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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.

Background: Recently it has been suggested that coronary microvascular dysfunction (CMD) may explain the high false-positive rate of exercise electrocardiographic stress testing (EST). However, patients with angina but non-obstructive coronary artery disease (ANOCA) present with a broader spectrum of coronary vasomotor dysfunction (CVDys), namely coronary artery spasm (CAS), CMD or a combination of both. We aim to investigate the diagnostic value of EST for the entire CVDys spectrum., Methods: We included patients who underwent coronary function testing (CFT) in the Radboud University Medical Center. For each patient we requested the most recent EST report. ESTs were denoted as positive for ischemia if clinically significant ST-segment depression was detected. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence intervals for the diagnosis of CVDys and its endotypes., Results: Of the 105 included patients (87 % women, mean age 57 (±8) years), 22 (21 %) had ischemia during EST. CVDys was diagnosed in 94 patients (90 %), of whom 58 patients had an isolated endotype (CAS: n = 51, CMD: n = 7) and 36 patients had CAS and CMD. Ischemia during EST yielded a high specificity and PPV for CVDys (specificity: 100 % (71.5-100 %), PPV: 100 % (84.6-100 %)), which remained reasonably similar for CAS (specificity: 94.4 % (72.7-99.9 %), PPV: 95.5 % (77.2-99.9 %)), but was lower for CMD (specificity: 85.5 % (74.2-93.1 %), PPV: 59.1 % (36.4-79.3 %))., Conclusions: Ischemia during EST is highly specific for CVDys in general and can be an indicator for CAS and to a lesser extent for CMD in patients with ANOCA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Continuous intracoronary thermodilution with saline allows for the accurate measurement of volumetric blood flow (Q) and absolute microvascular resistance (R μ ). However, this requires repositioning of the temperature sensor by the operator to measure the entry temperature of the saline infusate, denoted as T i ., Aims: We evaluated whether Ti could be predicted based on known parameters without compromising the accuracy of calculated Q. This would significantly simplify the technique and render it completely operator independent., Methods: In a derivation cohort of 371 patients with Q measured both at rest and during hyperaemia, multivariate linear regression was used to derive an equation for the prediction of T i . Agreement between standard Q (calculated with measured T i ) and simplified Q (calculated with predicted T i ) was assessed in a validation cohort of 120 patients that underwent repeat Q measurements. The accuracy of simplified Q was assessed in a second validation cohort of 23 patients with [ 15 O]H 2 O positron emission tomography (PET)-derived Q measurements., Results: Simplified Q exhibited strong agreement with standard Q (r=0.94, confidence interval [CI]: 0.93-0.95; intraclass correlation coefficient [ICC] 0.94, CI: 0.92-0.95; both p<0.001). Simplified Q exhibited excellent agreement with PET-derived Q (r=0.86, CI: 0.75-0.92; ICC=0.84, CI: 0.72-0.91; both p<0.001). Compared with standard Q, there were no statistically significant differences between correlation coefficients (p=0.29) or standard deviations of absolute differences with PET-derived Q (p=0.85)., Conclusions: Predicting T i resulted in an excellent agreement with measured T i for the assessment of coronary blood flow. It significantly simplifies continuous intracoronary thermodilution and renders absolute coronary flow measurements completely operator independent.

Competing Interests: Conflict of interest: P.D. have received consultancy fees and research grants from Philips, and P.D. has received a research grant from Abbott. The remaining authors have nothing to disclose.

Background: Mortality rates in patients with cardiogenic shock complicating acute myocardial infarction (AMICS) remain high despite advancements in AMI care. Our study aimed to investigate the impact of prehospital symptom duration on the prognosis of AMICS patients and those receiving mechanical circulatory support (MCS)., Methods and Results: We conducted a retrospective cohort study with data registered in the Netherlands Heart Registration. A total of 1,363 patients with AMICS who underwent percutaneous coronary intervention between 2017 and 2021 were included. Patients presenting after out-of-hospital cardiac arrest were excluded. Most patients were male (68%), with a median age of 69 years (IQR 61-77), predominantly presenting with ST-elevation myocardial infarction (86%). The overall 30-day mortality was 32%. Longer prehospital symptom duration was associated with a higher 30-day mortality with the following rates: < 3 h, 26%; 3-6 h, 29%; 6-24 h, 36%; ≥ 24 h, 46%; p < 0.001. In a subpopulation of AMICS patients with MCS (n = 332, 24%), symptom duration of > 24 h was associated with significantly higher mortality compared to symptom duration of < 24 h (59% vs 45%, p = 0.029). Multivariate analysis identified > 24 h symptom duration, age and in-hospital cardiac arrest as predictors of 30-day mortality in MCS patients., Conclusion: Prolonged prehospital symptom duration was associated with significantly increased 30-day mortality in patients presenting with AMICS. In AMICS patients treated with MCS, a symptom duration of > 24 h was an independent predictor of poor survival. These results emphasise the critical role of early recognition and intervention in the prognosis of AMICS patients., (© 2024. The Author(s).)

