Angina or ischemia with no obstructed coronary arteries: a specific diagnostic and therapeutic protocol

Riccardo Rinaldi; Francesco Spione; Filippo Maria Verardi; Pablo Vidal Calés; Víctor Arévalos; Rami Gabani; Daniel Cánovas; Montserrat Gutiérrez; Montserrat Pardo; Rosa Domínguez; Luis Pintor; Xavier Torres; Xavier Freixa; Ander Regueiro; Omar Abdul-Jawad Altisent; Manel Sabaté; Salvatore Brugaletta

doi:10.24875/RECICE.M23000418

. 2024 Jan 30;6(2):67–75. doi: 10.24875/RECICE.M23000418

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Angina or ischemia with no obstructed coronary arteries: a specific diagnostic and therapeutic protocol

Riccardo Rinaldi ^a,^b,^◊, Francesco Spione ^a,^c,^d,^◊, Filippo Maria Verardi ^a,^e, Pablo Vidal Calés ^a, Víctor Arévalos ^a, Rami Gabani ^a, Daniel Cánovas ^a, Montserrat Gutiérrez ^a, Montserrat Pardo ^a, Rosa Domínguez ^a, Luis Pintor ^f, Xavier Torres ^g, Xavier Freixa ^a, Ander Regueiro ^a, Omar Abdul-Jawad Altisent ^a, Manel Sabaté ^a, Salvatore Brugaletta ^a,^*

PMCID: PMC12097352 PMID: 40416352

ABSTRACT

Introduction and objectives:

A systematic approach to patients with angina with no obstructed coronary arteries (ANOCA) or ischemia with no obstructed coronary arteries (INOCA) patients is not routinely implemented.

Methods:

All consecutive patients diagnosed with ANOCA/INOCA were referred to a designated outpatient clinic for a screening visit to assess their eligibility for a NOCA program. If eligible, patients underwent scheduled coronary angiograms with coronary function testing and intracoronary acetylcholine provocation testing. Medical therapy was optimized accordingly. All patients were then followed up at 1, 3, 6, and 12 months. Baseline and 3-month follow-up assessments included the Seattle Angina Questionnaire (SAQ) and EuroQol-5D questionnaire.

Results:

Of 77 patients screened, 23 (29.9%) were excluded and 54 (70.1%) were included (29 [53.7%] with INOCA and 25 [46.3%] with ANOCA). Microvascular angina was diagnosed in 19 (35.2%) patients, vasospastic angina in 12 (22.2%), both microvascular angina and vasospastic angina in 18 (33.3%), and noncoronary chest pain in 5 (9.3%). There was a notable increase in the use of beta-blockers, calcium channel blockers and nitrates. Complications occurred in 3 (5.5%) patients. Compared with baseline, there was no difference in the mean EQ-5D score at the 3-month follow-up, but there was a significant improvement in the SAQ score related to physical limitations, angina stability, and disease perception, with no differences in angina frequency or treatment satisfaction. No events were recorded at the 1-year follow-up.

Conclusions:

A specific diagnostic and therapeutic protocol can be easily and safely implemented in routine clinical practice, leading to improvement in patients' quality of life.

Keywords: INOCA, ANOCA, Diagnosis, Therapy, Protocol

Abbreviations

ANOCA:: angina with no obstructed coronary arteries.
INOCA:: ischemia with no obstructed coronary arteries.

SEE RELATED CONTENT:

https://doi.org/10.24875/RECICE.M23000433

INTRODUCTION

Ischemic heart disease is the leading cause of disability and mortality worldwide and is commonly characterized by the presence of obstructive coronary artery disease (CAD) (defined as any coronary artery stenosis ≥ 50% in diameter).1 However, up to 60% to 70% of patients with angina and/or documented myocardial ischemia do not have angiographic evidence of CAD.2 This condition is defined as angina with no obstructed coronary arteries (ANOCA) or ischemia with no obstructed coronary arteries (INOCA) when associated with evidence of myocardial ischemia.3 Of note, despite the absence of CAD, these patients are at an increased risk of future cardiovascular events such as acute coronary syndrome, heart failure hospitalization, stroke, and repeat cardiovascular procedures compared with healthy individuals.4,5 Therefore, appropriate management in terms of diagnosis and treatment is of the utmost importance to improve patients' prognosis and outcomes.6 The Coronary Microvascular Angina (CorMicA) trial demonstrated that a strategy of adjunctive invasive testing for disorders of coronary function together with stratified medical therapy can improve outcomes (ie, reduction in angina severity and enhanced quality of life).7,8 However, there are still concerns about the implementation in real-world practice of a systematic diagnostic and therapeutic approach in INOCA and ANOCA patients, potentially impacting outcomes and quality of life.

We report our single-center experience of the implementation in clinical practice of a specific diagnostic and therapeutic protocol (no obstructed coronary arteries [NOCA] program) in INOCA and ANOCA patients.

METHODS

Eligibility criteria for the NOCA program

All consecutive patients diagnosed either at our hospital or at our referral centers with angina or ischemia with nonobstructive CAD on coronary angiography were referred to a specific outpatient clinic (the NOCA clinic at Hospital Clínic, Barcelona, Spain) for a screening visit. Nonobstructive CAD was defined as angiographic evidence of normal coronary arteries or diffuse atherosclerosis with stenosis < 50% and/or fractional flow reserve (FFR) > 0.80 if there was stenosis between 50% and 70%. During the screening visit, a team of expert cardiologists confirmed patients' eligibility for the NOCA program based on the following criteria: a) diagnosis of ANOCA, defined as stable, chronic typical angina symptoms (eg, chest pain precipitated by physical exertion or emotional stress and relieved by rest or nitroglycerine); b) diagnosis of INOCA, defined as the demonstration of myocardial ischemia identified by a noninvasive test with pharmacologic or exercise stress tests such as cardiac single photon emission computed tomography, cardiac magnetic resonance, stress electrocardiography, or echocardiography.3 The exclusion criteria were: a) atypical angina symptoms, and b) clearly identifiable noncoronary causes of chest pain (figure 1). The study protocol adhered to the Declaration of Helsinki and the study was approved by our institutional review committee. All patients provided written informed consent to be included in this program and study. The clinical ethics committee gave their approval for a retrospective analysis of the collected data.

NOCA program: diagnostic approach

After patient inclusion in the NOCA program, specialized counseling was provided by expert cardiologists and nurses. All patients were thoroughly informed about their disease, the importance of reaching a specific diagnosis, and the importance implementing tailored therapy. During the counseling sessions, the predicted benefits and low associated risks of an invasive procedure to specifically study coronary microcirculation and vasospasm were explained in detail. All patients provided written informed consent to undergo coronary angiography and intracoronary provocation testing with acetylcholine (ACh).

Subsequently, all patients underwent a scheduled coronary angiogram with a comprehensive diagnostic work-up consisting of the following: a) coronary function testing to assess coronary flow reserve (CFR) and the index of microvascular resistance (IMR); b) intracoronary ACh provocation testing to assess the presence of coronary vasomotion disorders (eg, epicardial or microvascular spasm).

Coronary function testing was performed using a pressure-temperature sensor guidewire (PressureWire X Guidewire and Coroventis CoroFlow Cardiovascular System, Abbott Vascular, United States) placed in the left anterior descending artery (LAD) as the prespecified target vessel, reflecting its subtended myocardial mass and coronary dominance. Steady-state hyperemia was induced using intravenous adenosine (140 µg/kg/min). If there was severe tortuosity of the LAD or evidence of myocardial ischemia in a region other than the territory of the LAD, the wire was placed in the right coronary artery or the left circumflex, as per the operator's decision. CFR was calculated using thermodilution, defined as resting mean transit time divided by hyperemic mean transit time (abnormal CFR was defined as ≤ 2.5). IMR was calculated as the product of distal coronary pressure at maximal hyperemia multiplied by the hyperemic mean transit time (normal value < 25).6,9

Intracoronary ACh provocation testing was performed with a standardized protocol involving serial ACh infusions for 20 seconds at increasing concentrations (2-20-100 µg in the left coronary artery with an interval of 2-3 minutes between each injection) with concomitant assessment of the patient's symptoms, electrocardiogram documentation, and angiographic scans. Patients taking vasoactive drugs (eg, calcium channel blockers and nitrates) underwent a wash-out period of at least 48 hours before the provocative test.10,11,12 Epicardial coronary spasm was defined as the reproduction of chest pain and ischemic electrocardiogram changes in association with a reduction in coronary diameter ≥ 90% from baseline in any epicardial coronary artery segment.13 Microvascular spasm was diagnosed when typical ischemic ST-segment changes (deviation ≥ 1 mm) and angina developed in the absence of epicardial coronary constriction (< 90% diameter reduction).14

Subsequently, patients were stratified into 4 endotypes: a) microvascular angina (MVA) (evidence of coronary microvascular dysfunction [CMD] defined as any abnormal CFR [< 2.5], IMR [≥ 25], or microvascular spasm); b) vasospastic angina (VSA) (CFR ≥ 2.5, IMR < 25 and epicardial spasm); c) both MVA and VSA (evidence of CMD and epicardial spasm); and d) noncoronary chest pain (CFR ≥ 2.5 and IMR < 25, with neither microvascular nor epicardial spasm).6

Any complications occurring during the invasive diagnostic work-up were documented, including bradyarrhythmias, atrial fibrillation, ventricular tachycardia or fibrillation, coronary perforations, death from any cause, and any other complications.

NOCA program: pharmacological and psychological therapeutic approach

Once the endotype was identified, medical treatment for each patient was optimized accordingly (table 1). In patients with MVA, treatment with beta-blockers and calcium channel blockers (CCBs) was started or up-titrated. Ranolazine was added if angina symptoms were not fully controlled by beta-blockers and CCBs. In patients with VSA, treatment with nondihydropyridine CCBs and long-acting nitrates was started or up-titrated. In patients with both MVA and VSA, treatment with nondihydropyridine CCBs or beta-blockers was started or up-titrated. In patients with noncoronary chest pain, vasoactive drugs were discontinued unless clinically indicated for other reasons. Additionally, treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and statins was started or up-titrated in all patients. If a patient showed intolerance or had contraindications to a specific medication (eg, asthma for beta-blockers, perimalleolar edema for CCBs, severe bradycardia for both beta-blockers and CCBs), the treatment was tailored and modified accordingly.

Table 1. Medical therapy according to the specific endotype of ANOCA/INOCA.

