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BACKGROUND AND AIMS: Diabetes mellitus (DM) is a risk factor for left ventricle (LV) diastolic dysfunction. Aim of this study was to investigate whether endothelial and/or autonomic dysfunction are associated with LV diastolic dysfunction in DM patients. METHODS: We studied 84 non-insulin-dependent type 2 DM (T2DM) patients with no heart disease by assessing: 1) LV diastolic function by echocardiography; 2) peripheral vasodilator function, by measuring flow-mediated dilation (FMD) and nitrate-mediate dilation (NMD); 3) heart rate variability (HRV) on 24-h Holter electrocardiographic monitoring. RESULTS: Twenty-five patients (29.8%) had normal LV diastolic function, while 47 (55.9%) and 12 (14.3%) showed a mild and moderate/severe diastolic dysfunction, respectively. FMD in these 3 groups was 5.25 ± 2.0, 4.95 ± 1.6 and 4.43 ± 1.8% (p = 0.42), whereas NMD was 10.8 ± 2.3, 8.98 ± 3.0 and 8.82 ± 3.2%, respectively (p = 0.02). HRV variables did not differ among groups. However, the triangular index tended to be lower in patients with moderate/severe diastolic dysfunction (p = 0.09) and a significant correlation was found between the E/e' ratio and both the triangular index (r = -0.26; p = 0.022) and LF amplitude (r = -0.29; p = 0.011). CONCLUSIONS: In T2DM patients an impairment of endothelium-independent, but not endothelium-dependent, dilatation seems associated with LV diastolic dysfunction. The possible role of cardiac autonomic dysfunction in diastolic dysfunction deserves investigation in larger populations of patients.
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Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/complicações , Diástole/fisiologia , Endotélio , Ventrículos do Coração , Humanos , Função Ventricular EsquerdaRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular events, but risk stratification of asymptomatic T2DM patients remains a challenging issue. We conducted a pilot study to assess whether endothelial dysfunction might help identify, among asymptomatic T2DM patients, those at increased risk of cardiovascular events. METHODS: We studied 61 consecutive T2DM patients with no evidence of cardiovascular disease and no insulin therapy. Endothelial function was assessed by flow-mediated dilation (FMD) of the right brachial artery. The primary endpoint was a combination of major cardiovascular events (MACE: cardiovascular death, acute coronary events, coronary interventions, and acute cerebrovascular accidents). FMD was repeated at follow-up in 48 patients (79%). RESULTS: A total of 10 MACE (16.4%) occurred during a mean follow-up of 48 months, including three acute myocardial infarctions, five coronary revascularizations for stable angina, and two acute ischaemic strokes. FMD at enrolment was lower in patients with compared with patients without MACE (3.78 ± 0.97% vs 4.70 ± 1.33%, respectively; P = .04). No other clinical or laboratory variables (age, diabetes duration, glycated haemoglobin, cardiovascular risk factors, drug therapy, and nitrate-mediated dilation) were associated with MACE. FMD at follow-up was also lower in patients with (n = 10) compared with those without (n = 38) MACE (3.66 ± 1.29 vs 4.85 ± 1.92; P = .006). CONCLUSIONS: Our data suggest that assessment of FMD might be helpful to identify patients at increased risk of MACE among individuals with asymptomatic T2DM; accordingly, a large study is warranted to adequately define the clinical utility of FMD assessment in the management of T2DM patients.
Assuntos
Biomarcadores/análise , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/patologia , Glicemia/análise , Feminino , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: A sizeable proportion of patients with primary stable microvascular angina (MVA; exercise-induced angina, positive exercise stress test [EST], normal coronary arteries) have recurrent symptoms during follow-up. There have been no previous studies, however, on the long-term results of EST and their correlation with symptom outcome.MethodsâandâResults:Follow-up EST was performed in 71 MVA patients at an average of 16.2 years (range, 5-25 years) from the first EST. Angina status was assessed on weekly frequency of angina episodes and nitroglycerin consumption and by whether symptoms had worsened, improved, or remained unchanged over time. At follow-up EST, 41 patients (group 1) had exercise-induced ischemia, whereas 30 patients (group 2) had negative EST. Compared to group 2, group 1 patients more frequently had exercise-induced dyspnea, and had a greater maximum ST-segment depression and a lower coronary blood flow response to adenosine and cold pressor test, but group 2 patients had a more frequent history of rest angina. No differences between the 2 groups were found at follow-up in angina status or change in symptom status during follow-up. CONCLUSIONS: Electrocardiogram results improve significantly in a sizeable proportion of patients with MVA. Changes in EST results, however, were not associated with clinical outcome.
Assuntos
Teste de Esforço , Angina Microvascular/fisiopatologia , Adenosina/farmacologia , Adulto , Circulação Coronária/efeitos dos fármacos , Dispneia , Eletrocardiografia , Feminino , Seguimentos , Humanos , Isquemia , Masculino , Angina Microvascular/diagnóstico , Angina Microvascular/patologia , Pessoa de Meia-Idade , Nitroglicerina/uso terapêuticoRESUMO
BACKGROUND: Because approximately 10% of patients with no-ST-segment elevation acute coronary syndrome (NSTE-ACS) show no obstructive coronary artery disease (NOCAD) on angiography, we assessed the spectrum of diagnoses and the predictors of outcome of these patients. METHODSâANDâRESULTS: We studied 178 patients admitted to a coronary care unit with an initial diagnosis of NSTE-ACS, based on clinical, ECG and laboratory data, but found to have NOCAD. The final diagnosis in these patients was heterogeneous; true NSTE-ACS (ie, coronary thrombosis on an unstable plaque) was ascertained in 1 patient (0.6%), whereas diagnosis at discharge was microvascular NSTE-ACS in 56.2% of patients, variant angina in 10.1%, myocarditis in 8.9%, takotsubo disease in 7.9%, tachyarrhythmia-related chest pain in 6.7%, and non-cardiac pain in 9.6%. At 24.5-month follow-up, 21 deaths (11.8%) had occurred, 9 (5.1%) from cardiovascular causes, including 2 (1.12%) coronary deaths. By multivariable Cox analysis, age only predicted global (hazard ratio [HR] 1.07 [1.02-1.12]; P=0.006) and cardiovascular (HR 1.08 [1.01-1.16]; P=0.04) mortality; non-coronary vascular disease was the main predictor of cardiovascular death or readmission for cardiovascular disease (HR 3.28 [1.75-6.14]; P<0.001) and coronary death or readmission for angina (HR 3.20 [1.26-8.14]; P=0.014). CONCLUSIONS: Patients with an initial diagnosis of NSTE-ACS constitute a heterogeneous population with different final diagnoses. Patients have a rather high rate of fatal events, most of which, however, are not related to coronary causes. (Circ J 2016; 80: 1600-1606).
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Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/fisiopatologia , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/terapia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
AIM: Diabetes is a major driver of cardiovascular disease, but the underlying mechanisms remain elusive. Prolyl-isomerase Pin1 recognizes specific peptide bonds and modulates function of proteins altering cellular homoeostasis. The present study investigates Pin1 role in diabetes-induced vascular disease. METHODS AND RESULTS: In human aortic endothelial cells (HAECs) exposed to high glucose, up-regulation of Pin1-induced mitochondrial translocation of pro-oxidant adaptor p66(Shc) and subsequent organelle disruption. In this setting, Pin1 recognizes Ser-116 inhibitory phosphorylation of endothelial nitric oxide synthase (eNOS) leading to eNOS-caveolin-1 interaction and reduced NO availability. Pin1 also mediates hyperglycaemia-induced nuclear translocation of NF-κB p65, triggering VCAM-1, ICAM-1, and MCP-1 expression. Indeed, gene silencing of Pin1 in HAECs suppressed p66(Shc)-dependent ROS production, restored NO release and blunted NF-kB p65 nuclear translocation. Consistently, diabetic Pin1(-/-) mice were protected against mitochondrial oxidative stress, endothelial dysfunction, and vascular inflammation. Increased expression and activity of Pin1 were also found in peripheral blood monocytes isolated from diabetic patients when compared with age-matched healthy controls. Interestingly, enough, Pin1 up-regulation was associated with impaired flow-mediated dilation, increased urinary 8-iso-prostaglandin F2α and plasma levels of adhesion molecules. CONCLUSIONS: Pin1 drives diabetic vascular disease by causing mitochondrial oxidative stress, eNOS dysregulation as well as NF-kB-induced inflammation. These findings provide molecular insights for novel mechanism-based therapeutic strategies in patients with diabetes.
Assuntos
Angiopatias Diabéticas/prevenção & controle , Doenças Mitocondriais/prevenção & controle , Estresse Oxidativo/fisiologia , Peptidilprolil Isomerase/fisiologia , Análise de Variância , Animais , Aorta/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Quimiocina CCL2/metabolismo , Citocromos c/biossíntese , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Técnicas de Silenciamento de Genes , Glucose/farmacologia , Humanos , Hiperglicemia/fisiopatologia , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Peptidilprolil Isomerase de Interação com NIMA , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src , Regulação para Cima/fisiologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Vasculite/fisiopatologiaRESUMO
OBJECTIVES: To assess the effects of isosorbide-5-mononitrate (ISMN) in patients with microvascular angina (MVA). METHODS: We randomized 20 MVA patients, treated with a ß-blocker or a calcium antagonist, to 60 mg slow-release ISMN (halved to 30 mg if not tolerated) or placebo once a day for 4 weeks; the patients were then switched to the other treatment for another 4 weeks. Their clinical status was assessed with the Seattle Angina Questionnaire (SAQ) and the EuroQoL score for quality of life. The exercise stress test (EST), coronary blood flow (CBF) response to nitrate and the cold pressor test (CPT), brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) were also assessed. RESULTS: Nine patients (45%) did not complete the ISMN phase due to side effects; 2 patients refused a follow-up. Nine patients completed the study. The SAQ and EuroQoL scores were significantly better with ISMN than with placebo, although the differences were small. No differences were found between the treatments in the EST results, CBF response to nitroglycerin (p = 0.55) and the CPT (p = 0.54), FMD (p = 0.26) and NMD (p = 0.35). CONCLUSIONS: In this study, a high proportion of MVA patients showed an intolerance to ISMN; in those tolerating the drug, significant effects on their angina status were observed, but the benefit appeared to be modest and independent of effects on coronary microvascular function.
Assuntos
Dinitrato de Isossorbida/análogos & derivados , Angina Microvascular/tratamento farmacológico , Vasodilatadores/efeitos adversos , Vasodilatadores/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Artéria Braquial/diagnóstico por imagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Estudos Cross-Over , Método Duplo-Cego , Ecocardiografia Doppler , Teste de Esforço , Feminino , Humanos , Dinitrato de Isossorbida/efeitos adversos , Dinitrato de Isossorbida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Qualidade de VidaRESUMO
OBJECTIVES: In this study, we assessed whether any abnormalities in coronary microvascular and peripheral vasodilator functions are present in patients with variant angina (VA) caused by epicardial coronary artery spasm (CAS). METHODS: We studied 23 patients with VA (i.e. angina at rest, ST-segment elevation during angina attacks and documented occlusive CAS at angiography) and 18 matched healthy controls. Endothelium-dependent and -independent coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to adenosine and the cold pressor test (CPT) in the left anterior descending artery by transthoracic Doppler echocardiography. Systemic endothelium-dependent and -independent arterial dilator function was assessed by measuring brachial flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), respectively. RESULTS: In VA patients, CBF responses to both adenosine (1.71 ± 0.25 vs. 2.97 ± 0.80, p < 0.01) and CPT (1.68 ± 0.23 vs. 2.58 ± 0.60, p < 0.01) were reduced compared to controls. Brachial FMD was also lower (3.87 ± 2.06 vs. 8.51 ± 2.95%, p < 0.01), but NMD was higher (16.7 ± 1.8 vs. 11.9 ± 1.4%, p < 0.01) in patients compared to controls. Differences were independent of the presence of coronary atherosclerotic lesions at angiography. CONCLUSIONS: Our data show that patients with VA have a generalized vascular dysfunction that involves both peripheral artery vessels and coronary microcirculation.