In at least one-half of the patients with angina or ischemia and nonobstructive coronary arteries undergoing coronary function testing, coronary artery spasm (CAS) is detected. CAS is associated with an adverse prognosis regarding recurrent complaints and ischemic events. Current treatment options are mainly focused on the complaints, not on the underlying pathophysiological process. In this review we discuss available evidence regarding the presence, amount, and morphology of atherosclerosis in CAS patients. The reviewed evidence confirmed that atherosclerosis and vulnerable plaque characteristics are often detected in patients with CAS. The amount of atherosclerosis is higher in patients with focal CAS compared with patients with diffuse CAS. Severity of atherosclerosis is associated with the presence of CAS and the prognosis in CAS patients with atherosclerotic stenosis is worse. Therefore, CAS patients with atherosclerosis might benefit from targeted atherosclerotic treatment. Longitudinal studies are needed to elucidate the exact relation between atherosclerosis and CAS., Competing Interests: Funding Support and Author Disclosures Dr Konst received a research grant from Abbott. Dr van de Hoef received speaker fees and institutional research grants from Abbott and Philips. Dr Ong received funding from the Berthold-Leibinger-Foundation; and received speaking honoraria from Philips/Volcano, Pfizer, Medtronic, Abbott, Amgen, and Bayer Healthcare. Dr van Royen received speaker fees from Abbott; and has received institutional research grants from Philips and Abbott. Dr Elias-Smale received a research grant from Abbott. Dr van Geuns received grants and personal fees from Boston Scientific, Abbott Vascular, AstraZeneca, Amgen, and Sanofi; and grants from InfraRedx. Dr Damman received research grants, consultancy, and speaker fees from Abbott; and research grants and speakers fees from Abbott, research grants from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It has been suggested that coronary microvascular function decreases with age, irrespective of the presence of epicardial atherosclerosis., Aims: Our aim is to quantitatively investigate the effects of age on microvascular function in patients with normal coronary arteries., Methods: In 314 patients with angina with no obstructive coronary artery disease (ANOCA), microcirculatory function was tested using the continuous thermodilution method. In 305 patients, the association between age and both resting and hyperaemic myocardial blood flow (Q), microvascular resistance (R μ ), absolute coronary flow reserve (CFR) and microvascular resistance reserve (MRR) was assessed. In addition, patients were divided into 3 groups to test for differences based on age quartiles (≤52 years [24.9%], 53-64 years [49.2%], ≥65 years [25.9%])., Results: The mean age was 59±9 years with a range from 22 to 79 years. The mean resting Q (Q rest ) was not different in the 3 age groups (88±34 mL/min, 82±29 mL/min, and 86±38 mL/min, R 2 =0.001; p=0.62). A trend towards a decreasing mean hyperaemic Q (Q max ) was observed with increasing age (223±79 mL/min, 209±84 mL/min, 200±80 mL/min, R 2 =0.010; p=0.083). The mean resting R μ (R μ,rest ) were 1,204±460 Wood units (WU), 1,260±411 WU, and 1,289±455 WU (p=0.23). The mean hyperaemic R μ (R μ,hyp ) increased significantly with advancing age (429±149 WU, 464±164 WU, 503±162 WU, R 2 =0.026; p=0.005). Consequently, MRR decreased with age (3.2±1.2, 3.1±1.0, 2.9±0.9; p=0.038). This trend was present in both the patients with (n=121) and without (n=184) coronary microvascular dysfunction (CMD)., Conclusions: There is an age-dependent physiological increase in minimal microvascular resistance and decrease in microvascular function, which is represented by a decreased MRR and is independent of atherosclerosis. The age-dependent decrease in MRR was present in both patients with and without CMD and was most evident in patients with smooth coronary arteries.