Pathogenic mechanism of MINOCA	Therapeutic implications
MVA	Beta-blockers (Nebivolol 2.5– 10 mg daily)
	CCBs (amlodipine 10 mg daily, or verapamil 240 mg daily, or diltiazem 90 mg twice daily)
	Ranolazine (375-750 mg twice daily)
VSA	Nondihydropyridine CCBs (verapamil 240 mg, or ciltiazem 90 mg twice daily)
VSA	Long-acting nitrates (isosorbide mononitrate 30 mg)
MVA and VSA	CCBs (verapamil or diltiazem) or beta-blockers
Noncoronary chest pain	Beta-blockers or dihydropyridine CCBs if clinically indicated (eg, hypertension)
	ACEi or ARB if clinically indicated
	Statins if clinically indicated

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ACEi, angiotensin-converting enzyme inhibitors; ANOCA, angina with no obstructed coronary arteries; ARB, angiotensin receptor blockers; CCBs, calcium channel blockers; INOCA, ischemia with no obstructed coronary arteries; MINOCA, myocardial infarction with non-obstructive coronary artery disease; MVA, microvascular angina; VSA, vasospastic angina.

Because stress is an important trigger factor for angina symptoms, all patients were also referred to a team of expert psychologists for psychological support.15

NOCA program: clinical outcome and quality of life evaluation

All patients were followed up at 1, 3, 6, and 12-months for treatment titration and assessment of clinical outcomes. At the time of coronary angiography (ie, baseline) and at the 3-month follow-up, all patients were administered the Seattle Angina Questionnaire (SAQ) and quality of life questionnaire (EuroQol-5D [EQ-5D]). The SAQ is a validated 19-item self-administered questionnaire that measures 5 dimensions of CAD: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception.16 The EQ-5D is a standardized, nondisease-specific questionnaire used to describe and evaluate patients' health status and was intended to complement other quality-of life measures.17 Figure 2 provides a visual representation of all the steps involved for patients included in the NOCA program.

Statistical analysis

Data distribution was assessed according to the Kolgormonov-Smirnov test. Continuous variables were compared using the unpaired Student t-test or the Mann– Whitney U test, as appropriate. The data are expressed as mean ± standard deviation (SD) or as median and interquartile range [IQR]. Categorical data are expressed as numbers and percentages and were evaluated using the chi-square test or Fisher exact test, as appropriate. A 2-sided P value < .05 was considered significant. All analyses were performed using SPSS version 21 (SPSS, United States).

RESULTS

Baseline characteristics of the study population

From January 2021 to December 2021, a total of 77 patients were screened at the NOCA clinic for inclusion in the NOCA program. Following the screening visit, 23 (29.9%) patients were excluded from the NOCA program: 12 due to atypical angina symptoms and 11 due to a clearly identifiable noncoronary cause. Consequently, 54 patients were included in the NOCA program (mean age 64.4 ± 9.4 years, 39 [63.9%] women). A total of 29 (53.7%) patients had INOCA and 25 (46.3%) had ANOCA. All clinical and angiographic characteristics of the study population are shown in table 1.

NOCA program: diagnosis of the specific endotype and complications

The results of the invasive functional assessment are presented in table 2. The mean IMR and CFR values were 21.2 ± 10.6 and 2.3 ± 1.4, respectively. MVA was diagnosed in 19 (35.2%) patients, VSA in 12 (22.2%), and both MVA and VSA in 18 (33.3%). Finally, 5 (9.3%) patients were diagnosed with noncoronary chest pain.

Table 2. Clinical and angiographic characteristics of patients included in the NOCA program.

Characteristics	Study population (n = 54)
Clinical characteristics
Age	64.4 ± 9.4
Female sex	39 (72.2)
Clinical presentation
ANOCA	25 (46.3)
INOCA	29 (53.7)
Diabetes mellitus	12 (22.2)
Hypertension	35 (64.8)
Dyslipidaemia	28 (51.9)
Former smokers	3 (5.7)
Current smoker	14 (25.9)
Familiar history of CV disease	5 (9.3)
Previous CV history
Prior MI	7 (13.0)
Prior PCI	8 (14.8)
Prior CABG	0 (0.0)
COPD	1 (1.9)
CKD (eGFR < 60 mL/min/m²)	4 (7.4)
Depression	15 (27.8)
Anxiety	19 (35.2)
Invasive functional evaluation
Vessel explored
LDA	48 (88.9)
LCx	3 (5.6)
RCA	3 (5.6)
IMR	21.2 ± 10.6
Increased IMR (≥ 25)	18 (33.3)
CFR	2.3 ± 1.4
Reduced CFR (< 2.5)	33 (61.1)
Increased IMR (≥ 25) and reduced CFR (< 2.5)	13 (24.1)
Diagnosis (endotype)
MVA	19 (35.2)
VSA	12 (22.2)
MVA and VSA	18 (33.3)
Noncoronary chest pain	5 (9.3)

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ANOCA, angina with no obstructed coronary arteries; CABG, coronary artery bypass graft surgery; CFR, coronary flow reserve; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; eGFR, estimated glomerular filtration rate; IMR, index of microcirculatory resistance; INOCA, ischemia with no obstructed coronary arteries; MI, myocardial infarction; MVA, microvascular angina; LAD, left anterior descending; LCx, left circumflex; PCI, percutaneous coronary intervention; RCA, right coronary artery; VSA, vasospastic angina. Values are expressed as No. (%), mean ± standard deviation or median [interquartile range].

Among INOCA patients, MVA was diagnosed in 11 (37.9%) patients, VSA in 7 (24.1%), both MVA and VSA in 8 (27.6%), and noncoronary chest pain in 3 (10.3%). Among ANOCA patients, MVA was diagnosed in 8 (32.0%) patients, VSA in 5 (20.0%), both MVA and VSA in 10 (40.0%), and noncoronary chest pain in 2 (8.0%). There were no statistically significant differences in the prevalence of any endotype between INOCA and ANOCA patients (all P > .05, figure 3).

Complications occurred in 3 (5.5%) patients during intracoronary ACh provocation testing: 2 (3.7%) patients had transient bradyarrhythmias and 1 (1.8%) patient had paroxysmal atrial fibrillation that spontaneously reverted to sinus rhythm.

NOCA program: treatment optimization according to the specific endotype

Inclusion in the NOCA program led to statistically significant changes in medications after diagnosis of the specific endotype. There was a significant increase in the use of beta-blockers (33.3% before vs 57.4% after, P = .008), nondihydropyridine CCBs (9.3% before vs 37.0% after, P < .001), and long-acting nitrates (46.3% before vs 63.0% after, P = .012). There were no statistically significant differences in any other medications before and after the invasive assessment (all P > .05, figure 4). All changes in medications according to the specific endotype of ANOCA/INOCA are shown in figure 5.

NOCA program: clinical outcome evaluation

At 3 months of follow-up, there was no statistically significant difference in the mean EQ-5D score compared with baseline (64.8 ± 18.1 at baseline vs 66.1 ± 17.1 at 3 months of follow-up, P = .302) (figure 6). However, there was a statistically significant improvement in the SAQ score in terms of physical limitations (59.7 ± 19.3 at baseline vs 66.2 ± 16.9 at 3 months of follow-up, P = .037), angina stability (57.1 ± 28.1 at baseline vs 75.8 ± 22.3 at 3 months of follow-up, P = .010), and disease perception (42.5 ± 13.9 at baseline vs 50.8 ± 16.3 at 3 months follow-up, P = .015). No statistically significant difference was found in angina frequency (74.3 ± 20.4 at baseline vs 80.7 ± 19.8 at 3 months of follow-up, P = .193) or treatment satisfaction (68.1 ± 12.6 at baseline vs 70.5 ± 12.5 at 3 months of follow-up, P = .950) (figure 7). No events were recorded at the 1-year follow-up.

DISCUSSION

The main results of our experience can be summarized as follows: a) the implementation of a specific diagnostic and therapeutic protocol (NOCA program) in patients with diagnosed with nonobstructive CAD is feasible and allowed a parsimonious use of medical resources; b) a comprehensive diagnostic work-up in INOCA and ANOCA patients is safe, with a low rate of mild and transient complications (5.5%); c) the inclusion of patients in the NOCA program led to significant changes in medications and a significant improvement in their angina symptoms at the 3-month follow-up with no adverse events at 1 year.

Although accumulating evidence has demonstrated that an approach consisting of a comprehensive diagnostic assessment and stratified medical therapy in INOCA and ANOCA is crucial to improve patients' prognosis, such an approach is far from routinely implemented in clinical practice.7,8 There are still concerns mainly related to the cost-benefit ratio, the associated prolonged procedural time, increased costs, and the risk of possible associated complications. Furthermore, in the most recent European Society of Cardiology guidelines, invasive coronary function testing is assigned a class IIa (“should be considered”) recommendation, while ACh provocation testing is supported by a class IIb recommendation (“may be considered”) to assess microvascular spasm and class IIa in patients under consideration for VSA.3 As a result, the management of these patients is commonly left to physicians' discretion or relies on the experience of each center. Consequently, diagnosis of a specific NOCA endotype is frequently missed, and medical therapy is not optimized. This, in turn, has a significant negative impact on patients' quality of life and clinical outcomes, as well as on health care costs, due to the need for repeat hospitalization or invasive procedures.18

In reporting our experience, we demonstrate that a specific diagnostic and therapeutic protocol (ie, the NOCA program) in patients with a previous diagnosis of nonobstructive CAD can be easily implemented in clinical practice. A key innovation of our study, compared with prior publications, is the creation and implementation of a specific protocol for the INOCA/ANOCA population. Additionally, our approach involves a screening visit with assessment by a team of expert cardiologists for patients with a suspected diagnosis of INOCA/ANOCA. This approach improves identification of such patients, and, in our experience, led to the exclusion of almost one third of patients (29.9%) due to atypical angina symptoms or no clearly identifiable coronary causes of chest pain. This is another novelty of our study that could be extremely relevant in the management of these patients. Indeed, the selection of patients to be included in the program may allow clinical resources to be directed to patients who are most likely to benefit, while avoiding repeat invasive procedures and related risks in patients with unclear indications. Additionally, the specialized counseling provided by cardiologists and nurses during the screening visit, together with psychological support, are likely to be vital components of the management of INOCA/ANOCA patients. Indeed, recent studies have demonstrated how psychological factors, such as chronic stress, anxiety, depression, and social stressors are involved in the pathogenesis of MVA and VSA.19-23 Mental stress has been demonstrated to determine CMD mainly through endothelium-dependent mechanisms and endothelial dysfunction.24 Similarly, by activating brain areas involved in regulation of neuroendocrine and autonomic nervous systems, mental stress can lead to hyperreactivity of vascular smooth muscle cells, autonomic nervous system dysfunction, oxidative stress, vascular inflammation, and endothelial dysfunction, resulting in an increased propensity to coronary vasospasm.25-27

Furthermore, in line with previous studies,28-30 our experience demonstrates that performing a comprehensive invasive diagnostic assessment for the diagnosis of the specific endotype in INOCA and ANOCA patients is safe and is associated with a low rate of mild and transient complications. For all these reasons, patients and clinicians should be reassured about the lack of serious complications and cardiologists should be strongly encouraged to implement a specific diagnostic and therapeutic program in these patients. Indeed, the availability of such a program for INOCA and ANOCA patients may have significant clinical and therapeutic implications, as, in our experience, it resulted in substantial changes in medications and a marked improvement at the 3-month follow-up of the SAQ questionnaire regarding physical limitations, angina frequency, and disease perception. The lower and nonsignificant improvement in the other parameters (eg, angina frequency and treatment satisfaction) could be attributed to the already high baseline values (74.5 ± 19.9 and 69.6 ± 11.9, respectively). Similarly, the absence of a significant improvement in the EQ-5D questionnaire at 3 months might be due to the short follow-up period or the fact that it is a nondisease-specific questionnaire designed to describe and assess patients' health status and is intended to complement other quality-of-life measures.31

Study limitations

Some limitations of this study should be acknowledged. First, this is a single-center study with a relatively small sample size and short follow-up. Second, we did not perform a cost-analysis and therefore we cannot speculate on the impact of the NOCA program on health care-related costs. Further studies in larger ANOCA and INOCA populations are warranted. Finally, the absence of a control group precluded a thorough assessment of the improvement in the quality of life among these patients.

