Clinical trial NCT05994729: Impact of Renal Denervation in Patients With Coronary Microvascular Dysfunction: Study Design and Rationale
Official title: Impact of Renal Denervation in Patients With Coronary Microvascular Dysfunction: Study Design and Rationale
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Coronary Microvascular Dysfunction
Resistant Hypertension
Hypertensive Heart Disease
Keywords: MVD
HHD
Lead sponsor: Aurelia Hospital
Sponsor class: OTHER
First posted: 2023-08-16
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Index of microvascular resistance (IMR)
timeFrame: 12 months
Secondary outcomes:
measure: Coronary Flow Reserve (CFR)
timeFrame: 12 months
measure: Mean transit time (TMN)
timeFrame: 12 months
measure: Systolic Blood Pressure (BP) on Ambulatory blood pressure monitoring (ABPM)
timeFrame: 12 Months
measure: Diastolic BP on ABPM
timeFrame: 12 Months
measure: Average BP on ABPM
timeFrame: 12 Months
measure: Time in Therapeutic BP Range
timeFrame: 12 Months
measure: BP Medication Burden
timeFrame: 12 Months
measure: Mini-SAQ Score (Seattle Angina Questionnaire)
timeFrame: 12 Months
measure: NTproBNP
timeFrame: 12 Months
Other outcomes:
Locations:
Study officials:
affiliation: Aurelia Hospital
name: Fabrizio Tomai, MD, FACC, FESC
role: PRINCIPAL_INVESTIGATOR
affiliation: Aurelia Hospital
name: stefano migliaro, MD
role: STUDY_CHAIR
References: