Outpatient Management of Patients With Angina With No Obstructive Coronary Arteries: How to Come to a Proper Diagnosis and Therapy.

Two-thirds of women and one-third of men who undergo a clinically indicated coronary angiography for stable angina, have no obstructive coronary artery disease (CAD). Coronary vascular dysfunction is a highly prevalent underlying cause of angina in these so called "Angina with No Obstructive Coronary Arteries (ANOCA)" patients, foremost in middle aged women. Coronary vascular dysfunction encompasses various endotypes, namely epicardial and microvascular coronary spasms, impaired vasodilatation, and increased microvascular resistance. ANOCA patients, especially those with underlying coronary vascular dysfunction, have an adverse cardiovascular prognosis, poor physical functioning, and a reduced quality of life. Since standard ischemia detection tests and coronary angiograms are not designed to diagnose coronary vascular dysfunction, this ischemic heart disease is often overlooked and hence undertreated. But adequate diagnosis is vital, so that treatment can be started to reduce symptoms, reduce healthcare costs and improve quality of life and cardiovascular prognosis. The purpose of this review is to give a contemporary overview of ANOCA with focus on coronary vascular dysfunction. We will provide a possible work-up of patients suspected of coronary vascular dysfunction in the outpatient clinical setting, based on the latest scientific insights and international consensus documents. We will discuss the value of ischemia detection testing, and non-invasive and invasive methods to diagnose coronary vascular dysfunction. Furthermore, we will go into pharmacological and non-pharmacological therapeutic options including anti-anginal regimens and lifestyle interventions.

Vasomotor dysfunction in patients with angina and nonobstructive coronary artery disease is dominated by vasospasm.

BACKGROUND: Coronary vasomotor dysfunction, comprising endotypes of coronary spasm and/or impaired microvascular dilatation (IMD), is common in patients with angina and no obstructive coronary arteries (ANOCA). However, there are discrepant reports regarding the prevalence of these endotypes. The objective of this study was to determine the prevalence of coronary vasomotor dysfunction in patients with ANOCA, underlying endotypes, and differences in clinical characteristics. METHODS: Prospective registry of patients with ANOCA that underwent clinically indicated invasive coronary function testing (CFT), including acetylcholine spasm testing (2-200 µg) to diagnose coronary spasm, and adenosine testing (140 µg/kg/min) to diagnose IMD, defined as an index of microvascular resistance ≥25 and/or coronary flow reserve <2.0. RESULTS: Of the 111 patients that completed CFT (88% female, mean age 54 years), 96 (86%) showed vasomotor dysfunction. The majority 93 (97%) had coronary spasm, 63% isolated and 34% combined with IMD. Isolated IMD was rare, occurring in only 3 patients (3%). Hypertension was more prevalent in patients with vasomotor dysfunction compared to those without (39% vs. 7%, p = 0.02). Obesity and a higher severity of angiographic atherosclerotic disease were more prevalent in patients with coronary spasm compared to those without (61% vs. 28%; 40% vs. 0%, respectively, both p < 0.01). No differences in angina characteristics were observed between patients with and without vasomotor dysfunction or between endotypes. CONCLUSIONS: Coronary vasomotor dysfunction is highly prevalent in patients with ANOCA, especially epicardial or microvascular vasospasm, whereas isolated IMD was rare. Performing a CFT without acetylcholine testing should be strongly discouraged.

Chiral Spin Spirals at the Surface of the van der Waals Ferromagnet Fe3GeTe2.

Topologically protected magnetic structures provide a robust platform for low power consumption devices for computation and data storage. Examples of these structures are skyrmions, chiral domain walls, and spin spirals. Here, we use scanning electron microscopy with polarization analysis to unveil the presence of chiral counterclockwise Néel spin spirals at the surface of a bulk van der Waals ferromagnet Fe3GeTe2 (FGT) at zero magnetic field. These Néel spin spirals survive up to FGT's Curie temperature of TC = 220 K, with little change in the periodicity p = 300 nm of the spin spiral throughout the studied temperature range. The formation of a spin spiral showing counterclockwise rotation strongly suggests the presence of a positive Dzyaloshinskii-Moriya interaction in FGT, which provides the first steps towards the understanding of the magnetic structure of FGT. Our results additionally pave the way for chiral magnetism in van der Waals materials and their heterostructures.

Magnetic Chirality Controlled by the Interlayer Exchange Interaction.

Chiral magnetism, wherein there is a preferred sense of rotation of the magnetization, determines the chiral nature of magnetic textures such as skyrmions, domain walls, or spin spirals. Current research focuses on identifying and controlling the interactions that define the magnetic chirality in thin film multilayers. The influence of the interfacial Dzyaloshinskii-Moriya interaction (IDMI) and, recently, the dipolar interactions have been reported. Here, we experimentally demonstrate that an indirect interlayer exchange interaction can be used as an additional tool to effectively manipulate the magnetic chirality. We image the chirality of magnetic domain walls in a coupled bilayer system using scanning electron microscopy with polarization analysis. Upon increasing the interlayer exchange coupling, we induce a transition of the magnetic chirality from clockwise rotating Néel walls to degenerate Bloch-Néel domain walls and we confirm our findings with micromagnetic simulations. In multilayered systems relevant for skyrmion research, a uniform magnetic chirality across the magnetic layers is often desired. Additional simulations show that this can be achieved for reduced IDMI values (up to 30%) when exploiting the interlayer exchange interaction. This work opens up new ways to control and tailor the magnetic chirality by the interlayer exchange interaction.

Tuning Magnetic Chirality by Dipolar Interactions.

The stabilization of chiral magnetic domain walls and skyrmions has been attributed to the actively investigated Dzyaloshinskii-Moriya interaction. Recently, however, predictions were made that suggest dipolar interactions can also stabilize chiral domain walls and skyrmions, but direct experimental evidence has been lacking. Here we show that dipolar interactions can indeed stabilize chiral domain walls by directly imaging the magnetic domain walls using scanning electron microscopy with polarization analysis in archetype Pt/CoB/Ir thin film multilayers. We further demonstrate the competition between the Dzyaloshinskii-Moriya and dipolar interactions by imaging a reversal of the domain wall chirality as a function of the magnetic layer thickness. Finally, we suggest that this competition can be tailored by a Ruderman-Kittel-Kasuya-Yosida interaction. Our work therefore reveals that dipolar interactions play a key role in the stabilization of chiral spin textures. This insight will open up new routes towards balancing interactions for the stabilization of chiral magnetism.