CONCLUSIONS

Our experience demonstrates that a specific diagnostic and therapeutic protocol (NOCA program) can be easily and safely implemented in routine clinical practice. Such a protocol could ensure the best care for INOCA and ANOCA patients, as well as improve their quality of life and avoid inappropriate treatments and incomplete investigations. Future evidence from randomized clinical trials or recommendations from international clinical guidelines supporting the implementation of a specific protocol in these patients are strongly warranted.

ETHICAL CONSIDERATIONS

The study protocol complied with the Declaration of Helsinki and the study was approved by our Institutional Review Committee. All patients gave written informed consent to be included in this program and study. The clinical ethics committee gave their approval for a retrospective analysis of the data collected. In this work, the possible variables of sex and gender have been taken into account.

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

No artificial intelligence tools were used during the preparation of this work.

AUTHORS' CONTRIBUTIONS

R. Rinaldi, F. Spione, F.M. Verardi: data extraction and analysis and manuscript drafting; R. Rinaldi, F. Spione, S. Brugaletta: design and manuscript revision; P. Vidal Calés, V. Arévalos, R. Gabani, D. Cánovas, M. Gutiérrez, M. Pardo, R. Domínguez, L. Pintor, X. Torres, X. Freixa, A. Regueiro, O. Abdul-Jawad Altisent, M. Sabaté: manuscript revision. All authors have read and agreed to the published version of the manuscript.

WHAT IS KNOWN ABOUT THE TOPIC?

– Up to 60% to 70% of patients with angina and/or documented myocardial ischemia do not have angiographic evidence of obstructive coronary artery disease. This condition is defined as angina with no obstructed coronary arteries (ANOCA) or ischemia with no obstructed coronary arteries (INOCA) when associated with evidence of myocardial ischaemia. There are still concerns about the implementation in real practice of a systematic diagnostic and therapeutic approach in INOCA and ANOCA patients, potentially impacting outcomes and quality of life.

WHAT DOES THIS STUDY ADD?

– The implementation of a specific protocol (NOCA program) in patients with a diagnosis of nonobstructive CAD is feasible and allowed parsimonious use of medical resources. A comprehensive invasive diagnostic assessment in INOCA or ANOCA patients is safe and is associated with a low rate of mild and transient complications. The availability of a specific diagnostic and therapeutic program for INOCA and ANOCA patients may have important clinical and therapeutic implications, as, in our experience, it led to significant changes in medications and a notable improvement at 3 months of follow-up in the SAQ questionnaire regarding physical limitations, angina frequency, and perception of the disease.

AGRADECIMIENTOS

F. Spione ha recibido una beca de investigación dentro del programa de doctorado Cardiopath.

Footnotes

FUNDING: This study received no funding.

BIBLIOGRAFÍA

1.Roth GA, Mensah GA, Johnson CO, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019:Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76:2982-3021. [DOI] [PMC free article] [PubMed]; Roth GA, Mensah GA, Johnson CO, et al. Global Burden of Cardiovascular Diseases and Risk Factors 1990-2019:Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76:2982–3021. doi: 10.1016/j.jacc.2020.11.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010;362:886-895. [DOI] [PMC free article] [PubMed]; Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010;362:886–895. doi: 10.1056/NEJMoa0907272. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Neumann FJ, Sechtem U, Banning AP, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407-477. [DOI] [PubMed]; Neumann FJ, Sechtem U, Banning AP, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407–477. doi: 10.1093/eurheartj/ehz425. [DOI] [PubMed] [Google Scholar]
4.Jespersen L, Hvelplund A, Abildstrøm SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734-744. [DOI] [PubMed]; Jespersen L, Hvelplund A, Abildstrøm SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734–744. doi: 10.1093/eurheartj/ehr331. [DOI] [PubMed] [Google Scholar]
5.Taqueti VR, Solomon SD, Shah AM, et al. Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction. Eur Heart J. 2018;39:840-849. [DOI] [PMC free article] [PubMed]; Taqueti VR, Solomon SD, Shah AM, et al. Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction. Eur Heart J. 2018;39:840–849. doi: 10.1093/eurheartj/ehx721. [DOI] [PMC free article] [PubMed] [Google Scholar]
6.Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology &Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020;41:3504-3520. [DOI] [PMC free article] [PubMed]; Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology &Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020;41:3504–3520. doi: 10.1093/eurheartj/ehaa503. [DOI] [PMC free article] [PubMed] [Google Scholar]
7.Ford TJ, Stanley B, Good R, et al. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina:The CorMicA Trial. J Am Coll Cardiol. 2018;72:2841-2855. [DOI] [PubMed]; Ford TJ, Stanley B, Good R, et al. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina:The CorMicA Trial. J Am Coll Cardiol. 2018;72:2841–2855. doi: 10.1016/j.jacc.2018.09.006. [DOI] [PubMed] [Google Scholar]
8.Ford TJ, Stanley B, Sidik N, et al. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020;13:33-45. [DOI] [PMC free article] [PubMed]; Ford TJ, Stanley B, Sidik N, et al. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA) JACC Cardiovasc Interv. 2020;13:33–45. doi: 10.1016/j.jcin.2019.11.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
9.Candreva A, Gallinoro E, van 't Veer M, et al. Basics of Coronary Thermodilution. JACC Cardiovasc Interv. 2021;14:595-605. [DOI] [PubMed]; Candreva A, Gallinoro E, van't Veer M, et al. Basics of Coronary Thermodilution. JACC Cardiovasc Interv. 2021;14:595–605. doi: 10.1016/j.jcin.2020.12.037. [DOI] [PubMed] [Google Scholar]
10.Montone RA, Meucci MC, De Vita A, Lanza GA, Niccoli G. Coronary provocative tests in the catheterization laboratory:Pathophysiological bases, methodological considerations and clinical implications. Atherosclerosis. 2021;318:14-21. [DOI] [PubMed]; Montone RA, Meucci MC, De Vita A, Lanza GA, Niccoli G. Coronary provocative tests in the catheterization laboratory:Pathophysiological bases, methodological considerations and clinical implications. Atherosclerosis. 2021;318:14–21. doi: 10.1016/j.atherosclerosis.2020.12.008. [DOI] [PubMed] [Google Scholar]
11.Ford TJ, Ong P, Sechtem U, et al. Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease:Why, How, and When. JACC Cardiovasc Interv. 2020;13:1847-1864. [DOI] [PMC free article] [PubMed]; Ford TJ, Ong P, Sechtem U, et al. Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease:Why, How, and When. JACC Cardiovasc Interv. 2020;13:1847–1864. doi: 10.1016/j.jcin.2020.05.052. [DOI] [PMC free article] [PubMed] [Google Scholar]
12.Gutiérrez E, Gómez-Lara J, Escaned J, et al. Assessment of the endothelial function and spasm provocation test performed by intracoronary infusion of acetylcholine. Technical report from the ACI-SEC;REC Interv Cardiol. 2021;3:286-296.; Gutiérrez E, Gómez-Lara J, Escaned J, et al. Assessment of the endothelial function and spasm provocation test performed by intracoronary infusion of acetylcholine. Technical report from the ACI-SEC. REC Interv Cardiol. 2021;3:286–296. [Google Scholar]
13.Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565-2568. [DOI] [PubMed]; Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565–2568. doi: 10.1093/eurheartj/ehv351. [DOI] [PubMed] [Google Scholar]
14.Ong P, Camici PG, Beltrame JF, et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018;250:16-20. [DOI] [PubMed]; Ong P, Camici PG, Beltrame JF, et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018;250:16–20. doi: 10.1016/j.ijcard.2017.08.068. [DOI] [PubMed] [Google Scholar]
15.Jespersen L, Abildstrøm SZ, Hvelplund A, Prescott E. Persistent angina:highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clin Res Cardiol. 2013;102:571-581. [DOI] [PubMed]; Jespersen L, Abildstrøm SZ, Hvelplund A, Prescott E. Persistent angina:highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clin Res Cardiol. 2013;102:571–581. doi: 10.1007/s00392-013-0568-z. [DOI] [PubMed] [Google Scholar]
16.Chan PS, Jones PG, Arnold SA, Spertus JA. Development and validation of a short version of the Seattle angina questionnaire. Circ Cardiovasc Qual Outcomes. 2014;7:640-647. [DOI] [PMC free article] [PubMed]; Chan PS, Jones PG, Arnold SA, Spertus JA. Development and validation of a short version of the Seattle angina questionnaire. Circ Cardiovasc Qual Outcomes. 2014;7:640–647. doi: 10.1161/CIRCOUTCOMES.114.000967. [DOI] [PMC free article] [PubMed] [Google Scholar]
17.Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20:1727-1736. [DOI] [PMC free article] [PubMed]; Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) Qual Life Res. 2011;20:1727–1736. doi: 10.1007/s11136-011-9903-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
18.Jespersen L, Abildstrom SZ, Hvelplund A, et al. Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease:a registry-based cohort study. PLoS One. 2014;9:93170. [DOI] [PMC free article] [PubMed]; Jespersen L, Abildstrom SZ, Hvelplund A, et al. Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease:a registry-based cohort study. PLoS One. 2014;9:e93170. doi: 10.1371/journal.pone.0093170. [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Smaardijk VR, Lodder P, Kop WJ, van Gennep B, Maas AHEM, Mommersteeg PMC. Sex- and Gender-Stratified Risks of Psychological Factors for Incident Ischemic Heart Disease:Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019;8:010859. [DOI] [PMC free article] [PubMed]; Smaardijk VR, Lodder P, Kop WJ, van Gennep B, Maas AHEM, Mommersteeg PMC. Sex- and Gender-Stratified Risks of Psychological Factors for Incident Ischemic Heart Disease:Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019;8:e010859. doi: 10.1161/JAHA.118.010859. [DOI] [PMC free article] [PubMed] [Google Scholar]
20.Mehta PK, Hermel M, Nelson MD, et al. Mental stress peripheral vascular reactivity is elevated in women with coronary vascular dysfunction:Results from the NHLBI-sponsored Cardiac Autonomic Nervous System (CANS) study. Int J Cardiol. 2018;251:8-13. [DOI] [PMC free article] [PubMed]; Mehta PK, Hermel M, Nelson MD, et al. Mental stress peripheral vascular reactivity is elevated in women with coronary vascular dysfunction:Results from the NHLBI-sponsored Cardiac Autonomic Nervous System (CANS) study. Int J Cardiol. 2018;251:8–13. doi: 10.1016/j.ijcard.2017.10.061. [DOI] [PMC free article] [PubMed] [Google Scholar]
21.Konst RE, Elias-Smale SE, Lier A, Bode C, Maas AHEM. Different cardiovascular risk factors and psychosocial burden in symptomatic women with and without obstructive coronary artery disease. Eur J Prev Cardiol. 2019;26:657-659. [DOI] [PMC free article] [PubMed]; Konst RE, Elias-Smale SE, Lier A, Bode C, Maas AHEM. Different cardiovascular risk factors and psychosocial burden in symptomatic women with and without obstructive coronary artery disease. Eur J Prev Cardiol. 2019;26:657–659. doi: 10.1177/2047487318814298. [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Gomez MA, Merz NB, Eastwood JA, et al. Psychological stress, cardiac symptoms, and cardiovascular risk in women with suspected ischaemia but no obstructive coronary disease. Stress Health. 2020;36:264-273. [DOI] [PMC free article] [PubMed]; Gomez MA, Merz NB, Eastwood JA, et al. Psychological stress, cardiac symptoms, and cardiovascular risk in women with suspected ischaemia but no obstructive coronary disease. Stress Health. 2020;36:264–273. doi: 10.1002/smi.2928. [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Bekendam MT, Vermeltfoort IAC, Kop WJ, Widdershoven JW, Mommersteeg PMC. Psychological factors of suspect coronary microvascular dysfunction in patients undergoing SPECT imaging. J Nucl Cardiol. 2022;29:768-778. [DOI] [PMC free article] [PubMed]; Bekendam MT, Vermeltfoort IAC, Kop WJ, Widdershoven JW, Mommersteeg PMC. Psychological factors of suspect coronary microvascular dysfunction in patients undergoing SPECT imaging. J Nucl Cardiol. 2022;29:768–778. doi: 10.1007/s12350-020-02360-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
24.Hammadah M, Kim JH, Al Mheid I, et al. Coronary and Peripheral Vasomotor Responses to Mental Stress. J Am Heart Assoc. 2018;7:008532. [DOI] [PMC free article] [PubMed]; Hammadah M, Kim JH, Al Mheid I, et al. Coronary and Peripheral Vasomotor Responses to Mental Stress. J Am Heart Assoc. 2018;7:e008532. doi: 10.1161/JAHA.118.008532. [DOI] [PMC free article] [PubMed] [Google Scholar]
25.Shah A, Chen C, Campanella C, et al. Brain correlates of stress-induced peripheral vasoconstriction in patients with cardiovascular disease. Psychophysiology. 2019;56:13291. [DOI] [PMC free article] [PubMed]; Shah A, Chen C, Campanella C, et al. Brain correlates of stress-induced peripheral vasoconstriction in patients with cardiovascular disease. Psychophysiology. 2019;56:e13291. doi: 10.1111/psyp.13291. [DOI] [PMC free article] [PubMed] [Google Scholar]
26.Hung MY, Mao CT, Hung MJ, et al. Coronary Artery Spasm as Related to Anxiety and Depression:A Nationwide Population-Based Study. Psychosom Med. 2019;81:237-245. [DOI] [PubMed]; Hung MY, Mao CT, Hung MJ, et al. Coronary Artery Spasm as Related to Anxiety and Depression:A Nationwide Population-Based Study. Psychosom Med. 2019;81:237–245. doi: 10.1097/PSY.0000000000000666. [DOI] [PubMed] [Google Scholar]
27.Crea F, Montone RA, Rinaldi R. Pathophysiology of Coronary Microvascular Dysfunction. Circ J. 2022;86:1319-1328. [DOI] [PubMed]; Crea F, Montone RA, Rinaldi R. Pathophysiology of Coronary Microvascular Dysfunction. Circ J. 2022;86:1319–1328. doi: 10.1253/circj.CJ-21-0848. [DOI] [PubMed] [Google Scholar]
28.Probst S, Seitz A, Martínez Pereyra V, et al. Safety assessment and results of coronary spasm provocation testing in patients with myocardial infarction with unobstructed coronary arteries compared with patients with stable angina and unobstructed coronary arteries. Eur Heart J Acute Cardiovasc Care. 2020:2048872620932422. [DOI] [PubMed]; Probst S, Seitz A, Martínez Pereyra V, et al. Safety assessment and results of coronary spasm provocation testing in patients with myocardial infarction with unobstructed coronary arteries compared with patients with stable angina and unobstructed coronary arteries. Eur Heart J Acute Cardiovasc Care. 2020;2048:20932422. doi: 10.1177/2048872620932422. [DOI] [PubMed] [Google Scholar]
29.Montone RA, Rinaldi R, Del Buono MG, et al. Safety and prognostic relevance of acetylcholine testing in patients with stable myocardial ischaemia or myocardial infarction and nonobstructive coronary arteries. EuroIntervention 2022;18:666-676. [DOI] [PMC free article] [PubMed]; Montone RA, Rinaldi R, Del Buono MG, et al. Safety and prognostic relevance of acetylcholine testing in patients with stable myocardial ischaemia or myocardial infarction and nonobstructive coronary arteries. EuroIntervention. 2022;18:e666–e676. doi: 10.4244/EIJ-D-21-00971. [DOI] [PMC free article] [PubMed] [Google Scholar]
30.Rinaldi R, Salzillo C, CaffèA, Montone RA. Invasive Functional Coronary Assessment in Myocardial Ischemia with Non-Obstructive Coronary Arteries:from Pathophysiological Mechanisms to Clinical Implications. Rev Cardiovasc Med. 2022;23:371. [DOI] [PMC free article] [PubMed]; Rinaldi R, Salzillo C, Caffè A, Montone RA. Invasive Functional Coronary Assessment in Myocardial Ischemia with Non-Obstructive Coronary Arteries:from Pathophysiological Mechanisms to Clinical Implications. Rev Cardiovasc Med. 2022;23:371. doi: 10.31083/j.rcm2311371. [DOI] [PMC free article] [PubMed] [Google Scholar]
31.EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199-208. [DOI] [PubMed]; EuroQol--a new facility for the measurement of health-related quality of life Health Policy. 1990;16:199–208. doi: 10.1016/0168-8510(90)90421-9. [DOI] [PubMed] [Google Scholar]

REC Interv Cardiol. 2024 Jan 30;6(2):67–75. [Article in Spanish]

Angina o isquemia con arterias coronarias no obstruidas: un protocolo diagnóstico y terapéutico específico

Abreviaturas

ANOCA:: angina sin arterias coronarias obstructivas.
INOCA:: isquemia sin arterias coronarias obstructivas.

VÉASE CONTENIDO RELACIONADO:

https://doi.org/10.24875/RECIC.M23000435

INTRODUCCIÓN

La cardiopatía isquémica es la principal causa de discapacidad y mortalidad en todo el mundo y se caracteriza comúnmente por la presencia de enfermedad coronaria (EC) obstructiva (definida como cualquier estenosis de las coronarias ≥ 50% de diámetro)1. No obstante, entre el 60 y el 70% de los pacientes con angina y/o isquemia miocárdica documentada carecen de evidencias angiográficas de EC2. Esta enfermedad se define como un cuadro de angina sin arterias coronarias obstructivas (ANOCA) o isquemia sin arterias coronarias obstructivas (INOCA) cuando se asocia a evidencias de isquemia miocárdica3. Se debe mencionar que, comparado con individuos sanos, a pesar de la ausencia de EC, estos pacientes corren un mayor riesgo de sufrir eventos cardiovasculares en el futuro tales como síndrome coronario agudo, hospitalización por insuficiencia cardíaca, accidente cerebrovascular y múltiples intervenciones cardiovasculares4,5. En este sentido, un manejo adecuado en términos de diagnóstico y tratamiento es de suma importancia para mejorar el pronóstico y los resultados de los pacientes6. El estudio CorMicA (Coronary microvascular angina) demostró que una estrategia de pruebas invasivas adyuvantes para el tratamiento de trastornos de la función coronaria y una terapia médica estratificada pueden llegar a mejorar los resultados (reducir la gravedad de la angina y mejorar la calidad de vida)7,8. No obstante, la correcta implementación en la práctica del mundo real de un enfoque diagnóstico y terapéutico sistemático en pacientes con INOCA y ANOCA sigue siendo objeto de debate, al ser algo que podría afectar los resultados y la calidad de vida de los pacientes.

Se informa de nuestra experiencia en un único centro sobre la implementación en la práctica clínica de un protocolo de diagnóstico y tratamiento específico (programa NOCA [arterias coronarias no obstructivas]) en pacientes con INOCA y ANOCA.

MÉTODOS

Criterios de elegibilidad para el programa NOCA

Todos los pacientes consecutivos diagnosticados en nuestro hospital o en centros de referencia con angina o isquemia con EC no obstructiva según la coronariografía se derivaron a una clínica ambulatoria específica (la clínica NOCA del Hospital Clínic de Barcelona) para una visita de cribado. La EC no obstructiva se definió como la evidencia angiográfica de coronarias normales o ateroesclerosis difusa con estenosis < 50% o una reserva fraccional de flujo (RFF) > 0,80 con un porcentaje de estenosis del 50-70%. Durante la visita de cribado, un equipo de cardiólogos expertos confirmó la elegibilidad de los pacientes para el programa NOCA según los siguientes criterios: a) diagnóstico de ANOCA, definido como síntomas típicos de angina crónica estable (como dolor torácico secundario a esfuerzo físico o estrés emocional y aliviado con reposo o nitroglicerina); b) diagnóstico de INOCA, definido como la confirmación de isquemia miocárdica identificada mediante pruebas no invasiva con pruebas de esfuerzo farmacológicas o de esfuerzo tales como tomografía computarizada por emisión de fotón único, resonancia magnética cardiaca, electrocardiograma de esfuerzo o ecocardiografía3. Los criterios de exclusión fueron: a) síntomas atípicos de angina y b) causas no coronarias claramente identificables del dolor torácico (figura 1). El protocolo del estudio se adhirió a la Declaración de Helsinki y el estudio fue aprobado el comité de revisión de nuestro centro. Todos los pacientes dieron su consentimiento informado por escrito antes de ser incluidos tanto en el programa NOCA como en el estudio. El comité de ética clínica dio su aprobación para el análisis retrospectivo de los datos recopilados.

Programa NOCA: abordaje diagnóstico

Tras la inclusión de los pacientes en el programa NOCA, cardiólogos y enfermeras expertos dieron asesoramiento especializado. Se informó minuciosamente a todos los pacientes sobre su enfermedad, la importancia de alcanzar un diagnóstico específico y de implementar una terapia personalizada. Durante las sesiones de asesoramiento, se explicaron, en detalle, los beneficios previstos y los bajos riesgos asociados a una intervención invasiva para el estudio específico de la microcirculación coronaria y el vasoespasmo. Todos los pacientes dieron su consentimiento informado por escrito antes de someterse a la coronariografía y las pruebas de vasorreactividad coronaria mediante la infusión de acetilcolina (ACh).

Posteriormente, a todos los pacientes se les hizo una coronariografía programada con una evaluación diagnóstica integral consistente en: a) pruebas de la función coronaria para medir la reserva de flujo coronario (RFC) y el índice de resistencia microcirculatoria (IRM); b) pruebas de provocación intracoronaria con ACh para valorar la presencia de trastornos de la vasomoción coronaria tales como espasmo epicárdico o espasmo microvascular.

Las pruebas de la función coronaria se llevaron a cabo con una guía con sensor de presión y temperatura (guía PressureWire X y sistema cardiovascular Coroventis CoroFlow, Abbott Vascular, Estados Unidos) que se colocó en la descendente anterior (DA) (el vaso diana predefinido) reflejando su masa miocárdica subyacente y dominancia coronaria. Se indujo hiperemia en estado estable mediante la infusión de adenosina intravenosa (140 μg/kg/min). Ante la presencia de tortuosidad grave de la DA o evidencia de isquemia miocárdica en una región distinta del territorio de la DA, la guía se colocó en la coronaria derecha o en la circunfleja izquierda a criterio del operador. La RFC se calculó mediante termodilución, definida como el tiempo de tránsito medio en reposo dividido por el tiempo de tránsito medio en hiperemia (los valores anómalos de la RFC se definieron como ≤ 2,5). El IRM se calculó como el producto de la presión coronaria distal en hiperemia máxima multiplicado por el tiempo de tránsito medio en hiperemia (valores normales < 25)6,9.

Las pruebas de provocación intracoronaria con ACh se hicieron siguiendo un protocolo estandarizado con infusiones seriadas de ACh durante 20 segundos a concentraciones crecientes (2-20-100 μg en la descendente anterior a intervalos de 2-3 minutos entre cada inyección), con evaluación concomitante de los síntomas del paciente, documentación electrocardiográfica y escaneos angiográficos. Los pacientes a tratamiento con fármacos vasoactivos tales como bloqueadores de los canales de calcio y nitratos tuvieron un periodo de eliminación de, como mínimo, 48 horas antes de la prueba de provocación10,11,12. El espasmo coronario epicárdico se definió como una reproducción del dolor torácico y cambios isquémicos en el electrocardiograma asociados a un descenso del diámetro coronario ≥ 90% con respecto a los valores basales en cualquier segmento de la arteria coronaria epicárdica13. Se diagnosticó espasmo microvascular ante la presencia de cambios típicos en el segmento ST isquémico (desviación ≥ 1 mm) y angina en ausencia de constricción coronaria epicárdica (reducción de diámetro < 90%)14.

Después, se estratificó a los pacientes en 4 endotipos: a) angina microvascular (AMV) (evidencia de disfunción microvascular coronaria [DMC] definida como la presencia de valores anómalos en la RFC [< 2,5], IRM [≥ 25] o espasmos microvasculares); b) angina vasoespástica (AV) (RFC ≥ 2,5, IRM < 25 y espasmos epicárdicos); c) AMV y AV (evidencia de DMC y espasmos epicárdicos); y d) dolor torácico de origen no coronario (RFC ≥ 2,5 y IRM < 25, sin espasmos microvasculares ni epicárdicos)6.

Se documentaron todas las complicaciones sobrevenidas durante el trabajo de diagnóstico invasivo, incluidas bradiarritmias, fibrilaciones auriculares, taquicardias o fibrilaciones ventriculares, perforaciones coronarias, mortalidad por cualquier causa, así como cualquier otra complicación.

Programa NOCA: abordaje terapéutico farmacológico y psicológico

Una vez identificado el endotipo, el tratamiento médico de cada paciente se optimizó convenientemente (tabla 1). En pacientes con AMV, se inició tratamiento o aumentó la dosis de bloqueadores beta y bloqueadores de los canales de calcio (BCC). Se añadió ranolazina cuando los síntomas anginosos no podían controlarse completamente con bloqueadores beta y BCC. En pacientes con AV, se inició tratamiento o aumentó la dosis de BCC no dihidropiridínicos y nitratos de acción prolongada. En pacientes con AMV y AV, se inició tratamiento o aumentó la dosis de BCC no dihidropiridínicos o beta-bloqueadores. En pacientes con dolor torácico de origen no coronario, se suspendieron los fármacos vasoactivos salvo que estuvieran clínicamente indicados por otras razones. También se inició tratamiento o aumentó la dosis de inhibidores de la enzima convertidora de angiotensina/bloqueadores de los receptores de angiotensina y estatinas en todos los pacientes. Si un paciente mostraba intolerancia o tenía contraindicaciones para un fármaco determinado (como, por ejemplo, asma para los bloqueadores beta, edema perimaleolar para los BCC, bradicardia grave tanto para los bloqueadores beta como para los BCC), el tratamiento se adaptaba y modificaba en consecuencia.

Tabla 1. Tratamiento médico según el endotipo específico de ANOCA/INOCA.

Mecanismo patogénico del MINOCA	Implicaciones terapéuticas
AMV	Bloqueadores beta (Nebivolol 2.5-10 mg al día)
	BCC (amlodipino 10 mg/día o verapamilo 240 mg/día o diltiazem 90 mg 2 veces al día)
	Ranolazina (375-750 mg 2 veces al día)
AV	BCC no dihidropiridínicos (verapamilo 240 mg al día o diltiazem 90 mg 2 veces al día)
AV	Nitratos de acción prolongada (mononitrato de isosorbida 30 mg)
AMV y AV	BCC (verapamilo o diltiazem) o bloqueadores beta
Dolor torácico no coronario	Bloqueadores beta o BCC dihidropiridínicos con indicación clínica (por ejemplo, en caso de hipertensión)
	IECA o BRA con indicación clínica
	Estatinas con indicación clínica

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AMV: angina microvascular; ANOCA: angina sin arterias coronarias obstructivas; AV: angina vasoespástica; BCC: bloqueadores de los canales de calcio; BRA: bloqueadores de los receptores de angiotensina; IECA: inhibidor de la enzima de conversión de la angiotensina; INOCA: isquemia sin arterias coronarias obstructivas; MINOCA: infarto agudo de miocardio sin enfermedad coronaria ateroesclerótica obstructiva.

Como el estrés es un factor desencadenante importante para los síntomas anginosos, se derivó a todos los pacientes a un equipo de psicólogos expertos para recibir apoyo psicológico15.

Programa NOCA: valoración de los resultados clínicos y la calidad de vida

Todos los pacientes tuvieron un seguimiento de 1, 3, 6 y 12 meses para la titulación del tratamiento y valoración de los resultados clínicos. En la coronariografía basal y en el seguimiento de 3 meses se entregó a todos los pacientes los cuestionarios de angina de Seattle (SAQ) y de calidad de vida (EuroQol-5D [EQ-5D]). El primero es un cuestionario validado de 19 ítems autoadministrado que mide 5 dimensiones de la EC: limitación física, estabilidad de la angina, frecuencia de los episodios anginosos, satisfacción con el tratamiento y percepción de la enfermedad16. El segundo es un cuestionario estandarizado no específico de enfermedad que se emplea para describir y valorar el estado de salud de los pacientes y cuyo objetivo principal fue complementar otras mediciones de la calidad de vida17. La figura 2 nos ofrece una representación visual de todos los pasos dados en pacientes incluidos en el programa NOCA.

Análisis estadístico

La distribución de los datos se valoró con la prueba de Kolmogorov. Las variables continuas se compararon con la prueba t de Student no emparejada o la prueba U de Mann-Whitney, según corresponda. Los datos se expresan como media ± desviación estándar (DE) o como mediana e intervalo intercuartílico [RIQ]. Los datos categóricos se expresan como números y porcentajes y se evaluaron con la prueba de la X2 o la prueba exacta de Fisher, según corresponda. Se consideró significativo un valor de p bilateral < 0,05. Todos los análisis se realizaron con el paquete de software estadístico SPSS, versión 21 (SPSS, Estados Unidos).

RESULTADOS

Características basales de la población del estudio

Durante el periodo comprendido entre enero de 2021 y diciembre de 2021, se cribó a un total de 77 pacientes en la clínica NOCA para determinar su elegibilidad para el programa NOCA. Tras la selección inicial, se excluyó a 23 pacientes (29,9%), 12 de ellos por presentar síntomas anginosos atípicos y 11 por causas no coronarias claramente identificables. Finalmente, se incluyó a 54 pacientes en el programa NOCA, con una media de edad de 64,4 ± 9,4 años, 39 de los cuales eran mujeres (63,9%), de los cuales se diagnosticó a 29 (53,7%) de INOCA y a 25 (46,3%) de ANOCA. Las características clínicas y angiográficas de la población del estudio se muestran en la tabla 1.

Programa NOCA: diagnóstico del endotipo específico y complicaciones

Los resultados de la valoración funcional invasiva se muestran en la tabla 2. Los valores medios tanto del IRM como de la RFC fueron 21,2 ± 10,6 y 2,3 ± 1.4, respectivamente. Se diagnosticó de AMV a 19 pacientes (35,2%), a 12 (22,2%) de AV y a 18 de AMV y AV (33,3%). Finalmente, se diagnosticó a 5 pacientes (9,3%) de dolor torácico no coronario.

Tabla 2. Características clínicas y angiográficas de pacientes incluidos en el programa NOCA.

