Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

• Disease Name: Coronary Vasospasm
• MONDO ID: (if available)
• Category: Complex

Research Objectives

Please provide a comprehensive research report on Coronary Vasospasm covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

• What is the disease? Provide a concise overview.
• What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
• What are the common synonyms and alternative names?
• Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

• Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
• Risk Factors:

  Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

• Genetic risk factors (causal variants, susceptibility loci, modifier genes)
• Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
• Protective Factors:

  Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

• Genetic protective factors (protective variants, modifier alleles)
• Environmental protective factors (diet, lifestyle, exposures that reduce risk)
• Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

  Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

• Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

  Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

• Pathogenic Variants:
• Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
• Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
• Variant type/class (missense, frameshift, nonsense, splice-site, structural)
• Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
• Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
• Functional consequences (loss of function, gain of function, dominant negative)
• Modifier Genes: Genes that modify disease severity or expression
• Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

  Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

• Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

  Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

• Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

  Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

• Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

  Search first: CDC databases, WHO, PubMed, NHANES

• Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

  Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

• Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

  Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

• Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

  Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

• Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

  Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

• Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

  Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

• Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

  Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

• Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

  Search first: PubMed, Gene Ontology, Reactome

• Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

  Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

• Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

  Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

• Molecular Profiling (if available):
• Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
• Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
• Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
• Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
• Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
• Advanced Technologies (if applicable):
• Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
• Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
• Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
• Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

• Organ Level:
• Primary organs directly affected
• Secondary organ involvement (complications, secondary effects)
• Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

  Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

• Tissue and Cell Level:
• Specific tissue types affected (epithelial, connective, muscle, nervous)
• Specific cell populations targeted (with Cell Ontology terms)

  Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

• Subcellular Level:
• Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

  Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

• Localization:
• Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
• Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

• Onset:
• Typical age of onset (congenital, pediatric, adult, geriatric)
• Onset pattern (acute, subacute, chronic, insidious)

  Search first: OMIM, Orphanet, HPO, PubMed

• Progression:
• Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
• Progression rate (rapid, slow, variable)
• Disease course pattern (episodic, relapsing-remitting, progressive, stable)
• Disease duration (self-limited, chronic lifelong)

  Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

• Patterns:
• Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
• Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

• Epidemiology:
• Prevalence (cases per 100,000 at given time)
• Incidence (new cases per 100,000 per year)

  Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

• For Genetic Etiology:
• Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
• Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
• Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
• Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
• Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
• Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
• Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
• Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
• Population Demographics:
• Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
• Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
• Geographic distribution of specific variants
• Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
• Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

• Clinical Tests:
• Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
• Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
• Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
• Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
• Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
• Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
• Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
• Genetic Testing:

  Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

• Overview of recommended genetic testing approach
• Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
• Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
• Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
• Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
• Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
• Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
• FISH > Search first: ClinVar, cytogenetics databases, PubMed
• Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
• Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
• Omics-Based Diagnostics (if applicable):
• RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
• Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
• Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
• Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
• Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
• Clinical Criteria:
• Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
• Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
• Screening:
• Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

• Survival and Mortality:
• Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
• Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
• Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
• Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
• Morbidity and Function:
• Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
• Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
• Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
• Disease Course:
• Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
• Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
• Prediction:
• Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
• Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

• Pharmacotherapy:
• Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
• Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
• Advanced Therapeutics:
• Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
• Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
• RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
• Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
• Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
• Surgical and Interventional:
• Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
• Supportive and Rehabilitative:
• Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
• Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
• Experimental:
• Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
• Treatment Outcomes:
• Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
• Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
• Treatment Strategy:
• Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
• Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
• Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

• Prevention Levels:
• Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
• Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
• Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
• Immunization: Vaccine strategies (if applicable)

  Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

• Screening and Early Detection:
• Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
• Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
• Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
• Behavioral Interventions: Lifestyle modifications to reduce risk

  Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

• Counseling: Genetic counseling (risk assessment, family planning guidance)

  Search first: NSGC resources, ACMG guidelines, GeneReviews

• Public Health:
• Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
• Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
• Prophylaxis: Preventive medications or procedures

  Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

• Taxonomy: Species affected (with NCBI Taxon identifiers)

  Search first: NCBI Taxonomy

• Breed: Specific breeds affected (with VBO identifiers if applicable)

  Search first: VBO (Vertebrate Breed Ontology)

• Gene: Orthologous genes in other species (with NCBI Gene IDs)

