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

Not Applicable
Not yet recruiting
Conditions
Hypertensive Heart Disease
Resistant Hypertension
Coronary Microvascular Dysfunction
Interventions
Diagnostic Test: Invasive Physiological Assessment of Coronary Circulation
Registration Number
NCT05994729
Lead Sponsor
Aurelia Hospital
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
87
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Candidates to RDN with ascertained CMDInvasive Physiological Assessment of Coronary CirculationPatients that are candidates to receive RDN for resistant/difficult to control hypertension, who also have documented coronary microvascular dysfunction
Primary Outcome Measures
NameTimeMethod
Index of microvascular resistance (IMR)12 months

Matched comparison of IMR from baseline to 12 months after RDN

Secondary Outcome Measures
NameTimeMethod
Systolic Blood Pressure (BP) on Ambulatory blood pressure monitoring (ABPM)12 Months

Matched Comparison of Average Systolic Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring

NTproBNP12 Months

Matched Comparison of Average NTproBNP

Mean transit time (TMN)12 months

Matched comparison of both resting and hyperemic TMN from baseline to 12 months after RDN

Diastolic BP on ABPM12 Months

Matched Comparison of Average Systolic Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring

Average BP on ABPM12 Months

Matched Comparison of Average Mean Blood Pressure measured on 24 hour Ambulatory Blood Pressure Monitoring

Time in Therapeutic BP Range12 Months

Matched Comparison of total time spent with both systolic and diastolic BP within normality range measured on 24 hour Ambulatory Blood Pressure Monitoring

BP Medication Burden12 Months

Matched Comparison of Total Number of BP medication prescribed to the subject

Mini-SAQ Score (Seattle Angina Questionnaire)12 Months

Matched Comparison of Average Score on Mini Seattle Angina Questionnaire (SAQ)

Coronary Flow Reserve (CFR)12 months

Matched comparison of CFR from baseline to 12 months after RDN

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