Prognostic significance of cold pressor test myocardial perfusion imaging in patients with ischemia and nonobstructive coronary arteries

Abstract

Correspondence to: Cunzhi Lu, MD. Department of Nuclear Medicine, Xuzhou Central Hospital, No. 199, Jiefangnan Road, Xuzhou 221009, China. Email: 13912045900@163.com; Yuetao Wang, MD. Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, No. 185, Juqian Street, Changzhou 213003, China; Institute of Clinical Translation of Nuclear Medicine and Molecular Imaging, Soochow University, Changzhou, China. Email: yuetao-w@163.com.

Background: Ischemia with nonobstructive coronary arteries (INOCA) is prevalent among patients with angina, is linked to major adverse cardiovascular events (MACEs), and is often driven by endothelial dysfunction. This study aimed to assess the efficacy of the cold pressor test (CPT) in identifying individuals at elevated risk for MACEs among patients with INOCA.

Methods: A total of 124 INOCA inpatients were included in the retrospective cohort study. Clinical data including age, gender, BMI, hypertension, hyperlipidemia, diabetes mellitus (DM), active smoking, and symptoms were collected from medical records. A positive CPT-myocardial perfusion imaging (MPI) result was considered to be the presence of a reversible perfusion defect with a summed difference score (SDS) ≥2. The patients were routinely followed-up according to standard protocol. An MACE was defined as a composite endpoint including all-cause mortality, late coronary revascularization [≥3 months following single-photon emission computed tomography (SPECT)-MPI], nonfatal myocardial infarction, rehospitalization due to angina, heart failure, and stroke.

Results: The number of positive CPT-MPI cases was 49 (39.5%) and that of negative CPT-MPI cases was 75 (60.5%). Compared with negative CPT-MPI, positive CPT-MPI group had a higher percentage of DM [16 (32.7%) vs. 13 (17.3%)], coronary atherosclerosis [33 (67.3%) vs. 32 (42.7%)], and ST-T segment changes on routine admission electrocardiogram (ECG) [37 (75.5%) vs. 42 (56.0%)] (all P values <0.05). Univariate and multivariate logistic regression analyses indicated coronary atherosclerosis as independent risk factor for positive CPT-MPI [odds ratio (OR) 2.68, 95% confidence interval (CI): 1.22-5.90; P=0.014]. The proportion of positive CPT-MPI was higher in patients with MACEs than in patients without them [6 (32.7%) vs. 16 (8%); P <0.05]. In the multivariate Cox proportional hazards model, only positive CPT-MPI (hazard ratio 2.97, 95% CI: 1.02-8.58; P=0.04) was significantly associated with MACE occurrence.

Conclusions: Among patients with INOCA <39.5% had positive CPT, which was significantly related to MACE occurrence. In patients with positive CPT, the risk of MACE increased twofold. Coronary atherosclerosis was the independent risk factor of positive CPT. CPT-MPI offers valuable insights for risk stratification and treatment decision-making in patients with INOCA, particularly in identifying those at higher risk of adverse cardiovascular events.

Keywords: Cold pressor test (CPT); endothelium dysfunction; ischemia and nonobstructive coronary arteries (INOCA); myocardial perfusion imaging (MPI).

Figure 1

Flowchart of patient inclusion. CABG, coronary artery bypass graft; CAG, coronary angiography; CPT, cold pressor test; INOCA, ischemia with nonobstructive coronary arteries; MPI, myocardial perfusion imaging; PCI, percutaneous coronary intervention.

Figure 2

A flowchart of the CPT procedure. CPT, cold pressor test; SPECT/CT, single-photon emission computed tomography/computed tomography; 99mTc-MIBI, Technetium-99m Methoxyisobutyl Isonitrile.

Figure 3

Kaplan-Meier survival curves for patients with INOCA with negative and positive CPT. CPT, cold pressor test; MACE, major adverse cardiovascular event; INOCA, ischemia with nonobstructive coronary arteries.

Figure 4

Case example. A 40-year-old female was admitted to the hospital with chest tightness for half a year and a history of diabetes for 1 year. The patient was diagnosed with INOCA (no significant stenosis was observed in CAG; exercise ECG results showed ST-T changes suggestive of myocardial ischemia) and received CPT-MPI. (A) The odd rows depict CPT, while the even rows show rest for short-axis, vertical long-axis, and horizontal long-axis images, and indicated a reversible perfusion defect at the inferior wall (red arrows). (B) The patient was instructed to immerse her foot in a container of cold water (0–5 ℃) for 1.5 minutes. (C-E) The CAG images of the LAD, LCX, and RCA, respectively, demonstrating a 20–30% stenosis in the proximal-to-middle segment of the RCA (white arrow). At 1-month follow-up, the patient was readmitted for recurrent chest pain. CAG, coronary angiography; CPT-MPI, cold pressor test myocardial perfusion imaging; ECG, electrocardiogram; INOCA, ischemia with nonobstructive coronary arteries; LAD, left anterior descending; LCX, left circumflex; RCA, right coronary artery.