  Search first: NCBI Gene

• Natural Disease:
• Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
• Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
• Comparative Biology:
• Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
• Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
• Transmission (if applicable):
• Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
• Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

• Model Types:
• Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
• Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
• Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
• Genetic Models:
• Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
• Model Characteristics:
• Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
• Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
• Applications:
• Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
• Resources:
• Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

• Cite primary literature (PMID preferred) for all mechanistic and clinical claims
• Prioritize recent reviews and landmark papers
• Include direct quotes from abstracts where possible to support key statements
• Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Coronary Vasospasm (Vasospastic Angina) — Comprehensive Disease Characteristics Report (2023–2024 prioritized)

Executive overview

Coronary vasospasm (CAS) is a transient, often reversible, hyperconstriction of epicardial coronary arteries and/or the coronary microcirculation that can cause myocardial ischemia ranging from angina to acute coronary syndrome (ACS), myocardial infarction with non‑obstructive coronary arteries (MINOCA), malignant arrhythmias, syncope, and sudden cardiac death. Contemporary frameworks treat epicardial vasospastic angina (VSA) and microvascular spasm as related but distinct endotypes within angina/ischemia with non‑obstructive coronary arteries (ANOCA/INOCA). (jenkins2024vasospasticanginaa pages 1-1, lanza2023managementofcoronary pages 1-2, huang2023invasiveevaluationfor pages 3-4)

Table: This table compiles the main quantitative findings on epidemiology, prognosis, diagnostic thresholds, safety, and recent genetics for coronary vasospasm/vasospastic angina. It is designed as a quick-reference evidence summary for knowledge-base curation and report writing.

1. Disease information

1.1 Definition and current clinical concept

• Vasospastic angina (VSA) is chest pain due to myocardial ischemia caused by epicardial coronary spasm, described as “a sudden narrowing of the vessels responsible for an inadequate supply of blood and oxygen.” (jenkins2024vasospasticanginaa pages 1-1)
• Synonyms and related terms used in modern reviews include coronary artery spasm (CAS), Prinzmetal angina, and variant angina. (jenkins2024vasospasticanginaa pages 1-1, lanza2023managementofcoronary pages 1-2, huang2023invasiveevaluationfor pages 7-8)
• CAS can be focal or diffuse, can occur in angiographically normal segments or coexist with plaques, and can manifest as classic rest angina, exertional angina, or ACS presentations. (lanza2023managementofcoronary pages 1-2, gurgoglione2024coronaryspasmtesting pages 9-10)

1.2 Key identifiers and ontology/coding

• MeSH
• Coronary Vasospasm — MeSH D003329 (as used in ClinicalTrials.gov derived condition browse for BELmicro registry). (NCT06089031 chunk 1)
• Angina Pectoris, Variant — MeSH D000788 (ClinicalTrials.gov condition browse for ReACHallenge). (NCT05618132 chunk 1)
• EFO (Open Targets)
• Coronary Vasospasm — EFO_0004225; Prinzmetal’s angina — EFO_1000013 (retrieved from Open Targets search; no MONDO mapping was available in the retrieved evidence). (elsabbagh2024coronaryarteryspasm—risk pages 7-8)
• MONDO: not retrieved from the accessible texts in this run; would require an ontology lookup outside the retrieved evidence.
• ICD-10/ICD-11: not retrieved from accessible texts in this run.

1.3 Data provenance

This report integrates (i) aggregated disease-level evidence from systematic reviews and narrative reviews and (ii) clinical trial registry metadata (ClinicalTrials.gov) describing real-world diagnostic implementation and ongoing trials. (woudstra2023metaanalysisandsystematic pages 1-2, lanza2023managementofcoronary pages 6-6, NCT05618132 chunk 1)

2. Etiology

2.1 Primary causal factors (mechanistic)

CAS/VSA is generally understood as a vasomotor disorder driven by the convergence of: 1) Endothelial dysfunction (impaired NO/vasodilator signaling with relative excess of vasoconstrictors), and 2) Vascular smooth muscle cell (VSMC) hyperreactivity/hypercontraction, prominently involving RhoA/Rho‑kinase (ROCK)–mediated calcium sensitization. (gurgoglione2024coronaryspasmtesting pages 2-4, godo2023coronarymicrovascularspasm pages 3-4, nishimiya2023mechanismsofcoronary pages 2-3)

2.2 Risk factors

From ANOCA cohorts undergoing spasm testing, common cardiovascular risk factors in epicardial spasm populations include smoking, dyslipidaemia, diabetes, and hypertension (approximate pooled prevalences listed in the evidence table). (woudstra2023metaanalysisandsystematic pages 8-9)

Common triggers discussed in modern reviews include stress-related autonomic surges and vasoactive exposures (e.g., cocaine, alcohol) and metabolic contributors such as magnesium deficiency. (jenkins2024vasospasticanginaa pages 1-3, huang2023invasiveevaluationfor pages 2-3, elsabbagh2024coronaryarteryspasm—risk pages 5-7)

2.3 Protective factors

Protective factors are not well quantified in the retrieved evidence. Mechanistically, preservation of endothelial NO signaling would be expected to be protective, and clinical use of vasodilators (CCBs) is foundational for preventing attacks. (huang2023invasiveevaluationfor pages 7-8, lanza2023managementofcoronary pages 6-6)

2.4 Gene–environment interactions

Reviews emphasize that genetic susceptibility (e.g., NO/ALDH2 pathways) may interact with exposures that increase oxidative stress and ROCK activity, notably smoking and stress, to increase spasm propensity. (gurgoglione2024coronaryspasmtesting pages 2-4, elsabbagh2024coronaryarteryspasm—risk pages 7-8)

3. Phenotypes

3.1 Core clinical phenotypes

Symptoms / clinical signs * Angina at rest often with a circadian pattern (e.g., early morning), classically in variant angina, though exertional or stress-triggered episodes also occur. (lanza2023managementofcoronary pages 1-2, jenkins2024vasospasticanginaa pages 1-3) * Transient ischemic ECG changes during attacks, including ST-segment elevation (classic) but also ST depression and T-wave changes. (jenkins2024vasospasticanginaa pages 1-1, lanza2023managementofcoronary pages 1-2)

Complications / severe phenotypes * Acute MI / ACS / MINOCA can occur when spasm is prolonged; reviews explicitly note that persistent spasm can lead to MI. (jenkins2024vasospasticanginaa pages 1-1) * Syncope and sudden cardiac death: VSA is associated with major adverse events including “sudden cardiac death, acute MI and syncope.” (jenkins2024vasospasticanginaa pages 1-1)

3.2 Phenotype characteristics

• Typical onset: adult; attacks may be episodic and fluctuating. (lanza2023managementofcoronary pages 1-2)
• Progression/course: variable; early period after onset may be particularly high risk (see Temporal Development). (lanza2023managementofcoronary pages 2-3)

3.3 Frequencies and quality-of-life impact

• In ANOCA populations, recurrent angina during follow-up is common (reported range 10–53%). (woudstra2023metaanalysisandsystematic pages 1-2)
• A recent review reported substantial psychosocial burden (e.g., “>70% impact on mental health”) in INOCA/VSA contexts. (jenkins2024vasospasticanginaa pages 1-3)

3.4 Suggested HPO terms (examples)

• Chest pain/angina: HP:0100749 (Angina pectoris)
• Syncope: HP:0001279
• Myocardial infarction: HP:0001658
• ST segment elevation: HP:0012252; ST segment depression: HP:0012253
• Ventricular fibrillation: HP:0001663

(These HPO identifiers are suggested for knowledge-base normalization; they are not explicitly enumerated in the retrieved papers.)

4. Genetic / molecular information

4.1 High-confidence genetic association (2024 GWAS)

A 2024 genetic association study identified RNF213 as a major susceptibility locus for VSA: * Overall association at RNF213 locus: OR 2.34 (95% CI 1.99–2.74; P=4.4×10−25). (hikino2024rnf213variantsvasospastic pages 1-2) * Lead variant rs112735431 (p.Arg4810Lys): OR 2.18 (95% CI 1.83–2.59; P=2.0×10−18); homozygotes showed a much larger effect (OR 18.34). (hikino2024rnf213variantsvasospastic pages 3-4, hikino2024rnf213variantsvasospastic pages 1-2) * Importantly, in follow-up among carriers without baseline CAD, this allele was associated with increased acute MI mortality: HR 2.71 (95% CI 1.57–4.65; P=3.3×10−4). (hikino2024rnf213variantsvasospastic pages 1-2)

4.2 Candidate genetic contributors cited in mechanistic reviews

Mechanistic/risk-factor reviews cite associations involving: * ALDH2 East Asian variant (associated with coronary spastic angina) (elsabbagh2024coronaryarteryspasm—risk pages 7-8) * NOS3/eNOS: T−786→C promoter variant “associated with coronary spasm” (elsabbagh2024coronaryarteryspasm—risk pages 7-8) * ACE variants described as a genetic risk factor for coronary spasm with implication in MI pathogenesis (elsabbagh2024coronaryarteryspasm—risk pages 7-8) * Paraoxonase polymorphism (Q192R) and PLC-δ1 variant (R257H) noted in review-level summaries (elsabbagh2024coronaryarteryspasm—risk pages 5-7, elsabbagh2024coronaryarteryspasm—risk pages 7-8)

Variant classification / allele frequencies: not available from the retrieved texts; curated variant-level annotation would require ClinVar/gnomAD retrieval.

4.3 Mechanistic molecular pathways (key nodes)

Core signaling nodes repeatedly emphasized: * NO–cGMP signaling (endothelium → VSMC) (gurgoglione2024coronaryspasmtesting pages 2-4) * Endothelin‑1 and other vasoconstrictors (gurgoglione2024coronaryspasmtesting pages 2-4, huang2023invasiveevaluationfor pages 2-3) * RhoA/ROCK → myosin phosphatase inhibition → increased MLC phosphorylation → VSMC hypercontraction (nishimiya2023mechanismsofcoronary pages 2-3, gurgoglione2024coronaryspasmtesting pages 19-20)

5. Environmental information

Environmental/lifestyle contributors commonly referenced include smoking (oxidative stress/inflammation), stress/catecholamine surges, and vasoactive substances (e.g., cocaine, alcohol). (huang2023invasiveevaluationfor pages 2-3, jenkins2024vasospasticanginaa pages 1-3)

6. Mechanism / pathophysiology (causal chains)

6.1 Upstream triggers

• Inflammation (adventitial/perivascular inflammation; cytokines such as IL‑1β) can upregulate ROCK activity and induce reproducible spasm in models. (nishimiya2023mechanismsofcoronary pages 1-2, nishimiya2023mechanismsofcoronary pages 2-3)
• Oxidative stress and impaired aldehyde detoxification (e.g., ALDH2 deficiency) may increase susceptibility via ROS-mediated endothelial impairment. (elsabbagh2024coronaryarteryspasm—risk pages 5-7)

6.2 Core pathophysiologic cascade (integrated model)

A consistent mechanistic chain described across modern reviews is: 1) Endothelial dysfunction → reduced NO bioavailability and impaired ACh-mediated vasodilation, allowing paradoxical vasoconstriction. (gurgoglione2024coronaryspasmtesting pages 2-4, huang2023invasiveevaluationfor pages 2-3) 2) ROCK-mediated Ca2+ sensitization in VSMCs → myosin phosphatase inhibition → increased myosin light-chain phosphorylation → hypercontraction. (nishimiya2023mechanismsofcoronary pages 2-3, gurgoglione2024coronaryspasmtesting pages 19-20) 3) Clinical spasm (epicardial and/or microvascular) → transient ischemia → angina/ECG changes; prolonged or severe episodes → arrhythmia, MI, cardiac arrest. (lanza2023managementofcoronary pages 1-2, jenkins2024vasospasticanginaa pages 1-1)

6.3 Suggested GO biological process terms (examples)

• Smooth muscle contraction: GO:0006939
• Regulation of blood vessel diameter: GO:0097746
• Response to oxidative stress: GO:0006979
• Inflammatory response: GO:0006954

6.4 Suggested Cell Ontology (CL) cell types (examples)

• Vascular smooth muscle cell: CL:0000192
• Endothelial cell: CL:0000115
• Macrophage: CL:0000235; Mast cell: CL:0000097

(These ontology terms are suggested for normalization; the reviews describe these cell types but do not enumerate ontology IDs.) (godo2023coronarymicrovascularspasm pages 3-4, nishimiya2023mechanismsofcoronary pages 1-2)

7. Anatomical structures affected

7.1 Organ/tissue

• Primary: coronary arteries (epicardial segments) and coronary microcirculation. (huang2023invasiveevaluationfor pages 3-4, gurgoglione2024coronaryspasmtesting pages 5-7)

7.2 Suggested UBERON terms (examples)

• Heart: UBERON:0000948
• Coronary artery: UBERON:0001621

8. Temporal development

• Episodes are often episodic, with a circadian pattern in classic VSA. (jenkins2024vasospasticanginaa pages 1-3)
• A management review emphasized that up to 75% of acute events (including sudden death) occur within the first 1–3 months after symptom onset, supporting an early “high-risk” window. (lanza2023managementofcoronary pages 2-3)

9. Inheritance and population

9.1 Epidemiology in tested ANOCA populations (meta-analysis)

A 2023 systematic review/meta-analysis of ANOCA patients undergoing spasm provocation testing reported: * Epicardial spasm prevalence 43% (range 16–73%), and microvascular spasm prevalence 25% (range 7–39%). (woudstra2023metaanalysisandsystematic pages 1-2) * Regional differences: epicardial spasm 52% in Asian vs 33% in Western cohorts (p=0.014). (woudstra2023metaanalysisandsystematic pages 1-2) * Sex differences: men more often epicardial spasm (≈61%); women more often microvascular spasm (≈64%). (woudstra2023metaanalysisandsystematic pages 1-2)

9.2 Genetic architecture

RNF213 rs112735431 is an East Asian–enriched risk allele with substantial VSA association and may stratify MI risk in carriers. (hikino2024rnf213variantsvasospastic pages 1-2)

10. Diagnostics

10.1 Standardized criteria (COVADIS-aligned)

Epicardial spasm / VSA (definitive evidence) * Nitrate-responsive angina plus objective evidence: transient ischemic ECG changes or angiographic documentation of spasm. (huang2023invasiveevaluationfor pages 3-4, marchini2024sheddinglighton pages 3-5) * During provocation, a positive test is defined by reproduction of symptoms, ischemic ECG changes, and ≥90% epicardial constriction (transient total/subtotal occlusion). (huang2023invasiveevaluationfor pages 3-4, marchini2024sheddinglighton pages 3-5)

Transient ischemic ECG thresholds (COVADIS-derived) * ST elevation ≥0.1 mV or ST depression ≥0.1 mV in ≥2 contiguous leads; negative U waves are also accepted. (marchini2024sheddinglighton pages 3-5)

Microvascular spasm * Typical symptoms and ischemic ECG changes after intracoronary ACh without epicardial spasm (no significant epicardial diameter reduction). (huang2023invasiveevaluationfor pages 3-4, marchini2024sheddinglighton pages 3-5)

10.2 Provocation testing and real-world implementation

Acetylcholine (ACh) provocation protocol (typical contemporary regimen) * Stepwise intracoronary dosing often uses LCA boluses 20–50–100 μg (some add 200 μg) and RCA 20–50 μg, separated by 2–3 minutes; ECG is monitored frequently and angiography performed after each dose or with symptoms/ECG changes. (gurgoglione2024coronaryspasmtesting pages 5-7)

Safety and adverse events * A 2024 review summarized that ACh testing has low but non-zero complication rates; serious complications and life‑threatening arrhythmias are rare and ACh-related death has not been reported. Quantitative safety figures summarized include early serious complication rates 0.3–0.4%, life‑threatening arrhythmias 0.5–0.6%, and meta-analytic estimates of major/minor complication frequencies. (gurgoglione2024coronaryspasmtesting pages 9-10)

Visual evidence (protocol/algorithm and protocol table) * ACh testing protocol flowchart and protocol comparison table are available from the retrieved figures/tables. (gurgoglione2024coronaryspasmtesting media 871e19c7, gurgoglione2024coronaryspasmtesting media ac042141)

10.3 Differential diagnosis (high-level)

In ANOCA/INOCA contexts, VSA must be distinguished from microvascular angina/CMD endotypes; invasive testing can clarify endotype for stratified therapy. (huang2023invasiveevaluationfor pages 3-4, woudstra2023metaanalysisandsystematic pages 11-12)

11. Outcomes / prognosis

11.1 Recurrent symptoms and MACE composition

In ANOCA cohorts with CAS, recurrent angina is common (10–53% across studies), and MACE is often dominated by rehospitalization/unstable angina rather than death/MI in many cohorts. (woudstra2023metaanalysisandsystematic pages 1-2, woudstra2023metaanalysisandsystematic pages 9-10)

11.2 Severe outcomes

Cardiac arrest due to CAS-related ventricular tachyarrhythmias is emphasized as “the most severe complication,” with reported prevalence in illustrative cohorts (≈2–4%). (lanza2023managementofcoronary pages 6-6)

12. Treatment

12.1 Pharmacotherapy (current practice pattern)

• First-line: Calcium channel blockers (CCBs) are first-line for CAS/VSA. (lanza2023managementofcoronary pages 6-6)
• Second-line/add-on: Long-acting nitrates (and where available nicorandil) can be added if symptoms are not controlled by CCBs. (lanza2023managementofcoronary pages 6-6)
• Nitrate strategy caution: long-acting nitrates may have drawbacks (tolerance, endothelial dysfunction concerns) and are recommended as adjuncts when CCBs are insufficient. (huang2023invasiveevaluationfor pages 7-8)

12.2 Refractory disease and device therapy

For refractory CAS, multiple alternative interventions have been proposed, including ROCK inhibition (fasudil), anti-adrenergic approaches, neural therapies, and in select cases device therapy (ICD/pacemaker) when syncope/cardiac arrest is attributable to CAS-related arrhythmias. (lanza2023managementofcoronary pages 6-6)

12.3 Mechanism-based therapy insight (expert synthesis)

Across mechanistic reviews, the centrality of ROCK-mediated VSMC hypercontraction supports investigation and selective use (where available) of ROCK inhibitors and other strategies that restore endothelial NO signaling or reduce inflammation/oxidative stress as mechanistically aligned approaches. (nishimiya2023mechanismsofcoronary pages 2-3, godo2023coronarymicrovascularspasm pages 3-4, gurgoglione2024coronaryspasmtesting pages 19-20)

12.4 Ongoing trials / real-world implementations (selected)

• ReACHallenge (NCT05618132) — “Stepwise Treatment and Acetylcholine Rechallenge…to guide patient-tailored treatment,” testing intracoronary verapamil ± nitroglycerin with ACh rechallenge in proven ACh-induced VSA; start date 2023‑01‑09. URL: https://clinicaltrials.gov/study/NCT05618132 (NCT05618132 chunk 1)
• BELmicro registry (NCT06089031) — multicenter registry of real-world coronary function testing (including ACh vasoreactivity testing) to quantify frequencies of CMD and vasospasm and track 1- and 3-year MACE; first posted 2023‑10‑18. URL: https://clinicaltrials.gov/study/NCT06089031 (NCT06089031 chunk 1)
• Spinal cord stimulation for refractory VSA (NCT06176391) — pilot study in refractory VSA, includes repeat ACh test at 6 months in consenting participants; first posted 2023‑12‑19. URL: https://clinicaltrials.gov/study/NCT06176391 (NCT06176391 chunk 1)
• Vericiguat in VSA (NCT06415227; ViVA) — randomized crossover phase 2 study targeting NO–sGC signaling; first posted 2024‑05‑16. URL: https://clinicaltrials.gov/study/NCT06415227 (NCT06415227 chunk 1)

12.5 Suggested MAXO terms (examples)

• Calcium channel blocker therapy; Nitrate therapy; Coronary angiography; Provocation testing; Implantable cardioverter-defibrillator implantation; Pacemaker implantation; Spinal cord stimulation. (These MAXO identifiers are suggested at the concept level; specific MAXO IDs were not present in the retrieved evidence.) (lanza2023managementofcoronary pages 6-6, NCT06176391 chunk 1)

13. Prevention

Evidence-based prevention in retrieved texts is mainly risk-factor and trigger management consistent with mechanistic drivers (e.g., smoking avoidance, stress reduction, adherence to vasodilator therapy). Stopping vasodilator therapy can provoke recurrence; early post-onset window is high risk. (lanza2023managementofcoronary pages 2-3, gurgoglione2024coronaryspasmtesting pages 2-4)

14. Other species / natural disease

No naturally occurring non-human disease model evidence was retrieved in this run.