Background: Due to aging of the population, the prevalence of aortic valve stenosis will increase drastically in upcoming years. Consequently, transcatheter aortic valve implantation (TAVI) procedures will also expand worldwide. Optimal selection of patients who benefit with improved symptoms and prognoses is key, since TAVI is not without its risks. Currently, we are not able to adequately predict functional outcomes after TAVI. Quality of life measurement tools and traditional functional assessment tests do not always agree and can depend on factors unrelated to heart disease. Activity tracking using wearable devices might provide a more comprehensive assessment., Objective: This study aimed to identify objective parameters (eg, change in heart rate) associated with improvement after TAVI for severe aortic stenosis from a wearable device., Methods: In total, 100 patients undergoing routine TAVI wore a Philips Health Watch device for 1 week before and after the procedure. Watch data were analyzed offline-before TAVI for 97 patients and after TAVI for 75 patients., Results: Parameters such as the total number of steps and activity time did not change, in contrast to improvements in the 6-minute walking test (6MWT) and physical limitation domain of the transformed WHOQOL-BREF questionnaire., Conclusions: These findings, in an older TAVI population, show that watch-based parameters, such as the number of steps, do not change after TAVI, unlike traditional 6MWT and QoL assessments. Basic wearable device parameters might be less appropriate for measuring treatment effects from TAVI., (© Rob Eerdekens, Jo Zelis, Herman ter Horst, Caia Crooijmans, Marcel van 't Veer, Danielle Keulards, Marcus Kelm, Gareth Archer, Titus Kuehne, Guus Brueren, Inge Wijnbergen, Nils Johnson, Pim Tonino. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Background: Coronary vasomotor dysfunction (CVDys) comprises coronary vasospasm (CVS) and/or coronary microvascular dysfunction (CMD) and is highly prevalent in patients with angina and non-obstructive coronary artery disease (ANOCA). Invasive coronary function testing (CFT) to diagnose CVDys is becoming more common, enabling pathophysiologic research of CVDys. This study aims to explore the electrophysiological characteristics of ANOCA patients with CVDys., Methods: We collected pre-procedural 12-lead electrocardiograms of ANOCA patients with CVS (n = 35), CMD (n = 24), CVS/CMD (n = 26) and patients without CVDys (CFT-, n = 23) who participated in the NL-CFT registry and underwent CFT. Heart axis and conduction times were compared between patients with CVS, CMD or CVS/CMD and patients without CVDys., Results: Heart axis, heart rate, PQ interval and QRS duration were comparable between the groups. A small prolongation of the QT-interval corrected with Bazett (QTcB) and Fridericia (QTcF) was observed in patients with CVDys compared to patients without CVDys (CVS vs CFT-: QTcB = 422 ± 18 vs 414 ± 18 ms (p = 0.14), QTcF = 410 ± 14 vs 406 ± 12 ms (p = 0.21); CMD vs CFT-: QTcB = 426 ± 17 vs 414 ± 18 ms (p = 0.03), QTcF = 413 ± 11 vs 406 ± 12 ms (p = 0.04); CVS/CMD vs CFT-: QTcB = 424 ± 17 vs 414 ± 18 ms (p = 0.05), QTcF = 414 ± 14 vs 406 ± 12 ms (p = 0.04))., Conclusions: Pre-procedural 12-lead electrocardiograms were comparable between patients with and without CVDys undergoing CFT except for a slightly longer QTc interval in patients with CVDys compared to patients without CVDys, suggesting limited cardiac remodeling in patients with CVDys., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background Coronary flow reserve (CFR) and microvascular resistance reserve (MRR) are physiological parameters to assess coronary microvascular dysfunction. CFR and MRR can be assessed using bolus or continuous thermodilution, and the correlation between these methods has not been clarified. Furthermore, their association with angina and quality of life is unknown. Methods and Results In total, 246 consecutive patients with angina and nonobstructive coronary arteries from the multicenter Netherlands Registry of Invasive Coronary Vasomotor Function Testing (NL-CFT) were investigated. The 36-item Short Form Health Survey Quality of Life and Seattle Angina questionnaires were completed by 153 patients before the invasive measurements. CFR and MRR were measured consecutively with bolus and continuous thermodilution. Mean continuous thermodilution-derived coronary flow reserve (CFR abs ) was significantly lower than mean bolus thermodilution-derived coronary flow reserve (CFR bolus ) (2.6±1.0 versus 3.5±1.8; P <0.001), with a modest correlation ( ρ =0.305; P <0.001). Mean continuous thermodilution-derived microvascular resistance reserve (MRR abs ) was also significantly lower than mean bolus thermodilution-derived MRR (MRR bolus ) (3.1±1.1 versus 4.2±2.5; P <0.001), with a weak correlation ( ρ =0.280; P <0.001). CFR bolus and MRR bolus showed no correlation with any of the angina and quality of life domains, whereas CFR abs and MRR abs showed a significant correlation with physical limitation ( P =0.005, P =0.009, respectively) and health ( P =0.026, P =0.012). In a subanalysis in patients in whom spasm was excluded, the correlation further improved (MRR abs versus physical limitation: ρ =0.363; P =0.041, MRR abs versus physical health: ρ =0.482; P =0.004). No association with angina frequency and stability was found. Conclusions Absolute flow measurements using continuous thermodilution to calculate CFR abs and MRR abs weakly correlate with, and are lower than, the surrogates CFR bolus and MRR bolus . Absolute flow parameters showed a relationship with physical complaints. No relationship with angina frequency and stability was found.