Características	Población del estudio (n = 54)
Características clínicas
Edad	64,4 ± 9,4
Sexo femenino	39 (72,2)
Presentación clínica
ANOCA	25 (46,3)
INOCA	29 (53,7)
Diabetes mellitus	12 (22,2)
Hipertensión	35 (64,8)
Dislipemia	28 (51,9)
Exfumadores	3 (5,7)
Fumadores en la actualidad	14 (25,9)
Antecedentes familiares de EC	5 (9,3)
Antecedentes de EC
IAM previo	7 (13,0)
ICP previa	8 (14,8)
CABG previa	0 (0,0)
EPOC	1 (1,9)
IRC (TFGe < 60 ml/min/m²)	4 (7,4)
Depresión	15 (27,8)
Ansiedad	19 (35,2)
Valoración funcional invasiva
Vasos explorados
DA	48 (88,9)
CXI	3 (5,6)
CD	3 (5,6)
IRM	21,2 ± 10,6
Valores elevados del IRM (≥ 25)	18 (33,3)
RFC	2,3 ± 1,4
Valores bajos de la RFC (< 2,5)	33 (61,1)
Valores elevados del IRM (≥ 25) y valores bajos de la RFC (< 2,5)	13 (24,1)
Diagnóstico (endotipo)
AMV	19 (35,2)
AV	12 (22,2)
AMV y AV	18 (33,3)
Dolor torácico no coronario	5 (9,3)

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AMV: angina microvascular; ANOCA: angina de arterias coronarias no obstructivas; AV: angina vasoespástica; CABG: cirugía de revascularización aortocoronaria; CD: coronaria derecha; CXI: circunfleja izquierda; DA: descendente anterior; EC: enfermedad cardiovascular; EPOC: enfermedad pulmonar obstructiva crónica; IAM: infarto agudo de miocardio; ICP: intervención coronaria percutánea; IRM: índice de resistencia microcirculatoria; INOCA: isquemia de arterias coronarias no obstructivas; IRC: insuficiencia renal crónica; RFC: reserva de flujo coronario; TFGe: tasa de filtración glomerular estimada. Los valores expresan nº (%), media ± desviación estándar o mediana [intervalo intercuartílico].

Entre los pacientes con INOCA, se diagnosticó AMV en 11 pacientes (37,9%), AV en 7 (24,1%), AMV y AV en 8 (27,6%) y dolor torácico no coronario en 3 (10,3%). Entre aquellos con ANOCA, se diagnosticó AMV en 8 pacientes (32,0%), AV en 5 (20,0%), AMV y AV en 10 (40,0%), y dolor torácico no coronario en 2 (8,0%). No hubo diferencias estadísticamente significativas en la prevalencia de ningún endotipo entre los pacientes con INOCA y ANOCA (todos los valores de p > 0,05, figura 3).

Hubo complicaciones en 3 pacientes (5,5%) durante la prueba de provocación intracoronaria con ACh: 2 pacientes (3,7%) experimentaron bradiarritmias transitorias y 1 paciente (1,8%) fibrila- ción auricular paroxística que revirtió espontáneamente al ritmo sinusal.

Programa NOCA: Optimización del tratamiento según el endotipo específico

La inclusión en el programa NOCA provocó cambios estadísticamente significativos en los fármacos tras el diagnóstico del endotipo específico. Aumentó significativamente el uso de bloqueadores beta (33,3 antes frente al 57,4% después; p = 0,008), BCC no dihidropiridínicos (9,3 antes frente al 37,0% después; p < 0,001) y nitratos de acción prolongada (46,3 antes frente al 63,0% después; p = 0,012). No hubo diferencias estadísticamente significativas en ningún otro fármaco antes ni después de la evaluación invasiva (todos los valores de p > 0,05; figura 4). Todos los cambios de fármacos adaptados al endotipo específico de ANOCA/INOCA se muestran en la figura 5.

Programa NOCA: valoración de los resultados clínicos

A los 3 meses de seguimiento, no se observó ninguna diferencia estadísticamente significativa en la puntuación media obtenida en el EQ-5D frente a los valores basales (64,8 ± 18,1 al principio frente a 66,1 ± 17,1 a los 3 meses de seguimiento; p = 0,302) (figura 6), No obstante, sí hubo una mejoría estadísticamente significativa en la puntuación obtenida en el SAQ en las limitaciones físicas (59,7 ± 19,3 al principio frente a 66,2 ± 16,9 a los 3 meses de seguimiento; p = 0,037), la estabilidad de la angina (57,1 ± 28,1 al principio frente a 75,8 ± 22,3 a los 3 meses de seguimiento; p = 0,010), así como en la percepción de la enfermedad (42,5 ± 13,9 al principio frente a 50,8 ± 16,3 a los 3 meses de seguimiento; p = 0,015), No se hallaron diferencias estadísticamente significativas en la frecuencia de los episodios anginosos (74,3 ± 20,4 al principio frente a 80,7 ± 19,8 a los 3 meses de seguimiento; p = 0,193) ni en la satisfacción con el tratamiento (68,1 ± 12,6 al principio frente a 70,5 ± 12,5 a los 3 meses de seguimiento; p = 0,950) (figura 7). Tampoco se registraron reacciones adversas tras 1 año de seguimiento.

DISCUSIÓN

Los principales resultados de nuestra experiencia se pueden resumir de la siguiente manera: a) la implementación de un protocolo diagnóstico y terapéutico específico (programa NOCA) en pacientes diagnosticados de EC no obstructiva es factible y permitió un uso eficiente de los recursos médicos; b) un estudio diagnóstico integral de pacientes con INOCA y ANOCA resulta seguro y tiene un índice bajo de complicaciones leves y transitorias (5,5%); c) la inclusión de pacientes en el programa NOCA provocó cambios significativos en los fármacos y mejoró notablemente los síntomas anginosos de los pacientes tras 3 meses de seguimiento, sin eventos adversos al cabo 1 año.

A pesar de que la evidencia acumulada ha venido a confirmar que un abordaje que englobe una valoración diagnóstica integral y una terapia médica estratificada en pacientes con INOCA y ANOCA se antoja esencial a la hora de mejorar el pronóstico de los pacientes, dicho abordaje todavía está lejos de poderse implementar de manera rutinaria en la práctica clínica7,8. Todavía preocupa la relación coste-beneficios, el mayor tiempo asociado la intervención, los mayores costes asociados y el riesgo de posibles complicaciones. Además, en las guías más recientes publicadas por la Sociedad Europea de Cardiología, las pruebas invasivas de la función coronaria han recibido una recomendación de clase IIa («debería considerarse»), cuando las pruebas de provocación con ACh vienen respaldadas por una recomendación de clase IIb («puede considerarse») para la valoración del espasmo microvascular y una recomendación de clase IIa en pacientes con AV3. Como resultado, el tratamiento de estos pacientes suele dejarse a criterio médico o a la experiencia de cada centro. Como consecuencia, el diagnóstico de un endotipo NOCA específico se suele pasar por alto y el tratamiento médico no se suele optimizar, lo que a su vez, influye muy negativamente tanto en la calidad de vida y los resultados clínicos de los pacientes como en el gasto médico por la necesidad de nuevas hospitalizaciones o intervenciones invasivas18.

Al participar nuestra propia experiencia, demostramos que un protocolo diagnóstico y terapéutico específico (es decir, el programa NOCA) en pacientes con un diagnóstico previo de EC no obstructiva se puede implementar fácilmente en la práctica clínica. Una innovación clave de nuestro estudio frente a publicaciones previas, es la creación e implementación de un protocolo específico para la población de INOCA/ANOCA. Además, nuestro enfoque incorpora visitas de cribado a equipos de cardiólogos expertos para pacientes con sospecha diagnóstica de INOCA/ANOCA. Este enfoque mejora la identificación de estos pacientes y, según nuestra experiencia, excluyó a casi un tercio de los pacientes (29,9%) por la presencia de síntomas anginosos atípicos o causas no coronarias claramente identificables de dolor torácico. Esta es otra novedad de nuestro estudio que podría ser sumamente relevante para el manejo de estos pacientes. La selección de pacientes para incluir en el programa permitiría dirigir los recursos clínicos a aquellos pacientes más propensos a beneficiarse evitando, así, tener que repetir intervenciones invasivas y riesgos de pacientes con indicaciones poco claras. Además, el asesoramiento especializado proporcionado por cardiólogos y enfermeras durante las visitas de cribado, sumado al apoyo psicológico, probablemente sean un componente vital en el abordaje y tratamiento de pacientes con INOCA/ANOCA. De hecho, estudios recientes han demostrado que factores psicológicos tales como el estrés crónico, la ansiedad, la depresión y los factores de estrés social están implicados en la patogénesis tanto de la AMV como de la AV19-23. El estrés mental ha demostrado ser determinante, sobre todo en la DMC a través de mecanismos dependientes del endotelio y de la disfunción endotelial24. Asimismo, al activar áreas del cerebro implicadas en la regulación de los sistemas neuroendocrino y nervioso autónomo, el estrés mental puede provocar hiperreactividad de las células musculares lisas vasculares, disfunción del sistema nervioso autónomo, estrés oxidativo, inflamación vascular y disfunción endotelial, todo ello conducente a una mayor propensión a sufrir vasoespasmos coronarios25-27.

Coincidiendo con lo descrito en otros estudios publicados28-30, nuestra experiencia demuestra que una valoración diagnóstica invasiva integral encaminada a diagnosticar endotipos específicos en pacientes con INOCA y ANOCA es segura y tiene un índice bajo de complicaciones leves y transitorias. Por tanto, médicos y pacientes deben estar tranquilos ante la ausencia de complicaciones graves y se debe alentar a los cardiólogos a implementar programas de diagnóstico y tratamiento específico de estos pacientes. La disponibilidad de dicho programa para pacientes con INOCA y ANOCA puede tener importantes implicaciones clínicas y terapéuticas, ya que, según nuestra experiencia, provocó cambios sustanciales en los fármacos y mejoras significativas en el cuestionario SAQ a los 3 meses en lo referente a las limitaciones físicas, frecuencia de los episodios anginosos y percepción de la enfermedad. Las mejoras más leves y menos significativas descritas en otros parámetros (por ejemplo, frecuencia de los episodios anginosos y satisfacción con el tratamiento) serían atribuibles a valores de referencia altos per se (74,5 ± 19,9 y 69,6 ± 11,9, respectivamente). Asimismo, la falta de mejoras significativas en el cuestionario EQ-5D a los 3 meses podría deberse al corto periodo de seguimiento o que es un cuestionario no específico de la enfermedad diseñado para describir y evaluar el estado de salud de los pacientes que se ha de complementar con otras mediciones de la calidad de vida31.

Limitaciones del estudio

Se deben reconocer algunas limitaciones propias de este estudio. En primer lugar, se trata de un estudio unicéntrico con un tamaño de muestra relativamente pequeño y un seguimiento corto. En segundo lugar, como no se realizó un análisis de costes, no se puede especular sobre el impacto que tuvo el programa NOCA en los costes de la atención sanitaria. Se necesitan más estudios en poblaciones más grandes con ANOCA e INOCA. Finalmente, la ausencia de un grupo de control impidió una valoración integral de la mejora en la calidad de vida de estos pacientes.

CONCLUSIONES

Nuestra experiencia viene a demostrar que un protocolo diagnóstico y terapéutico específico (programa NOCA) puede implementarse de manera fácil y segura en la práctica clínica habitual. Dicho protocolo garantizaría mejores cuidados para pacientes con INOCA y ANOCA, mejoras en la calidad de vida y evitar tratamientos inadecuados e investigaciones incompletas. Es imprescindible disponer de nuevas evidencias de futuros ensayos clínicos aleatorizados o de recomendaciones procedentes de guías clínicas internacionales que respalden la implementación de un protocolo específico en estos pacientes.

