Impact of Renal Denervation in Patients With Coronary Microvascular Dysfunction: Study Design and Rationale (IMPRESSION)

Long-standing hypertension may cause an impairment in microvascular coronary circulation which is involved in many different cardiac conditions. Renal denervation (RDN) has been successfully proven as a valuable and powerful therapeutic choice to consider for patients with resistant hypertension; moreover this procedure looks promising in other cardiac disease such as heart failure and atrial fibrillation, given its ability to downregulate sympathetic nervous system The aim of this study is to explore the effect of renal denervation and blood pressure control on coronary microvascular dysfunction.

This is a multicenter, prospective, non randomized, open-label, interventional study. Consecutive patients with resistant hypertension, non obstructive coronary artery disease and documented microvascular dysfunction will be enrolled. Patients will undergo renal denervation by Spyral Symplicity 3 and re-assessment of coronary microvascular function 12 months after the procedure. Primary endpoint will be the difference in average index of microcirculatory resistance value.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Microvascular Dysfunction; Resistant Hypertension; Hypertensive Heart Disease
• Intervention / Treatment: Diagnostic test: Invasive Physiological Assessment of Coronary Circulation

Detailed Description

The aim of this study is to evaluate the effect of radiofrequency RDN performed with Spyral Symplicity 3 on microvascular function in patients with ascertained hypertension related coronary microvascular dysfunction (hy-CMD) and/or hypertensive cardiomyopathy. Our hypothesis is that RDN could improve invasive parameters of microvascular function in patients with hy-CMD; these would mean that RDN would be able to at least partially revert the pathogenesis of hy-CMD.

The study design comprises an initial rule-in and enrollment phase, required to properly select the target population, followed by the actual study procedural phase.

Patients amenable to RDN will be hospitalized and enter the rule-in phase to check for eligibility.

Before performing the actual RDN, patients will be asked for the written informed consent to receive physiological evaluation.

Only patients that will be diagnosed with hy-CMD will eventually enter the actual study phase.

This phase will comprise repeated outpatients visits, according to a predetermined schedule, including a new hospitalization at 12 months to reassess coronary microvascular physiology.

• Study Type: Interventional
• Enrollment (Estimated): 87
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fabrizio Tomai, MD, FACC, FESC; Phone Number: 0039 06 65975725; Email: fabriziotomai@gmail.com
• Study Contact Backup: Name: stefano migliaro, MD; Phone Number: 0039 3453373825; Email: migliaro.stefano@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Rul-in Phase Inclusion Criteria:

• Non obstructive stable coronary artery disease (CAD) on invasive coronary angiography (defined as the absence of either >50% angiographic stenosis or any flow limiting lesion on functional evaluation)
• Suspected diagnosis of difficult to control/ resistant hypertension for which renal denervation by radiofrequency ablation with Spyral Symplicity 3 could be considered.

Rule-in Phase Exclusion Criteria:

• Initiation of either nitrates, beta-blocker or calcium channel blocker less than 30 days before the end of the rule-in phase
• Physiological assessment performed during first medical contact documenting preserved coronary microvascular function
• Physiological assessment performed at the "first contact" hospitalization followed by modification of medical therapy during the rule-in phase, before RDN
• Acceptable blood pressure control after medical treatment optimization
• Identification of secondary causes of hypertension
• Renal artery anatomy not suitable for RDN
• Ejection fraction below 30%
• Life expectancy below 1 year
• Indication to cardiac surgery
• Adenosine allergy
• Pregnancy
• Large necrotic area documented by either MRI, SPECT or combination of ECG signs + Echocardiographic images.
• Hemodynamic instability
• Refuse to sign informed consent
• Age below 18 or above 80

Study Phase Inclusion Criteria:

• Having coronary microvascular dysfunction documented by invasive functional assessment (IMR>25 and or CFR < 2)
• Fulfilling all the rule-in phase inclusion criteria without any rule-in phase exclusion criteria

Study Phase Exclusion Criteria:

• Refuse to sign informed consent
• Evidence of newly detected obstructive CAD on invasive coronary angiography performed 6 months after RDN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Candidates to RDN with ascertained CMD; Patients that are candidates to receive RDN for resistant/difficult to control hypertension, who also have documented coronary microvascular dysfunction

Diagnostic test: Invasive Physiological Assessment of Coronary Circulation; After 2 months long rule-in phase required to exclude the unsuitable patients, study population will undergo RDN as indicated to treat resistant or difficult to control hypertension; 12 months after RDN, they will undergo invasive physiological study, comprehensive of Coronary Flow Reserve, Index of Microvascular Resistance, Mean Transit Time. These data will be then compared to the baseline ones obtained during the screening phase.; Other Names: IMR; CFR; Tmn

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Index of microvascular resistance (IMR)	Matched comparison of IMR from baseline to 12 months after RDN	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary Flow Reserve (CFR)	Matched comparison of CFR from baseline to 12 months after RDN	12 months
Mean transit time (TMN)	Matched comparison of both resting and hyperemic TMN from baseline to 12 months after RDN	12 months
Systolic Blood Pressure (BP) on Ambulatory blood pressure monitoring (ABPM)	Matched Comparison of Average Systolic Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring	12 Months
Diastolic BP on ABPM	Matched Comparison of Average Systolic Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring	12 Months
Average BP on ABPM	Matched Comparison of Average Mean Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring	12 Months
Time in Therapeutic BP Range	Matched Comparison of total time spent with both systolic and diastolic BP within normality range measured on 24 hour Ambulatory Blood Pressure Monitoring	12 Months
BP Medication Burden	Matched Comparison of Total Number of BP medication prescribed to the subject	12 Months
Mini-SAQ Score (Seattle Angina Questionnaire)	Matched Comparison of Average Score on Mini Seattle Angina Questionnaire (SAQ)	12 Months
NTproBNP	Matched Comparison of Average NTproBNP	12 Months

Collaborators and Investigators

• Sponsor: Aurelia Hospital
• Investigators: Principal Investigator: Fabrizio Tomai, MD, FACC, FESC, Aurelia Hospital; Study Chair: stefano migliaro, MD, Aurelia Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 9, 2023
• First Submitted That Met QC Criteria: August 9, 2023
• First Posted (Actual): August 16, 2023

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 22, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: MVD; HHD
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases
• Other Study ID Numbers: AH Card. 08-23

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No