Assuntos
Angina Pectoris Variante/fisiopatologia , Artéria Braquial/fisiopatologia , Circulação Coronária/fisiologia , Vasoespasmo Coronário/complicações , Microcirculação/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Idoso , Angina Pectoris Variante/etiologia , Estudos de Casos e Controles , Vasoespasmo Coronário/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vasodilatação/fisiologiaRESUMO
Background: Detection of myocardial bridge (MB) at angiography suggests it has a role in ischaemic-related symptoms in patients with angina without obstructive coronary artery disease. However, evidence that MB may cause myocardial ischaemia is limited. Methods: We studied 41 patients with MB of the left anterior descending coronary artery and otherwise normal coronary arteries. Fourteen patients with normal coronary arteries and without MB served as controls. All subjects underwent a maximal treadmill exercise stress test (EST) under ECG monitoring. Standard and speckle-tracking echocardiography were performed at baseline and immediately after peak EST. Results: EST duration and peak heart rate and systolic pressure were similar in the two groups. A positive EST (ST-segment depression .1 mm) was found in 18 patients in the MB group (43.9%) and none in the control group (p=0.001). No abnormalities in both left ventricle systolic and diastolic function were found between the two groups in the standard echocardiographic evaluation. Global and segmental (anterior, inferior) longitudinal strain (LS) did not differ at baseline between the groups. There was a small increase in global LS during EST in MB patients but not in the control group (p=0.01). Similar trends were found for regional LSs, with differences being significant for the medium (p=0.028) and apical (p=0.032) anterior segments. No differences in echocardiographic parameters and both global and segmental LSs were observed between MB patients with ischaemic ECG changes during EST versus those without. Conclusion: Our findings do not support the notion that MB results in significant degrees of myocardial ischaemia during maximal myocardial work.
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AIMS: A wide QRS with left bundle branch block pattern is usually required for cardiac resynchronization therapy (CRT) in patients with dilated cardiomyopathy. However, â¼30% of patients do not benefit from CRT. We evaluated whether a detailed analysis of QRS complex can improve prediction of CRT success. METHODS AND RESULTS: We studied 51 patients (67.3 + 9.5 years, 36 males) with classical indication to CRT. Twelve-lead electrocardiogram (ECG) (50 mm/s, 0.05 mV/mm) was obtained before and 3 months after CRT. The following ECG intervals were measured in leads V1 and V6: (i) total QRS duration; (ii) QRS onset-R wave peak; (iii) R wave peak-S wave peak (RS-V1 and RS-V6); (iv) S wave peak-QRS end; and (v) difference between QR in V6 and in V1. Patients were considered as responder when left ventricular ejection fraction (LVEF) increased by ≥5% and New York Heart Association class by ≥1 after 3 months of CRT. Of ECG intervals, only basal RS-V1 was longer in responders (n = 36) compared with non-responders (52.9 ± 11.8 vs. 44.0 ± 12.6 ms, P = 0.021). Among patients with RS-V1 ≥45 ms 83% responded to CRT vs. 33% of those with RS-V1 < 45 ms (P < 0.001). RS-V1 ≥ 45 ms was independently associated with response to CRT in multivariable analysis (odds ratio 9.8; P = 0.002). A reduction of RS-V1 ≥ 10 ms by CRT also significantly predicted clinical response. RS-V1 shortening correlated with improvement in LVEF (r = -0.45; P < 0.001) and in MS (r = 0.46; P < 0.001). CONCLUSION: Our data point out that RS-V1 interval and its changes with CRT may help to identify patients who are most likely to benefit from CRT.
Assuntos
Terapia de Ressincronização Cardíaca , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/terapia , Eletrocardiografia/métodos , Idoso , Bloqueio de Ramo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
OBJECTIVES: The aim of our study was to assess the prognostic value of heart rate variability (HRV) in ST-segment elevation acute myocardial infarction (STEMI) patients treated by percutaneous transluminal coronary angioplasty (PTCA) and optimal medical therapy. METHODS: We enrolled 182 consecutive patients with a first STEMI (59.1 ± 11 years; 82.4% men) treated by primary PTCA. HRV was assessed on 24-hour Holter ECG recordings before discharge and 1 and 6 months after discharge. The primary end point was the occurrence of major clinical events (MCE), defined as death or new acute myocardial infarction (AMI). RESULTS: At a follow-up of 42 ± 23 months, MCE occurred in 14 patients (7.6%; 3 deaths and 11 re-AMIs). HRV parameters before discharge were significantly lower in patients with MCE, with standard deviation of all RR intervals (SDNN) and very low frequency and low frequency (LF) amplitude being the most predictive variables. HRV assessed at follow-up instead did not significantly predict MCE. At multivariate analysis, only SDNN (HR 0.97; p = 0.02) and LF (HR 0.90; p = 0.04) remained significantly associated with MCE. Lower tertile SDNN and LF values were associated with a multivariate HR of 3.91 (p = 0.015) and of 2.92 (p = 0.048), respectively. Similar results were observed considering re-AMI only as the end point. CONCLUSIONS: In STEMI patients treated by PTCA, HRV assessed before discharge was an independent predictor of MCE and re-AMI.
Assuntos
Angioplastia Coronária com Balão , Frequência Cardíaca/fisiologia , Infarto do Miocárdio/fisiopatologia , Idoso , Intervalo Livre de Doença , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , PrognósticoRESUMO
PURPOSE: To assess the effects of short-acting nitrates on exercise stress test (EST) results and the relation between EST results and coronary blood flow (CBF) response to nitrates in patients with microvascular angina (MVA). METHODS: We completed 2 symptom/sign limited ESTs on 2 separate days, in a random sequence and in pharmacological washout, in 29 MVA patients and in 24 patients with obstructive coronary artery disease (CAD): one EST was performed without any intervention (control EST, C-EST), and the other after sublingual isosorbide dinitrate, 5 mg (nitrate EST, N-EST). CBF response to nitroglycerin (25 µg) was assessed in the left anterior descending coronary artery by transthoracic Doppler-echocardiography. RESULTS: At C-EST. ST-segment depression ≥1 mm (STD) was induced in 26 (90 %) and 23 (96 %) MVA and CAD patients, respectively (p=0.42), whereas at N-EST, STD was induced in 25 (86 %) and 14 (56 %) MVA and CAD patients, respectively (p=0.01). Time and rate pressure product at 1 mm STD increased during N-EST, compared to C-EST, in CAD patients (475±115 vs. 365±146 s, p<0.001; and 23511±4352 vs. 20583±6234 bpmâmmHg, respectively, p=0.01), but not in MVA patients (308±160 vs. 284±136 s; p=0.19; and 21290±5438 vs. 20818±4286 bpmâmmHg, respectively, p=0.35). In MVA patients, a significant correlation was found between heart rate at STD during N-EST and CBF response to nitroglycerin (r=0.40, p=0.04). CONCLUSIONS: Short-acting nitrates improve EST results in CAD, but not in MVA patients. In MVA patients a lower nitrate-dependent coronary microvascular dilation may contribute to the lack of effects of nitrates on EST results.
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Arteriopatias Oclusivas/diagnóstico , Teste de Esforço/efeitos dos fármacos , Dinitrato de Isossorbida/farmacologia , Angina Microvascular/diagnóstico , Vasodilatadores/farmacologia , Idoso , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/fisiopatologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Angiografia Coronária , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Estudos Cross-Over , Ecocardiografia Doppler , Feminino , Humanos , Dinitrato de Isossorbida/administração & dosagem , Masculino , Microcirculação/efeitos dos fármacos , Angina Microvascular/diagnóstico por imagem , Angina Microvascular/fisiopatologia , Pessoa de Meia-Idade , Vasodilatadores/administração & dosagemRESUMO
Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous group of clinical entities characterized by clinical evidence of acute myocardial infarction (AMI) with normal or near-normal coronary arteries on coronary angiography (stenosis < 50%) and without an over the alternative diagnosis for the acute presentation. Its prevalence ranges from 6% to 11% among all patients with AMI, with a predominance of young, nonwhite females with fewer traditional risks than those with an obstructive coronary artery disease (MI-CAD). MINOCA can be due to either epicardial causes such as rupture or fissuring of unstable nonobstructive atherosclerotic plaque, coronary artery spasm, spontaneous coronary dissection and cardioembolism in-situ or microvascular causes. Besides, also type-2 AMI due to supply-demand mismatch and Takotsubo syndrome must be considered as a possible MINOCA cause. Because of the complex etiology and a limited amount of evidence, there is still some confusion around the management and treatment of these patients. Therefore, the key focus of this condition is to identify the underlying individual mechanisms to achieve patient-specific treatments. Clinical history, electrocardiogram, echocardiography, and coronary angiography represent the first-level diagnostic investigations, but coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offer additional information to understand the underlying cause of MINOCA. Although the prognosis is slightly better compared with MI-CAD patients, MINOCA is not always benign and depends on the etiopathology. This review analyzes all possible pathophysiological mechanisms that could lead to MINOCA and provides the most specific and appropriate therapeutic approach in each scenario.
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Doença da Artéria Coronariana , Infarto do Miocárdio , Feminino , Humanos , MINOCA , Fatores de Risco , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Angiografia Coronária/efeitos adversos , Vasos Coronários/diagnóstico por imagemRESUMO
Up to 50% of patients presenting with stable, mainly exercise-induced, chest pain and 10-20% of those admitted to hospital with chest pain suggesting an acute coronary syndrome show normal or near-normal coronary arteries at angiography. Coronary microvascular dysfunction (CMD) is a major cause of symptoms in these patients. However, controversial data exist about their prognosis. In this article, we critically review characteristics and results of the main studies that assessed clinical outcome of patients with angina chest pain and nonobstructive coronary artery disease presenting with either a stable angina pattern or an acute coronary syndrome. Published data indicate that the patients included in most studies are heterogeneous and a major determinant of clinical outcome is the presence of atherosclerotic, albeit not obstructive, coronary artery disease. Long-term prognosis seems instead excellent in patients with totally normal coronary arteries and a syndrome of CMD-related stable angina (microvascular angina). On the other hand, the prognostic impact of CMD in patients presenting with an acute coronary syndrome needs to be better assessed in future studies.
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Síndrome Coronariana Aguda , Angina Estável , Doença da Artéria Coronariana , Isquemia Miocárdica , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/diagnóstico por imagem , Angina Estável/diagnóstico por imagem , Dor no Peito/etiologia , Doença da Artéria Coronariana/complicações , Humanos , Isquemia Miocárdica/complicaçõesRESUMO
A large number of studies has demonstrated that abnormalities of coronary microcirculation may be responsible for both acute and chronic cardiac ischemic syndromes. In clinical practice the microvascular origin of myocardial ischemia and angina is usually considered in patients who are found to have normal or near-normal coronary arteries at angiography. In this article, we review the diagnostic approach to patients with suspected coronary microvascular dysfunction as a cause of ischemic syndromes and also suggest a classification of chronic and acute microvascular coronary ischemic syndrome, including myocardial infarction with normal coronary arteries.
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Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Angina Microvascular , Isquemia Miocárdica , Síndrome Coronariana Aguda/etiologia , Dor no Peito , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária , Humanos , Microcirculação , Angina Microvascular/diagnóstico por imagem , Isquemia Miocárdica/complicaçõesRESUMO
BACKGROUND: Coronary microvascular dysfunction (CMD) may cause symptoms of myocardial ischemia (microvascular angina [MVA]), but recent studies suggested that it might also contribute to the syndrome of heart failure with preserved ejection fraction (HFpEF). In this study we assessed the relation of CMD with findings of HFpEF in MVA patients. METHODS: We enrolled 36 consecutive patients with MVA, in whom we assessed: 1) coronary blood flow (CBF) response to adenosine and cold pressor test (CPT) by color-Doppler echocardiography of the left anterior descending coronary artery; 2) complete echocardiographic examination; 3) N-terminal-pro-B-natriuretic peptide (NT-proBNP); 4) grade of dyspnea by the modified Medical Research Scale. RESULTS: Among patients, 15 had definite HFpEF findings (group 1), 12 had equivocal HFpEF findings (group 2) and 9 had no evidence of HFpEF findings (group 3). Group 1 patients were older, had more cardiovascular risk factors and higher NT-proBNP levels (P=0.018), and showed a higher prevalence of diastolic dysfunction. Left ventricle dimensions and systolic function, however, did not differ among groups. Dyspnea was also not significantly different among groups (P=0.19). CBF to adenosine was 1.85±0.47, 1.78±0.40 1.49±0.32 in group 1, 2 and 3, respectively (P=0.13). Similarly, CBF response to CPT was 1.57±0.4, 1.49±0.2 and 1.45±0.3 in the 3 groups, respectively (P=0.74). Both CBF response to adenosine and CPT showed no relation with the severity of dyspnea symptoms. CONCLUSIONS: Our data suggest that in patients with MVA there is no relation between the grade of impairment of coronary microvascular dilatation and findings of HFpEF.
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Insuficiência Cardíaca , Isquemia Miocárdica , Humanos , Insuficiência Cardíaca/complicações , Volume Sistólico , AdenosinaRESUMO
Both the latest European guidelines on chronic coronary syndromes and the American guidelines on chest pain have underlined the importance of noninvasive imaging to select patients to be referred to invasive angiography. Nevertheless, although coronary stenosis has long been considered the main determinant of inducible ischemia and symptoms, growing evidence has demonstrated the importance of other underlying mechanisms (e.g., vasospasm, microvascular disease, energetic inefficiency). The search for a pathophysiology-driven treatment of these patients has therefore emerged as an important objective of multimodality imaging, integrating "anatomical" and "functional" information. We here provide an up-to-date guide for the choice and the interpretation of the currently available noninvasive anatomical and/or functional tests, focusing on emerging techniques (e.g., coronary flow velocity reserve, stress-cardiac magnetic resonance, hybrid imaging, functional-coronary computed tomography angiography, etc.), which could provide deeper pathophysiological insights to refine diagnostic and therapeutic pathways in the next future.
Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Valor Preditivo dos Testes , SíndromeRESUMO
BACKGROUND AND AIMS: Previous studies showed that troponin blood levels may increase after exercise. In this study, we assessed whether, among patients with suspected of having stable angina, the increase in troponin I (TnI) levels after exercise stress test (EST) might help identify those with obstructive coronary artery disease (CAD) and myocardial ischemia. METHODS: We performed maximal treadmill EST in 50 patients (age 64â±â9 years; 38 men) admitted to our Cardiology Department to undergo elective coronary angiography because of a suspicion of stable angina. TnI was measured before and 12âh after EST. RESULTS: TnI increased after EST compared with baseline in the whole population (from 0.44â±â0.76 to 0.84â±â1.12âng/dl, Pâ<â0.001). No difference in TnI increase was observed between patients with obstructive CAD (nâ=â29; 0.61â±â0.90-1.13â±â1.33âng/dl) and no obstructive CAD (NO-CAD; nâ=â21; 0.21â±â0.46-0.44â±â0.54âng/dl; Pâ=â0.51). There was also no significant difference in post-EST TnI increase between patients with positive EST (nâ=â34; 0.56â±â0.89-1.05â±â1.28âng/dl) or negative EST (nâ=â16; 0.19â±â0.26-0.39â±â0.43âng/dl; Pâ=â0.16). Moreover, no significant difference was observed in the post-EST TnI increase among groups of patients with positive EST and obstructive CAD, positive EST and NO-CAD, negative EST and obstructive CAD and negative EST and NO-CAD (Pâ=â0.12). No clinical or EST variable was associated with post-EST TnI increase, although there was a tendency for a greater increase in those achieving a heart rate more than 85 vs. less than 85% of maximal predicted heart rate during EST (Pâ=â0.075). CONCLUSION: TnI increase after EST in patients with suspected stable angina is largely independent of the results of coronary angiography and EST.
Assuntos
Angina Estável , Angiografia Coronária , Estenose Coronária , Teste de Esforço , Frequência Cardíaca , Troponina I/sangue , Angina Estável/sangue , Angina Estável/diagnóstico , Biomarcadores/sangue , Angiografia Coronária/métodos , Angiografia Coronária/estatística & dados numéricos , Estenose Coronária/sangue , Estenose Coronária/diagnóstico , Correlação de Dados , Exercício Físico/fisiologia , Teste de Esforço/métodos , Teste de Esforço/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangueRESUMO
BACKGROUND: A sizeable number of patients with a diagnosis of non-ST segment elevation acute coronary syndrome show non-obstructive coronary artery disease. In this study we assessed whether differences in vascular and cardiac autonomic function exist between non-ST segment elevation acute coronary syndrome patients with obstructive or non-obstructive coronary artery disease. METHODS AND RESULTS: Systemic endothelium-dependent and independent vascular dilator function (assessed by flow-mediated dilation and nitrate-mediated dilation of the brachial artery, respectively) and cardiac autonomic function (assessed by time-domain and frequency-domain heart rate variability parameters) were assessed on admission in 120 patients with a diagnosis of non-ST segment elevation acute coronary syndrome. Patients were divided into two groups according to coronary angiography findings: (a) 59 (49.2%) with obstructive coronary artery disease (≥50% stenosis in any epicardial arteries); (b) 61 (50.8%) with non-obstructive coronary artery disease. No significant differences between the two groups were found in both flow-mediated dilation (5.03 ± 2.6 vs. 5.40 ± 2.5%, respectively; P = 0.37) and nitrate-mediated dilatation (6.79 ± 2.8 vs. 7.30 ± 3.4%, respectively; P = 0.37). No significant differences were also observed between the two groups both in time-domain and frequency-domain heart rate variability variables, although the triangular index tended to be lower in obstructive coronary artery disease patients (30.2 ± 9.5 vs. 33.9 ± 11.6, respectively; P = 0.058). Neither vascular nor heart rate variability variables predicted the recurrence of angina, requiring emergency room admission or re-hospitalisation, during 11.3 months of follow-up. CONCLUSIONS: Among patients admitted with a diagnosis of non-ST segment elevation acute coronary syndrome we found no significant differences in systemic vascular dilator function and cardiac autonomic function between those with obstructive coronary artery disease and those with non-obstructive coronary artery disease.