Primary Stable Microvascular Angina
2017; Lippincott Williams & Wilkins; Volume: 135; Issue: 20 Linguagem: Inglês
10.1161/circulationaha.117.027685
ISSN1524-4539
AutoresGaetano Antonio Lanza, Monica Filice, Antonio De Vita, Priscilla Lamendola, Angelo Villano, Francesco Spera, Michele Golino, Elisabetta Rota, Alessia Argirò, Filippo Crea,
Tópico(s)Takotsubo Cardiomyopathy and Associated Phenomena
ResumoHomeCirculationVol. 135, No. 20Primary Stable Microvascular Angina Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBPrimary Stable Microvascular AnginaA Long-Term Clinical Follow-Up Study Gaetano Antonio Lanza, MD, Monica Filice, MD, Antonio De Vita, MD, Priscilla Lamendola, MD, Angelo Villano, MD, Francesco Spera, MD, Michele Golino, MD, Elisabetta Rota, MD, Alessia Argirò, MD and Filippo Crea, MD Gaetano Antonio LanzaGaetano Antonio Lanza From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. , Monica FiliceMonica Filice From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. , Antonio De VitaAntonio De Vita From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. , Priscilla LamendolaPriscilla Lamendola From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. , Angelo VillanoAngelo Villano From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. , Francesco SperaFrancesco Spera From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. , Michele GolinoMichele Golino From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. , Elisabetta RotaElisabetta Rota From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. , Alessia ArgiròAlessia Argirò From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. and Filippo CreaFilippo Crea From Institute of Cardiology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy. Originally published16 May 2017https://doi.org/10.1161/CIRCULATIONAHA.117.027685Circulation. 2017;135:1982–1984Previous studies of patients with primary stable microvascular angina showed excellent prognosis despite frequent recurrence of symptoms.1,2 Recent large studies challenged this view, however, reporting a sizeable rate of major adverse cardiovascular events (MACE) in patients with stable angina and no obstructive coronary artery disease.3,4 To get further insight into this clinical controversy, we performed long-term follow-up of a rather large population of patients with microvascular angina.We included in this study all patients with primary stable microvascular angina who participated in clinical investigations performed at our institute between 1991 and 2011. All patients had exercise-induced angina, positive exercise stress test, angiographically normal coronary arteries, and no other relevant cardiac or systemic disease.5 In suspected cases, coronary spasm was excluded by ergonovine test.Patients were carefully characterized for cardiovascular risk factors and symptoms. All patients gave their informed consent to participate in the study, which was approved by our institutional review board.Follow-up was done by clinical visits or structured telephone interview. In the case of death, its cause was established from interview of patient's relatives and, when necessary, clinical records and death certificates.Clinical events included total, cardiovascular, and cardiac death, nonfatal acute myocardial infarction or unstable angina, coronary revascularization, other major cardiovascular events (stroke, transient ischemic attack, pulmonary embolism, etc), emergency room access, hospital admission, and repeat coronary angiography. Finally, patients were asked to report whether their symptoms improved, remained unchanged, or worsened over time. Data were also analyzed to identify predictors of the following clinical end points: (1) total mortality, (2) MACE (cardiovascular death, acute myocardial infarction, coronary revascularization), (3) emergency room access for angina, and (4) lack of symptom improvement.The association of variables with end points was tested by univariable and multivariable Cox regression analysis. Variables showing 2-sided P<0.1 at univariable analysis were included in multivariable models. Data were analyzed with SPSS 21.0 (SPSS Italia). The multivariable association of variables with end points is reported as hazard ratio (HR) with 95% confidence interval (CI).Basal clinical data of patients and follow-up results are summarized in the Table. The population included 250 patients. Vital state was ascertained for 240 patients (96%). At a median follow-up of 16.0 years (interquartile interval, 12–21), total, cardiovascular, and coronary mortality were 10.8%, 3.75%, and 0.83%, respectively (annual rates, 0.68%, 0.23%, and 0.05%, respectively).Among 207 patients with appropriate data, MACE occurred in 17.9% (1.12% per year). Sixty-five of these patients (31.4%) underwent ≥1 new coronary angiograms, and obstructive stenoses were found in 11 patients (5.3%) who underwent coronary revascularization (percutaneous in 9, surgical in 1, both in 1).Full follow-up was obtained in 181 of 224 living patients (80.8%). Access to emergency room and rehospitalization for angina were reported by 56.9% and 37.6% of patients, respectively. Worsening of symptoms was reported by 12 patients (6.6%), whereas 127 (70.2%) reported reduction of angina episodes, with 30 (16.6%) reporting absence of any angina attack.Variables predictive of an individual end point at univariable analysis were also predictive of the end point at multivariable analysis. These variables included: (1) age (HR per 1-year increments, 1.14; CI, 1.08–1.20), smoking (HR, 2.95; CI, 1.09–8.00) and history of dyspnea (HR, 0.13; CI, 0.02–0.97) for total mortality; (2) age (HR, 1.08; CI, 1.03–1.12) and smoking (HR, 3.13; CI, 1.29–7.63) for MACE; (3) age (HR, 1.04; CI, 1.01–1.06) and dyspnea (HR, 1.55; CI, 1.04–2.31) for emergency room access; and (4) angina at rest (HR, 2.20; CI, 1.21–4.01) and dyspnea (HR, 1.87; CI, 1.07–3.24) for lack of symptom improvement.To the best of our knowledge, this work is the largest clinical study with the longest follow-up of patients with primary stable microvascular angina. Our data show an excellent long-term prognosis of these patients, with rates of fatal events in the range of very low risk (<1% per year) and lower than expected according to data of the Italian population (total and cardiac mortality rates in 2012 of 0.92% and 0.18%, respectively).Moreover, of 65 patients who repeated coronary angiography, only 11 (5.3% of patients with appropriate data) showed obstructive coronary artery disease, also suggesting a low rate of coronary atherosclerosis progression in these patients.Our data differ from recent studies that reported significant rates of MACE in angina patients with nonobstructive coronary artery disease.2,3 These studies, however, included heterogeneous populations, with patients possibly having subcritical coronary atherosclerosis, arrhythmias, and reduced left ventricular function.It is notable that at variance with previous findings,1,2 our data show that long-term symptomatic outcome can also be better than previously found because most patients reported reduction of angina episodes, and 17% reported no symptoms at all.Although only age and smoking were independently associated with hard events, a history of dyspnea was a predictor of symptom-related end points. Dyspnea, however, was also inversely related to death, suggesting that a closer medical observation and management of patients with this symptom might have contributed, at least in part, to their better clinical outcome.Table. Main Clinical Characteristics of Patients and Clinical Events at Follow-UpClinical Data at Enrollment (n=250) Age (y, mean±SD)55.5±9 Female sex, n (%)182 (72.8) Cardiovascular risk factors, n (%) Family history of coronary artery disease64 (25.6) Hypertension147 (58.8) Hypercholesterolemia122 (48.8) Obesity30 (12.0) Diabetes mellitus36 (14.4) Smoking22 (8.8) Associated symptoms, n (%) Rest angina42 (16.8) Dyspnea80 (32.0)Clinical events, n (%) Total deaths*26 (10.8) Cardiovascular deaths*9 (3.75) Major nonfatal cardiovascular events, n (%)† Acute myocardial infarction8 (3.9) Stroke/transient ischemic attack14 (6.8) Coronary revascularization11 (5.3) Major adverse cardiovascular events†37 (17.9) Coronary angiography†65 (31.4) Obstructive stenosis11 (5.3) Nonobstructive stenosis12 (5.8) Hospital referral for angina, n (%)§ Emergency room access103 (56.9) Hospital admission68 (37.6) Angina status, n (%)§ Improved127 (70.2) Unchanged42 (23.2) Worsened12 (6.6)*Data referred to 240 patients.†Data referred to 207 patients with appropriate data.§Data referred to 181 patients with full follow-up assessment.Gaetano Antonio Lanza, MDMonica Filice, MDAntonio De Vita, MDPriscilla Lamendola, MDAngelo Villano, MDFrancesco Spera, MDMichele Golino, MDElisabetta Rota, MDAlessia Argirò, MDFilippo Crea, MDDisclosuresNone.FootnotesCirculation is available at http://circ.ahajournals.org.Correspondence to: Gaetano A. Lanza, MD, Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168 Rome, Italy. E-mail [email protected]References1. Lamendola P, Lanza GA, Spinelli A, Sgueglia GA, Di Monaco A, Barone L, Sestito A, Crea F. Long-term prognosis of patients with cardiac syndrome X.Int J Cardiol. 2010; 140:197–199. doi: 10.1016/j.ijcard.2008.11.026.CrossrefMedlineGoogle Scholar2. Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA. Cardiac syndrome X: clinical characteristics and left ventricular function. Long-term follow-up study.J Am Coll Cardiol. 1995; 25:807–814. doi: 10.1016/0735-1097(94)00507-M.CrossrefMedlineGoogle Scholar3. Gulati M, Cooper-DeHoff RM, McClure C, Johnson BD, Shaw LJ, Handberg EM, Zineh I, Kelsey SF, Arnsdorf MF, Black HR, Pepine CJ, Merz CN. 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Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management.Circulation. 2010; 121:2317–2325. doi: 10.1161/CIRCULATIONAHA.109.900191.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By De Vita A, Pizzi C, Tritto I, Morrone D, Villano A, Bergamaschi L and Lanza G (2022) Clinical outcomes of patients with coronary microvascular dysfunction in absence of obstructive coronary atherosclerosis, Journal of Cardiovascular Medicine, 10.2459/JCM.0000000000001305, Publish Ahead of Print Masi S, Rizzoni D, Taddei S, Widmer R, Montezano A, Lüscher T, Schiffrin E, Touyz R, Paneni F, Lerman A, Lanza G and Virdis A (2020) Assessment and pathophysiology of microvascular disease: recent progress and clinical implications, European Heart Journal, 10.1093/eurheartj/ehaa857, 42:26, (2590-2604), Online publication date: 8-Jul-2021. Dzeshka M (2021) Coronary microvascular dysfunction–Exploring the hidden part of the iceberg, Trends in Cardiovascular Medicine, 10.1016/j.tcm.2021.08.013, Online publication date: 1-Aug-2021. Sucato V, Novo G, Saladino A, Rubino M, Caronna N, Luparelli M, D'Agostino A, Novo S, Evola S and Galassi A (2020) Ischemia in patients with no obstructive coronary artery disease: classification, diagnosis and treatment of coronary microvascular dysfunction, Coronary Artery Disease, 10.1097/MCA.0000000000000855, 31:5, (472-476), Online publication date: 1-Aug-2020. Sucato V, Novo G, Saladino A, Evola S and Galassi A Coronary microvascular dysfunction, Minerva Cardioangiologica, 10.23736/S0026-4725.20.05070-7, 68:2 Lanza G, Crea F and Kaski J (2019) Clinical outcomes in patients with primary stable microvascular angina: is the jury still out?, European Heart Journal - Quality of Care and Clinical Outcomes, 10.1093/ehjqcco/qcz029, 5:4, (283-291), Online publication date: 1-Oct-2019. Lanza G, Filice M, De Vita A, Villano A, Manfredonia L, Lamendola P and Crea F (2018) Microvascular Angina ― Long-Term Exercise Stress Test Follow-up ―, Circulation Journal, 10.1253/circj.CJ-17-0657, 82:4, (1070-1075), . Antonio Lanza G, Vita A and Kaski J (2018) 'Primary' Microvascular Angina: Clinical Characteristics, Pathogenesis and Management, Interventional Cardiology Review, 10.15420/icr.2018.15.2, 13:3, (108), . Gould K and Johnson N (2018) Coronary Physiology Beyond Coronary Flow Reserve in Microvascular Angina, Journal of the American College of Cardiology, 10.1016/j.jacc.2018.07.106, 72:21, (2642-2662), Online publication date: 1-Nov-2018. May 16, 2017Vol 135, Issue 20 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.117.027685PMID: 28507253 Originally publishedMay 16, 2017 Keywordsangina pectorisoutcomePDF download Advertisement SubjectsChronic Ischemic Heart DiseaseClinical StudiesMortality/SurvivalQuality and Outcomes
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