Patty Winkler

Background and Aims: Comprehensive evaluation by invasive coronary function test (CFT) of patients with angina and non-obstructive coronary artery disease is recommended in the current guidelines. The prognosis of patients with CFT-proven coronary vasomotor dysfunction (CVDys) is less well-known. Methods: Patients that provided consent for the previously published NL-CFT registry who underwent clinically indicated invasive CFT between 1 February 2019 and 1 June 2024 were included. Patients with CVDys, defined as an abnormal spasm provocation test and/or microvascular functional assessment, were compared to patients with normal CFT. The primary outcome of major adverse cardiovascular events and emergency room visits for angina (MACE-EA) was defined as a composite of all-cause death, acute coronary syndrome, stroke/transient ischaemic attack, revascularization, repeat angiography without intervention, heart failure hospitalizations, and unplanned hospitalizations or emergency room visits due to angina. Results: In total, 1355 patients were included. In 79.8%, CFT was abnormal, and vasospasm was the most prevalent endotype. In 1252 patients, follow-up of clinical events was complete. During a mean follow-up of 33 ± 13 months, CVDys patients had almost double the number of primary outcome events compared with patients with a normal CFT (31.2% vs 16.8%, P < .001), driven by emergency care visits for angina. Secondary clinical endpoints including death, myocardial infarction, stroke, or revascularization were low and comparable between the groups. Conclusions: The long-term risk of MACE-EA is doubled in ANOCA patients with CFT-confirmed CVDys compared with normal CFT results. Events are dominated by emergency room visits due to angina, illustrating the high disease burden of CVDys. Their (angina-related) health status is significantly worse at follow-up.

Background: Diabetes is a known risk factor of acute coronary syndrome (ACS). However, diabetes de novo and prediabetes are also common in ACS patients. This study explored the prevalence of prediabetes and diabetes de novo in ACS patients, glucose-mediating therapy at discharge, and compared the prevalence of 30-day major adverse cardiac and cerebrovascular events (MACCE) in patients with prediabetes and diabetes de novo with known diabetes. Methods: ACS patients with measured haemoglobin A1c (HbA1c) from the South-East Netherlands Heart Registry, a prospective, multicentre registry of patients undergoing percutaneous coronary intervention (PCI), were analysed. Patients were stratified into two groups: known diabetes, and prediabetes (HbA1c 39–47 mmol/mol) or diabetes de novo (HbA1c ≥ 48 mmol/mol). Outcomes were analysed at 30 days post-PCI. Results: HbA1c was available in 34.1% of ACS patients (n = 1836), of whom 526 (28.7%) had known diabetes, 619 (33.7%) prediabetes, and 180 (9.8%) diabetes de novo. Compared with patients with known diabetes, patients with prediabetes and diabetes de novo had a significantly higher risk of MACCE (HR = 1.81, 95% CI 1.12–2.93, p = 0.016) after multivariable adjustment. At discharge, 59% of patients with diabetes de novo received no insulin, metformin, nor sodium-glucose co-transporter-2 inhibitor, compared with 16% of patients with known diabetes (p < 0.001). Conclusions: Impaired glucose metabolism without known diabetes was observed in nearly 45% of ACS patients and they demonstrated a significantly higher risk of 30-day MACCE compared with patients with known diabetes. Despite clear guideline recommendations, routine screening for hyperglycaemia and the appropriate initiation of glucose-mediating therapy remain underutilised in clinical practice.

Background: Mental stress is a well-known trigger of cardiac symptoms in patients with coronary artery spasms. Hence, stress management is recommended along with medical therapy. However, specific programs for patients with coronary spasms are lacking. We collaborated with patients to develop a smartphone-based app as a tailored solution. The app provides biofeedback based on heart rate variability–driven stress level estimations. Objective: This study aimed to evaluate the effect of a biofeedback-driven smartphone stress management app on cardiac symptoms in women with coronary vasospasms. Methods: We enrolled 117 women aged 18 to 70 years diagnosed with coronary vasospasms, as confirmed by a gold standard coronary function test. A multicenter, single-sequence, 2-period crossover study was conducted, comprising a 4-week control period followed by a 4-week period using the Wavy intervention app. The intervention comprised breathing-based exercises that were prompted when measured stress levels were too high. The primary outcome was the Seattle Angina Questionnaire Summary Score, and the secondary outcomes included the 36-Item Short Form Health Survey and the Perceived Stress Scale-10 items. Additionally, the user experience and the impact of the breathing exercise on heart rate variability were evaluated. Results: A total of 102 patients completed the study, yet no significant improvements were observed in the Seattle Angina Questionnaire following the intervention period, with the control group scores at 50.4 (SD 15.4) and the intervention group scores at 50.9 (SD 15.0; P=.92). Similarly, no differences were found in the 36-Item Short Form Health Survey and the Perceived Stress Score. However, the 1236 breathing relaxation exercises performed during the study led to a significant improvement in heart rate variability, as indicated by a median root mean square of successive differences increase from 18.59 (IQR 8.38-36.58) milliseconds before the exercises to 34.93 (IQR 24.19-50.64) milliseconds after the exercises (z=−13.72; P<.001). Furthermore, two-thirds of participants (68/102, 66.7%) indicated that they would use a more refined version of the app in the future. Conclusions: A 4-week intervention using the Wavy app did not significantly alleviate anginal symptoms in female patients with coronary vasospasms. However, the breathing exercises demonstrated a notable improvement in heart rate variability, suggesting a reduction in stress levels. Patient feedback indicated broad support for the app and its wearable-based functionality, emphasizing the need for substantial refinements. Future development should incorporate patient perspectives to optimize the app as a comprehensive lifestyle management tool. Trial Registration: ClinicalTrials.gov NCT06171893; https://classic.clinicaltrials.gov/ct2/show/NCT06171893

