Cardioneuroablation for Variant Angina

N/AActive Not RecruitingNCT06992830

Zhibing Lu16 enrolled

Overview

Variant angina, also known as vasospastic angina, is a form of chest pain caused by temporary spasms of the coronary arteries, which reduce blood flow to the heart. These spasms often occur at rest and may lead to serious complications, including life-threatening heart rhythm problems and sudden cardiac death. While most patients improve with medications such as calcium channel blockers and nitrates, some continue to have symptoms despite treatment. In addition, some patients are unable or unwilling to take medications regularly, which further limits effective management. These cases are referred to as medication-refractory or drug-intolerant variant angina. The autonomic nervous system, which controls involuntary functions like heart rate and blood vessel tone, is believed to play an important role in the development of coronary artery spasms. Recent research suggests that imbalances in autonomic activity, particularly excessive parasympathetic signals, may trigger these spasms. Cardioneuroablation (CNA) is a minimally invasive procedure that uses a catheter to target specific nerve clusters called cardiac ganglionated plexi, located on the surface of the heart. These plexi are important centers of autonomic control and are mostly made up of parasympathetic nerve cells. Originally developed to treat conditions such as fainting spells and certain types of abnormal heart rhythms, CNA works by selectively reducing abnormal parasympathetic activity in the heart. This study is designed to explore whether CNA can help relieve chest pain and reduce coronary spasms in patients with variant angina who do not respond to medications or cannot take them consistently. The study will evaluate the safety, practicality, and potential benefits of this approach as a new treatment option for a difficult-to-manage heart condition.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

cardioneuroablationPROCEDURE

Participants diagnosed with medication-refractory variant angina or those unable or unwilling to take medications regularly will undergo a catheter-based cardioneuroablation (CNA) procedure. CNA targets epicardial cardiac ganglionated plexi (GP), which are clusters of autonomic ganglia involved in parasympathetic modulation of cardiac function. The procedure is designed to reduce parasympathetic overactivity contributing to coronary artery spasms. Ablation will be performed using a radiofrequency catheter to eliminate GP areas identified by anatomical landmarks and electrophysiological mapping. No control or sham procedure is included in this single-arm study.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * age between 18 and 80 years; * variant angina; * positive ergonovine provocation test; * refractory to antispasmodic drug therapy, or inability to achieve adequate symptom control due to drug intolerance, poor adherence, or unwillingness to take medications regularly. Exclusion Criteria: * cardiogenic shock; * chronic heart failure; * life expectancy less than 12 months; * current participation in another clinical study without completing the primary endpoint visit; inability to provide informed consent; * women of childbearing potential without effective contraception or who are breastfeeding; * coronary artery stenosis ≥50% or FFR ≤0.80; * sick sinus syndrome or high-degree AV block without pacemaker; * systolic blood pressure \<90mmHg or heart rate \<50 bpm; * allergy to diltiazem, nitrates, or nitroglycerin.

Outcomes

Primary Outcomes

Change in Frequency of Coronary Spasm Episodes

The number of coronary spasm episodes will be recorded before and after the procedure using 24-hour Holter ECG and integrated dynamic ECG device. Reduction in episode frequency will be used to evaluate treatment efficacy.

Time frame: Baseline and up to 6 months post-procedure

Change in Angina Attack Frequency

The frequency of chest pain episodes will be assessed through patient diaries and clinical interviews to evaluate symptom relief after treatment.

Time frame: Baseline and up to 6 months after treatment

Severity of Coronary Spasms

Severity will be assessed using imaging findings and clinical scoring systems, such as the Canadian Cardiovascular Society (CCS) Angina Grading Scale, to compare pre- and post-procedural status. CCS Angina Grading Scale ranges from Class I (least severe) to Class IV (most severe), with higher scores indicating worse angina severity. Additional imaging-based assessments (e.g., degree of coronary artery narrowing on angiography) will be qualitatively or semi-quantitatively described.

Time frame: Baseline and up to 6 months post-procedure

Electrocardiographic Changes

Standard 12-lead ECGs and 24-hour Holter monitoring will be analyzed for changes in ST-segment shifts and arrhythmias before and after the procedure.

Time frame: Baseline and up to 6 months

Major Adverse Cardiovascular Events

Incidence of cardiovascular events including arrhythmia, cardiac arrest, cardiac death, and acute myocardial infarction will be recorded during follow-up.

Time frame: From procedure until 6 months post-procedure

Heart Rate Variability (HRV) Changes

HRV parameters will be analyzed from 24-hour Holter ECG to assess autonomic modulation following ablation.

Time frame: Baseline and 1, 3, and 6 months post-treatment

Requirement for Anti-Anginal Medications

Dosage and frequency of anti-anginal drug use will be recorded to assess dependence on medication after CNA.

Time frame: Baseline and up to 6 months post-procedure

Secondary Outcomes

Acute Procedural Success Rate

Defined as successful identification and ablation of ganglionated plexi without intraoperative complications.

Time frame: Intraoperative (immediate post-procedure)

Incidence of Acute Procedural Complications

Includes intraoperative events such as vascular injury, pericardial effusion, and procedural arrhythmias.

Time frame: Within 24 hours post-procedure

Short-term Postoperative Complications

Includes post-procedural complications such as bleeding, infection, and arrhythmias.

Time frame: Up to 30 days post-procedure

Mid- to Long-Term Complications

Includes recurrence of coronary spasm, new myocardial infarction, and worsening of cardiac function.

Time frame: From 30 days to 12 months post-procedure

Biomarker Monitoring (e.g., Cardiac Enzymes and Inflammatory Markers)

Serum levels of specific biomarkers will be measured to evaluate myocardial injury and systemic inflammation. These include cardiac enzymes (e.g., troponin I/T, CK-MB) and inflammatory markers (e.g., C-reactive protein \[CRP\], interleukin-6 \[IL-6\]). Blood samples will be collected at baseline and within 72 hours post-ablation. Levels will be quantified using standard laboratory assays, and changes will be compared to evaluate procedure-related biological responses.

Time frame: Baseline and within 72 hours post-procedure

Comparison of parameters related to coronary vasospasm induced by ergonovine provocation testing before and after CNA

Time frame: Periprocedural

Cardioneuroablation for Variant Angina

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes