a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. Fifteen subjects admitted for defibrillator implantation and ejection fraction ≤35% on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 Hz, 4 ms pulse width, and ≤20 mA. Changes in maximum positive dP/dt (dP/dt ) indicated changes in ventricular contractility. Of 15 enrolled subjects, 5 were not studied due to equipment failure or abnormal pulmonary arterial anatomy. In the remaining subjects, dP/dt increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt (dP/dt ), mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. In this first-in-human study, we demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. This benign increase in contractility may benefit patients admitted for acute decompensated heart failure.
AbstractList Morbidity and mortality outcomes for patients admitted for acute decompensated heart failure are poor and have not significantly changed in decades. Current therapies are focused on symptom relief by addressing signs and symptoms of congestion. The objective of this study was to test a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. Fifteen subjects admitted for defibrillator implantation and ejection fraction ≤35% on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 Hz, 4 ms pulse width, and ≤20 mA. Changes in maximum positive dP/dt (dP/dt ) indicated changes in ventricular contractility. Of 15 enrolled subjects, 5 were not studied due to equipment failure or abnormal pulmonary arterial anatomy. In the remaining subjects, dP/dt increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt (dP/dt ), mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. In this first-in-human study, we demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. This benign increase in contractility may benefit patients admitted for acute decompensated heart failure.
Morbidity and mortality outcomes for patients admitted for acute decompensated heart failure are poor and have not significantly changed in decades. Current therapies are focused on symptom relief by addressing signs and symptoms of congestion. The objective of this study was to test a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery.BACKGROUNDMorbidity and mortality outcomes for patients admitted for acute decompensated heart failure are poor and have not significantly changed in decades. Current therapies are focused on symptom relief by addressing signs and symptoms of congestion. The objective of this study was to test a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery.Fifteen subjects admitted for defibrillator implantation and ejection fraction ≤35% on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 Hz, 4 ms pulse width, and ≤20 mA. Changes in maximum positive dP/dt (dP/dtMax) indicated changes in ventricular contractility.METHODSFifteen subjects admitted for defibrillator implantation and ejection fraction ≤35% on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 Hz, 4 ms pulse width, and ≤20 mA. Changes in maximum positive dP/dt (dP/dtMax) indicated changes in ventricular contractility.Of 15 enrolled subjects, 5 were not studied due to equipment failure or abnormal pulmonary arterial anatomy. In the remaining subjects, dP/dtMax increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt (dP/dtMin), mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure.RESULTSOf 15 enrolled subjects, 5 were not studied due to equipment failure or abnormal pulmonary arterial anatomy. In the remaining subjects, dP/dtMax increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt (dP/dtMin), mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure.In this first-in-human study, we demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. This benign increase in contractility may benefit patients admitted for acute decompensated heart failure.CONCLUSIONSIn this first-in-human study, we demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. This benign increase in contractility may benefit patients admitted for acute decompensated heart failure.
Author Stylos, Lee
Goedeke, Steve
Neužil, Petr
Y. Reddy, Vivek
Málek, Filip
Petrů, Jan
AuthorAffiliation Na Homolce Hospital, Prague, Czech Republic (V.Y.R., J.P., F.M., P.N.). Icahn School of Medicine at Mount Sinai, NY (V.Y.R.). Cardionomic Inc, New Brighton, MN (L.S., S.G.)
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SubjectTerms Aged
Autonomic Nervous System - physiopathology
Cardiac Pacing, Artificial - adverse effects
Cardiac Pacing, Artificial - methods
Female
Heart - innervation
Heart Failure - diagnosis
Heart Failure - physiopathology
Heart Failure - therapy
Humans
Male
Middle Aged
Myocardial Contraction
Proof of Concept Study
Recovery of Function
Time Factors
Treatment Outcome
Ventricular Function, Left
Title Novel Neuromodulation Approach to Improve Left Ventricular Contractility in Heart Failure: A First-in-Human Proof-of-Concept Study
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