15. Model organisms

Mechanistic understanding is supported by animal model literature (e.g., inflammatory IL‑1β adventitial exposure inducing spasm; ROCK inhibition suppressing spasm physiology), but explicit model-system metadata (strain, organism IDs) was not fully captured in the retrieved excerpts. (nishimiya2023mechanismsofcoronary pages 2-3)

Notes on evidence quality and gaps

• The strongest quantitative epidemiology in this run is for CAS prevalence in ANOCA cohorts undergoing provocation testing, not population-wide incidence/prevalence; heterogeneity in protocols/definitions is a major limitation emphasized by the meta-analysis. (woudstra2023metaanalysisandsystematic pages 1-2, woudstra2023metaanalysisandsystematic pages 2-4)
• The strongest genetic evidence in this run is the 2024 RNF213 GWAS, whereas ALDH2/NOS3/ACE findings are presented largely as prior association literature within review summaries in the retrieved excerpts (effect sizes not available here). (hikino2024rnf213variantsvasospastic pages 1-2, elsabbagh2024coronaryarteryspasm—risk pages 7-8)

Key recent sources (URLs; publication dates)

• Woudstra et al., 2023-03, Frontiers in Cardiovascular Medicine (systematic review/meta-analysis): https://doi.org/10.3389/fcvm.2023.1129159 (woudstra2023metaanalysisandsystematic pages 1-2)
• Jenkins et al., 2024-01, Therapeutic Advances in Cardiovascular Disease (review): https://doi.org/10.1177/17539447241230400 (jenkins2024vasospasticanginaa pages 1-1)
• Gurgoglione et al., 2024-02, Life (review; ACh testing protocols/safety; includes figures/tables): https://doi.org/10.3390/life14030292 (gurgoglione2024coronaryspasmtesting pages 5-7, gurgoglione2024coronaryspasmtesting pages 9-10, gurgoglione2024coronaryspasmtesting media 871e19c7)
• Hikino et al., 2024-08, JAMA Cardiology (GWAS/genetic association): https://doi.org/10.1001/jamacardio.2024.1483 (hikino2024rnf213variantsvasospastic pages 1-2)
• Lanza & Shimokawa, 2023-05, European Cardiology Review (management review): https://doi.org/10.15420/ecr.2022.47 (lanza2023managementofcoronary pages 6-6)
• Marchini et al., 2024-06, Cardiovascular Drugs and Therapy (systematic review): https://doi.org/10.1007/s10557-022-07351-x (marchini2024sheddinglighton pages 3-5)

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22. (NCT05618132 chunk 1): ReACHallenge Trial: Acetylcholine Rechallenge After Pretreatment With Vasoactive Drugs. University Hospital, Antwerp. 2023. ClinicalTrials.gov Identifier: NCT05618132

23. (elsabbagh2024coronaryarteryspasm—risk pages 7-8): Farah El-Sabbagh, Noha M. Mesbah, Dina M Abo-El-Matty, and Tarek A. Abdelaziz. Coronary artery spasm—risk factors and pathophysiological mechanisms. Records of Pharmaceutical and Biomedical Sciences, 8:191-198, May 2024. URL: https://doi.org/10.21608/rpbs.2024.327931.1332, doi:10.21608/rpbs.2024.327931.1332. This article has 0 citations.

24. (gurgoglione2024coronaryspasmtesting pages 2-4): Filippo Luca Gurgoglione, Luigi Vignali, Rocco Antonio Montone, Riccardo Rinaldi, Giorgio Benatti, Emilia Solinas, Antonio Maria Leone, Domenico Galante, Gianluca Campo, Simone Biscaglia, Italo Porto, Stefano Benenati, and Giampaolo Niccoli. Coronary spasm testing with acetylcholine: a powerful tool for a personalized therapy of coronary vasomotor disorders. Life, 14:292, Feb 2024. URL: https://doi.org/10.3390/life14030292, doi:10.3390/life14030292. This article has 16 citations.