CONSIDERACIONES ÉTICAS

El protocolo del estudio se realizó de conformidad con lo dispuesto en la Declaración de Helsinki y el estudio fue aprobado por nuestro Comité de Revisión Institucional. Todos los pacientes dieron su consentimiento informado por escrito antes de ser incluidos en este programa y estudio. El comité de ética clínica dio su aprobación para un análisis retrospectivo de los datos recopilados. En este trabajo, se han tenido en cuenta las posibles variables de sexo y género.

DECLARACIÓN SOBRE EL USO DE INTELIGENCIA ARTIFICIAL

No se utilizaron herramientas de inteligencia artificial durante la preparación de este trabajo.

CONTRIBUCIÓN DE LOS AUTORES

R. Rinaldi, F. Spione y F.M. Verardi: extracción y análisis de datos y redacción del manuscrito; R. Rinaldi, F. Spione y S. Brugaletta: diseño y revisión del manuscrito; P. Vidal Calés, V. Arévalos, R. Gabani, D. Cánovas, M. Gutiérrez, M. Pardo, R. Domínguez, L. Pintor, X. Torres, X. Freixa, A. Regueiro, O. Abdul-Jawad Altisent y M. Sabaté: revisión del manuscrito. Todos los autores han leído y aceptado la versión publicada del manuscrito.

¿QUÉ SE SABE DEL TEMA?

– Entre el 60 y 70% de los pacientes con angina y/o evidencia documentada de isquemia miocárdica no presentan evidencias angiográficas de enfermedad coronaria obstructiva. Esta patologÍa se define como un cuadro de angina sin arterias coronarias obstructivas (ANOCA) o isquemia sin arterias coronarias obstructivas (INOCA) ante posibles evidencias de isquemia miocárdica. Sigue preocupando la implementación en la práctica clínica real de un abordaje diagnóstico y terapéutico sistemático en pacientes con INOCA y ANOCA que pudiese influir tanto en los resultados como en la calidad de vida de los pacientes.

¿QUÉ APORTA DE NUEVO?

– La implementación de un protocolo específico (programa NOCA) en pacientes diagnosticados de EC no obstructiva es factible y permitió un uso eficiente de los recursos médicos. La valoración diagnóstica invasiva integral en pacientes con INOCA o ANOCA resulta segura y se asocia a un índice bajo de complicaciones leves y transitorias. La disponibilidad de un programa diagnóstico y terapéutico específico para pacientes con INOCA y ANOCA podría tener importantes implicaciones clínicas y terapéuticas, ya que, según nuestra experiencia, condujo a cambios farmacológicos significativos y a una notable mejoría tras 3 meses de seguimiento en el cuestionario SAQ en lo referente a las limitaciones físicas, la frecuencia de los episodios anginosos y la percepción de la enfermedad.

ACKNOWLEDGMENTS

F. Spione has been supported by a research grant provided by the Cardiopath PhD program.

Footnotes

FINANCIACIÓN: Ninguna.

[B1] 1.Roth GA, Mensah GA, Johnson CO, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019:Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76:2982-3021. [DOI] [PMC free article] [PubMed]; Roth GA, Mensah GA, Johnson CO, et al. Global Burden of Cardiovascular Diseases and Risk Factors 1990-2019:Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76:2982–3021. doi: 10.1016/j.jacc.2020.11.010. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B2] 2.Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010;362:886-895. [DOI] [PMC free article] [PubMed]; Patel MR, Peterson ED, Dai D, et al. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010;362:886–895. doi: 10.1056/NEJMoa0907272. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B3] 3.Neumann FJ, Sechtem U, Banning AP, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407-477. [DOI] [PubMed]; Neumann FJ, Sechtem U, Banning AP, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J. 2020;41:407–477. doi: 10.1093/eurheartj/ehz425. [DOI] [PubMed] [Google Scholar]

[B4] 4.Jespersen L, Hvelplund A, Abildstrøm SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734-744. [DOI] [PubMed]; Jespersen L, Hvelplund A, Abildstrøm SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734–744. doi: 10.1093/eurheartj/ehr331. [DOI] [PubMed] [Google Scholar]

[B5] 5.Taqueti VR, Solomon SD, Shah AM, et al. Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction. Eur Heart J. 2018;39:840-849. [DOI] [PMC free article] [PubMed]; Taqueti VR, Solomon SD, Shah AM, et al. Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction. Eur Heart J. 2018;39:840–849. doi: 10.1093/eurheartj/ehx721. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B6] 6.Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology &Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020;41:3504-3520. [DOI] [PMC free article] [PubMed]; Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology &Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J. 2020;41:3504–3520. doi: 10.1093/eurheartj/ehaa503. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B7] 7.Ford TJ, Stanley B, Good R, et al. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina:The CorMicA Trial. J Am Coll Cardiol. 2018;72:2841-2855. [DOI] [PubMed]; Ford TJ, Stanley B, Good R, et al. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina:The CorMicA Trial. J Am Coll Cardiol. 2018;72:2841–2855. doi: 10.1016/j.jacc.2018.09.006. [DOI] [PubMed] [Google Scholar]

[B8] 8.Ford TJ, Stanley B, Sidik N, et al. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA). JACC Cardiovasc Interv. 2020;13:33-45. [DOI] [PMC free article] [PubMed]; Ford TJ, Stanley B, Sidik N, et al. 1-Year Outcomes of Angina Management Guided by Invasive Coronary Function Testing (CorMicA) JACC Cardiovasc Interv. 2020;13:33–45. doi: 10.1016/j.jcin.2019.11.001. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B9] 9.Candreva A, Gallinoro E, van 't Veer M, et al. Basics of Coronary Thermodilution. JACC Cardiovasc Interv. 2021;14:595-605. [DOI] [PubMed]; Candreva A, Gallinoro E, van't Veer M, et al. Basics of Coronary Thermodilution. JACC Cardiovasc Interv. 2021;14:595–605. doi: 10.1016/j.jcin.2020.12.037. [DOI] [PubMed] [Google Scholar]

[B10] 10.Montone RA, Meucci MC, De Vita A, Lanza GA, Niccoli G. Coronary provocative tests in the catheterization laboratory:Pathophysiological bases, methodological considerations and clinical implications. Atherosclerosis. 2021;318:14-21. [DOI] [PubMed]; Montone RA, Meucci MC, De Vita A, Lanza GA, Niccoli G. Coronary provocative tests in the catheterization laboratory:Pathophysiological bases, methodological considerations and clinical implications. Atherosclerosis. 2021;318:14–21. doi: 10.1016/j.atherosclerosis.2020.12.008. [DOI] [PubMed] [Google Scholar]

[B11] 11.Ford TJ, Ong P, Sechtem U, et al. Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease:Why, How, and When. JACC Cardiovasc Interv. 2020;13:1847-1864. [DOI] [PMC free article] [PubMed]; Ford TJ, Ong P, Sechtem U, et al. Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease:Why, How, and When. JACC Cardiovasc Interv. 2020;13:1847–1864. doi: 10.1016/j.jcin.2020.05.052. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B12] 12.Gutiérrez E, Gómez-Lara J, Escaned J, et al. Assessment of the endothelial function and spasm provocation test performed by intracoronary infusion of acetylcholine. Technical report from the ACI-SEC;REC Interv Cardiol. 2021;3:286-296.; Gutiérrez E, Gómez-Lara J, Escaned J, et al. Assessment of the endothelial function and spasm provocation test performed by intracoronary infusion of acetylcholine. Technical report from the ACI-SEC. REC Interv Cardiol. 2021;3:286–296. [Google Scholar]

[B13] 13.Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565-2568. [DOI] [PubMed]; Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565–2568. doi: 10.1093/eurheartj/ehv351. [DOI] [PubMed] [Google Scholar]

[B14] 14.Ong P, Camici PG, Beltrame JF, et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018;250:16-20. [DOI] [PubMed]; Ong P, Camici PG, Beltrame JF, et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018;250:16–20. doi: 10.1016/j.ijcard.2017.08.068. [DOI] [PubMed] [Google Scholar]

[B15] 15.Jespersen L, Abildstrøm SZ, Hvelplund A, Prescott E. Persistent angina:highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clin Res Cardiol. 2013;102:571-581. [DOI] [PubMed]; Jespersen L, Abildstrøm SZ, Hvelplund A, Prescott E. Persistent angina:highly prevalent and associated with long-term anxiety, depression, low physical functioning, and quality of life in stable angina pectoris. Clin Res Cardiol. 2013;102:571–581. doi: 10.1007/s00392-013-0568-z. [DOI] [PubMed] [Google Scholar]

