Jos W. M. G. Widdershoven

Objective: Recurrent cardiac health care utilization (HCU) is common in patients with nonobstructive coronary artery disease (NOCAD), yet long-term mental health, personality, and health status contributing to repeated emergency department visits (ED) and diagnostic testing remain unclear. This study examined 10-year patterns and predictors of recurrent cardiac HCU in patients with NOCAD. Methods: In total 546 patients (52% women) were followed with ED visits or repeat diagnostic tests. Baseline assessments included anxiety, depressive symptoms, type D personality, fatigue, health status, and disease-specific quality of life. Negative binomial regression evaluated associations between baseline mental health and health status and total HCU, with adjustment for age, sex, education, obesity, diabetes, and major adverse cardiac events (MACE). Sex-stratified and MACE-stratified analyses were explored. Results: During follow-up, 24% of the patients experienced a single, and 26% multiple HCU. Higher anxiety, fatigue, poorer physical health, more frequent angina, and lower quality of life were associated with greater HCU, in age and sex-adjusted models. After full adjustment, lower baseline quality of life, diabetes, and subsequent MACE remained independent predictors. Sex-stratified analyses showed that baseline angina frequency and lower quality of life predicted HCU in women. Most patients with recurrent HCU did not develop MACE, suggesting that subjective symptom burden, rather than disease progression, was the main driver of long-term HCU. Conclusions: Recurrent HCU is frequent in NOCAD and is strongly influenced by baseline quality of life and cardiometabolic risk. These findings highlight the need to address symptom burden in NOCAD to reduce recurrent testing and improve long-term outcomes. Clinical Trial Registration: ClinicalTrials.gov (NCT01788241) https://clinicaltrials.gov/study/NCT01788241.

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.