25. (godo2023coronarymicrovascularspasm pages 3-4): Shigeo Godo, Jun Takahashi, Takashi Shiroto, Satoshi Yasuda, and Hiroaki Shimokawa. Coronary microvascular spasm: clinical presentation and diagnosis. European Cardiology Review, Mar 2023. URL: https://doi.org/10.15420/ecr.2022.50, doi:10.15420/ecr.2022.50. This article has 14 citations.

26. (nishimiya2023mechanismsofcoronary pages 2-3): Kensuke Nishimiya, Jun Takahashi, Kazuma Oyama, Yasuharu Matsumoto, Satoshi Yasuda, and Hiroaki Shimokawa. Mechanisms of coronary artery spasm. European Cardiology Review, May 2023. URL: https://doi.org/10.15420/ecr.2022.55, doi:10.15420/ecr.2022.55. This article has 18 citations.

27. (jenkins2024vasospasticanginaa pages 1-3): Kenny Jenkins, Graziella Pompei, Nandine Ganzorig, Sarah Brown, John Beltrame, and Vijay Kunadian. Vasospastic angina: a review on diagnostic approach and management. Therapeutic Advances in Cardiovascular Disease, Jan 2024. URL: https://doi.org/10.1177/17539447241230400, doi:10.1177/17539447241230400. This article has 56 citations and is from a peer-reviewed journal.

28. (huang2023invasiveevaluationfor pages 2-3): Jingwen Huang, Rebecca Steinberg, Matthew J Brown, Stéphane Rinfret, and Olga Toleva. Invasive evaluation for coronary vasospasm. US Cardiology Review, Jun 2023. URL: https://doi.org/10.15420/usc.2022.33, doi:10.15420/usc.2022.33. This article has 5 citations.

29. (elsabbagh2024coronaryarteryspasm—risk pages 5-7): Farah El-Sabbagh, Noha M. Mesbah, Dina M Abo-El-Matty, and Tarek A. Abdelaziz. Coronary artery spasm—risk factors and pathophysiological mechanisms. Records of Pharmaceutical and Biomedical Sciences, 8:191-198, May 2024. URL: https://doi.org/10.21608/rpbs.2024.327931.1332, doi:10.21608/rpbs.2024.327931.1332. This article has 0 citations.

30. (gurgoglione2024coronaryspasmtesting pages 19-20): Filippo Luca Gurgoglione, Luigi Vignali, Rocco Antonio Montone, Riccardo Rinaldi, Giorgio Benatti, Emilia Solinas, Antonio Maria Leone, Domenico Galante, Gianluca Campo, Simone Biscaglia, Italo Porto, Stefano Benenati, and Giampaolo Niccoli. Coronary spasm testing with acetylcholine: a powerful tool for a personalized therapy of coronary vasomotor disorders. Life, 14:292, Feb 2024. URL: https://doi.org/10.3390/life14030292, doi:10.3390/life14030292. This article has 16 citations.

31. (nishimiya2023mechanismsofcoronary pages 1-2): Kensuke Nishimiya, Jun Takahashi, Kazuma Oyama, Yasuharu Matsumoto, Satoshi Yasuda, and Hiroaki Shimokawa. Mechanisms of coronary artery spasm. European Cardiology Review, May 2023. URL: https://doi.org/10.15420/ecr.2022.55, doi:10.15420/ecr.2022.55. This article has 18 citations.

32. (gurgoglione2024coronaryspasmtesting media ac042141): Filippo Luca Gurgoglione, Luigi Vignali, Rocco Antonio Montone, Riccardo Rinaldi, Giorgio Benatti, Emilia Solinas, Antonio Maria Leone, Domenico Galante, Gianluca Campo, Simone Biscaglia, Italo Porto, Stefano Benenati, and Giampaolo Niccoli. Coronary spasm testing with acetylcholine: a powerful tool for a personalized therapy of coronary vasomotor disorders. Life, 14:292, Feb 2024. URL: https://doi.org/10.3390/life14030292, doi:10.3390/life14030292. This article has 16 citations.

33. (NCT06415227 chunk 1): Jan J. Piek, MD, PhD. The Impact of Vericiguat on Microvascular Function in Patients with Documented Vasospastic Angina Pectoris. Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA). 2025. ClinicalTrials.gov Identifier: NCT06415227