Registro internazionale prospettico per lo studio dei pazienti con angina microvascolare

Responsabili di progetto

Ornella Rimoldi, Hiroaki Shimokawa

Accordo

GIAPPONE - JSPS - Japan Society for the Promotion of Science

Bando

CNR-JSPS 2016-2017

Dipartimento

Scienze biomediche

Area tematica

Scienze biomediche

Stato del progetto

Nuovo

Proposta di ricerca

Up to 40% of patients undergoing diagnostic coronary angiography for typical chest pain had no significant stenosis 1. Estimates from the Women's Ischemia Syndrome Evaluation (WISE) database in the USA showed that there are at least 3~4 million patients in the USA alone who have signs and symptoms of ischemia despite no evidence of obstructive atherosclerosis2, 3. These symptoms are associated with poor quality of life, psychological distress and health-care costs that approximate those patients with obstructive coronary artery disease (CAD). The term of "microvascular angina (MVA)" was introduced for those patients who appeared to have heightened sensitivity of the coronary microcirculation to vasoconstrictor stimuli associated with an impaired microvascular vasodilator capacity4. In addition to the classic mechanisms atherosclerotic plaques and vasospasm that lead to myocardial ischemia, coronary microvascular dysfunction (CMD) including MVA has emerged as a third potential mechanism of myocardial ischemia as seen in patients with CAD or hypertrophic cardiomyopathy or those with severe acute ischemia such as Tako-tsubo syndrome. Novel more sensitive assessment of ischemia such as the estimate of the coronary flow reserve (CRF) have demonstrated that almost all patients with MVA and ECG alterations during stress test exhibit myocardial regional hypoperfusion and impaired CRF5.
At present, invasive coronary angiography (ICA) is widely considered the gold standard for the detection and characterization of ischemic heart disease in patient who are symptomatic. However, it is mainly focused on "anatomical" features of the disease, i.e. on the changes in coronary lumen caused by abnormalities in the wall of large epicardial coronary arteries, but not on its functional correlates. ICA does not allow the of study coronary microcirculatory function which is increasingly recognized as an independent determinant of impaired blood flow, disease progression and adverse prognosis and hence potential target of early treatment4. With a more fitting diagnostic algorithm the number of invasive coronary angiographies, the number of inappropriate revascularizations, and health costs due to inappropriate management could be reduced.
The long-term prognosis of these patients is still controversial, studies in women have reported adverse cardiovascular outcomes with non-obstructive CAD and MVA including cardiac death (53% sudden death) stroke and new onset heart failure2. There is urgent need for a precise diagnostic algorithm that may help to identify and treat these patients who appear to be at risk and are often misdiagnosed. Novel strategies should be based on non-invasive methods, should be cost-effective and ready for large scale clinical utilization in the next few years.
We intend to propose an international collaborative study aimed at building up a multi-ethnic database to elucidate the risk factors, clinical features, diagnostic methods, treatments and prognosis of patients with microvascular angina (MVA).
The registry which will involve patients with MVA is multinational, multicentre, observational , prospective, longitudinal cohort. The registration period will take 2 years with a FU of 5 years. Patients will undergo clinical assessment and receive standard of care treatment by the treating physician. Patients will not receive experimental intervention or medication.
In order to collect the patients' medical history ,clinical examination and instrumental data we will design an electronic case report form in agreement with the guidelines of the Japanese Coronary Spasm Association. Local Database for entering the data will be constructed, continuously updated and interfaced with Central Database in Japan.
Target population patients with angina and ischemic ECG changes without evidence of obstructive coronary stenosis > 50% of vessel lumen or documented episodes of spasm of the epicardial coronary arteries. Eligible subjects will be enrolled consecutively.
Data collection, performed by the investigators, will include the following variables:
Demography, cardiovascular risk factors. Disease characteristics: features of the anginal attack (rest, effort, diurnal variation, frequency, ECG changes, arrhythmias), reasons for diagnosis (spontaneous attack, provocation tests). Tests : ECG, 24 h Holter ECG recording, TT echocardiogram, SPECT, PET, cardiac MRI, echo Doppler CFR. Invasive coronary angiography . Blood tests. Current medications. Seattle angina questionnaire. Outcomes during index hospitalization.
Follow-up (Once a year telephone or outpatient clinic visits
Recording of Occurrence of cardiovascular events, symptom (presence or absence of attack), 24 h Holter ECG recording, blood tests, Seattle angina questionnaire (SAQ), change of Medications
Recording of adverse events: cardiovascular death, fatal AMI, hospitalization for heart failure, arrhythmia, stroke, unstable angina.
Data Analysis: Since the objectives of this registry are descriptive in nature, no formal hypothesis testing will be done. Continuous variables and percentages will be computed to describe the patient population. Medians (with quartiles) or means (with standard deviation) will be computed as appropriate. Categorical values will be compared by chi-square test and continuous variables will be compared by two-tailed Wilcoxon rank sum test. The event rates and corresponding 95% confidence intervals (CI) during follow up will be estimated. Additionally univariable Cox regression models will be assumed to test the association between the end points and baseline covariates. Multivariate models will identify independent predictive variables.
1 Patel et al NEJM 2010;362:886
2 Pepine et alJ Am Coll Cardiol 2010;55:2825
3 Gulati et al Arch Int Med 2009;169:843
4 Camici and Crea NEJM 2007;356:830
5 Camici, d'Amati and Rimoldi Nature Rev Cardiology 2015;12:48

Obiettivi della ricerca

To collect data by means of electronic case record forms. All variables assessed in the electronic case record form will be pre-defined, and will be collected directly from the patients, and/or from the medical records.
To assess the value of integrating clinical profiles and biomarkers with non-invasively defined anatomo-functional categories to select independent predictors of patient outcome.
To identify new reliable end-points for prevention and treatment.
To disseminate registry results to scientific community, patient organisations and public health authorities.
To provide guidance on the clinical efficacy of diagnostic tools, cost-effectiveness and readiness for large scale clinical utilization in the next few years.
To promote new prevention and treatment programs.

Ultimo aggiornamento: 29/04/2025