BACKGROUND Mental stress is a well-known trigger of cardiac symptoms in patients with coronary artery spasms. Hence, stress management is recommended beyond medical therapy. However, specific programs for patients with coronary spasms are lacking. We collaborated with patients to develop a smartphone-based application as a tailored solution. The application provides biofeedback based on HRV-driven stress level estimations. OBJECTIVE Our study aimed to evaluate the effect of a biofeedback-driven smartphone stress management application on cardiac symptoms in women with coronary vasospasms. METHODS We enrolled 117 women aged 18-70 diagnosed with coronary vasospasms, as confirmed by a gold standard coronary function test. A multicenter single sequence 2-period cross-over study was performed, consisting of a four-week control period followed by four weeks using the Wavy intervention app. The intervention comprised suggested breathing-based exercises if measured stress levels were too high. The primary outcome was the Seattle Angina Questionnaire summary score; secondary outcomes included quality of life using the SF-36, stress by means of the PSS-10. Additionally, the user experience and the impact of the breathing exercise on HRV were evaluated. RESULTS Within the 102 patients that finished the study, no significant improvements were observed in the SAQ-SS scores following the intervention period, with control group values at 50.4 ± 15.4 SD and intervention group values at 50.9 ± 15.0 SD. Similarly, no differences were found in the quality-of-life and perceived stress m hebben tezamen met patiënten en een ergotherapeut nieuwe functionaliteiten etrics. However, the 1,236 breathing relaxation exercises performed during the study led to a significant improvement in heart rate variability (HRV), as indicated by a median (IQR) RMSSD increase from 18.59 ms (8.38–36.58) before the exercises to 34.93 ms (24.19–50.64) after the exercises (Z = -13.72, p < 0.001). Furthermore, two-thirds of participants indicated they would use a more refined version in the future. CONCLUSIONS A four-week intervention using the Wavy application did not significantly alleviate anginal symptoms in female patients with coronary vasospasms. However, the breathing exercises demonstrated a notable improvement in HRV values, suggesting a reduction in stress levels. Patient feedback indicated broad support for the application and its wearable-based functionality, emphasizing the need for substantial refinements. Future development should incorporate patient perspectives to optimize the application as a comprehensive lifestyle management tool. CLINICALTRIAL ClinicalTrials.gov Identifier: NCT06171893. Assessing the Effect of the 'Wavy' Application, on Stress and Burden of Disease in Women With INOCA, available at https://classic.clinicaltrials.gov/ct2/show/NCT06171893.

Background: A coronary function test (CFT) is the recommended diagnostic test to identify coronary vasomotor dysfunction as a cause of symptoms in patients with angina and nonobstructive coronary arteries (ANOCA). Acetylcholine is the commonly used pharmacological agent for spasm provocation. We aimed to investigate an association between severity of symptoms and provocative acetylcholine dose. Methods and Results: We included ANOCA patients undergoing clinically indicated CFT from the Netherlands Registry of Invasive Coronary Vasomotor Function Testing: NL‐CFT. Patients with epicardial spasm (n=251) were divided according to acetylcholine spasm triggering dose: low (2–20 mcg, EpiLOW), middle (100 mcg, EpiMIDDLE) or high (200 mcg, EpiHIGH). Patients with microvascular spasm (n=157) were analyzed irrespective of triggering dose. The patient groups were compared to each other and to a control group with negative CFT results (n=101). We assessed mean Seattle Angina Questionnaire angina frequency and summary scores at baseline and follow‐up and the proportion of patients improving or deteriorating. An inverse relationship between provocation dosage and angina frequency at baseline was found in epicardial spasm: the lower the triggering dose, the more frequently patients experienced angina (EpiLOW 48±20, EpiMIDDLE 53±21, EpiHIGH 57±19, microvascular spasm 61±21, controls 64±21, overall P =0.003). A trend was seen toward most patients improving in the high triggering dose group, and most patients deteriorating in the low triggering dose group. Conclusions: A significant dose‐dependent relationship between spasm provocation and anginal complaints exists. Acetylcholine provocation dose could be incorporated as a risk stratification factor or surrogate outcome in future clinical trials. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06083155.