In patients with angina pectoris undergoing a coronary angiography (CAG) up to 40% do not have obstructive coronary artery disease (CAD). The majority of patients with no obstructive CAD are women with a frequency of up to 70% compared to 50% in men. These patients are diagnosed as having angina and non-obstructive coronary arteries (ANOCA). There are two endotypes of ANOCA. The first endotype is microvascular angina (MVA) caused by a combination of structural microcirculatory remodelling and functional arteriolar dysregulation, also called coronary microvascular dysfunction (CMD). The second endotype is vasospastic angina (VSA) caused by epicardial coronary artery spasm that occurs when a hyper-reactive epicardial coronary segment is exposed to a vasoconstrictor stimulus. Both endotypes of ANOCA are associated with significantly greater one-year risk of myocardial infarction (MI) and all-cause mortality, have a significantly impaired quality of life and have a high health care resource utilisation.

The current treatment for ANOCA consists of three aspects. The first aspect is managing lifestyle factors such as weight management, smoking cessation and exercise. The second aspect is managing known cardiovascular risk factors such as hypertension, dyslipidaemia and diabetes mellitus. And the third aspect is antianginal medication. In both endotypes ACE inhibitors or angiotensin II receptor blockers should be considered. In MVA the antianginal medication that can be used are betablocker, calcium channel blocker, nicorandil, ranolazine, ivabradine and/or trimetazidine. In VSA calcium channel blocker, long-acting nitrate and/or nicorandil can be initiated as antianginal therapy. Despite these treatment option approximately 25% of ANOCA patients have refractory angina symptoms.

A possible treatment modality for ANOCA patients with refractory angina pectoris is spinal cord stimulation (SCS) or transcutaneous electrical nerve stimulation (TENS). Previous research (in patients with cardiac syndrome X) has shown that SCS improves time until angina and ischaemia, significantly less angina and an improvement in quality of life. These findings suggest that SCS and/or TENS could be a possible treatment modality for patients with ANOCA.

The aim of this pilot study is to investigate whether treatment with TENS during a one month period leads to a significant reduction of angina pectoris and therefore a significant improvement in quality of life in patients with proven ANOCA, encompassing both endotypes (MVA and VSA).

Inclusion Criteria:

• Angina and no obstructive coronary artery disease (ANOCA) (CCS class III or IV)

• Microvascular angina (MVA):

  • FFR > 0.8
  • CFR < 2.0
  • IMR ≥ 25

• Vasospastic angina (VSA):

  • FFR > 0.8
  • CFR ≥ 2.0
  • IMR < 25
  • During acetylcholine testing: ≥ 90% diameter reduction, angina pectoris and ischaemic ECG changes

• Persisting angina pectoris despite optimal medical therapy (OMT) defined as:

  • MVA: Betablocker, calcium channel blocker, nicorandil and/or ivabradine (Important side note: ranolazine and trimetazidine cannot be prescribed in the Netherlands).
  • VSA: Calcium channel blocker, long-acting nitrate and/or nicorandil. In the maximum tolerated dose. If the patient is currently not using one of the medications due to side-effects, this should be clearly stated.

• Age > 18 years

Exclusion Criteria:

• Both endotypes (VSA and MVA) present based on CFT findings.
• Inability to give informed consent
• Inability to perform a 6-minute walking test
• The presence of a cardiac implanted electronic device (CIED); pacemaker and/or Implantable Cardiac Defibrillator (ICD). Due to the risk of interference between TENS and CIED
• Presence of a spinal cord stimulator for another indication such as complex regional pain syndrome, failed back surgery syndrome, etc.