[B16] 16.Chan PS, Jones PG, Arnold SA, Spertus JA. Development and validation of a short version of the Seattle angina questionnaire. Circ Cardiovasc Qual Outcomes. 2014;7:640-647. [DOI] [PMC free article] [PubMed]; Chan PS, Jones PG, Arnold SA, Spertus JA. Development and validation of a short version of the Seattle angina questionnaire. Circ Cardiovasc Qual Outcomes. 2014;7:640–647. doi: 10.1161/CIRCOUTCOMES.114.000967. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B17] 17.Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20:1727-1736. [DOI] [PMC free article] [PubMed]; Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) Qual Life Res. 2011;20:1727–1736. doi: 10.1007/s11136-011-9903-x. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B18] 18.Jespersen L, Abildstrom SZ, Hvelplund A, et al. Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease:a registry-based cohort study. PLoS One. 2014;9:93170. [DOI] [PMC free article] [PubMed]; Jespersen L, Abildstrom SZ, Hvelplund A, et al. Burden of hospital admission and repeat angiography in angina pectoris patients with and without coronary artery disease:a registry-based cohort study. PLoS One. 2014;9:e93170. doi: 10.1371/journal.pone.0093170. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B19] 19.Smaardijk VR, Lodder P, Kop WJ, van Gennep B, Maas AHEM, Mommersteeg PMC. Sex- and Gender-Stratified Risks of Psychological Factors for Incident Ischemic Heart Disease:Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019;8:010859. [DOI] [PMC free article] [PubMed]; Smaardijk VR, Lodder P, Kop WJ, van Gennep B, Maas AHEM, Mommersteeg PMC. Sex- and Gender-Stratified Risks of Psychological Factors for Incident Ischemic Heart Disease:Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019;8:e010859. doi: 10.1161/JAHA.118.010859. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B20] 20.Mehta PK, Hermel M, Nelson MD, et al. Mental stress peripheral vascular reactivity is elevated in women with coronary vascular dysfunction:Results from the NHLBI-sponsored Cardiac Autonomic Nervous System (CANS) study. Int J Cardiol. 2018;251:8-13. [DOI] [PMC free article] [PubMed]; Mehta PK, Hermel M, Nelson MD, et al. Mental stress peripheral vascular reactivity is elevated in women with coronary vascular dysfunction:Results from the NHLBI-sponsored Cardiac Autonomic Nervous System (CANS) study. Int J Cardiol. 2018;251:8–13. doi: 10.1016/j.ijcard.2017.10.061. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B21] 21.Konst RE, Elias-Smale SE, Lier A, Bode C, Maas AHEM. Different cardiovascular risk factors and psychosocial burden in symptomatic women with and without obstructive coronary artery disease. Eur J Prev Cardiol. 2019;26:657-659. [DOI] [PMC free article] [PubMed]; Konst RE, Elias-Smale SE, Lier A, Bode C, Maas AHEM. Different cardiovascular risk factors and psychosocial burden in symptomatic women with and without obstructive coronary artery disease. Eur J Prev Cardiol. 2019;26:657–659. doi: 10.1177/2047487318814298. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B22] 22.Gomez MA, Merz NB, Eastwood JA, et al. Psychological stress, cardiac symptoms, and cardiovascular risk in women with suspected ischaemia but no obstructive coronary disease. Stress Health. 2020;36:264-273. [DOI] [PMC free article] [PubMed]; Gomez MA, Merz NB, Eastwood JA, et al. Psychological stress, cardiac symptoms, and cardiovascular risk in women with suspected ischaemia but no obstructive coronary disease. Stress Health. 2020;36:264–273. doi: 10.1002/smi.2928. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B23] 23.Bekendam MT, Vermeltfoort IAC, Kop WJ, Widdershoven JW, Mommersteeg PMC. Psychological factors of suspect coronary microvascular dysfunction in patients undergoing SPECT imaging. J Nucl Cardiol. 2022;29:768-778. [DOI] [PMC free article] [PubMed]; Bekendam MT, Vermeltfoort IAC, Kop WJ, Widdershoven JW, Mommersteeg PMC. Psychological factors of suspect coronary microvascular dysfunction in patients undergoing SPECT imaging. J Nucl Cardiol. 2022;29:768–778. doi: 10.1007/s12350-020-02360-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B24] 24.Hammadah M, Kim JH, Al Mheid I, et al. Coronary and Peripheral Vasomotor Responses to Mental Stress. J Am Heart Assoc. 2018;7:008532. [DOI] [PMC free article] [PubMed]; Hammadah M, Kim JH, Al Mheid I, et al. Coronary and Peripheral Vasomotor Responses to Mental Stress. J Am Heart Assoc. 2018;7:e008532. doi: 10.1161/JAHA.118.008532. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B25] 25.Shah A, Chen C, Campanella C, et al. Brain correlates of stress-induced peripheral vasoconstriction in patients with cardiovascular disease. Psychophysiology. 2019;56:13291. [DOI] [PMC free article] [PubMed]; Shah A, Chen C, Campanella C, et al. Brain correlates of stress-induced peripheral vasoconstriction in patients with cardiovascular disease. Psychophysiology. 2019;56:e13291. doi: 10.1111/psyp.13291. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B26] 26.Hung MY, Mao CT, Hung MJ, et al. Coronary Artery Spasm as Related to Anxiety and Depression:A Nationwide Population-Based Study. Psychosom Med. 2019;81:237-245. [DOI] [PubMed]; Hung MY, Mao CT, Hung MJ, et al. Coronary Artery Spasm as Related to Anxiety and Depression:A Nationwide Population-Based Study. Psychosom Med. 2019;81:237–245. doi: 10.1097/PSY.0000000000000666. [DOI] [PubMed] [Google Scholar]

[B27] 27.Crea F, Montone RA, Rinaldi R. Pathophysiology of Coronary Microvascular Dysfunction. Circ J. 2022;86:1319-1328. [DOI] [PubMed]; Crea F, Montone RA, Rinaldi R. Pathophysiology of Coronary Microvascular Dysfunction. Circ J. 2022;86:1319–1328. doi: 10.1253/circj.CJ-21-0848. [DOI] [PubMed] [Google Scholar]

[B28] 28.Probst S, Seitz A, Martínez Pereyra V, et al. Safety assessment and results of coronary spasm provocation testing in patients with myocardial infarction with unobstructed coronary arteries compared with patients with stable angina and unobstructed coronary arteries. Eur Heart J Acute Cardiovasc Care. 2020:2048872620932422. [DOI] [PubMed]; Probst S, Seitz A, Martínez Pereyra V, et al. Safety assessment and results of coronary spasm provocation testing in patients with myocardial infarction with unobstructed coronary arteries compared with patients with stable angina and unobstructed coronary arteries. Eur Heart J Acute Cardiovasc Care. 2020;2048:20932422. doi: 10.1177/2048872620932422. [DOI] [PubMed] [Google Scholar]

[B29] 29.Montone RA, Rinaldi R, Del Buono MG, et al. Safety and prognostic relevance of acetylcholine testing in patients with stable myocardial ischaemia or myocardial infarction and nonobstructive coronary arteries. EuroIntervention 2022;18:666-676. [DOI] [PMC free article] [PubMed]; Montone RA, Rinaldi R, Del Buono MG, et al. Safety and prognostic relevance of acetylcholine testing in patients with stable myocardial ischaemia or myocardial infarction and nonobstructive coronary arteries. EuroIntervention. 2022;18:e666–e676. doi: 10.4244/EIJ-D-21-00971. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B30] 30.Rinaldi R, Salzillo C, CaffèA, Montone RA. Invasive Functional Coronary Assessment in Myocardial Ischemia with Non-Obstructive Coronary Arteries:from Pathophysiological Mechanisms to Clinical Implications. Rev Cardiovasc Med. 2022;23:371. [DOI] [PMC free article] [PubMed]; Rinaldi R, Salzillo C, Caffè A, Montone RA. Invasive Functional Coronary Assessment in Myocardial Ischemia with Non-Obstructive Coronary Arteries:from Pathophysiological Mechanisms to Clinical Implications. Rev Cardiovasc Med. 2022;23:371. doi: 10.31083/j.rcm2311371. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B31] 31.EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199-208. [DOI] [PubMed]; EuroQol--a new facility for the measurement of health-related quality of life Health Policy. 1990;16:199–208. doi: 10.1016/0168-8510(90)90421-9. [DOI] [PubMed] [Google Scholar]

PERMALINK

Angina or ischemia with no obstructed coronary arteries: a specific diagnostic and therapeutic protocol

Riccardo Rinaldi

Francesco Spione

Filippo Maria Verardi

Pablo Vidal Calés

Víctor Arévalos

Rami Gabani

Daniel Cánovas

Montserrat Gutiérrez

Montserrat Pardo

Rosa Domínguez

Luis Pintor

Xavier Torres

Xavier Freixa

Ander Regueiro

Omar Abdul-Jawad Altisent

Manel Sabaté

Salvatore Brugaletta

ABSTRACT

Introduction and objectives:

Methods:

Results:

Conclusions:

RESUMEN

Introducción y objetivos:

Métodos:

Resultados:

Conclusiones:

Abbreviations

INTRODUCTION

METHODS

Eligibility criteria for the NOCA program

Figure 1. Central illustration. Flowchart for the inclusion of patients in the NOCA program. Cath lab, catheterization laboratory; INOCA: ischemia with no obstructed coronary arteries; NOCA, no obstructed coronary arteries; NOCAD, nonobstructive coronary artery disease.

NOCA program: diagnostic approach

NOCA program: pharmacological and psychological therapeutic approach

Table 1. Medical therapy according to the specific endotype of ANOCA/INOCA.

NOCA program: clinical outcome and quality of life evaluation

Figure 2. Visual representation of the NOCA program. EQ-5D, EuroQol-5D; NOCA, no obstructed coronary arteries; SAQ, Seattle Angina Questionnaire.

Statistical analysis

RESULTS

Baseline characteristics of the study population

NOCA program: diagnosis of the specific endotype and complications

Table 2. Clinical and angiographic characteristics of patients included in the NOCA program.

Figure 3. Prevalence of the different endotypes among INOCA and ANOCA patients. ANOCA, angina with no obstructed coronary arteries; INOCA, ischemia with no obstructed coronary arteries; MVA, microvascular angina; NCCP, noncoronary chest pain; VSA, vasospastic angina.

NOCA program: treatment optimization according to the specific endotype

NOCA program: clinical outcome evaluation

Figure 6. Differences in EuroQol-5D (EQ-5D) score at baseline and at 3 months of follow-up.

Figure 7. Differences in SAQ score at baseline and at 3 months of follow-up. AF, angina frequency; AS, angina stability; DP, disease perception; EQ-5D, EuroQol-5D; PL, physical limitations; SAQ, Seattle Angina Questionnaire; TS, treatment satisfaction.

DISCUSSION

Study limitations

CONCLUSIONS

ETHICAL CONSIDERATIONS

STATEMENT ON THE USE OF ARTIFICIAL INTELLIGENCE

AUTHORS' CONTRIBUTIONS

AGRADECIMIENTOS

Footnotes

BIBLIOGRAFÍA

Angina o isquemia con arterias coronarias no obstruidas: un protocolo diagnóstico y terapéutico específico

Abreviaturas

INTRODUCCIÓN

MÉTODOS

Criterios de elegibilidad para el programa NOCA

Figura 1. Figura central. Diagrama de flujo para la inclusión de pacientes en el programa NOCA. INOCA: isquemia sin arterias coronarias obstructivas; NOCA: arterias coronarias no obstructivas; ECNO: enfermedad coronaria no obstructiva; SH: sala de hemodinámica.

Programa NOCA: abordaje diagnóstico

Programa NOCA: abordaje terapéutico farmacológico y psicológico

Tabla 1. Tratamiento médico según el endotipo específico de ANOCA/INOCA.

Programa NOCA: valoración de los resultados clínicos y la calidad de vida

Figura 2. Representación visual del programa NOCA. EQ-5D: EuroQol-5D; NOCA: arterias coronarias no obstructivas; SAQ: cuestionario de angina de Seattle. * Consultar el texto para tener más información.

Análisis estadístico

RESULTADOS

Características basales de la población del estudio

Programa NOCA: diagnóstico del endotipo específico y complicaciones

Tabla 2. Características clínicas y angiográficas de pacientes incluidos en el programa NOCA.

Figura 3. Prevalencia de los diferentes endotipos entre pacientes con INOCA y ANOCA. AMV: angina microvascular; ANOCA: angina con arterias coronarias no obstructivas; AV: angina vasoespástica; DTNC: dolor torácico no coronario; INOCA: isquemia con arterias coronarias no obstructivas.

Programa NOCA: Optimización del tratamiento según el endotipo específico

Programa NOCA: valoración de los resultados clínicos

Figura 6. Diferencias en la puntuación obtenida en el cuestionario EuroQol-5D (EQ-5D) al principio y a los 3 meses de seguimiento.

DISCUSIÓN

Limitaciones del estudio