What does a Relative Risk Reduction (RRR) value of 1.5 in a coronary catheterization (coronary cath) test indicate for a patient with microvascular dysfunction?

Understanding RRR Value of 1.5 in Coronary Microvascular Dysfunction

A resistive reserve ratio (RRR) of 1.5 indicates impaired coronary microvascular dilation function and confirms the presence of coronary microvascular dysfunction, as this value falls well below the diagnostic threshold of 2.0. 1

What RRR Measures

RRR is a novel physiological index that evaluates coronary microvascular dilation capacity by measuring the change in microvascular resistance from rest to maximal hyperemia using continuous thermodilution techniques. 2, 1

• RRR represents the ratio of resting microvascular resistance to hyperemic microvascular resistance 1
• Normal RRR values are ≥2.0, indicating preserved microvascular vasodilatory capacity 1
• RRR <2.0 is abnormal and diagnostic of coronary microvascular dysfunction 1, 3

Clinical Significance of RRR 1.5

Your patient's RRR of 1.5 indicates severely impaired microvascular vasodilatory reserve, meaning the coronary microcirculation can only reduce its resistance by 1.5-fold during maximal hyperemia, compared to the normal 2-fold or greater reduction. 1

Diagnostic Performance

• RRR has an area under the curve of 0.84 for detecting coronary microvascular dysfunction, demonstrating excellent diagnostic accuracy 1
• RRR correlates strongly with other established microvascular indices including coronary flow reserve (CFR <2.0) and index of microcirculatory resistance (IMR ≥25) 1, 3
• In patients with angina and non-obstructive coronary artery disease, 44% have abnormal RRR, confirming microvascular dysfunction as the cause of symptoms 3

Associated Clinical Factors

Several factors are independently associated with impaired RRR values like 1.5:

• Previous myocardial infarction (strongest predictor) 1
• Anemia (lower hemoglobin levels) 1
• Heart failure (elevated brain natriuretic peptide) 1
• Cardiovascular risk factors including hypertension and diabetes 4

Prognostic Implications

Impaired RRR carries significant prognostic implications beyond symptom burden:

• Patients with coronary microvascular dysfunction have a 9.4% rate of death or myocardial infarction by 4 years, even without obstructive coronary disease 5
• Impaired coronary flow reserve (which correlates with low RRR) is associated with elevated hazard for major coronary events at 10-year follow-up 6
• Nonobstructive coronary artery disease with microvascular dysfunction increases risk of all-cause death and myocardial infarction 6

Comparison with Other Microvascular Indices

RRR should be interpreted alongside complementary microvascular measurements:

• Microvascular resistance reserve (MRR): Similar to RRR with area under curve 0.85; your patient likely has MRR <2.0 as well 1
• Index of microcirculatory resistance (IMR): Abnormal if ≥25 units; indicates structural microvascular disease 2, 7
• Coronary flow reserve (CFR): Abnormal if <2.0; represents combined epicardial and microvascular function 2

The 2024 ESC guidelines emphasize that continuous thermodilution-derived measurements (including RRR and MRR) have shown higher reproducibility than bolus thermodilution methods, making RRR a reliable diagnostic parameter. 2

Clinical Management Based on RRR 1.5

With confirmed microvascular dysfunction (RRR 1.5), initiate stratified medical therapy:

First-Line Therapy

• Beta-blockers (bisoprolol) targeting resting heart rate 55-60 bpm as first-line antianginal therapy 7, 6
• Consider ivabradine as superior alternative, which demonstrates better effects on coronary collateral flow and coronary flow reserve compared to bisoprolol 7
• ACE inhibitors or ARBs as baseline therapy 7, 6
• High-intensity statin therapy regardless of LDL levels 7, 6
• Aspirin as baseline antiplatelet therapy 7, 6

Second-Line Options

• Non-dihydropyridine calcium channel blockers (diltiazem or verapamil) if inadequate response to beta-blockers 7
• Ranolazine for refractory symptoms, particularly with microvascular spasm 7
• Trimetazidine as add-on therapy 7

Critical Contraindication

Do not use beta-blockers if vasospastic angina component exists, as they can precipitate spasm by leaving α-mediated vasoconstriction unopposed. 7 Acetylcholine provocative testing should have been performed during catheterization to exclude this. 5

Specialist Referral Recommendation

Refer to an interventional cardiologist or advanced heart failure/preventive cardiologist at a center with expertise in invasive coronary function testing and INOCA (ischemia with non-obstructive coronary arteries) programs. 6 Specialist-guided invasive testing and stratified medical therapy improves angina severity by 11.7 units on the Seattle Angina Questionnaire compared to conventional management. 6